890 results on '"Kivipelto, M"'
Search Results
2. Potentially Modifiable Dementia Risk Factors in Canada: An Analysis of Canadian Longitudinal Study on Aging with a Multi-Country Comparison
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Son, S., Speechley, M., Zou, G. Y., Kivipelto, M., Mangialasche, F., Feldman, H. H., Chertkow, H., Belleville, S., Nygaard, H., Hachinski, V., Pieruccini-Faria, F., and Montero-Odasso, Manuel
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- 2024
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3. Evaluation of Clinical Meaningfulness of Fortasyn Connect in Terms of “Time Saved”
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Dickson, Samuel P., Solomon, A., Kivipelto, M., Hartmann, T., van Hees, A. M. J., Brownlee, A., Haaland, B., Mallinckrodt, C. H., and Hendrix, S. B.
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- 2024
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4. Temporal Muscle Thickness Predicts Mortality and Disability in Older Adults Diagnosed with Mild Dementia
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Borda, Miguel German, Baldera, J. Patricio, Patino-Hernandez, D., Westman, E., Pérez-Zepeda, M. U., Tarazona-Santabalbina, F. J., Wakabayashi, H., Arai, H., Kivipelto, M., and Aarsland, D.
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- 2024
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5. Combined Evidence for a Long-Term, Clinical Slowing Effect of Multinutrient Intervention in Prodromal Alzheimer’s Disease: Post-Hoc Analysis of 3-Year Data from the LipiDiDiet Trial
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Hendrix, Suzanne B., Soininen, H., Solomon, A., Visser, P. J., van Hees, A. M. J., Counotte, D. S., Nicodemus-Johnson, J., Dickson, S. P., Blennow, K., Kivipelto, M., and Hartmann, T.
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- 2023
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6. Frontoparietal atrophy trajectories in cognitively unimpaired elderly individuals using longitudinal Bayesian clustering
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Lorenzon, G., Poulakis, K., Mohanty, R., Kivipelto, M., Eriksdotter, M., Ferreira, D., and Westman, E.
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- 2024
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7. Family Members’ Experiences of Young-Onset Dementia: Becoming Responsible Yet Feeling Powerless
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Aspö M, Visser LNC, Kivipelto M, Boström AM, and Seiger Cronfalk B
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yod ,relative ,psychosocial support ,qualitative ,health care system ,Medicine (General) ,R5-920 - Abstract
Malin Aspö,1,2 Leonie NC Visser,1,3,4 Miia Kivipelto,1,2,5,6 Anne-Marie Boström,2,6,7 Berit Seiger Cronfalk7 1Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; 2Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden; 3Department of Medical Psychology, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, the Netherlands; 4Amsterdam Public Health Research Institute, Quality of Care, Amsterdam, the Netherlands; 5Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London, London, UK; 6Stockholms Sjukhem, Research & Development Unit, Stockholm, Sweden; 7Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Stockholm, SwedenCorrespondence: Malin Aspö, Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, 171 64, Sweden, Tel +4672-582 32 39, Email malin.aspo@ki.sePurpose: Dementia is often associated with old age but can also occur in midlife. The latter is commonly referred to as young-onset dementia (YOD). The diagnosis not only has an impact on the persons with YOD but also on their family members. For family members, the diagnosis changes their lives, as responsibilities and roles alter when the care and wellbeing of the relative increasingly come into focus. The aim of this study was to explore family members’ experiences of sharing lives with a relative diagnosed with YOD – from onset of symptoms until the person relocated to a nursing home.Patients and Methods: The study has a qualitative approach with in-depth interviews. In total, the study included 15 family members aged ≥ 18 years participated, all with a relative diagnosed with dementia before the age of 65. At the time of the interview, all had a relative living in a nursing home. The interviews were analyzed using thematic analysis.Results: Two key themes were identified: Becoming responsible and Dealing with the situation. Family members found themselves increasingly responsible for many parts of their relatives’ lives and forced to make decisions on their behalf. This was experienced as being lonely, as family members wished to share their responsibility. Despite of their efforts to control and deal with their situation, family members reported a lack of power to influence certain factors, such as access to appropriate healthcare services, causing feelings of distress.Conclusion: These findings emphasize the need of improved and tailored support and guidance for family members of persons with YOD. Further, the findings highlight the importance of increased knowledge and awareness among social workers and other healthcare professionals regarding support to family members of persons with YOD.Keywords: YOD, relative, psychosocial support, qualitative, health care system
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- 2023
8. Experiences of Active Everyday Life Among Persons with Prodromal Alzheimer’s Disease: A Qualitative Study
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Fallahpour M, Fritz H, Thunborg C, Akenine U, and Kivipelto M
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alzheimer’s disease ,everyday life ,activity ,participation ,prevention ,qualitative method ,Medicine (General) ,R5-920 - Abstract
Mandana Fallahpour,1,2 Heather Fritz,3 Charlotta Thunborg,2,4 Ulrika Akenine,2 Miia Kivipelto2,5,6 1Department of Neurobiology, Care Sciences and Society, Division of Occupational Therapy, Karolinska Institutet, Stockholm, Sweden; 2Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; 3School of Occupational Therapy, Pacific Northwest University of Health Sciences, Yakima, WA, USA; 4School of Health, Care and Social Welfare, Department of Physiotherapy, Mälardalen University, Västerås, Sweden; 5Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 6Stockholms Sjukhem, Research & Development Unit, Stockholm, SwedenCorrespondence: Mandana Fallahpour, Department of Neurobiology, Care Sciences and Society, Division of Occupational Therapy, Karolinska Institutet, Stockholm, Sweden, Email mandana.fallahpour@ki.seIntroduction: Identifying strategies to prevent or delay cognitive decline among the rising numbers of elderly is acknowledged as a global public health priority. Research suggests that an active lifestyle in terms of participation in activities has the potential to reduce the risk of later-life cognitive decline. The concept of “active everyday life”, however, needs to be further explored.Aim: The study aimed to explore and describe the active everyday lives of persons with prodromal Alzheimer’s disease (AD) in terms of quality of participation in activities and perceived restrictions.Methods: This qualitative study was part of a larger project, the MIND-ADMINI trial. Nine in-depth interviews were conducted with seven participants (2 males, 5 females; mean age of 72.3) at baseline before the intervention. The data were collected from January to October 2018 and analyzed using the grounded theory approach.Results: Four categories emerged from the analysis: (i) active body and mind; (ii) doing desired meaningful activities to feel engaged, contented, and satisfied; (iii) doing in the context of being connected to others; (iv) ability in making decisions and taking actions. From these categories, which presented the key elements of an active everyday life, a core category was identified: Living a complete life in flow.Conclusion: The findings suggest key elements of participation quality that contribute to an active life. The identified elements are important to be considered in rehabilitation to provide opportunities and possibilities for participation to enable and improve the quality of participation among persons with cognitive impairments.Keywords: Alzheimer’s disease, everyday life, activity, participation, prevention, qualitative method
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- 2022
9. Blood Derived Amyloid Biomarkers for Alzheimer’s Disease Prevention
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Udeh-Momoh, C., Zheng, B., Sandebring-Matton, A., Novak, G., Kivipelto, M., Jönsson, L., and Middleton, Lefkos
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- 2022
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10. Mechanisms Underlying Non-Pharmacological Dementia Prevention Strategies: A Translational Perspective
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Alanko, V., Udeh-Momoh, C., Kivipelto, M., and Sandebring-Matton, Anna
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- 2022
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11. Experiences of Participation in a Multimodal Preventive Trial MIND-ADMINI Among Persons with Prodromal Alzheimer’s Disease: A Qualitative Study
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Akenine U, Thunborg C, Kivipelto M, and Fallahpour M
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alzheimer’s disease ,multimodal prevention ,participation ,qualitative method. ,Medicine (General) ,R5-920 - Abstract
Ulrika Akenine,1 Charlotta Thunborg,1,2 Miia Kivipelto,1– 4 Mandana Fallahpour1,5 1Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; 2School of Health, Care and Social Welfare, Department of Physiotherapy, Mälardalen University, Västerås, Sweden; 3Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 4Stockholms Sjukhem, Research & Development Unit, Stockholm, Sweden; 5Department of Neurobiology, Care Sciences and Society, Division of Occupational Therapy, Karolinska Institutet, Stockholm, SwedenCorrespondence: Ulrika AkenineKarolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska vägen 37A, QA32, SE-171 64, Solna, Stockholm, SwedenTel +46 70 667 99 67Email ulrika.akenine@ki.seMandana FallahpourKarolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Occupational Therapy, Alfred Nobels Allé 23, SE-141 83 Huddinge, Stockholm, SwedenTel +46 8 524 838 56Email mandana.fallahpour@ki.seIntroduction: Alzheimer’s disease (AD) is one of the world’s leading public health challenges. One-third of AD cases are attributable to modifiable vascular and lifestyle-related risk factors. The Multimodal Preventive Trial for Alzheimer’s Disease, MIND-ADMINI a 6-month multinational parallel-group randomized controlled trial (RCT), targeted persons with prodromal AD and built on the positive outcomes from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial. The intervention consisted of four main components of (i) physical exercise training program, (ii) nutrition guidance, (iii) cognitive training, and (iv) social stimulation, as well as (iv) monitoring of metabolic/vascular risk factors.Aim: The study aimed to explore and describe the experiences of participation in MIND-ADMINI among persons with prodromal AD.Methods: This qualitative study was part of the larger MIND-ADMINI project. Eight participants were interviewed twice, before and after the intervention. The data was analyzed using qualitative content analysis.Results: The results are presented as categories of (i) knowledge of AD and prevention, (ii) motives for study participation, (iii) experiences of the received information about the study, (iv) taking the decision to participate, (v) expectations on study participation, (vi) experiences of study participation and (vii) internal and external factors influencing study participation.Conclusion: The MIND-ADMINI was well-tolerated by the participants. At the beginning of the study, the number of tasks and visits was perceived as burdensome but was later well-tolerated. The participant’ knowledge about AD and prevention increased during the trial. Their motives for participating in MIND-ADMINI were described as both altruistic and self-beneficial. Health benefits from the study components, access to specialized medical care were identified as benefits. Managing the intensive flow of information was described a major challenge. The participants’ needs for personalized support during the trial stress the importance of applying a person-centered approach providing the preventive trials.Keywords: Alzheimer’s disease, multimodal prevention, participation, qualitative method
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- 2022
12. Cognitive reserve, cortisol, and Alzheimer's disease biomarkers : A memory clinic study
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Yerramalla, M. S., Darin-Mattsson, A., Udeh-Momoh, C. T., Holleman, J., Kåreholt, Ingemar, Aspö, M., Hagman, G., Kivipelto, M., Solomon, A., Marseglia, A., Sindi, S., Yerramalla, M. S., Darin-Mattsson, A., Udeh-Momoh, C. T., Holleman, J., Kåreholt, Ingemar, Aspö, M., Hagman, G., Kivipelto, M., Solomon, A., Marseglia, A., and Sindi, S.
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INTRODUCTION: Cognitive reserve might mitigate the risk of Alzheimer's dementia among memory clinic patients. No study has examined the potential modifying role of stress on this relation. METHODS: We examined cross-sectional associations of the cognitive reserve index (CRI; education, occupational complexity, physical and leisure activities, and social health) with cognitive performance and AD-related biomarkers among 113 memory clinic patients. The longitudinal association between CRI and cognition over a 3-year follow-up was assessed. We examined whether associations were influenced by perceived stress and five measures of diurnal salivary cortisol. RESULTS: Higher CRI scores were associated with better cognition. Adjusting for cortisol measures reduced the beneficial association of CRI on cognition. A higher CRI score was associated with better working memory in individuals with higher (favorable) cortisol AM/PM ratio, but not among individuals with low cortisol AM/PM ratio. No association was found between CRI and AD-related biomarkers. DISCUSSION: Physiological stress reduces the neurocognitive benefits of cognitive reserve among memory clinic patients. Highlights: Physiological stress may reduce the neurocognitive benefits accrued from cognitively stimulating and enriching life experiences (cognitive reserve [CR]) in memory clinic patients. Cortisol awakening response modified the relation between CR and P-tau181, a marker of Alzheimer's disease (AD). Effective stress management techniques for AD and related dementia prevention are warranted.
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- 2024
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13. Digital Screening for Cognitive Impairment — A Proof of Concept Study
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Bloniecki, Victor, Hagman, G., Ryden, M., and Kivipelto, M.
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- 2021
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14. Correction to: Bisphosphonates and mortality: confounding in observational studies
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Bergman, J., Nordström, A., Hommel, A., Kivipelto, M., and Nordström, P.
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- 2021
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15. Erratum to: Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease
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Hendrix, Suzanne B., Soininen, H., van Hees, A. M. J., Ellison, N., Visser, P. J., Solomon, A., Attali, A., Blennow, K., Kivipelto, M., and Hartmann, T.
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- 2023
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16. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores (Nature Communications, (2021), 12, 1, (3417), 10.1038/s41467-021-22491-8)
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de Rojas I., de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernandez, I, Montrreal, L, Antunez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, Gonzalez-Perez, A, Calero, M, Franco-Macias, E, Macias, J, Blesa, R, Cervera-Carles, L, Menendez-Gonzalez, M, Frank-Garcia, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, Garcia-Madrona, S, Garcia-Gonzalez, P, Alarcon-Martin, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Perez-Cordon, A, Benussi, A, Rabano, A, Padovani, A, Squassina, A, de Mendonca, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gomez, A, Martin Montes, A, Sanabria, A, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Stahlbom, A, Tybjaerg-Hansen, A, Hartmann, A, Spottke, A, Corbaton-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martinez Rodriguez, C, Munoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grunblatt, E, Dardiotis, E, Duzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Kucukali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbaek, G, Ortega, G, Chene, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fliessbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Lowenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sanchez-Arjona, M, Dalmasso, M, Martinez-Larrad, M, Arcaro, M, Nothen, M, Fernandez-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossu, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Mecocci, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hagg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Smith, A, Saenz, A, Bizzarro, A, Lauria, A, Vacca, A, Solomon, A, Anastasiou, A, Richardson, A, Boland, A, Koivisto, A, Daniele, A, Greco, A, Marianthi, A, Mcguinness, B, Fin, B, Ferrari, C, Custodero, C, Ferrarese, C, Ingino, C, Mangone, C, Reyes Toso, C, Martinez, C, Cuesta, C, Muchnik, C, Joachim, C, Ortiz, C, Besse, C, Johansson, C, Zoia, C, Laske, C, Anastasiou, C, Palacio, D, Politis, D, Janowitz, D, Craig, D, Mann, D, Neary, D, Jurgen, D, Daian, D, Belezhanska, D, Kohler, E, Castano, E, Koutsouraki, E, Chipi, E, De Roeck, E, Costantini, E, Vardy, E, Piras, F, Roveta, F, Prestia, F, Assogna, F, Salani, F, Sala, G, Lacidogna, G, Novack, G, Wilcock, G, Thonberg, H, Kolsch, H, Weber, H, Boecker, H, Etchepareborda, I, Piaceri, I, Tuomilehto, J, Lindstrom, J, Laczo, J, Johnston, J, Deleuze, J, Harris, J, Schott, J, Priller, J, Bacha, J, Snowden, J, Lisso, J, Mihova, K, Traykov, L, Morelli, L, Brusco, L, Rainer, M, Takalo, M, Bjerke, M, Del Zompo, M, Serpente, M, Sanchez Abalos, M, Rios, M, Peltonen, M, Herrman, M, Kohler, M, Rojo, M, Jones, M, Orsini, M, Medel, N, Olivar, N, Fox, N, Salvadori, N, Hooper, N, Galeano, P, Solis, P, Bastiani, P, Passmore, P, Heun, R, Antikainen, R, Olaso, R, Perneczky, R, Germani, S, Lopez-Garcia, S, Love, S, Mehrabian, S, Bagnoli, S, Kochen, S, Andreoni, S, Teipel, S, Todd, S, Pickering-Brown, S, Natunen, T, Tegos, T, Laatikainen, T, Strandberg, T, Polvikoski, T, Matoska, V, Ciullo, V, Cores, V, Solfrizzi, V, Lisetti, V, Sevillano, Z, Aguilera, N, Alarcon, E, Boada, M, Buendia, M, Canabate, P, Carracedo, A, Diego, S, Gailhajenet, A, Guitart, M, Ibarria, M, Lafuente, A, Maronas, O, Martin, E, Martinez, M, Marquie, M, Mauleon, A, Moreno, M, Orellana, A, Pancho, A, Peleja, E, Preckler, S, Real, L, Ruiz, A, Saez, M, Serrano-Rios, M, Tarraga, L, Vargas, L, Adarmes-Gomez, A, Alonso, M, Alvarez, V, Amer-Ferrer, G, Antequera, M, Bernal, M, Bullido, M, Burguera, J, Carrillo, F, Carrion-Claro, M, Casajeros, M, Clarimon, J, Cruz-Gamero, J, de Pancorbo, M, Escuela, R, Garrote-Espina, L, Garcia-Alberca, J, Garcia Madrona, S, Garcia-Ribas, G, Gomez-Garre, P, Hevilla, S, Jesus, S, Labrador Espinosa, M, Legaz, A, Lleo, A, Lopez de Munain, A, Macias-Garcia, D, Manzanares, S, Marin, M, Marin-Munoz, J, Marin, T, Martinez, B, Martinez, V, Martinez-Lage Alvarez, P, Medina, M, Mendioroz Iriarte, M, Mir, P, Molinuevo, J, Pastor, P, Perez Tur, J, Perinan-Tocino, T, Pineda-Sanchez, R, Pinol-Ripoll, G, Real de Asua, D, Rodrigo, S, Sanchez del Valle Diaz, R, Sanchez-Juan, P, Sastre, I, Vicente, M, Vigo-Ortega, R, Vivancos, L, Macleod, C, Mccracken, C, Brayne, C, Bresner, C, Grozeva, D, Bellou, E, Sommerville, E, Matthews, F, Leonenko, G, Menzies, G, Windle, G, Harwood, J, Phillips, J, Bennett, K, Luckuck, L, Clare, L, Woods, R, Saad, S, Burholt, V, Kehoe, P, Scheltens, P, Holstege, H, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sanchez-Valle, R, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, de Rojas I., Moreno-Grau S., Tesi N., Grenier-Boley B., Andrade V., Jansen I. E., Pedersen N. L., Stringa N., Zettergren A., Hernandez I., Montrreal L., Antunez C., Antonell A., Tankard R. M., Bis J. C., Sims R., Bellenguez C., Quintela I., Gonzalez-Perez A., Calero M., Franco-Macias E., Macias J., Blesa R., Cervera-Carles L., Menendez-Gonzalez M., Frank-Garcia A., Royo J. L., Moreno F., Huerto Vilas R., Baquero M., Diez-Fairen M., Lage C., Garcia-Madrona S., Garcia-Gonzalez P., Alarcon-Martin E., Valero S., Sotolongo-Grau O., Ullgren A., Naj A. C., Lemstra A. W., Benaque A., Perez-Cordon A., Benussi A., Rabano A., Padovani A., Squassina A., de Mendonca A., Arias Pastor A., Kok A. A. L., Meggy A., Pastor A. B., Espinosa A., Corma-Gomez A., Martin Montes A., Sanabria A., DeStefano A. L., Schneider A., Haapasalo A., Kinhult Stahlbom A., Tybjaerg-Hansen A., Hartmann A. M., Spottke A., Corbaton-Anchuelo A., Rongve A., Borroni B., Arosio B., Nacmias B., Nordestgaard B. G., Kunkle B. W., Charbonnier C., Abdelnour C., Masullo C., Martinez Rodriguez C., Munoz-Fernandez C., Dufouil C., Graff C., Ferreira C. B., Chillotti C., Reynolds C. A., Fenoglio C., Van Broeckhoven C., Clark C., Pisanu C., Satizabal C. L., Holmes C., Buiza-Rueda D., Aarsland D., Rujescu D., Alcolea D., Galimberti D., Wallon D., Seripa D., Grunblatt E., Dardiotis E., Duzel E., Scarpini E., Conti E., Rubino E., Gelpi E., Rodriguez-Rodriguez E., Duron E., Boerwinkle E., Ferri E., Tagliavini F., Kucukali F., Pasquier F., Sanchez-Garcia F., Mangialasche F., Jessen F., Nicolas G., Selbaek G., Ortega G., Chene G., Hadjigeorgiou G., Rossi G., Spalletta G., Giaccone G., Grande G., Binetti G., Papenberg G., Hampel H., Bailly H., Zetterberg H., Soininen H., Karlsson I. K., Alvarez I., Appollonio I., Giegling I., Skoog I., Saltvedt I., Rainero I., Rosas Allende I., Hort J., Diehl-Schmid J., Van Dongen J., Vidal J. -S., Lehtisalo J., Wiltfang J., Thomassen J. Q., Kornhuber J., Haines J. L., Vogelgsang J., Pineda J. A., Fortea J., Popp J., Deckert J., Buerger K., Morgan K., Fliessbach K., Sleegers K., Molina-Porcel L., Kilander L., Weinhold L., Farrer L. A., Wang L. -S., Kleineidam L., Farotti L., Parnetti L., Tremolizzo L., Hausner L., Benussi L., Froelich L., Ikram M. A., Deniz-Naranjo M. C., Tsolaki M., Rosende-Roca M., Lowenmark M., Hulsman M., Spallazzi M., Pericak-Vance M. A., Esiri M., Bernal Sanchez-Arjona M., Dalmasso M. C., Martinez-Larrad M. T., Arcaro M., Nothen M. M., Fernandez-Fuertes M., Dichgans M., Ingelsson M., Herrmann M. J., Scherer M., Vyhnalek M., Kosmidis M. H., Yannakoulia M., Schmid M., Ewers M., Heneka M. T., Wagner M., Scamosci M., Kivipelto M., Hiltunen M., Zulaica M., Alegret M., Fornage M., Roberto N., van Schoor N. M., Seidu N. M., Banaj N., Armstrong N. J., Scarmeas N., Scherbaum N., Goldhardt O., Hanon O., Peters O., Skrobot O. A., Quenez O., Lerch O., Bossu P., Caffarra P., Dionigi Rossi P., Sakka P., Mecocci P., Hoffmann P., Holmans P. A., Fischer P., Riederer P., Yang Q., Marshall R., Kalaria R. N., Mayeux R., Vandenberghe R., Cecchetti R., Ghidoni R., Frikke-Schmidt R., Sorbi S., Hagg S., Engelborghs S., Helisalmi S., Botne Sando S., Kern S., Archetti S., Boschi S., Fostinelli S., Gil S., Mendoza S., Mead S., Ciccone S., Djurovic S., Heilmann-Heimbach S., Riedel-Heller S., Kuulasmaa T., del Ser T., Lebouvier T., Polak T., Ngandu T., Grimmer T., Bessi V., Escott-Price V., Giedraitis V., Deramecourt V., Maier W., Jian X., Pijnenburg Y. A. L., Smith A. D., Saenz A., Bizzarro A., Lauria A., Vacca A., Solomon A., Anastasiou A., Richardson A., Boland A., Koivisto A., Daniele A., Greco A., Marianthi A., McGuinness B., Fin B., Ferrari C., Custodero C., Ferrarese C., Ingino C., Mangone C., Reyes Toso C., Martinez C., Cuesta C., Muchnik C., Joachim C., Ortiz C., Besse C., Johansson C., Zoia C. P., Laske C., Anastasiou C., Palacio D. L., Politis D. G., Janowitz D., Craig D., Mann D. M., Neary D., Jurgen D., Daian D., Belezhanska D., Kohler E., Castano E. M., Koutsouraki E., Chipi E., De Roeck E., Costantini E., Vardy E. R. L. C., Piras F., Roveta F., Prestia F. A., Assogna F., Salani F., Sala G., Lacidogna G., Novack G., Wilcock G., Thonberg H., Kolsch H., Weber H., Boecker H., Etchepareborda I., Piaceri I., Tuomilehto J., Lindstrom J., Laczo J., Johnston J., Deleuze J. -F., Harris J., Schott J. M., Priller J., Bacha J. I., Snowden J., Lisso J., Mihova K. Y., Traykov L., Morelli L., Brusco L. I., Rainer M., Takalo M., Bjerke M., Del Zompo M., Serpente M., Sanchez Abalos M., Rios M., Peltonen M., Herrman M. J., Kohler M., Rojo M., Jones M., Orsini M., Medel N., Olivar N., Fox N. C., Salvadori N., Hooper N. M., Galeano P., Solis P., Bastiani P., Passmore P., Heun R., Antikainen R., Olaso R., Perneczky R., Germani S., Lopez-Garcia S., Love S., Mehrabian S., Bagnoli S., Kochen S., Andreoni S., Teipel S., Todd S., Pickering-Brown S., Natunen T., Tegos T., Laatikainen T., Strandberg T., Polvikoski T. M., Matoska V., Ciullo V., Cores V., Solfrizzi V., Lisetti V., Sevillano Z., Aguilera N., Alarcon E., Boada M., Buendia M., Canabate P., Carracedo A., Diego S., Gailhajenet A., Guitart M., Ibarria M., Lafuente A., Maronas O., Martin E., Martinez M. T., Marquie M., Mauleon A., Moreno M., Orellana A., Pancho A., Peleja E., Preckler S., Real L. M., Ruiz A., Saez M. E., Serrano-Rios M., Tarraga L., Vargas L., Adarmes-Gomez A. D., Alonso M. D., Alvarez V., Amer-Ferrer G., Antequera M., Bernal M., Bullido M. J., Burguera J. A., Carrillo F., Carrion-Claro M., Casajeros M. J., Clarimon J., Cruz-Gamero J. M., de Pancorbo M. M., Escuela R., Garrote-Espina L., Garcia-Alberca J. M., Garcia Madrona S., Garcia-Ribas G., Gomez-Garre P., Hevilla S., Jesus S., Labrador Espinosa M. A., Legaz A., Lleo A., Lopez de Munain A., Macias-Garcia D., Manzanares S., Marin M., Marin-Munoz J., Marin T., Martinez B., Martinez V., Martinez-Lage Alvarez P., Medina M., Mendioroz Iriarte M., Mir P., Molinuevo J. L., Pastor P., Perez Tur J., Perinan-Tocino T., Pineda-Sanchez R., Pinol-Ripoll G., Real de Asua D., Rodrigo S., Sanchez del Valle Diaz R., Sanchez-Juan P., Sastre I., Vicente M. P., Vigo-Ortega R., Vivancos L., Macleod C., McCracken C., Brayne C., Bresner C., Grozeva D., Bellou E., Sommerville E. W., Matthews F., Leonenko G., Menzies G., Windle G., Harwood J., Phillips J., Bennett K., Luckuck L., Clare L., Woods R., Saad S., Burholt V., Kehoe P. G., Scheltens P., Holstege H., Amouyel P., Schellenberg G. D., Williams J., Seshadri S., van Duijn C. M., Mather K. A., Sanchez-Valle R., Blennow K., Huisman M., Andreassen O. A., Posthuma D., van der Flier W. M., Ramirez A., Lambert J. -C., van der Lee S. 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Frikke-Schmidt, R, Sorbi, S, Hagg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Smith, A, Saenz, A, Bizzarro, A, Lauria, A, Vacca, A, Solomon, A, Anastasiou, A, Richardson, A, Boland, A, Koivisto, A, Daniele, A, Greco, A, Marianthi, A, Mcguinness, B, Fin, B, Ferrari, C, Custodero, C, Ferrarese, C, Ingino, C, Mangone, C, Reyes Toso, C, Martinez, C, Cuesta, C, Muchnik, C, Joachim, C, Ortiz, C, Besse, C, Johansson, C, Zoia, C, Laske, C, Anastasiou, C, Palacio, D, Politis, D, Janowitz, D, Craig, D, Mann, D, Neary, D, Jurgen, D, Daian, D, Belezhanska, D, Kohler, E, Castano, E, Koutsouraki, E, Chipi, E, De Roeck, E, Costantini, E, Vardy, E, Piras, F, Roveta, F, Prestia, F, Assogna, F, 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Ibarria, M, Lafuente, A, Maronas, O, Martin, E, Martinez, M, Marquie, M, Mauleon, A, Moreno, M, Orellana, A, Pancho, A, Peleja, E, Preckler, S, Real, L, Ruiz, A, Saez, M, Serrano-Rios, M, Tarraga, L, Vargas, L, Adarmes-Gomez, A, Alonso, M, Alvarez, V, Amer-Ferrer, G, Antequera, M, Bernal, M, Bullido, M, Burguera, J, Carrillo, F, Carrion-Claro, M, Casajeros, M, Clarimon, J, Cruz-Gamero, J, de Pancorbo, M, Escuela, R, Garrote-Espina, L, Garcia-Alberca, J, Garcia Madrona, S, Garcia-Ribas, G, Gomez-Garre, P, Hevilla, S, Jesus, S, Labrador Espinosa, M, Legaz, A, Lleo, A, Lopez de Munain, A, Macias-Garcia, D, Manzanares, S, Marin, M, Marin-Munoz, J, Marin, T, Martinez, B, Martinez, V, Martinez-Lage Alvarez, P, Medina, M, Mendioroz Iriarte, M, Mir, P, Molinuevo, J, Pastor, P, Perez Tur, J, Perinan-Tocino, T, Pineda-Sanchez, R, Pinol-Ripoll, G, Real de Asua, D, Rodrigo, S, Sanchez del Valle Diaz, R, Sanchez-Juan, P, Sastre, I, Vicente, M, Vigo-Ortega, R, Vivancos, L, Macleod, C, Mccracken, C, Brayne, C, Bresner, C, Grozeva, D, Bellou, E, Sommerville, E, Matthews, F, Leonenko, G, Menzies, G, Windle, G, Harwood, J, Phillips, J, Bennett, K, Luckuck, L, Clare, L, Woods, R, Saad, S, Burholt, V, Kehoe, P, Scheltens, P, Holstege, H, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sanchez-Valle, R, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, de Rojas I., Moreno-Grau S., Tesi N., Grenier-Boley B., Andrade V., Jansen I. E., Pedersen N. L., Stringa N., Zettergren A., Hernandez I., Montrreal L., Antunez C., Antonell A., Tankard R. M., Bis J. C., Sims R., Bellenguez C., Quintela I., Gonzalez-Perez A., Calero M., Franco-Macias E., Macias J., Blesa R., Cervera-Carles L., Menendez-Gonzalez M., Frank-Garcia A., Royo J. L., Moreno F., Huerto Vilas R., Baquero M., Diez-Fairen M., Lage C., Garcia-Madrona S., Garcia-Gonzalez P., Alarcon-Martin E., Valero S., Sotolongo-Grau O., Ullgren A., Naj A. C., Lemstra A. W., Benaque A., Perez-Cordon A., Benussi A., Rabano A., Padovani A., Squassina A., de Mendonca A., Arias Pastor A., Kok A. A. L., Meggy A., Pastor A. B., Espinosa A., Corma-Gomez A., Martin Montes A., Sanabria A., DeStefano A. L., Schneider A., Haapasalo A., Kinhult Stahlbom A., Tybjaerg-Hansen A., Hartmann A. M., Spottke A., Corbaton-Anchuelo A., Rongve A., Borroni B., Arosio B., Nacmias B., Nordestgaard B. G., Kunkle B. W., Charbonnier C., Abdelnour C., Masullo C., Martinez Rodriguez C., Munoz-Fernandez C., Dufouil C., Graff C., Ferreira C. B., Chillotti C., Reynolds C. A., Fenoglio C., Van Broeckhoven C., Clark C., Pisanu C., Satizabal C. L., Holmes C., Buiza-Rueda D., Aarsland D., Rujescu D., Alcolea D., Galimberti D., Wallon D., Seripa D., Grunblatt E., Dardiotis E., Duzel E., Scarpini E., Conti E., Rubino E., Gelpi E., Rodriguez-Rodriguez E., Duron E., Boerwinkle E., Ferri E., Tagliavini F., Kucukali F., Pasquier F., Sanchez-Garcia F., Mangialasche F., Jessen F., Nicolas G., Selbaek G., Ortega G., Chene G., Hadjigeorgiou G., Rossi G., Spalletta G., Giaccone G., Grande G., Binetti G., Papenberg G., Hampel H., Bailly H., Zetterberg H., Soininen H., Karlsson I. K., Alvarez I., Appollonio I., Giegling I., Skoog I., Saltvedt I., Rainero I., Rosas Allende I., Hort J., Diehl-Schmid J., Van Dongen J., Vidal J. -S., Lehtisalo J., Wiltfang J., Thomassen J. Q., Kornhuber J., Haines J. L., Vogelgsang J., Pineda J. A., Fortea J., Popp J., Deckert J., Buerger K., Morgan K., Fliessbach K., Sleegers K., Molina-Porcel L., Kilander L., Weinhold L., Farrer L. A., Wang L. -S., Kleineidam L., Farotti L., Parnetti L., Tremolizzo L., Hausner L., Benussi L., Froelich L., Ikram M. A., Deniz-Naranjo M. C., Tsolaki M., Rosende-Roca M., Lowenmark M., Hulsman M., Spallazzi M., Pericak-Vance M. A., Esiri M., Bernal Sanchez-Arjona M., Dalmasso M. C., Martinez-Larrad M. T., Arcaro M., Nothen M. M., Fernandez-Fuertes M., Dichgans M., Ingelsson M., Herrmann M. J., Scherer M., Vyhnalek M., Kosmidis M. H., Yannakoulia M., Schmid M., Ewers M., Heneka M. T., Wagner M., Scamosci M., Kivipelto M., Hiltunen M., Zulaica M., Alegret M., Fornage M., Roberto N., van Schoor N. M., Seidu N. M., Banaj N., Armstrong N. J., Scarmeas N., Scherbaum N., Goldhardt O., Hanon O., Peters O., Skrobot O. A., Quenez O., Lerch O., Bossu P., Caffarra P., Dionigi Rossi P., Sakka P., Mecocci P., Hoffmann P., Holmans P. A., Fischer P., Riederer P., Yang Q., Marshall R., Kalaria R. N., Mayeux R., Vandenberghe R., Cecchetti R., Ghidoni R., Frikke-Schmidt R., Sorbi S., Hagg S., Engelborghs S., Helisalmi S., Botne Sando S., Kern S., Archetti S., Boschi S., Fostinelli S., Gil S., Mendoza S., Mead S., Ciccone S., Djurovic S., Heilmann-Heimbach S., Riedel-Heller S., Kuulasmaa T., del Ser T., Lebouvier T., Polak T., Ngandu T., Grimmer T., Bessi V., Escott-Price V., Giedraitis V., Deramecourt V., Maier W., Jian X., Pijnenburg Y. A. L., Smith A. D., Saenz A., Bizzarro A., Lauria A., Vacca A., Solomon A., Anastasiou A., Richardson A., Boland A., Koivisto A., Daniele A., Greco A., Marianthi A., McGuinness B., Fin B., Ferrari C., Custodero C., Ferrarese C., Ingino C., Mangone C., Reyes Toso C., Martinez C., Cuesta C., Muchnik C., Joachim C., Ortiz C., Besse C., Johansson C., Zoia C. P., Laske C., Anastasiou C., Palacio D. L., Politis D. G., Janowitz D., Craig D., Mann D. M., Neary D., Jurgen D., Daian D., Belezhanska D., Kohler E., Castano E. M., Koutsouraki E., Chipi E., De Roeck E., Costantini E., Vardy E. R. L. C., Piras F., Roveta F., Prestia F. A., Assogna F., Salani F., Sala G., Lacidogna G., Novack G., Wilcock G., Thonberg H., Kolsch H., Weber H., Boecker H., Etchepareborda I., Piaceri I., Tuomilehto J., Lindstrom J., Laczo J., Johnston J., Deleuze J. -F., Harris J., Schott J. M., Priller J., Bacha J. I., Snowden J., Lisso J., Mihova K. Y., Traykov L., Morelli L., Brusco L. I., Rainer M., Takalo M., Bjerke M., Del Zompo M., Serpente M., Sanchez Abalos M., Rios M., Peltonen M., Herrman M. J., Kohler M., Rojo M., Jones M., Orsini M., Medel N., Olivar N., Fox N. C., Salvadori N., Hooper N. M., Galeano P., Solis P., Bastiani P., Passmore P., Heun R., Antikainen R., Olaso R., Perneczky R., Germani S., Lopez-Garcia S., Love S., Mehrabian S., Bagnoli S., Kochen S., Andreoni S., Teipel S., Todd S., Pickering-Brown S., Natunen T., Tegos T., Laatikainen T., Strandberg T., Polvikoski T. M., Matoska V., Ciullo V., Cores V., Solfrizzi V., Lisetti V., Sevillano Z., Aguilera N., Alarcon E., Boada M., Buendia M., Canabate P., Carracedo A., Diego S., Gailhajenet A., Guitart M., Ibarria M., Lafuente A., Maronas O., Martin E., Martinez M. T., Marquie M., Mauleon A., Moreno M., Orellana A., Pancho A., Peleja E., Preckler S., Real L. M., Ruiz A., Saez M. E., Serrano-Rios M., Tarraga L., Vargas L., Adarmes-Gomez A. D., Alonso M. D., Alvarez V., Amer-Ferrer G., Antequera M., Bernal M., Bullido M. J., Burguera J. A., Carrillo F., Carrion-Claro M., Casajeros M. J., Clarimon J., Cruz-Gamero J. M., de Pancorbo M. M., Escuela R., Garrote-Espina L., Garcia-Alberca J. M., Garcia Madrona S., Garcia-Ribas G., Gomez-Garre P., Hevilla S., Jesus S., Labrador Espinosa M. A., Legaz A., Lleo A., Lopez de Munain A., Macias-Garcia D., Manzanares S., Marin M., Marin-Munoz J., Marin T., Martinez B., Martinez V., Martinez-Lage Alvarez P., Medina M., Mendioroz Iriarte M., Mir P., Molinuevo J. L., Pastor P., Perez Tur J., Perinan-Tocino T., Pineda-Sanchez R., Pinol-Ripoll G., Real de Asua D., Rodrigo S., Sanchez del Valle Diaz R., Sanchez-Juan P., Sastre I., Vicente M. P., Vigo-Ortega R., Vivancos L., Macleod C., McCracken C., Brayne C., Bresner C., Grozeva D., Bellou E., Sommerville E. W., Matthews F., Leonenko G., Menzies G., Windle G., Harwood J., Phillips J., Bennett K., Luckuck L., Clare L., Woods R., Saad S., Burholt V., Kehoe P. G., Scheltens P., Holstege H., Amouyel P., Schellenberg G. D., Williams J., Seshadri S., van Duijn C. M., Mather K. A., Sanchez-Valle R., Blennow K., Huisman M., Andreassen O. A., Posthuma D., van der Flier W. M., Ramirez A., Lambert J. -C., and van der Lee S. J.
- Abstract
The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article.
- Published
- 2023
17. Dementia Prevention: A Global Challenge in Urgent Need of Solutions
- Author
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Price, G., Udeh-Momoh, C., Kivipelto, M., and Middleton, Lefkos T.
- Published
- 2022
- Full Text
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18. Clinical trials and late‐stage drug development for Alzheimer's disease: an appraisal from 1984 to 2014
- Author
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Schneider, LS, Mangialasche, F, Andreasen, N, Feldman, H, Giacobini, E, Jones, R, Mantua, V, Mecocci, P, Pani, L, Winblad, B, and Kivipelto, M
- Subjects
Patient Safety ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Clinical Trials and Supportive Activities ,Aging ,Acquired Cognitive Impairment ,Neurosciences ,Brain Disorders ,Clinical Research ,Dementia ,Neurodegenerative ,Alzheimer's Disease ,5.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Development of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Alzheimer Disease ,Biomarkers ,Cholinesterase Inhibitors ,Dopamine Agents ,Drug Monitoring ,Humans ,Medication Therapy Management ,Memantine ,Memory Disorders ,Nootropic Agents ,Practice Guidelines as Topic ,Randomized Controlled Trials as Topic ,Alzheimer ,clinical trial ,dementia ,drug development ,treatment ,Clinical Sciences ,Cardiovascular System & Hematology - Abstract
The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer's disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild-to-moderate Alzheimer's disease criteria, recently extending to early or prodromal Alzheimer disease or 'mild cognitive impairment due to Alzheimer's disease', for drugs considered to be disease modifying. The duration of trials has remained at 6-12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living, global change and severity ratings have persisted as the primary clinically relevant outcomes. Regulatory guidance and oversight have evolved to allow for enrichment of early-stage Alzheimer's disease trial samples using biomarkers and phase-specific outcomes. In conclusion, validated drug targets for Alzheimer's disease remain to be developed. Only drugs that affect an aspect of cholinergic function have shown consistent, but modest, clinical effects in late-phase trials. There is opportunity for substantial improvements in drug discovery and clinical development methods.
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- 2014
19. Bisphosphonates and mortality: confounding in observational studies?
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Bergman, J., Nordström, A., Hommel, A., Kivipelto, M., and Nordström, P.
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- 2019
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20. Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease
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Hendrix, Suzanne B., Soininen, H., van Hees, A. M. J., Ellison, N., Visser, P. J., Solomon, A., Attali, A., Blennow, K., Kivipelto, M., and Hartmann, T.
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- 2019
- Full Text
- View/download PDF
21. New insights into the genetic etiology of Alzheimer's disease and related dementias
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Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. J., Launer, L., Lauria, A., Lee, C. -Y., Lehtisalo, J., Lerch, O., Lleó, A., Longstreth, W., Lopez, O., de Munain, A. L., Love, S., Löwemark, M., Luckcuck, L., Lunetta, K. L., Ma, Y., Macías, J., Macleod, C. A., Maier, W., Mangialasche, F., Spallazzi, M., Marquié, M., Marshall, R., Martin, E. R., Montes, A. M., Rodríguez, C. M., Masullo, C., Mayeux, R., Mead, S., Mecocci, P., Medina, M., Meggy, A., Mehrabian, S., Mendoza, S., Menéndez-González, M., Mir, P., Moebus, S., Mol, M., Molina-Porcel, L., Montrreal, L., Morelli, L., Moreno, F., Morgan, K., Mosley, T., Nöthen, M. M., Muchnik, C., Mukherjee, S., Nacmias, B., Ngandu, T., Nicolas, G., Nordestgaard, B. G., Olaso, R., Orellana, A., Orsini, M., Ortega, G., Padovani, A., Paolo, C., Papenberg, G., Parnetti, L., Pasquier, F., Pastor, P., Peloso, G., Pérez-Cordón, A., Pérez-Tur, J., Pericard, P., Peters, O., Pijnenburg, Y. A. L., Pineda, J. A., Piñol-Ripoll, G., Pisanu, C., Polak, T., Popp, J., Posthuma, D., Priller, J., Puerta, R., Quenez, O., Quintela, I., Thomassen, J. Q., Rábano, A., Rainero, I., Rajabli, F., Ramakers, I., Real, L. M., Reinders, M. J. T., Reitz, C., Reyes-Dumeyer, D., Ridge, P., Riedel-Heller, S., Riederer, P., Roberto, N., Rodriguez-Rodriguez, E., Rongve, A., Allende, I. R., Rosende-Roca, M., Royo, J. L., Rubino, E., Rujescu, D., Sáez, M. E., Sakka, P., Saltvedt, I., Sanabria, Á., Sánchez-Arjona, M. B., Sanchez-Garcia, F., Juan, P. S., Sánchez-Valle, R., Sando, S. B., Sarnowski, C., Satizabal, C. L., Scamosci, M., Scarmeas, N., Scarpini, E., Scheltens, P., Scherbaum, N., Scherer, M., Schmid, M., Schneider, A., Schott, J. M., Selbæk, G., Seripa, D., Serrano, M., Sha, J., Shadrin, A. A., Skrobot, O., Slifer, S., Snijders, G. J. L., Soininen, H., Solfrizzi, V., Solomon, A., Song, Y. E., Sorbi, S., Sotolongo-Grau, O., Spalletta, G., Spottke, A., Squassina, A., Stordal, E., Tartan, J. P., Tárraga, L., Tesí, N., Thalamuthu, A., Thomas, T., Tosto, G., Traykov, L., Tremolizzo, L., Tybjærg-Hansen, A., Uitterlinden, A., Ullgren, A., Ulstein, I., Valero, S., Valladares, O., Broeckhoven, C. V., Vance, J., Vardarajan, B. N., van der Lugt, A., Dongen, J. V., van Rooij, J., van Swieten, J., Vandenberghe, R., Verhey, F., Vidal, J. -S., Vogelgsang, J., Vyhnalek, M., Wagner, M., Wallon, D., Wang, L. -S., Wang, R., Weinhold, L., Wiltfang, J., Windle, G., Woods, B., Yannakoulia, M., Zare, H., Zhao, Y., Zhang, X., Zhu, C., Zulaica, M., Laczo, J., Matoska, V., Serpente, M., Assogna, F., Piras, F., Ciullo, V., Shofany, J., Ferrarese, C., Andreoni, S., Sala, G., Zoia, C. P., Zompo, M. D., Benussi, A., Bastiani, P., Takalo, M., Natunen, T., Laatikainen, T., Tuomilehto, J., Antikainen, R., Strandberg, T., Lindström, J., Peltonen, M., Abraham, R., Al-Chalabi, A., Bass, N. J., Brayne, C., Brown, K. S., Collinge, J., Craig, D., Deloukas, P., Fox, N., Gerrish, A., Gill, M., Gwilliam, R., Harold, D., Hollingworth, P., Johnston, J. A., Jones, L., Lawlor, B., Livingston, G., Lovestone, S., Lupton, M., Lynch, A., Mann, D., Mcguinness, B., Mcquillin, A., O’Donovan, M. C., Owen, M. J., Passmore, P., Powell, J. F., Proitsi, P., Rossor, M., Shaw, C. E., Smith, A. D., Gurling, H., Todd, S., Mummery, C., Ryan, N., Lacidogna, G., Adarmes-Gómez, A., Mauleón, A., Pancho, A., Gailhajenet, A., Lafuente, A., Macias-García, D., Martín, E., Pelejà, E., Carrillo, F., Merlín, I. S., Garrote-Espina, L., Vargas, L., Carrion-Claro, M., Marín, M., Labrador, M., Buendia, M., Alonso, M. 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M, Humphrey, J, Biessels, G, Jian, X, Johansson, C, Jun, G, Kastumata, Y, Kauwe, J, Kehoe, P, Kilander, L, Ståhlbom, A, Kivipelto, M, Koivisto, A, Kornhuber, J, Kosmidis, M, Kukull, W, Kuksa, P, Kunkle, B, Kuzma, A, Lage, C, Laukka, E, Launer, L, Lauria, A, Lee, C, Lehtisalo, J, Lerch, O, Lleó, A, Longstreth, W, Lopez, O, de Munain, A, Love, S, Löwemark, M, Luckcuck, L, Lunetta, K, Ma, Y, Macías, J, Macleod, C, Maier, W, Mangialasche, F, Spallazzi, M, Marquié, M, Marshall, R, Martin, E, Montes, A, Rodríguez, C, Masullo, C, Mayeux, R, Mead, S, Mecocci, P, Medina, M, Meggy, A, Mehrabian, S, Mendoza, S, Menéndez-González, M, Mir, P, Moebus, S, Mol, M, Molina-Porcel, L, Montrreal, L, Morelli, L, Moreno, F, Morgan, K, Mosley, T, Nöthen, M, Muchnik, C, Mukherjee, S, Nacmias, B, Ngandu, T, Nicolas, G, Nordestgaard, B, Olaso, R, Orellana, A, Orsini, M, Ortega, G, Padovani, A, Paolo, C, Papenberg, G, Parnetti, L, Pasquier, F, Pastor, P, Peloso, G, Pérez-Cordón, A, Pérez-Tur, J, Pericard, P, Peters, O, Pijnenburg, Y, Pineda, J, Piñol-Ripoll, G, Pisanu, C, Polak, T, Popp, J, Posthuma, D, Priller, J, Puerta, R, Quenez, O, Quintela, I, Thomassen, J, Rábano, A, Rainero, I, Rajabli, F, Ramakers, I, Real, L, Reinders, M, Reitz, C, Reyes-Dumeyer, D, Ridge, P, Riedel-Heller, S, Riederer, P, Roberto, N, Rodriguez-Rodriguez, E, Rongve, A, Allende, I, Rosende-Roca, M, Royo, J, Rubino, E, Rujescu, D, Sáez, M, Sakka, P, Saltvedt, I, Sanabria, Á, Sánchez-Arjona, M, Sanchez-Garcia, F, Juan, P, Sánchez-Valle, R, Sando, S, Sarnowski, C, Satizabal, C, Scamosci, M, Scarmeas, N, Scarpini, E, Scheltens, P, Scherbaum, N, Scherer, M, Schmid, M, Schneider, A, Schott, J, Selbæk, G, Seripa, D, Serrano, M, Sha, J, Shadrin, A, Skrobot, O, Slifer, S, Snijders, G, Soininen, H, Solfrizzi, V, Solomon, A, Song, Y, Sorbi, S, Sotolongo-Grau, O, Spalletta, G, Spottke, A, Squassina, A, Stordal, E, Tartan, J, Tárraga, L, Tesí, N, Thalamuthu, A, Thomas, T, Tosto, G, Traykov, L, Tremolizzo, L, Tybjærg-Hansen, A, Uitterlinden, A, Ullgren, A, Ulstein, I, Valero, S, Valladares, O, Broeckhoven, C, Vance, J, Vardarajan, B, van der Lugt, A, Dongen, J, van Rooij, J, van Swieten, J, Vandenberghe, R, Verhey, F, Vidal, J, Vogelgsang, J, Vyhnalek, M, Wagner, M, Wallon, D, Wang, L, Wang, R, Weinhold, L, Wiltfang, J, Windle, G, Woods, B, Yannakoulia, M, Zare, H, Zhao, Y, Zhang, X, Zhu, C, Zulaica, M, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Farrer, L, Psaty, B, Ghanbari, M, Raj, T, Sachdev, P, Mather, K, Jessen, F, Ikram, M, de Mendonça, A, Hort, J, Tsolaki, M, Pericak-Vance, M, Amouyel, P, Williams, J, Frikke-Schmidt, R, Clarimon, J, Deleuze, J, Rossi, G, Seshadri, S, Andreassen, O, Ingelsson, M, Hiltunen, M, Sleegers, K, Schellenberg, G, van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, VU University medical center, Amsterdam Neuroscience - Neurodegeneration, Neurology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, APH - Personalized Medicine, APH - Methodology, Bellenguez, Céline [0000-0002-1240-7874], Küçükali, Fahri [0000-0002-3835-9639], Amin, Najaf [0000-0002-8944-1771], Holmans, Peter A [0000-0003-0870-9412], van der Lee, Sven J [0000-0003-1606-8643], Costa, Marcos R [0000-0002-4928-2163], Kuulasmaa, Teemu [0000-0002-1795-7314], Yang, Qiong [0000-0002-3658-1375], de Rojas, Itziar [0000-0002-2148-381X], Bis, Joshua C [0000-0002-3409-1110], Yaqub, Amber [0000-0002-3579-8054], Prokic, Ivana [0000-0002-0370-1473], Chapuis, Julien [0000-0002-5802-2857], Ahmad, Shahzad [0000-0002-8658-3790], Giedraitis, Vilmantas [0000-0003-3423-2021], Garcia-Gonzalez, Pablo [0000-0003-0125-5403], Alcolea, Daniel [0000-0002-3819-3245], Alvarez, Ignacio [0000-0002-8537-3935], Tsolaki, Anthoula [0000-0002-5563-7776], Baquero, Miquel [0000-0002-6861-1831], Pastor, Ana Belén [0000-0001-9637-4688], Berr, Claudine [0000-0001-5254-7655], Bessi, Valentina [0000-0002-6176-3584], Boada, Mercè 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Sachdev, Perminder [0000-0002-9595-3220], Mather, Karen [0000-0003-4143-8941], Ikram, M Arfan [0000-0003-0372-8585], Tsolaki, Magda [0000-0002-2072-8010], Pericak-Vance, Margaret A [0000-0001-7283-8804], Amouyel, Philippe [0000-0001-9088-234X], Williams, Julie [0000-0002-4069-0259], Frikke-Schmidt, Ruth [0000-0003-4084-5027], Seshadri, Sudha [0000-0001-6135-2622], Andreassen, Ole A [0000-0002-4461-3568], Sleegers, Kristel [0000-0002-0283-2332], van Duijn, Cornelia M [0000-0002-2374-9204], Sims, Rebecca [0000-0002-3885-1199], van der Flier, Wiesje M [0000-0001-8766-6224], Ramirez, Alfredo [0000-0003-4991-763X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Complex Trait Genetics, Clinical sciences, Neuroprotection & Neuromodulation, Pathologic Biochemistry and Physiology, Clinical Biology, Epidemiology, Internal Medicine, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)
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tau Proteins/genetics ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Neurologi ,MED/03 - GENETICA MEDICA ,45/43 ,Medizin ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,genetics [Alzheimer Disease] ,Genome-Wide Association Study ,Humans ,tau Proteins ,Alzheimer Disease ,Cognitive Dysfunction ,VARIANTS ,pathology [Alzheimer Disease] ,Tau Proteins ,Settore BIO/13 - Biologia Applicata ,Cognitive Dysfunction/psychology ,692/699/375/365/1283 ,IMPUTATION ,article ,1184 Genetics, developmental biology, physiology ,Biología y Biomedicina / Biología ,AMYLOID-BETA ,Settore MED/26 - NEUROLOGIA ,Neurology ,psychology [Cognitive Dysfunction] ,Medical Genetics ,Human ,Neuroscience(all) ,631/208/205/2138 ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,ddc:570 ,Genetics ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Medicinsk genetik ,MED/26 - NEUROLOGIA ,Alzheimer Disease/genetics ,neurology ,tau Protein ,NECROSIS-FACTOR-ALPHA ,RISK LOCI ,genetics [tau Proteins] ,PREDICTION MODELS ,Human medicine ,GENERATION ,RESPONSES - Abstract
25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not
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- 2022
22. Health-related quality of life in a multidomain intervention trial to prevent cognitive decline (FINGER)
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Kivipelto, M., Ngandu, T., Lehtisalo, J., Laatikainen, T., Soininen, H., Strandberg, T., Antikainen, R., Jula, A., Tuomilehto, J., Peltonen, M., Levälahti, E., Lindström, J., Rauramaa, R., Pajala, S., Hänninen, T., Solomon, A., Paajanen, T., Mangialasche, F., and Strandberg, T.E.
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- 2017
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23. Dementia prevention:the potential long-term cost-effectiveness of the FINGER prevention program
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Wimo, A. (Anders), Handels, R. (Ron), Antikainen, R. (Riitta), Eriksdotter, M. (Maria), Jönsson, L. (Linus), Knapp, M. (Martin), Kulmala, J. (Jenni), Laatikainen, T. (Tiina), Lehtisalo, J. (Jenni), Peltonen, M. (Markku), Sköldunger, A. (Anders), Soininen, H. (Hilkka), Solomon, A. (Alina), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Ngandu, T. (Tiia), Kivipelto, M. (Miia), Wimo, A. (Anders), Handels, R. (Ron), Antikainen, R. (Riitta), Eriksdotter, M. (Maria), Jönsson, L. (Linus), Knapp, M. (Martin), Kulmala, J. (Jenni), Laatikainen, T. (Tiina), Lehtisalo, J. (Jenni), Peltonen, M. (Markku), Sköldunger, A. (Anders), Soininen, H. (Hilkka), Solomon, A. (Alina), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Ngandu, T. (Tiia), and Kivipelto, M. (Miia)
- Abstract
Introduction: The aim of this study was to estimate the potential cost-effectiveness of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) program. Methods: A life-time Markov model with societal perspective, simulating a cohort of people at risk of dementia reflecting usual care and the FINGER program. Results: Costs were 1,653,275 and 1,635,346 SEK and quality-adjusted life years (QALYs) were 8.636 and 8.679 for usual care and the FINGER program, respectively, resulting in savings of 16,928 SEK (2023 US$) and 0.043 QALY gains per person, supporting extended dominance for the FINGER program. A total of 1623 dementia cases were avoided with 0.17 fewer person-years living with dementia. The sensitivity analysis confirmed the conclusions in most scenarios. Discussion: The model provides support that programs like FINGER have the potential to be cost-effective in preventing dementia. Results at the individual level are rather modest, but the societal benefits can be substantial because of the large potential target population.
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- 2023
24. Association of Sarcopenia and Its Defining Components with the Degree of Cognitive Impairment in a Memory Clinic Population
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Larsson, L. E., Wang, R., Cederholm, T., Wiggenraad, F., Rydén, M., Hagman, G., Hellénius, M. -L, Kivipelto, M., Thunborg, Charlotta, Larsson, L. E., Wang, R., Cederholm, T., Wiggenraad, F., Rydén, M., Hagman, G., Hellénius, M. -L, Kivipelto, M., and Thunborg, Charlotta
- Abstract
Background: Sarcopenia and cognitive impairment are two leading causes of disabilities. Objective: The objective was to examine the prevalence of sarcopenia and investigate the association between sarcopenia diagnostic components (muscle strength, muscle mass, and physical performance) and cognitive impairment in memory clinic patients. Methods: 368 patients were included (age 59.0±7.25 years, women: 58.7%), displaying three clinical phenotypes of cognitive impairments, i.e., subjective cognitive impairment (SCI, 57%), mild cognitive impairment (MCI, 26%), and Alzheimer's disease (AD, 17%). Sarcopenia was defined according to diagnostic algorithm recommended by the European Working Group on Sarcopenia in Older People. Components of sarcopenia were grip strength, bioelectrical impedance analysis, and gait speed. They were further aggregated into a score (0-3 points) by counting the numbers of limited components. Multi-nominal logistic regression was applied. Results: Probable sarcopenia (i.e., reduced grip strength) was observed in 9.6% of the patients, and 3.5% were diagnosed with sarcopenia. Patients with faster gait speed showed less likelihood of MCI (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.06-0.90) and AD (OR: 0.12, 95% CI: 0.03-0.60). One or more limited sarcopenia components was associated with worse cognitive function. After adjusting for potential confounders, the association remained significant only for AD (OR 4.29, 95% CI 1.45-11.92). Conclusion: The results indicate a connection between the sarcopenia components and cognitive impairments. Limitations in the sarcopenia measures, especially slow walking speed, were related to poorer cognitive outcomes. More investigationsare required to further verify the causal relationship between sarcopenia and cognitive outcomes.
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- 2023
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25. Multimodal Precision Prevention - A New Direction in Alzheimer’s Disease
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Barbera, M., primary, Perera, D., additional, Matton, A., additional, Mangialasche, F., additional, Rosenberg, A., additional, Middleton, L., additional, Ngandu, T., additional, Solomon, A., additional, and Kivipelto, M., additional
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- 2023
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26. Body mass index and Mini Nutritional Assessment-Short Form as predictors of in-geriatric hospital mortality in older adults with COVID-19
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Kananen, L., primary, Eriksdotter, M., additional, Boström, A.M., additional, Kivipelto, M., additional, Annetorp, M., additional, Metzner, C., additional, Bäck Jerlardtz, V., additional, Engström, M., additional, Johnson, P., additional, Lundberg, L.G., additional, Åkesson, E., additional, Sühl Öberg, C., additional, Hägg, S., additional, Religa, D., additional, Jylhävä, J., additional, and Cederholm, T., additional
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- 2022
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27. Erratum to: Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease (The Journal of Prevention of Alzheimer's Disease, (2019), (1-5), 10.14283/jpad.2019.33)
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Hendrix, Suzanne B., Soininen, H., van Hees, A. M. J., Ellison, N., Visser, P. J., Solomon, A., Attali, A., Blennow, K., Kivipelto, M., Hartmann, T., Neurology, and Amsterdam Neuroscience - Neurodegeneration
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The article «Alzheimer’s Disease Composite Score: a Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer’s Disease», written by S.B. Hendrix, H. Soininen, A.M.J. van Hees, N. Ellison, P.J. Visser, A. Solomon, A. Attali, K. Blennow, M. Kivipelto, T. Hartmann, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on 10 September 2019 without open access.
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- 2023
28. Self‐rated physical fitness and estimated maximal oxygen uptake in relation to all‐cause and cause‐specific mortality
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Solomon, A., Borodulin, K., Ngandu, T., Kivipelto, M., Laatikainen, T., and Kulmala, J.
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- 2018
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29. Association of long-term dietary fat intake, exercise, and weight with later cognitive function in the Finnish Diabetes Prevention Study
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Lehtisalo, Jenni, Lindström, J., Ngandu, T., Kivipelto, M., Ahtiluoto, S., Ilanne-Parikka, P., Keinänen-Kiukaanniemi, S., Eriksson, J. G., Uusitupa, M., Tuomilehto, J., Luchsinger, J., and For The Finnish Diabetes Prevention Study (DPS)
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- 2016
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30. Body mass index and Mini Nutritional Assessment-Short Form as predictors of in-geriatric hospital mortality in older adults with COVID-19
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Kananen, L., Eriksdotter, M., Boström, A. M., Kivipelto, M., Annetorp, M., Metzner, C., Bäck Jerlardtz, V., Engström, M., Johnson, P., Lundberg, L. G., Åkesson, E., Sühl Öberg, C., Hägg, S., Religa, D., Jylhävä, J., Cederholm, Tommy, Kananen, L., Eriksdotter, M., Boström, A. M., Kivipelto, M., Annetorp, M., Metzner, C., Bäck Jerlardtz, V., Engström, M., Johnson, P., Lundberg, L. G., Åkesson, E., Sühl Öberg, C., Hägg, S., Religa, D., Jylhävä, J., and Cederholm, Tommy
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Background & Aims: Overweight and obesity have been consistently reported to carry an increased risk for poorer outcomes in coronavirus disease 2019 (COVID-19) in adults. Existing reports mainly focus on in-hospital and intensive care unit mortality in patient cohorts usually not representative of the population with the highest mortality, i.e. the very old and frail patients. Accordingly, little is known about the risk patterns related to body mass and nutrition in very old patients. Our aim was to assess the relationship between body mass index (BMI), nutritional status and in-geriatric hospital mortality among geriatric patients treated for COVID-19. As a reference, the analyses were performed also in patients treated for other diagnoses than COVID-19. Methods: We analyzed up to 10,031 geriatric patients with a median age of 83 years of which 1409 (14%) were hospitalized for COVID-19 and 8622 (86%) for other diagnoses in seven geriatric hospitals in the Stockholm region, Sweden during March 2020-January 2021. Data were available in electronic hospital records. The associations between 1) BMI and 2) nutritional status, assessed using the Mini-Nutritional Assessment - Short Form (MNA-SF) scale, and short-term in-geriatric hospital mortality were analyzed using logistic regression. Results: After adjusting for age, sex, comorbidity, polypharmacy, frailty and the wave of the pandemic (first vs. second), underweight defined as BMI<18.5 increased the risk of in-hospital mortality in COVID-19 patients (odds ratio [OR] = 2.30; confidence interval [CI] = 1.17-4.31). Overweight and obesity were not associated with in-hospital mortality. Malnutrition; i.e. MNA-SF 0-7 points, increased the risk of in-hospital mortality in patients treated for COVID-19 (OR = 2.03; CI = 1.16-3.68) and other causes (OR = 6.01; CI = 2.73-15.91). Conclusions: Our results indicate that obesity is not a risk factor for very old patients with COVID-19, but emphasize the role of underweight an, De två sista författarna delar sistaförfattarskapet
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- 2022
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31. Multimodal Preventive Trial for Alzheimer’s Disease : MIND-ADmini Pilot Trial Study Design and Progress
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Sindi, S., Thunborg, C., Rosenberg, A., Andersen, P., Andrieu, S., Broersen, L.M., Coley, N., Couderc, C., Duval, C.Z., Faxen-Irving, G., Hagman, G., Hallikainen, M., Håkansson, K., Lehtisalo, J., Levak, N., Mangialasche, F., Pantel, J., Kekkonen, E., Rydström, A., Stigsdotter-Neely, A., Wimo, Anders, Ngandu, T., Soininen, H., Hartmann, T., Solomon, A., Kivipelto, M., Sindi, S., Thunborg, C., Rosenberg, A., Andersen, P., Andrieu, S., Broersen, L.M., Coley, N., Couderc, C., Duval, C.Z., Faxen-Irving, G., Hagman, G., Hallikainen, M., Håkansson, K., Lehtisalo, J., Levak, N., Mangialasche, F., Pantel, J., Kekkonen, E., Rydström, A., Stigsdotter-Neely, A., Wimo, Anders, Ngandu, T., Soininen, H., Hartmann, T., Solomon, A., and Kivipelto, M.
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Background Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer’s disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. Objectives To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. Methods MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/ care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. Results Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. Conclusions For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharm
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- 2022
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32. Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer’s disease
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Dehghan, A., Pinto, R.C., Karaman, I., Huang, J., Durainayagam, B.R., Ghanbari, M., Nazeer, A., Zhong, Q., Liggi, S., Whiley, L., Mustafa, R., Kivipelto, M., Solomon, A., Ngandu, T., Kanekiyo, T., Aikawa, T., Radulescu, C.I., Barnes, S.J., Graça, G., Chekmeneva, E., Camuzeaux, S., Lewis, M.R., Kaluarachchi, M.R., Ikram, M.A., Holmes, E., Tzoulaki, I., Matthews, P.M., Griffin, J.L., Elliott, P., Dehghan, A., Pinto, R.C., Karaman, I., Huang, J., Durainayagam, B.R., Ghanbari, M., Nazeer, A., Zhong, Q., Liggi, S., Whiley, L., Mustafa, R., Kivipelto, M., Solomon, A., Ngandu, T., Kanekiyo, T., Aikawa, T., Radulescu, C.I., Barnes, S.J., Graça, G., Chekmeneva, E., Camuzeaux, S., Lewis, M.R., Kaluarachchi, M.R., Ikram, M.A., Holmes, E., Tzoulaki, I., Matthews, P.M., Griffin, J.L., and Elliott, P.
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Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer’s disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10−5 to 1.3 × 10−44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049–1.4 × 10−5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD.
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- 2022
33. Occupational complexity and cognition in the FINGER multidomain intervention trial
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Rydström, A. (Anders), Darin-Mattsson, A. (Alexander), Kåreholt, I. (Ingemar), Ngandu, T. (Tiia), Lehtisalo, J. (Jenni), Solomon, A. (Alina), Antikainen, R. (Riitta), Bäckman, L. (Lars), Hänninen, T. (Tuomo), Laatikainen, T. (Tiina), Levälahti, E. (Esko), Lindström, J. (Jaana), Paajanen, T. (Teemu), Havulinna, S. (Satu), Peltonen, M. (Markku), Sindi, S. (Shireen), Soininen, H. (Hilkka), Neely, A. S. (Anna Stigsdotter), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Kivipelto, M. (Miia), Mangialasche, F. (Francesca), Rydström, A. (Anders), Darin-Mattsson, A. (Alexander), Kåreholt, I. (Ingemar), Ngandu, T. (Tiia), Lehtisalo, J. (Jenni), Solomon, A. (Alina), Antikainen, R. (Riitta), Bäckman, L. (Lars), Hänninen, T. (Tuomo), Laatikainen, T. (Tiina), Levälahti, E. (Esko), Lindström, J. (Jaana), Paajanen, T. (Teemu), Havulinna, S. (Satu), Peltonen, M. (Markku), Sindi, S. (Shireen), Soininen, H. (Hilkka), Neely, A. S. (Anna Stigsdotter), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Kivipelto, M. (Miia), and Mangialasche, F. (Francesca)
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Introduction: Lifetime exposure to occupational complexity is linked to late-life cognition, and may affect benefits of preventive interventions. Methods: In the 2-year multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated, through post hoc analyses (N = 1026), the association of occupational complexity with cognition. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Results: Higher levels of occupational complexity were associated with better baseline cognition. Measures of occupational complexity had no association with intervention effects on cognition, except for occupational complexity with data, which was associated with the degree of intervention-related gains for executive function. Discussion: In older adults at increased risk for dementia, higher occupational complexity is associated with better cognition. The cognitive benefit of the FINGER intervention did not vary significantly among participants with different levels of occupational complexity. These exploratory findings require further testing in larger studies.
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- 2022
34. Cognitive performance at time of AD diagnosis:a clinically augmented register-based study
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Alenius, M. (Minna), Hokkanen, L. (Laura), Koskinen, S. (Sanna), Hallikainen, I. (Ilona), Hänninen, T. (Tuomo), Karrasch, M. (Mira), Raivio, M. M. (Minna M.), Laakkonen, M.-L. (Marja-Liisa), Krüger, J. (Johanna), Suhonen, N.-M. (Noora-Maria), Kivipelto, M. (Miia), Ngandu, T. (Tiia), Alenius, M. (Minna), Hokkanen, L. (Laura), Koskinen, S. (Sanna), Hallikainen, I. (Ilona), Hänninen, T. (Tuomo), Karrasch, M. (Mira), Raivio, M. M. (Minna M.), Laakkonen, M.-L. (Marja-Liisa), Krüger, J. (Johanna), Suhonen, N.-M. (Noora-Maria), Kivipelto, M. (Miia), and Ngandu, T. (Tiia)
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We aimed to evaluate the feasibility of using real-world register data for identifying persons with mild Alzheimer’s disease (AD) and to describe their cognitive performance at the time of diagnosis. Patients diagnosed with AD during 2010–2013 (aged 60–81 years) were identified from the Finnish national health registers and enlarged with a smaller private sector sample (total n = 1,268). Patients with other disorders impacting cognition were excluded. Detailed clinical and cognitive screening data (the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery [CERAD-nb]) were obtained from local health records. Adequate cognitive data were available for 389 patients with mild AD (31%) of the entire AD group. The main reasons for not including patients in analyses of cognitive performance were AD diagnosis at a moderate/severe stage (n = 266, 21%), AD diagnosis given before full register coverage (n = 152, 12%), and missing CERAD-nb data (n = 139, 11%). The cognitive performance of persons with late-onset AD (n = 284), mixed cerebrovascular disease and AD (n = 51), and other AD subtypes (n = 54) was compared with that of a non-demented sample (n = 1980) from the general population. Compared with the other AD groups, patients with late-onset AD performed the worst in word list recognition, while patients with mixed cerebrovascular disease and AD performed the worst in constructional praxis and clock drawing tests. A combination of national registers and local health records can be used to collect data relevant for cognitive screening; today, the process is laborious, but it could be improved in the future with refined search algorithms and electronic data.
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- 2022
35. Association between cognition, health related quality of life, and costs in a population at risk for cognitive decline
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Janssen, N. (Niels), Handels, R. L. (Ron L.), Wimo, A. (Anders), Antikainen, R. (Riitta), Laatikainen, T. (Tiina), Soininen, H. (Hilkka), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Kivipelto, M. (Miia), Evers, S. M. (Silvia M.A.A.), Verhey, F. R. (Frans R.J.), Ngandu, T. (Tiia), Janssen, N. (Niels), Handels, R. L. (Ron L.), Wimo, A. (Anders), Antikainen, R. (Riitta), Laatikainen, T. (Tiina), Soininen, H. (Hilkka), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Kivipelto, M. (Miia), Evers, S. M. (Silvia M.A.A.), Verhey, F. R. (Frans R.J.), and Ngandu, T. (Tiia)
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Background: The association between health-related quality of life (HRQoL) and care costs in people at risk for cognitive decline is not well understood. Studying this association could reveal the potential benefits of increasing HRQoL and reducing care costs by improving cognition. Objective: In this exploratory data analysis we investigated the association between cognition, HRQoL utilities and costs in a well-functioning population at risk for cognitive decline. Methods: An exploratory data analysis was conducted using longitudinal 2-year data from the FINGER study (n = 1,120). A change score analysis was applied using HRQoL utilities and total medical care costs as outcome. HRQoL utilities were derived from the Short Form Health Survey-36 (SF-36). Total care costs comprised visits to a general practitioner, medical specialist, nurse, and days at hospital. Analyses were adjusted for activities of daily living (ADL) and depressive symptoms. Results: Although univariable analysis showed an association between cognition and HRQoL utilities, multivariable analysis showed no association between cognition, HRQoL utilities and total care costs. A one-unit increase in ADL limitations was associated with a -0.006 (p < 0.001) decrease in HRQoL utilities and a one-unit increase in depressive symptoms was associated with a -0.004 (p < 0.001) decrease in HRQoL utilities. Conclusions: The level of cognition in people at-risk for cognitive decline does not seem to be associated with HRQoL utilities. Future research should examine the level at which cognitive decline starts to affect HRQoL and care costs. Ideally, this would be done by means of cross-validation in populations with various stages of cognitive functioning and decline.
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- 2022
36. Effect of a multi-domain lifestyle intervention on cardiovascular risk in older people:the FINGER trial
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Lehtisalo, J. (Jenni), Rusanen, M. (Minna), Solomon, A. (Alina), Antikainen, R. (Riitta), Laatikainen, T. (Tiina), Peltonen, M. (Markku), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Soininen, H. (Hilkka), Kivipelto, M. (Miia), Ngandu, T. (Tiia), Lehtisalo, J. (Jenni), Rusanen, M. (Minna), Solomon, A. (Alina), Antikainen, R. (Riitta), Laatikainen, T. (Tiina), Peltonen, M. (Markku), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Soininen, H. (Hilkka), Kivipelto, M. (Miia), and Ngandu, T. (Tiia)
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Aims: Joint prevention of cardiovascular disease (CVD) and dementia could reduce the burden of both conditions. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated a beneficial effect on cognition (primary outcome) and we assessed the effect of this lifestyle intervention on incident CVD (pre-specified secondary outcome). Methods and results: FINGER enrolled 1259 individuals aged 60–77 years (ClinicalTrials.gov NCT01041989). They were randomized (1:1) to a 2-year multi-domain intervention with diet, physical and cognitive activity, and vascular monitoring (n = 631), or general health advice (n = 628). National registries provided data on CVD including stroke, transient ischaemic attack (TIA), or coronary heart event. During an average of 7.4 years, 229 participants (18%) had at least one CVD diagnosis: 107 in the intervention group and 122 in the control group. The incidence of cerebrovascular events was lower in the intervention than the control group: hazard ratio (HR) for combined stroke/TIA was 0.71 [95% confidence interval (CI): 0.51–0.99] after adjusting for background characteristics. Hazard ratio for coronary events was 0.84 (CI: 0.56–1.26) and total CVD events 0.80 (95% CI: 0.61–1.04). Among those with history of CVD (n = 145), the incidence of both total CVD events (HR: 0.50, 95% CI: 0.28–0.90) and stroke/TIA (HR: 0.40, 95% CI: 0.20–0.81) was lower in the intervention than the control group. Conclusion: A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those who had history of CVD.
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- 2022
37. The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER)
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Ngandu, T. (Tiia), Lehtisalo, J. (Jenni), Korkki, S. (Saana), Solomon, A. (Alina), Coley, N. (Nicola), Antikainen, R. (Riitta), Bäckman, L. (Lars), Hänninen, T. (Tuomo), Lindström, J. (Jaana), Laatikainen, T. (Tiina), Paajanen, T. (Teemu), Havulinna, S. (Satu), Peltonen, M. (Markku), Neely, A. S. (Anna Stigsdotter), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Soininen, H. (Hilkka), Kivipelto, M. (Miia), Ngandu, T. (Tiia), Lehtisalo, J. (Jenni), Korkki, S. (Saana), Solomon, A. (Alina), Coley, N. (Nicola), Antikainen, R. (Riitta), Bäckman, L. (Lars), Hänninen, T. (Tuomo), Lindström, J. (Jaana), Laatikainen, T. (Tiina), Paajanen, T. (Teemu), Havulinna, S. (Satu), Peltonen, M. (Markku), Neely, A. S. (Anna Stigsdotter), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Soininen, H. (Hilkka), and Kivipelto, M. (Miia)
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Introduction: Lifestyle interventions may prevent cognitive decline, but the sufficient dose of intervention activities and lifestyle changes is unknown. We investigated how intervention adherence affects cognition in the FINGER trial (pre-specified subgroup analyses). Methods: FINGER is a multicenter randomized controlled trial examining the efficacy of multidomain lifestyle intervention (ClinicalTrials.gov NCT01041989). A total of 1260 participants aged 60 to 77 with increased dementia risk were randomized to a lifestyle intervention and control groups. Percentage of completed intervention sessions, and change in multidomain lifestyle score (self-reported diet; physical, cognitive, and social activity; vascular risk) were examined in relation to change in Neuropsychological Test Battery (NTB) scores. Results: Active participation was associated with better trajectories in NTB total and all cognitive subdomains. Improvement in lifestyle was associated with improvement in NTB total and executive function. Discussion: Multidomain lifestyle changes are beneficial for cognitive functioning, but future interventions should be intensive enough, and supporting adherence is essential.
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- 2022
38. Experiences of Active Everyday Life Among Persons with Prodromal Alzheimer’s Disease : A Qualitative Study
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Fallahpour, M., Fritz, H., Thunborg, Charlotta, Akenine, U., Kivipelto, M., Fallahpour, M., Fritz, H., Thunborg, Charlotta, Akenine, U., and Kivipelto, M.
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Introduction: Identifying strategies to prevent or delay cognitive decline among the rising numbers of elderly is acknowledged as a global public health priority. Research suggests that an active lifestyle in terms of participation in activities has the potential to reduce the risk of later-life cognitive decline. The concept of “active everyday life”, however, needs to be further explored. Aim: The study aimed to explore and describe the active everyday lives of persons with prodromal Alzheimer’s disease (AD) in terms of quality of participation in activities and perceived restrictions. Methods: This qualitative study was part of a larger project, the MIND-ADMINI trial. Nine in-depth interviews were conducted with seven participants (2 males, 5 females; mean age of 72.3) at baseline before the intervention. The data were collected from January to October 2018 and analyzed using the grounded theory approach. Results: Four categories emerged from the analysis: (i) active body and mind; (ii) doing desired meaningful activities to feel engaged, contented, and satisfied; (iii) doing in the context of being connected to others; (iv) ability in making decisions and taking actions. From these categories, which presented the key elements of an active everyday life, a core category was identified: Living a complete life in flow. Conclusion: The findings suggest key elements of participation quality that contribute to an active life. The identified elements are important to be considered in rehabilitation to provide opportunities and possibilities for participation to enable and improve the quality of participation among persons with cognitive impairments.
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- 2022
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39. Psychosocial determinants for adherence to a healthy lifestyle and intervention participation in the FINGER trial:an exploratory analysis of a randomised clinical trial
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Neuvonen, E. (Elisa), Lehtisalo, J. (Jenni), Solomon, A. (Alina), Antikainen, R. (Riitta), Havulinna, S. (Satu), Hänninen, T. (Tuomo), Laatikainen, T. (Tiina), Lindström, J. (Jaana), Rautio, N. (Nina), Soininen, H. (Hilkka), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Kivipelto, M. (Miia), Ngandu, T. (Tiia), Neuvonen, E. (Elisa), Lehtisalo, J. (Jenni), Solomon, A. (Alina), Antikainen, R. (Riitta), Havulinna, S. (Satu), Hänninen, T. (Tuomo), Laatikainen, T. (Tiina), Lindström, J. (Jaana), Rautio, N. (Nina), Soininen, H. (Hilkka), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Kivipelto, M. (Miia), and Ngandu, T. (Tiia)
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Background and aims: Psychosocial factors may affect adherence to lifestyle interventions and lifestyle changes. The role of psychosocial factors in dementia prevention needs more research. We aimed at clarify the issue in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). Methods: The population included 1260 participants aged 60–77 years at risk for cognitive decline, randomised to a multidomain lifestyle intervention or regular health advice for 2 years. Adherence was evaluated as participation in the provided activities and actual lifestyle changes, separately for each domain (diet, exercise, social/cognitive activity, vascular risk management) and combined into multidomain. Psychosocial factors were measured at trial baseline (depressive symptoms; study perception; health-related quality of life, HRQoL) and earlier life (hopelessness; satisfaction with family life, achievements, and financial situation). Results: Depressive symptoms, hopelessness, and nonpositive study perception were negatively and HRQoL positively associated with participation in the multidomain intervention. Depressive symptoms, lower HRQoL, hopelessness and dissatisfaction with financial situation were associated with unhealthier lifestyles at baseline. Baseline depressive symptoms and lower HRQoL predicted less improvement in lifestyle, but did not modify the intervention effect on lifestyle change. Discussion and conclusions: Several psychosocial factors were associated with participation in lifestyle intervention, while fewer of them contributed to lifestyle changes. Although the intervention was beneficial for lifestyle changes independent of psychosocial factors, those most in need of lifestyle improvement were less likely to be active. Tailoring lifestyle-modifying strategies based on the need for psychosocial support may add efficacy in future trials.
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- 2022
40. Associations of depressive symptoms and cognition in the FINGER trial:a secondary analysis of a randomised clinical trial
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Neuvonen, E. (Elisa), Lehtisalo, J. (Jenni), Ngandu, T. (Tiia), Levälahti, E. (Esko), Antikainen, R. (Riitta), Hänninen, T. (Tuomo), Laatikainen, T. (Tiina), Lindström, J. (Jaana), Paajanen, T. (Teemu), Soininen, H. (Hilkka), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Kivipelto, M. (Miia), Solomon, A. (Alina), Neuvonen, E. (Elisa), Lehtisalo, J. (Jenni), Ngandu, T. (Tiia), Levälahti, E. (Esko), Antikainen, R. (Riitta), Hänninen, T. (Tuomo), Laatikainen, T. (Tiina), Lindström, J. (Jaana), Paajanen, T. (Teemu), Soininen, H. (Hilkka), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Kivipelto, M. (Miia), and Solomon, A. (Alina)
- Abstract
Depression and cognition are associated, but the role of depressive symptoms in lifestyle interventions to prevent dementia needs further study. We investigated the intervention effect on depressive symptoms and their associations with cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER; NCT01041989), a two-year multidomain lifestyle trial. One thousand two-hundred and sixty individuals (60–77 years) at risk for dementia were randomised into a multidomain intervention (diet, exercise, cognitive training, and vascular/metabolic risk monitoring) or control group (regular health advice). Depressive symptoms (Zung scale) and cognition (modified Neuropsychological Test Battery) were evaluated at baseline, 12, and 24 months. One thousand one-hundred and twenty-five participants had baseline Zung data. Mean Zung score decreased 0.73 (SD 5.6) points in the intervention and 0.36 (5.6) points in the control group, with nonsignificant between-group difference (group × time coefficient −0.006, 95% CI −0.019 to 0.007). Overall, higher baseline Zung score was associated with less improvement in global cognition (−0.140, p = 0.005) and memory (−0.231, p = 0.005). Participants with clinically significant baseline depressive symptoms (Zung ≥ 40 points) had less intervention benefit to executive functioning (group × time × Zung −0.096, 95% CI −0.163 to −0.028). Change in Zung score was not associated with change in cognition. Clinically significant depressive symptoms warrant more attention when designing dementia-prevention interventions.
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- 2022
41. Experiences of Participation in a Multimodal Preventive Trial MIND-AD(MINI) Among Persons with Prodromal Alzheimer's Disease: A Qualitative Study : A Qualitative Study
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Akenine, U., Thunborg, Charlotta, Kivipelto, M., Fallahpour, M., Akenine, U., Thunborg, Charlotta, Kivipelto, M., and Fallahpour, M.
- Abstract
Introduction: Alzheimer's disease (AD) is one of the world's leading public health challenges. One-third of AD cases are attributable to modifiable vascular and lifestyle related risk factors. The Multimodal Preventive Trial for Alzheimer's Disease, MINDADMINI a 6-month multinational parallel-group randomized controlled trial (RCT), targeted persons with prodromal AD and built on the positive outcomes from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial. The intervention consisted of four main components of (i) physical exercise training program, (ii) nutrition guidance, (iii) cognitive training, and (iv) social stimulation, as well as (iv) monitoring of metabolic/vascular risk factors. Aim: The study aimed to explore and describe the experiences of participation in MINDADMINI among persons with prodromal AD. Methods: This qualitative study was part of the larger MIND-ADMINI project. Eight participants were interviewed twice, before and after the intervention. The data was analyzed using qualitative content analysis. Results: The results are presented as categories of (i) knowledge of AD and prevention, (ii) motives for study participation, (iii) experiences of the received information about the study, (iv) taking the decision to participate, (v) expectations on study participation, (vi) experiences of study participation and (vii) internal and external factors influencing study participation. Conclusion: The MIND-ADMINI was well-tolerated by the participants. At the beginning of the study, the number of tasks and visits was perceived as burdensome but was later well tolerated. The participant' knowledge about AD and prevention increased during the trial. Their motives for participating in MIND-ADMINI were described as both altruistic and self beneficial. Health benefits from the study components, access to specialized medical care were identified as benefits. Managing the intensive flow of information was descr
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- 2022
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42. New insights into the genetic etiology of Alzheimer's disease and related dementias
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Bellenguez, C. Küçükali, F. Jansen, I.E. Kleineidam, L. Moreno-Grau, S. Amin, N. Naj, A.C. Campos-Martin, R. Grenier-Boley, B. Andrade, V. Holmans, P.A. Boland, A. Damotte, V. van der Lee, S.J. Costa, M.R. Kuulasmaa, T. Yang, Q. de Rojas, I. Bis, J.C. Yaqub, A. Prokic, I. Chapuis, J. Ahmad, S. Giedraitis, V. Aarsland, D. Garcia-Gonzalez, P. Abdelnour, C. Alarcón-Martín, E. Alcolea, D. Alegret, M. Alvarez, I. Álvarez, V. Armstrong, N.J. Tsolaki, A. Antúnez, C. Appollonio, I. Arcaro, M. Archetti, S. Pastor, A.A. Arosio, B. Athanasiu, L. Bailly, H. Banaj, N. Baquero, M. Barral, S. Beiser, A. Pastor, A.B. Below, J.E. Benchek, P. Benussi, L. Berr, C. Besse, C. Bessi, V. Binetti, G. Bizarro, A. Blesa, R. Boada, M. Boerwinkle, E. Borroni, B. Boschi, S. Bossù, P. Bråthen, G. Bressler, J. Bresner, C. Brodaty, H. Brookes, K.J. Brusco, L.I. Buiza-Rueda, D. Bûrger, K. Burholt, V. Bush, W.S. Calero, M. Cantwell, L.B. Chene, G. Chung, J. Cuccaro, M.L. Carracedo, Á. Cecchetti, R. Cervera-Carles, L. Charbonnier, C. Chen, H.-H. Chillotti, C. Ciccone, S. Claassen, J.A.H.R. Clark, C. Conti, E. Corma-Gómez, A. Costantini, E. Custodero, C. Daian, D. Dalmasso, M.C. Daniele, A. Dardiotis, E. Dartigues, J.-F. de Deyn, P.P. de Paiva Lopes, K. de Witte, L.D. Debette, S. Deckert, J. Del Ser, T. Denning, N. DeStefano, A. Dichgans, M. Diehl-Schmid, J. Diez-Fairen, M. Rossi, P.D. Djurovic, S. Duron, E. Düzel, E. Dufouil, C. Eiriksdottir, G. Engelborghs, S. Escott-Price, V. Espinosa, A. Ewers, M. Faber, K.M. Fabrizio, T. Nielsen, S.F. Fardo, D.W. Farotti, L. Fenoglio, C. Fernández-Fuertes, M. Ferrari, R. Ferreira, C.B. Ferri, E. Fin, B. Fischer, P. Fladby, T. Fließbach, K. Fongang, B. Fornage, M. Fortea, J. Foroud, T.M. Fostinelli, S. Fox, N.C. Franco-Macías, E. Bullido, M.J. Frank-García, A. Froelich, L. Fulton-Howard, B. Galimberti, D. García-Alberca, J.M. García-González, P. Garcia-Madrona, S. Garcia-Ribas, G. Ghidoni, R. Giegling, I. Giorgio, G. Goate, A.M. Goldhardt, O. Gomez-Fonseca, D. González-Pérez, A. Graff, C. Grande, G. Green, E. Grimmer, T. Grünblatt, E. Grunin, M. Gudnason, V. Guetta-Baranes, T. Haapasalo, A. Hadjigeorgiou, G. Haines, J.L. Hamilton-Nelson, K.L. Hampel, H. Hanon, O. Hardy, J. Hartmann, A.M. Hausner, L. Harwood, J. Heilmann-Heimbach, S. Helisalmi, S. Heneka, M.T. Hernández, I. Herrmann, M.J. Hoffmann, P. Holmes, C. Holstege, H. Vilas, R.H. Hulsman, M. Humphrey, J. Biessels, G.J. Jian, X. Johansson, C. Jun, G.R. Kastumata, Y. Kauwe, J. Kehoe, P.G. Kilander, L. Ståhlbom, A.K. Kivipelto, M. Koivisto, A. Kornhuber, J. Kosmidis, M.H. Kukull, W.A. Kuksa, P.P. Kunkle, B.W. Kuzma, A.B. Lage, C. Laukka, E.J. Launer, L. Lauria, A. Lee, C.-Y. Lehtisalo, J. Lerch, O. Lleó, A. Longstreth, W., Jr Lopez, O. de Munain, A.L. Love, S. Löwemark, M. Luckcuck, L. Lunetta, K.L. Ma, Y. Macías, J. MacLeod, C.A. Maier, W. Mangialasche, F. Spallazzi, M. Marquié, M. Marshall, R. Martin, E.R. Montes, A.M. Rodríguez, C.M. Masullo, C. Mayeux, R. Mead, S. Mecocci, P. Medina, M. Meggy, A. Mehrabian, S. Mendoza, S. Menéndez-González, M. Mir, P. Moebus, S. Mol, M. Molina-Porcel, L. Montrreal, L. Morelli, L. Moreno, F. Morgan, K. Mosley, T. Nöthen, M.M. Muchnik, C. Mukherjee, S. Nacmias, B. Ngandu, T. Nicolas, G. Nordestgaard, B.G. Olaso, R. Orellana, A. Orsini, M. Ortega, G. Padovani, A. Paolo, C. Papenberg, G. Parnetti, L. Pasquier, F. Pastor, P. Peloso, G. Pérez-Cordón, A. Pérez-Tur, J. Pericard, P. Peters, O. Pijnenburg, Y.A.L. Pineda, J.A. Piñol-Ripoll, G. Pisanu, C. Polak, T. Popp, J. Posthuma, D. Priller, J. Puerta, R. Quenez, O. Quintela, I. Thomassen, J.Q. Rábano, A. Rainero, I. Rajabli, F. Ramakers, I. Real, L.M. Reinders, M.J.T. Reitz, C. Reyes-Dumeyer, D. Ridge, P. Riedel-Heller, S. Riederer, P. Roberto, N. Rodriguez-Rodriguez, E. Rongve, A. Allende, I.R. Rosende-Roca, M. Royo, J.L. Rubino, E. Rujescu, D. Sáez, M.E. Sakka, P. Saltvedt, I. Sanabria, Á. Sánchez-Arjona, M.B. Sanchez-Garcia, F. Juan, P.S. Sánchez-Valle, R. Sando, S.B. Sarnowski, C. Satizabal, C.L. Scamosci, M. Scarmeas, N. Scarpini, E. Scheltens, P. Scherbaum, N. Scherer, M. Schmid, M. Schneider, A. Schott, J.M. Selbæk, G. Seripa, D. Serrano, M. Sha, J. Shadrin, A.A. Skrobot, O. Slifer, S. Snijders, G.J.L. Soininen, H. Solfrizzi, V. Solomon, A. Song, Y. Sorbi, S. Sotolongo-Grau, O. Spalletta, G. Spottke, A. Squassina, A. Stordal, E. Tartan, J.P. Tárraga, L. Tesí, N. Thalamuthu, A. Thomas, T. Tosto, G. Traykov, L. Tremolizzo, L. Tybjærg-Hansen, A. Uitterlinden, A. Ullgren, A. Ulstein, I. Valero, S. Valladares, O. Broeckhoven, C.V. Vance, J. Vardarajan, B.N. van der Lugt, A. Dongen, J.V. van Rooij, J. van Swieten, J. Vandenberghe, R. Verhey, F. Vidal, J.-S. Vogelgsang, J. Vyhnalek, M. Wagner, M. Wallon, D. Wang, L.-S. Wang, R. Weinhold, L. Wiltfang, J. Windle, G. Woods, B. Yannakoulia, M. Zare, H. Zhao, Y. Zhang, X. Zhu, C. Zulaica, M. Farrer, L.A. Psaty, B.M. Ghanbari, M. Raj, T. Sachdev, P. Mather, K. Jessen, F. Ikram, M.A. de Mendonça, A. Hort, J. Tsolaki, M. Pericak-Vance, M.A. Amouyel, P. Williams, J. Frikke-Schmidt, R. Clarimon, J. Deleuze, J.-F. Rossi, G. Seshadri, S. Andreassen, O.A. Ingelsson, M. Hiltunen, M. Sleegers, K. Schellenberg, G.D. van Duijn, C.M. Sims, R. van der Flier, W.M. Ruiz, A. Ramirez, A. Lambert, J.-C. EADB GR@ACE DEGESCO EADI GERAD Demgene FinnGen ADGC CHARGE
- Abstract
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022. The Author(s).
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- 2022
43. Blood Derived Amyloid Biomarkers for Alzheimer's Disease Prevention
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Udeh-Momoh, C, Zheng, B, Sandebring-Matton, A, Novak, G, Kivipelto, M, Jönsson, L, and Middleton, L
- Abstract
BACKGROUND: Reliable, widely accessible and affordable biomarkers for predicting Alzheimer's disease (AD) brain pathology status are a necessity to aid development of prevention strategies in cognitively healthy at-risk older adults, at the right timepoint. Measurements of the key neuropathological hallmark beta-amyloid (Aβ) by PET neuroimaging or cerebrospinal fluid measures reflect its accumulation in the brain, yet recent methodological advancements now enable blood-based measures reflecting cerebral amyloid burden. OBJECTIVES: The current study validated the capacity of plasma Aβ42/Aβ40 measured using six different assays to predict amyloid positivity in a subgroup of cognitively unimpaired (CU) participants in the ADNI study and assessed its ability to discriminate CU from AD cases. We also explored economic viability of using two different plasma amyloid assays for pre-screening in AD prevention trials and as routine clinical diagnostic tool, versus amyloid PET alone. DESIGN: A cross-sectional analysis of plasma and brain amyloid data, including comparative cost analysis of the plasma biomarkers in relation to brain amyloid PET. SETTING: Alzheimer's Disease Neuroimaging Initiative (ADNI). PARTICIPANTS: ADNI participants consisting of 115 CU, mild cognitive impairment and AD cases who had plasma Aβ42/Aβ40 measured with six platforms. MEASUREMENTS: Plasma Aβ42/Aβ40 was measured via six different platforms: three immunoassays (Roche, Quanterix and ADx Neurosciences) and three mass spectrometry (MS) based assays (WashU, Shimadzu and Gothenburg). Aβ-PET imaging was conducted within three months of plasma sampling using [18F]florbetapir. RESULTS: There was a weak to moderate correlation of plasma Aβ42/Aβ40 ratio between platforms. The MS-based WashU test had the highest capacity to discriminate between CU and AD (area under the curve, AUC = 0.734, 95% CI: 0.613-0.854; P = 0.008). Within the CU group, the WashU plasma amyloid test had the best discriminative capacity to distinguish Aβ+ from Aβ- (AUC = 0.753, 95% CI: 0.601-0.905; P = 0.003) closely followed by the immunoassay from Roche (AUC = 0.737, 95% CI: 0.597-0.877; P = 0.006). The exploratory economic analyses showed that the use of Roche or WashU plasma amyloid assay as a pre-screening tool prior to Aβ-PET scans for clinical trial recruitment significantly reduced total screening cost (saving up to $5882 per recruited patient) expected in an AD prevention trial. CONCLUSIONS: With few available treatment strategies, dementia prevention is a global priority. CU individuals at risk for AD are the target population for dementia prevention but have been poorly studied. Our findings confirming diagnostic value of ultrasensitive immunoassays and high-performance immunoprecipitation coupled with MS for measurement of plasma Aβ42/Aβ40 to detect PET amyloid positivity in CU participants allude to potential clinical utility of this biomarker. Plasma Aβ42/Aβ40 could be optimal for pre-selecting at-risk candidates for more invasive and expensive investigations across AD prevention clinical trials and clinical care for a rapidly ageing population.
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- 2021
44. Multimodal Preventive Trial for Alzheimer’s Disease: MIND-ADmini Pilot Trial Study Design and Progress
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Sindi, S., primary, Thunborg, C., additional, Rosenberg, A., additional, Andersen, P., additional, Andrieu, S., additional, Broersen, L.M., additional, Coley, N., additional, Couderc, C., additional, Duval, C.Z., additional, Faxen-Irving, G., additional, Hagman, G., additional, Hallikainen, M., additional, Håkansson, K., additional, Lehtisalo, J., additional, Levak, N., additional, Mangialasche, F., additional, Pantel, J., additional, Kekkonen, E., additional, Rydström, A., additional, Stigsdotter-Neely, A., additional, Wimo, A., additional, Ngandu, T., additional, Soininen, H., additional, Hartmann, T., additional, Solomon, A., additional, and Kivipelto, M., additional
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- 2022
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45. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
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de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. Deckert, J. Buerger, K. Morgan, K. Fließbach, K. Sleegers, K. Molina-Porcel, L. Kilander, L. Weinhold, L. Farrer, L.A. Wang, L.-S. Kleineidam, L. Farotti, L. Parnetti, L. Tremolizzo, L. Hausner, L. Benussi, L. Froelich, L. Ikram, M.A. Deniz-Naranjo, M.C. Tsolaki, M. Rosende-Roca, M. Löwenmark, M. Hulsman, M. Spallazzi, M. Pericak-Vance, M.A. Esiri, M. Bernal Sánchez-Arjona, M. Dalmasso, M.C. Martínez-Larrad, M.T. Arcaro, M. Nöthen, M.M. Fernández-Fuertes, M. Dichgans, M. Ingelsson, M. Herrmann, M.J. Scherer, M. Vyhnalek, M. Kosmidis, M.H. Yannakoulia, M. Schmid, M. Ewers, M. Heneka, M.T. Wagner, M. Scamosci, M. Kivipelto, M. Hiltunen, M. Zulaica, M. Alegret, M. Fornage, M. Roberto, N. van Schoor, N.M. Seidu, N.M. Banaj, N. Armstrong, N.J. Scarmeas, N. Scherbaum, N. Goldhardt, O. Hanon, O. Peters, O. Skrobot, O.A. Quenez, O. Lerch, O. Bossù, P. Caffarra, P. Dionigi Rossi, P. Sakka, P. Hoffmann, P. Holmans, P.A. Fischer, P. Riederer, P. Yang, Q. Marshall, R. Kalaria, R.N. Mayeux, R. Vandenberghe, R. Cecchetti, R. Ghidoni, R. Frikke-Schmidt, R. Sorbi, S. Hägg, S. Engelborghs, S. Helisalmi, S. Botne Sando, S. Kern, S. Archetti, S. Boschi, S. Fostinelli, S. Gil, S. Mendoza, S. Mead, S. Ciccone, S. Djurovic, S. Heilmann-Heimbach, S. Riedel-Heller, S. Kuulasmaa, T. del Ser, T. Lebouvier, T. Polak, T. Ngandu, T. Grimmer, T. Bessi, V. Escott-Price, V. Giedraitis, V. Deramecourt, V. Maier, W. Jian, X. Pijnenburg, Y.A.L. Smith, A.D. Saenz, A. Bizzarro, A. Lauria, A. Vacca, A. Solomon, A. Anastasiou, A. Richardson, A. Boland, A. Koivisto, A. Daniele, A. Greco, A. Marianthi, A. McGuinness, B. Fin, B. Ferrari, C. Custodero, C. Ferrarese, C. Ingino, C. Mangone, C. Reyes Toso, C. Martínez, C. Cuesta, C. Muchnik, C. Joachim, C. Ortiz, C. Besse, C. Johansson, C. Zoia, C.P. Laske, C. Anastasiou, C. Palacio, D.L. Politis, D.G. Janowitz, D. Craig, D. Mann, D.M. Neary, D. Jürgen, D. Daian, D. Belezhanska, D. Kohler, E. Castaño, E.M. Koutsouraki, E. Chipi, E. De Roeck, E. Costantini, E. Vardy, E.R.L.C. Piras, F. Roveta, F. Piras, F. Prestia, F.A. Assogna, F. Salani, F. Sala, G. Lacidogna, G. Novack, G. Wilcock, G. Thonberg, H. Kölsch, H. Weber, H. Boecker, H. Etchepareborda, I. Piaceri, I. Tuomilehto, J. Lindström, J. Laczo, J. Johnston, J. Deleuze, J.-F. Harris, J. Schott, J.M. Priller, J. Bacha, J.I. Snowden, J. Lisso, J. Mihova, K.Y. Traykov, L. Morelli, L. Brusco, L.I. Rainer, M. Takalo, M. Bjerke, M. Del Zompo, M. Serpente, M. Sanchez Abalos, M. Rios, M. Peltonen, M. Herrman, M.J. Kosmidis, M.H. Kohler, M. Rojo, M. Jones, M. Orsini, M. Medel, N. Olivar, N. Fox, N.C. Salvadori, N. Hooper, N.M. Galeano, P. Solis, P. Bastiani, P. Mecocci, P. Passmore, P. Heun, R. Antikainen, R. Olaso, R. Perneczky, R. Germani, S. López-García, S. Love, S. Mehrabian, S. Bagnoli, S. Kochen, S. Andreoni, S. Teipel, S. Todd, S. Pickering-Brown, S. Natunen, T. Tegos, T. Laatikainen, T. Strandberg, T. Polvikoski, T.M. Matoska, V. Ciullo, V. Cores, V. Solfrizzi, V. Lisetti, V. Sevillano, Z. Abdelnour, C. Aguilera, N. Alarcon, E. Alegret, M. Benaque, A. Boada, M. Buendia, M. Cañabate, P. Carracedo, A. Corbatón-Anchuelo, A. Diego, S. Espinosa, A. Gailhajenet, A. Gil, S. Guitart, M. Hernández, I. Ibarria, M. Lafuente, A. Macias, J. Maroñas, O. Martín, E. Martínez, M.T. Marquié, M. Mauleón, A. Montrreal, L. Moreno-Grau, S. Moreno, M. Orellana, A. Ortega, G. Pancho, A. Pelejá, E. Pérez-Cordon, A. Pineda, J.A. Preckler, S. Quintela, I. Real, L.M. Rosende-Roca, M. Ruiz, A. Sáez, M.E. Sanabria, A. Serrano-Rios, M. Sotolongo-Grau, O. Tárraga, L. Valero, S. Vargas, L. Adarmes-Gómez, A.D. Alarcón-Martín, E. Alonso, M.D. Álvarez, I. Álvarez, V. Amer-Ferrer, G. Antequera, M. Antúnez, C. Baquero, M. Bernal, M. Blesa, R. Boada, M. Buiza-Rueda, D. Bullido, M.J. Burguera, J.A. Calero, M. Carrillo, F. Carrión-Claro, M. Casajeros, M.J. Clarimón, J. Cruz-Gamero, J.M. de Pancorbo, M.M. del Ser, T. Diez-Fairen, M. Escuela, R. Garrote-Espina, L. Fortea, J. Franco-Macías, E. Frank-García, A. García-Alberca, J.M. Garcia Madrona, S. Garcia-Ribas, G. Gómez-Garre, P. Hernández, I. Hevilla, S. Jesús, S. Labrador Espinosa, M.A. Lage, C. Legaz, A. Lleó, A. Lopez de Munain, A. López-García, S. Macias-García, D. Manzanares, S. Marín, M. Marín-Muñoz, J. Marín, T. Marquié, M. Martín Montes, A. Martínez, B. Martínez, C. Martínez, V. Martínez-Lage Álvarez, P. Medina, M. Mendioroz Iriarte, M. Mir, P. Molinuevo, J.L. Pastor, P. Pérez Tur, J. Periñán-Tocino, T. Pineda-Sanchez, R. Piñol-Ripoll, G. Rábano, A. Real de Asúa, D. Rodrigo, S. Rodríguez-Rodríguez, E. Royo, J.L. Ruiz, A. Sanchez del Valle Díaz, R. Sánchez-Juan, P. Sastre, I. Valero, S. Vicente, M.P. Vigo-Ortega, R. Vivancos, L. Macleod, C. McCracken, C. Brayne, C. Bresner, C. Grozeva, D. Bellou, E. Sommerville, E.W. Matthews, F. Leonenko, G. Menzies, G. Windle, G. Harwood, J. Phillips, J. Bennett, K. Luckuck, L. Clare, L. Woods, R. Saad, S. Burholt, V. Jansen, I.E. Rongve, A. Kehoe, P.G. Garcia-Ribas, G. Sánchez-Juan, P. Pastor, P. Pérez-Tur, J. Piñol-Ripoll, G. Lopez de Munain, A. García-Alberca, J.M. Bullido, M.J. Álvarez, V. Lleó, A. Real, L.M. Scheltens, P. Holstege, H. Marquié, M. Sáez, M.E. Carracedo, Á. Amouyel, P. Schellenberg, G.D. Williams, J. Seshadri, S. van Duijn, C.M. Mather, K.A. Sánchez-Valle, R. Serrano-Ríos, M. Orellana, A. Tárraga, L. Blennow, K. Huisman, M. Andreassen, O.A. Posthuma, D. Clarimón, J. Boada, M. van der Flier, W.M. Ramirez, A. Lambert, J.-C. van der Lee, S.J. Ruiz, A. EADB contributors The GR@ACE study group DEGESCO consortium IGAP (ADGC, CHARGE, EADI, GERAD) PGC-ALZ consortia
- Abstract
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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- 2021
46. Telomere length change in a multidomain lifestyle intervention to prevent cognitive decline:a randomized clinical trial
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Sindi, S. (Shireen), Solomon, A. (Alina), Kåreholt, I. (Ingemar), Hovatta, I. (Iiris), Antikainen, R. (Riitta), Hänninen, T. (Tuomo), Levälahti, E. (Esko), Laatikainen, T. (Tiina), Lehtisalo, J. (Jenni), Lindström, J. (Jaana), Paajanen, T. (Teemu), Peltonen, M. (Markku), Singh Khalsa, D. (Dharma), Wolozin, B. (Benjamin), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Soininen, H. (Hilkka), Ngandu, T. (Tiia), Kivipelto, M. (Miia), and F. S. (FINGER Study Group)
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behavioural intervention ,dementia prevention ,telomeres ,older adults - Abstract
Background: Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs). Methods: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60–77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989). Results: This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was −0.016 (0.19) in the intervention group and −0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI −0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: −0.005 (95% CI −0.010 to −0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI −0.011 to 0.264). Conclusions: This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits. Clinical Trials Registration Number: NCT01041989
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- 2021
47. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
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de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I. E., Pedersen, N. L., Stringa, N., Zettergren, A., Hernandez, I., Montrreal, L., Antunez, C., Antonell, A., Tankard, R. M., Bis, J. C., Sims, R., Bellenguez, C., Quintela, I., Gonzalez-Perez, A., Calero, M., Franco-Macias, E., Macias, J., Blesa, R., Cervera-Carles, L., Menendez-Gonzalez, M., Frank-Garcia, A., Royo, J. L., Moreno, F., Huerto Vilas, R., Baquero, M., Diez-Fairen, M., Lage, C., Garcia-Madrona, S., Garcia-Gonzalez, P., Alarcon-Martin, E., Valero, S., Sotolongo-Grau, O., Ullgren, A., Naj, A. C., Lemstra, A. W., Benaque, A., Perez-Cordon, A., Benussi, A., Rabano, A., Padovani, A., Squassina, A., de Mendonca, A., Arias Pastor, A., Kok, A. A. L., Meggy, A., Pastor, A. B., Espinosa, A., Corma-Gomez, A., Martin Montes, A., Sanabria, A., DeStefano, A. L., Schneider, A., Haapasalo, A., Kinhult Stahlbom, A., Tybjaerg-Hansen, A., Hartmann, A. M., Spottke, A., Corbaton-Anchuelo, A., Rongve, A., Borroni, B., Arosio, B., Nacmias, B., Nordestgaard, B. G., Kunkle, B. W., Charbonnier, C., Abdelnour, C., Masullo, C., Martinez Rodriguez, C., Munoz-Fernandez, C., Dufouil, C., Graff, C., Ferreira, C. B., Chillotti, C., Reynolds, C. A., Fenoglio, C., Van Broeckhoven, C., Clark, C., Pisanu, C., Satizabal, C. L., Holmes, C., Buiza-Rueda, D., Aarsland, D., Rujescu, D., Alcolea, D., Galimberti, D., Wallon, D., Seripa, D., Grunblatt, E., Dardiotis, E., Duzel, E., Scarpini, E., Conti, E., Rubino, E., Gelpi, E., Rodriguez-Rodriguez, E., Duron, E., Boerwinkle, E., Ferri, E., Tagliavini, F., Kucukali, F., Pasquier, F., Sanchez-Garcia, F., Mangialasche, F., Jessen, F., Nicolas, G., Selbaek, G., Ortega, G., Chene, G., Hadjigeorgiou, G., Rossi, G., Spalletta, G., Giaccone, G., Grande, G., Binetti, G., Papenberg, G., Hampel, H., Bailly, H., Zetterberg, H., Soininen, H., Karlsson, I. K., Alvarez, I., Appollonio, I., Giegling, I., Skoog, I., Saltvedt, I., Rainero, I., Rosas Allende, I., Hort, J., Diehl-Schmid, J., Van Dongen, J., Vidal, J. -S., Lehtisalo, J., Wiltfang, J., Thomassen, J. Q., Kornhuber, J., Haines, J. L., Vogelgsang, J., Pineda, J. A., Fortea, J., Popp, J., Deckert, J., Buerger, K., Morgan, K., Fliessbach, K., Sleegers, K., Molina-Porcel, L., Kilander, L., Weinhold, L., Farrer, L. A., Wang, L. -S., Kleineidam, L., Farotti, L., Parnetti, L., Tremolizzo, L., Hausner, L., Benussi, L., Froelich, L., Ikram, M. A., Deniz-Naranjo, M. C., Tsolaki, M., Rosende-Roca, M., Lowenmark, M., Hulsman, M., Spallazzi, M., Pericak-Vance, M. A., Esiri, M., Bernal Sanchez-Arjona, M., Dalmasso, M. C., Martinez-Larrad, M. T., Arcaro, M., Nothen, M. M., Fernandez-Fuertes, M., Dichgans, M., Ingelsson, M., Herrmann, M. J., Scherer, M., Vyhnalek, M., Kosmidis, M. H., Yannakoulia, M., Schmid, M., Ewers, M., Heneka, M. T., Wagner, M., Scamosci, M., Kivipelto, M., Hiltunen, M., Zulaica, M., Alegret, M., Fornage, M., Roberto, N., van Schoor, N. M., Seidu, N. M., Banaj, N., Armstrong, N. J., Scarmeas, N., Scherbaum, N., Goldhardt, O., Hanon, O., Peters, O., Skrobot, O. A., Quenez, O., Lerch, O., Bossu, P., Caffarra, P., Dionigi Rossi, P., Sakka, P., Hoffmann, P., Holmans, P. A., Fischer, P., Riederer, P., Yang, Q., Marshall, R., Kalaria, R. N., Mayeux, R., Vandenberghe, R., Cecchetti, R., Ghidoni, R., Frikke-Schmidt, R., Sorbi, S., Hagg, S., Engelborghs, S., Helisalmi, S., Botne Sando, S., Kern, S., Archetti, S., Boschi, S., Fostinelli, S., Gil, S., Mendoza, S., Mead, S., Ciccone, S., Djurovic, S., Heilmann-Heimbach, S., Riedel-Heller, S., Kuulasmaa, T., del Ser, T., Lebouvier, T., Polak, T., Ngandu, T., Grimmer, T., Bessi, V., Escott-Price, V., Giedraitis, V., Deramecourt, V., Maier, W., Jian, X., Pijnenburg, Y. A. L., Smith, A. D., Saenz, A., Bizzarro, A., Lauria, A., Vacca, A., Solomon, A., Anastasiou, A., Richardson, A., Boland, A., Koivisto, A., Daniele, A., Greco, A., Marianthi, A., McGuinness, B., Fin, B., Ferrari, C., Custodero, C., Ferrarese, C., Ingino, C., Mangone, C., Reyes Toso, C., Martinez, C., Cuesta, C., Muchnik, C., Joachim, C., Ortiz, C., Besse, C., Johansson, C., Zoia, C. P., Laske, C., Anastasiou, C., Palacio, D. L., Politis, D. G., Janowitz, D., Craig, D., Mann, D. M., Neary, D., Jurgen, D., Daian, D., Belezhanska, D., Kohler, E., Castano, E. M., Koutsouraki, E., Chipi, E., De Roeck, E., Costantini, E., Vardy, E. R. L. C., Piras, F., Roveta, F., Prestia, F. A., Assogna, F., Salani, F., Sala, G., Lacidogna, G., Novack, G., Wilcock, G., Thonberg, H., Kolsch, H., Weber, H., Boecker, H., Etchepareborda, I., Piaceri, I., Tuomilehto, J., Lindstrom, J., Laczo, J., Johnston, J., Deleuze, J. -F., Harris, J., Schott, J. M., Priller, J., Bacha, J. I., Snowden, J., Lisso, J., Mihova, K. Y., Traykov, L., Morelli, L., Brusco, L. I., Rainer, M., Takalo, M., Bjerke, M., Del Zompo, M., Serpente, M., Sanchez Abalos, M., Rios, M., Peltonen, M., Herrman, M. J., Kohler, M., Rojo, M., Jones, M., Orsini, M., Medel, N., Olivar, N., Fox, N. C., Salvadori, N., Hooper, N. M., Galeano, P., Solis, P., Bastiani, P., Mecocci, P., Passmore, P., Heun, R., Antikainen, R., Olaso, R., Perneczky, R., Germani, S., Lopez-Garcia, S., Love, S., Mehrabian, S., Bagnoli, S., Kochen, S., Andreoni, S., Teipel, S., Todd, S., Pickering-Brown, S., Natunen, T., Tegos, T., Laatikainen, T., Strandberg, T., Polvikoski, T. M., Matoska, V., Ciullo, V., Cores, V., Solfrizzi, V., Lisetti, V., Sevillano, Z., Aguilera, N., Alarcon, E., Boada, M., Buendia, M., Canabate, P., Carracedo, A., Diego, S., Gailhajenet, A., Guitart, M., Ibarria, M., Lafuente, A., Maronas, O., Martin, E., Martinez, M. T., Marquie, M., Mauleon, A., Moreno, M., Orellana, A., Pancho, A., Peleja, E., Preckler, S., Real, L. M., Ruiz, A., Saez, M. E., Serrano-Rios, M., Tarraga, L., Vargas, L., Adarmes-Gomez, A. D., Alonso, M. D., Alvarez, V., Amer-Ferrer, G., Antequera, M., Bernal, M., Bullido, M. J., Burguera, J. A., Carrillo, F., Carrion-Claro, M., Casajeros, M. J., Clarimon, J., Cruz-Gamero, J. M., de Pancorbo, M. M., Escuela, R., Garrote-Espina, L., Garcia-Alberca, J. M., Garcia Madrona, S., Garcia-Ribas, G., Gomez-Garre, P., Hevilla, S., Jesus, S., Labrador Espinosa, M. A., Legaz, A., Lleo, A., Lopez de Munain, A., Macias-Garcia, D., Manzanares, S., Marin, M., Marin-Munoz, J., Marin, T., Martinez, B., Martinez, V., Martinez-Lage Alvarez, P., Medina, M., Mendioroz Iriarte, M., Mir, P., Molinuevo, J. L., Pastor, P., Perez Tur, J., Perinan-Tocino, T., Pineda-Sanchez, R., Pinol-Ripoll, G., Real de Asua, D., Rodrigo, S., Sanchez del Valle Diaz, R., Sanchez-Juan, P., Sastre, I., Vicente, M. P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, C., Bresner, C., Grozeva, D., Bellou, E., Sommerville, E. W., Matthews, F., Leonenko, G., Menzies, G., Windle, G., Harwood, J., Phillips, J., Bennett, K., Luckuck, L., Clare, L., Woods, R., Saad, S., Burholt, V., Kehoe, P. G., Perez-Tur, J., Scheltens, P., Holstege, H., Amouyel, P., Schellenberg, G. D., Williams, J., Seshadri, S., van Duijn, C. M., Mather, K. A., Sanchez-Valle, R., Blennow, K., Huisman, M., Andreassen, O. A., Posthuma, D., van der Flier, W. M., Ramirez, A., Lambert, J. -C., and van der Lee, S. J.
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Age of Onset ,Aged ,Aged, 80 and over ,Alzheimer Disease ,Amyloid beta-Protein Precursor ,Apolipoproteins E ,Case-Control Studies ,Cohort Studies ,Datasets as Topic ,Female ,Follow-Up Studies ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Heterozygote ,Humans ,Male ,Middle Aged ,Polymorphism, Single Nucleotide ,Risk Assessment ,Risk Factors ,Multifactorial Inheritance - Published
- 2021
48. Change in CAIDE dementia risk score and neuroimaging biomarkers during a 2-year multidomain lifestyle randomized controlled trial:results of a post-hoc subgroup analysis
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Stephen, R. (Ruth), Ngandu, T. (Tiia), Liu, Y. (Yawu), Peltonen, M. (Markku), Antikainen, R. (Riitta), Kemppainen, N. (Nina), Laatikainen, T. (Tiina), Lötjönen, J. (Jyrki), Rinne, J. (Juha), Strandberg, T. (Timo), Tuomilehto, J. (Jaakko), Vanninen, R. (Ritva), Soininen, H. (Hilkka), Kivipelto, M. (Miia), Solomon, A. (Alina), and h. F. (he FINGER Study Group)
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Prevention ,Risk reduction ,Dementia ,Hippocampus - Abstract
The CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Risk Score is a validated tool estimating dementia risk. It was previously associated with imaging biomarkers. However, associations between dementia risk scores (including CAIDE) and dementia-related biomarkers have not been studied in the context of an intervention. This study investigated associations between change in CAIDE score and change in neuroimaging biomarkers (brain magnetic resonance imaging [MRI] and Pittsburgh Compound B-positron emission tomography [PiB-PET] measures) during the 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) (post-hoc analyses). FINGER targeted at-risk older adults, aged 60–77 years, from the general population. Participants were randomized to either multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice). Neuroimaging (MRI and PiB-PET) data from baseline and 2-year visits were used. A toal of 112 participants had repeated brain MRI measures (hippocampal, total gray matter, and white matter lesion volumes, and Alzheimer’s disease signature cortical thickness). Repeated PiB-PET scans were available for 39 participants. Reduction in CAIDE score (indicating lower dementia risk) during the intervention was associated with less decline in hippocampus volume in the intervention group, but not the control group (Randomization group × CAIDE change interaction β coefficient = −0.40, p = .02). Associations for other neuroimaging measures were not significant. The intervention may have benefits on hippocampal volume in individuals who succeed in improving their overall risk level as indicated by a reduction in CAIDE score. This exploratory finding requires further testing and validation in larger studies.
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- 2021
49. Development of the First WHO Guidelines for Risk Reduction of Cognitive Decline and Dementia: Lessons Learned and Future Directions
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Stephen, R, Barbera, M, Peters, R, Ee, N, Zheng, L, Lehtisalo, J, Kulmala, J, Håkansson, K, Chowdhary, N, Dua, T, Solomon, A, Anstey, KJ, Kivipelto, M, Stephen, R, Barbera, M, Peters, R, Ee, N, Zheng, L, Lehtisalo, J, Kulmala, J, Håkansson, K, Chowdhary, N, Dua, T, Solomon, A, Anstey, KJ, and Kivipelto, M
- Abstract
The first WHO guidelines for risk reduction of cognitive decline and dementia marked an important milestone in the field of dementia prevention. In this paper, we discuss the evidence reviewed as part of the guidelines development and present the main themes emerged from its synthesis, to inform future research and policies on dementia risk reduction. The role of intervention effect-size; the mismatch between observational and intervention-based evidence; the heterogeneity of evidence among intervention trials; the importance of intervention duration; the role of timing of exposure to a certain risk factor and interventions; the relationship between intervention intensity and response; the link between individual risk factors and specific dementia pathologies; and the need for tailored interventions emerged as the main themes. The interaction and clustering of individual risk factors, including genetics, was identified as the overarching theme. The evidence collected indicates that multidomain approaches targeting simultaneously multiple risk factors and tailored at both individual and population level, are likely to be most effective and feasible in dementia risk reduction. The current status of multidomain intervention trials aimed to cognitive impairment/dementia prevention was also briefly reviewed. Primary results were presented focusing on methodological differences and the potential of design harmonization for improving evidence quality. Since multidomain intervention trials address a condition with slow clinical manifestation—like dementia—in a relatively short time frame, the need for surrogate outcomes was also discussed, with a specific focus on the potential utility of dementia risk scores. Finally, we considered how multidomain intervention could be most effectively implemented in a public health context and the implications world-wide for other non-communicable diseases targeting common risk factors, taking into account the limited evidence in low-midd
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- 2021
50. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores
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de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernández, I, Montrreal, L, Antúnez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, González-Perez, A, Calero, M, Franco-Macías, E, Macías, J, Blesa, R, Cervera-Carles, L, Menéndez-González, M, Frank-García, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, García-Madrona, S, García-González, P, Alarcón-Martín, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Pérez-Cordón, A, Benussi, A, Rábano, A, Padovani, A, Squassina, A, de Mendonça, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gómez, A, Martín Montes, A, Sanabria, Á, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Ståhlbom, A, Tybjærg-Hansen, A, Hartmann, A, Spottke, A, Corbatón-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martínez Rodríguez, C, Muñoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grünblatt, E, Dardiotis, E, Düzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Küçükali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbæk, G, Ortega, G, Chêne, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fließbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Löwenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sánchez-Arjona, M, Dalmasso, M, Martínez-Larrad, M, Arcaro, M, Nöthen, M, Fernández-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossù, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hägg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, Del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Kehoe, P, Garcia-Ribas, G, Sánchez-Juan, P, Pastor, P, Pérez-Tur, J, Piñol-Ripoll, G, Lopez de Munain, A, García-Alberca, J, Bullido, M, Álvarez, V, Lleó, A, Real, L, Mir, P, Medina, M, Scheltens, P, Holstege, H, Marquié, M, Sáez, M, Carracedo, Á, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sánchez-Valle, R, Serrano-Ríos, M, Orellana, A, Tárraga, L, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, Clarimón, J, Boada, M, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, Ruiz, A, de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E, Pedersen, Nancy L, Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M, Bis, Joshua C, Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C, Lemstra, Afina W, Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A L, Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anas, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L, Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M, Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G, Kunkle, Brian W, Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B, Chillotti, Caterina, Reynolds, Chandra A, Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L, Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K, Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L, Vogelgsang, Jonathan, Pineda, Juan A, Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A, Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M Arfan, Deniz-Naranjo, M Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A, Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M, Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J, Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H, Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T, Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M, Seidu, Nazib M, Banaj, Nerisa, Armstrong, Nicola J, Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Hoffmann, Per, Holmans, Peter A, Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N, Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, Del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A L, Andreoni, Simona, Ferrarese, Carlo, Sala Gessica, Zoia, Chiara Paola, Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J, Álvarez, Victoria, Lleó, Alberto, Real, Luis M, Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D, Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M, Mather, Karen A, Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A, Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M, Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J, Ruiz, Agustín, de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernández, I, Montrreal, L, Antúnez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, González-Perez, A, Calero, M, Franco-Macías, E, Macías, J, Blesa, R, Cervera-Carles, L, Menéndez-González, M, Frank-García, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, García-Madrona, S, García-González, P, Alarcón-Martín, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Pérez-Cordón, A, Benussi, A, Rábano, A, Padovani, A, Squassina, A, de Mendonça, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gómez, A, Martín Montes, A, Sanabria, Á, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Ståhlbom, A, Tybjærg-Hansen, A, Hartmann, A, Spottke, A, Corbatón-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martínez Rodríguez, C, Muñoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grünblatt, E, Dardiotis, E, Düzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Küçükali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbæk, G, Ortega, G, Chêne, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fließbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Löwenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sánchez-Arjona, M, Dalmasso, M, Martínez-Larrad, M, Arcaro, M, Nöthen, M, Fernández-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossù, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hägg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, Del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Kehoe, P, Garcia-Ribas, G, Sánchez-Juan, P, Pastor, P, Pérez-Tur, J, Piñol-Ripoll, G, Lopez de Munain, A, García-Alberca, J, Bullido, M, Álvarez, V, Lleó, A, Real, L, Mir, P, Medina, M, Scheltens, P, Holstege, H, Marquié, M, Sáez, M, Carracedo, Á, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sánchez-Valle, R, Serrano-Ríos, M, Orellana, A, Tárraga, L, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, Clarimón, J, Boada, M, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, Ruiz, A, de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E, Pedersen, Nancy L, Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M, Bis, Joshua C, Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C, Lemstra, Afina W, Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A L, Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anas, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L, Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M, Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G, Kunkle, Brian W, Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B, Chillotti, Caterina, Reynolds, Chandra A, Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L, Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K, Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L, Vogelgsang, Jonathan, Pineda, Juan A, Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A, Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M Arfan, Deniz-Naranjo, M Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A, Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M, Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J, Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H, Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T, Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M, Seidu, Nazib M, Banaj, Nerisa, Armstrong, Nicola J, Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Hoffmann, Per, Holmans, Peter A, Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N, Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, Del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A L, Andreoni, Simona, Ferrarese, Carlo, Sala Gessica, Zoia, Chiara Paola, Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J, Álvarez, Victoria, Lleó, Alberto, Real, Luis M, Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D, Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M, Mather, Karen A, Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A, Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M, Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J, and Ruiz, Agustín
- Abstract
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.
- Published
- 2021
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