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4. Conclusion

Author

Dröes, Rose-Marie, primary, Orrell, Martin, additional, and Verhey, Frans R. J., additional

Published
2022
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6. The unique training programme of INDUCT

Author

Dassen, Fania C.M., primary, Bartels, Sara Laureen, additional, Christie, Hannah, additional, Van den Block, Lieve, additional, de Vugt, Marjolein, additional, and Verhey, Frans R. J., additional

Published
2022
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8. Health burden in type 2 diabetes and prediabetes in The Maastricht Study

Author

Veugen, Marja G. J., Onete, Veronica G., Henry, Ronald M. A., Brunner-La Rocca, Hans-Peter, Koster, Annemarie, Dagnelie, Pieter C., Schaper, Nicolaas C., Sep, Simone J. S., van der Kallen, Carla J. H., van Boxtel, Martin P. J., Reesink, Koen D., Schouten, Johannes S., Savelberg, Hans H. C. M., Köhler, Sebastian, Verhey, Frans R., van den Bergh, Joop P. W., Schram, Miranda T., and Stehouwer, Coen D. A.

Published
2022
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9. Correction: Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease

Author

Visser, Pieter Jelle, Reus, Lianne M., Gobom, Johan, Jansen, Iris, Dicks, Ellen, van der Lee, Sven J., Tsolaki, Magda, Verhey, Frans R. J., Popp, Julius, Martinez-Lage, Pablo, Vandenberghe, Rik, Lleó, Alberto, Molinuevo, José Luís, Engelborghs, Sebastiaan, Freund-Levi, Yvonne, Froelich, Lutz, Sleegers, Kristel, Dobricic, Valerija, Lovestone, Simon, Streffer, Johannes, Vos, Stephanie J. B., Bos, Isabelle, Smit, August B., Blennow, Kaj, Scheltens, Philip, Teunissen, Charlotte E., Bertram, Lars, Zetterberg, Henrik, and Tijms, Betty M.

Published
2022
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10. Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease

Author

Visser, Pieter Jelle, Reus, Lianne M., Gobom, Johan, Jansen, Iris, Dicks, Ellen, van der Lee, Sven J., Tsolaki, Magda, Verhey, Frans R. J., Popp, Julius, Martinez-Lage, Pablo, Vandenberghe, Rik, Lleó, Alberto, Molinuevo, José Luís, Engelborghs, Sebastiaan, Freund-Levi, Yvonne, Froelich, Lutz, Sleegers, Kristel, Dobricic, Valerija, Lovestone, Simon, Streffer, Johannes, Vos, Stephanie J. B., Bos, Isabelle, Smit, August B., Blennow, Kaj, Scheltens, Philip, Teunissen, Charlotte E., Bertram, Lars, Zetterberg, Henrik, and Tijms, Betty M.

Published
2022
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11. Associations between plasma kynurenines and cognitive function in individuals with normal glucose metabolism, prediabetes and type 2 diabetes: the Maastricht Study

Author

Bakker, Lieke, Ramakers, Inez H. G. B., van Boxtel, Martin P. J., Schram, Miranda T., Stehouwer, Coen D. A., van der Kallen, Carla J. H., Dagnelie, Pieter C., van Greevenbroek, Marleen M. J., Wesselius, Anke, Midttun, Øivind, Ueland, Per M., Verhey, Frans R. J., Eussen, Simone J. P. M., and Köhler, Sebastian

Published
2021
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14. Strategic infarct locations for post-stroke cognitive impairment: a pooled analysis of individual patient data from 12 acute ischaemic stroke cohorts

Author

Weaver, Nick A, Kuijf, Hugo J, Aben, Hugo P, Abrigo, Jill, Bae, Hee-Joon, Barbay, Mélanie, Best, Jonathan G, Bordet, Régis, Chappell, Francesca M, Chen, Christopher P L H, Dondaine, Thibaut, van der Giessen, Ruben S, Godefroy, Olivier, Gyanwali, Bibek, Hamilton, Olivia K L, Hilal, Saima, Huenges Wajer, Irene M C, Kang, Yeonwook, Kappelle, L Jaap, Kim, Beom Joon, Köhler, Sebastian, de Kort, Paul L M, Koudstaal, Peter J, Kuchcinski, Gregory, Lam, Bonnie Y K, Lee, Byung-Chul, Lee, Keon-Joo, Lim, Jae-Sung, Lopes, Renaud, Makin, Stephen D J, Mendyk, Anne-Marie, Mok, Vincent C T, Oh, Mi Sun, van Oostenbrugge, Robert J, Roussel, Martine, Shi, Lin, Staals, Julie, del C Valdés-Hernández, Maria, Venketasubramanian, Narayanaswamy, Verhey, Frans R J, Wardlaw, Joanna M, Werring, David J, Xin, Xu, Yu, Kyung-Ho, van Zandvoort, Martine J E, Zhao, Lei, Biesbroek, J Matthijs, and Biessels, Geert Jan

Published
2021
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16. Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD

Author

Lawlor, Brian, Segurado, Ricardo, Kennelly, Sean, Olde Rikkert, Marcel G.M., Howard, Robert, Pasquier, Florence, Börjesson-Hanson, Anne, Tsolaki, Magda, Lucca, Ugo, Molloy, D. William, Coen, Robert, Riepe, Matthias W., Kálmán, János, Kenny, Rose Anne, Cregg, Fiona, O'Dwyer, Sarah, Walsh, Cathal, Adams, Jessica, Banzi, Rita, Breuilh, Laetitia, Daly, Leslie, Hendrix, Suzanne, Aisen, Paul, Gaynor, Siobhan, Sheikhi, Ali, Taekema, Diana G., Verhey, Frans R., Nemni, Raffaello, Nobili, Flavio, Franceschi, Massimo, Frisoni, Giovanni, Zanetti, Orazio, Konsta, Anastasia, Anastasios, Orologas, Nenopoulou, Styliani, Tsolaki-Tagaraki, Fani, Pakaski, Magdolna, Dereeper, Olivier, Sayette, Vincent de la, Sénéchal, Olivier, Lavenu, Isabelle, Devendeville, Agnès, Calais, Gauthier, Crawford, Fiona, Mullan, Michael, Aalten, Pauline, Berglund, Maria A., Claassen, Jurgen A., De Heus, Rianne A., De Jong, Daan L.K., Godefroy, Olivier, Hutchinson, Siobhan, Ioannou, Aikaterini, Jonsson, Michael, Kent, Annette, Kern, Jürgen, Nemtsas, Petros, Panidou, Minoa-Kalliopi, Abdullah, Laila, Paris, Daniel, Santoso, Angelina M., van Spijker, Gerrita J., Spiliotou, Martha, Thomoglou, Georgia, Wallin, Anders, Dyer, Adam H., Murphy, Claire, and Kennelly, Sean P.

Published
2020
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20. The association of hyperglycaemia and insulin resistance with incident depressive symptoms over 4 years of follow-up: The Maastricht Study

Author

Geraets, Anouk F. J., Köhler, Sebastian, Muzambi, Rutendo, Schalkwijk, Casper G., Oenema, Anke, Eussen, Simone J. P. M., Dagnelie, Pieter C., Stehouwer, Coen D. A., Schaper, Nicolaas C., Henry, Ronald M. A., van der Kallen, Carla J. H., Wesselius, Anke, Koster, Annemarie, Verhey, Frans R. J., and Schram, Miranda T.

Published
2020
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22. Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions

Author

Reus, Lianne M., Jansen, Iris E., Mol, Merel O., van Ruissen, Fred, van Rooij, Jeroen, van Schoor, Natasja M., Tesi, Niccolò, Reinders, Marcel J. T., Huisman, Martijn A., Holstege, Henne, Visser, Pieter Jelle, de Boer, Sterre C. M., Hulsman, Marc, Ahmad, Shahzad, Amin, Najaf, Uitterlinden, Andre G., Ikram, Arfan, van Duijn, Cornelia M., Seelaar, Harro, Ramakers, Inez H. G. B., Verhey, Frans R. J., van der Lugt, Aad, Claassen, Jurgen A. H. R., Jan Biessels, Geert, De Deyn, Peter Paul, Scheltens, Philip, van der Flier, Wiesje M., van Swieten, John C., Pijnenburg, Yolande A. L., and van der Lee, Sven J.

Published
2021
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27. Smartphone-Based Experience Sampling in People With Mild Cognitive Impairment: Feasibility and Usability Study

Author

Bartels, Sara Laureen, van Knippenberg, Rosalia J M, Malinowsky, Camilla, Verhey, Frans R J, and de Vugt, Marjolein E

Subjects
Geriatrics, RC952-954.6
Abstract

BackgroundDaily functioning of people with cognitive disorders such as mild cognitive impairment (MCI) is usually depicted by retrospective questionnaires, which can be memory-biased and neglect fluctuations over time or contexts. ObjectiveThis study examines the feasibility and usability of applying the experience sampling method (ESM) in people with MCI to provide a detailed and dynamic picture of behavioral, emotional, and cognitive patterns in everyday life. MethodsFor 6 consecutive days, 21 people with MCI used an ESM app on their smartphones. At 8 semi-random timepoints per day, participants filled in momentary questionnaires on mood, activities, social context, and subjective cognitive complaints. Feasibility was determined through self-reports and observable human-technology interactions. Usability was demonstrated on an individual and group level. ResultsOf the 21 participants, 3 dropped out due to forgetting to carry their smartphones or forgetting the study instructions. In the remaining 18 individuals, the compliance rate was high, at 78.7%. Participants reported that momentary questions reflected their daily experiences well. Of the 18 participants, 13 (72%) experienced the increase in awareness of their own memory functions as pleasant or neutral. ConclusionsSupport was found for the general feasibility of smartphone-based experience sampling in people with MCI. However, many older adults with MCI are currently not in possession of smartphones, and study adherence seems challenging for a minority of individuals. Momentary data can increase the insights into daily patterns and may guide the person-tailored development of self-management strategies in clinical settings.

Published
2020
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31. The frequency and influence of dementia risk factors in prodromal Alzheimer's disease

Author

Bos, Isabelle, Vos, Stephanie J., Frölich, Lutz, Kornhuber, Johannes, Wiltfang, Jens, Maier, Wolfgang, Peters, Oliver, Rüther, Eckhart, Engelborghs, Sebastiaan, Niemantsverdriet, Ellis, De Roeck, Ellen Elisa, Tsolaki, Magda, Freund-Levi, Yvonne, Johannsen, Peter, Vandenberghe, Rik, Lleó, Alberto, Alcolea, Daniel, Frisoni, Giovanni B., Galluzzi, Samantha, Nobili, Flavio, Morbelli, Silvia, Drzezga, Alexander, Didic, Mira, van Berckel, Bart N., Salmon, Eric, Bastin, Christine, Dauby, Solene, Santana, Isabel, Baldeiras, Inês, de Mendonça, Alexandre, Silva, Dina, Wallin, Anders, Nordlund, Arto, Coloma, Preciosa M., Wientzek, Angelika, Alexander, Myriam, Novak, Gerald P., Gordon, Mark Forrest, Wallin, Åsa K., Hampel, Harald, Soininen, Hilkka, Herukka, Sanna-Kaisa, Scheltens, Philip, Verhey, Frans R., and Visser, Pieter Jelle

Published
2017
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33. Contributions of modifiable risk factors to increased dementia risk in depression.

Author

Geraets, Anouk F. J., Leist, Anja K., Deckers, Kay, Verhey, Frans R. J., Schram, Miranda T., and Köhler, Sebastian

Subjects
DEMENTIA risk factors, DEMENTIA prevention, STRUCTURAL equation modeling, CONFIDENCE intervals, AGE distribution, RISK assessment, SEX distribution, INCOME, MENTAL depression, CENTER for Epidemiologic Studies Depression Scale, DESCRIPTIVE statistics, RESEARCH funding, LONGITUDINAL method, EDUCATIONAL attainment, MIDDLE age
Abstract

Background: Individuals with depression have an increased dementia risk, which might be due to modifiable risk factors for dementia. This study investigated the extent to which the increased risk for dementia in depression is explained by modifiable dementia risk factors. Methods: We used data from the English Longitudinal Study of Ageing (2008–2009 to 2018–2019), a prospective cohort study. A total of 7460 individuals were included [mean(standard deviation) age, 65.7 ± 9.4 years; 3915(54.7%) were women]. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale-8 (score ≥3) or self-reported doctor's diagnosis. Ten modifiable risk factors for dementia were combined in the 'LIfestyle for BRAin health' (LIBRA) score. Dementia was determined by physician diagnosis, self-reported Alzheimer's disease or the shortened version of the Informant Questionnaire on Cognitive Decline in the Elderly (average score ≥3.38). Structural equation modelling was used to test mediation of LIBRA score. Results: During 61 311 person-years, 306 individuals (4.1%) developed dementia. Participants aged 50–70 years with depressive symptoms had higher LIBRA scores [difference(s.e.) = 1.15(0.10)] and a 3.59 times increased dementia risk [HR(95% CI) = 3.59(2.20–5.84)], adjusted for age, sex, education, wealth and clustering at the household level. In total, 10.4% of the dementia risk was mediated by differences in LIBRA score [indirect effect: HR = 1.14(1.03–1.26)], while 89.6% was attributed to a direct effect of depressive symptoms on dementia risk [direct effect: HR = 3.14(2.20–5.84)]. Conclusions: Modifiable dementia risk factors can be important targets for the prevention of dementia in individuals with depressive symptoms during midlife. Yet, effect sizes are small and other aetiological pathways likely exist. [ABSTRACT FROM AUTHOR]

Published
2023
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35. Determinants of quality of life in family caregivers in MCI:a comparison with mild dementia

Author

Tan, Eva Y. L., Janssen, Niels, Handels, Ron, Ramakers, Inez H. G. B., Verhey, Frans R. J., van der Flier, Wiesje M., Melis, René J. F., Olde Rikkert, Marcel G. M., Schols, Jos M. G. A., and de Vugt, Marjolein E.

Abstract

Objectives: The aim of the current study was to investigate the health-related quality of life (HRQol) of the family caregiver in MCI, explore possible determinants and study possible differences with mild dementia. Methods: This secondary data analysis included 145 persons with MCI and 154 persons with dementia and their family caregivers from two Dutch cohort studies. HRQoL was measured with the VAS of the EuroQol-5D-3L version. Regressions analyses were conducted to examine potential demographic and clinical determinants of the caregiver’s HRQoL. Results: The mean EQ5D-VAS in family caregivers of persons with MCI was 81.1 (SD 15.7), and did not significantly differ from family caregivers in mild dementia (81.9 (SD 13.0)). In MCI, patient measurements were not significantly associated with caregiver mean EQ5D-VAS. Concerning caregiver characteristics, being a spouse and a lower educational level were associated with a lower mean EQ5D-VAS (in a multiple linear regression model: unstandardized B −8.075, p = 0.013 and unstandardized B −6.162, p = 0.037 resp.). In mild dementia, the NPI item irritability showed an association with caregiver EQ5D-VAS in bivariate linear regression analyses. Conclusion: Results indicate that especially family caregiver characteristics seem to influence family caregiver HRQoL in MCI. Future research should include other potential determinants such as burden, coping strategies and relationship quality.

Published
2023

39. Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia

Author

Jansen, Willemijn J., Ossenkoppele, Rik, Tijms, Betty M., Fagan, Anne M., Hansson, Oskar, Klunk, William E., van der Flier, Wiesje M., Villemagne, Victor L., Frisoni, Giovanni B., Fleisher, Adam S., Lleó, Alberto, Mintun, Mark A., Wallin, Anders, Engelborghs, Sebastiaan, Na, Duk L., Chételat, Gäel, Molinuevo, José Luis, Landau, Susan M., Mattsson, Niklas, Kornhuber, Johannes, Sabri, Osama, Rowe, Christopher C., Parnetti, Lucilla, Popp, Julius, Fladby, Tormod, Jagust, William J., Aalten, Pauline, Lee, Dong Young, Vandenberghe, Rik, Resende de Oliveira, Catarina, Kapaki, Elisabeth, Froelich, Lutz, Ivanoiu, Adrian, Gabryelewicz, Tomasz, Verbeek, Marcel M., Sanchez-Juan, Páscual, Hildebrandt, Helmut, Camus, Vincent, Zboch, Marzena, Brooks, David J., Drzezga, Alexander, Rinne, Juha O., Newberg, Andrew, de Mendonça, Alexandre, Sarazin, Marie, Rabinovici, Gil D., Madsen, Karine, Kramberger, Milica G., Nordberg, Agneta, Mok, Vincent, Mroczko, Barbara, Wolk, David A., Meyer, Philipp T., Tsolaki, Magda, Scheltens, Philip, Verhey, Frans R. J., Visser, Pieter Jelle, Aarsland, Dag, Alcolea, Daniel, Alexander, Myriam, Almdahl, Ina S., Arnold, Steven E., Baldeiras, Inês, Barthel, Henryk, van Berckel, Bart N.M., Blennow, Kaj, van Buchem, Mark A., Cavedo, Enrica, Chen, Kewei, Chipi, Elena, Cohen, Ann D., Förster, Stefan, Fortea, Juan, Frederiksen, Kristian S., Freund-Levi, Yvonne, Gkatzima, Olymbia, Gordon, Mark Forrest, Grimmer, Timo, Hampel, Harald, Hausner, Lucrezia, Hellwig, Sabine, Herukka, Sanna-Kaisa, Johannsen, Peter, Klimkowicz-Mrowiec, Aleksandra, Köhler, Sebastian, Koglin, Norman, van Laere, Koen, de Leon, Mony, Lisetti, Viviana, Maier, Wolfgang, Marcusson, Jan, Meulenbroek, Olga, Møllergård, Hanne M., Morris, John C., Nordlund, Arto, Novak, Gerald P., Paraskevas, George P., Perera, Gayan, Peters, Oliver, Ramakers, Inez H. G. B., Rami, Lorena, Rodríguez-Rodríguez, Eloy, Roe, Catherine M., Rot, Uros, Rüther, Eckart, Santana, Isabel, Schröder, Johannes, Seo, Sang W., Soininen, Hilkka, Spiru, Luiza, Stomrud, Erik, Struyfs, Hanne, Teunissen, Charlotte E., Vos, Stephanie J. B., van Waalwijk van Doorn, Linda J. C., Waldemar, Gunhild, Wallin, Åsa K., Wiltfang, Jens, and Zetterberg, Henrik

Published
2018
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41. MRI predictors of amyloid pathology: results from the EMIF-AD Multimodal Biomarker Discovery study

Author

ten Kate, Mara, Redolfi, Alberto, Peira, Enrico, Bos, Isabelle, Vos, Stephanie J., Vandenberghe, Rik, Gabel, Silvy, Schaeverbeke, Jolien, Scheltens, Philip, Blin, Olivier, Richardson, Jill C., Bordet, Regis, Wallin, Anders, Eckerstrom, Carl, Molinuevo, José Luis, Engelborghs, Sebastiaan, Van Broeckhoven, Christine, Martinez-Lage, Pablo, Popp, Julius, Tsolaki, Magdalini, Verhey, Frans R. J., Baird, Alison L., Legido-Quigley, Cristina, Bertram, Lars, Dobricic, Valerija, Zetterberg, Henrik, Lovestone, Simon, Streffer, Johannes, Bianchetti, Silvia, Novak, Gerald P., Revillard, Jerome, Gordon, Mark F., Xie, Zhiyong, Wottschel, Viktor, Frisoni, Giovanni, Visser, Pieter Jelle, and Barkhof, Frederik

Published
2018
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42. Correction to: Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline

Author

Bos, Isabelle, Verhey, Frans R., Ramakers, Inez H. G. B., Jacobs, Heidi I. L., Soininen, Hilkka, Freund-Levi, Yvonne, Hampel, Harald, Tsolaki, Magda, Wallin, Åsa K., van Buchem, Mark A., Oleksik, Ania, Verbeek, Marcel M., Rikkert, Marcel Olde, van der Flier, Wiesje M., Scheltens, Philip, Aalten, Pauline, Visser, Pieter Jelle, and Vos, Stephanie J. B.

Published
2018
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44. Distinct Patterns Link the BDNF Val66Met Polymorphism to Alzheimer's Disease Pathology

Author

Riphagen, Joost M, van Hooren, Roy W E, Kenis, Gunter, Verhey, Frans R J, Jacobs, Heidi I L, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, Psychology 1, Psychology 4, MUMC+: MA Niet Med Staf Psychiatrie (9), RS: MHeNs - R3 - Neuroscience, Basic Neuroscience 1, and MUMC+: MA Med Staf Spec Psychiatrie (9)

Subjects
INTERLEUKIN-6, BETA, interleukin 6, tau Proteins, brain-derived neurotropic growth factor, phosphorylated tau, APOLIPOPROTEIN-E, MECHANISMS, NEUROINFLAMMATION, Apolipoproteins E, Alzheimer Disease, Humans, Cognitive Dysfunction, Inflammation, Amyloid beta-Peptides, General Neuroscience, Brain-Derived Neurotrophic Factor, CYTOKINES, ASSOCIATION, General Medicine, Alzheimer's disease, IMPAIRMENT, amyloid-beta, Peptide Fragments, Psychiatry and Mental health, Clinical Psychology, COGNITIVE DECLINE, Geriatrics and Gerontology, Biomarkers, NEUROTROPHIC FACTOR
Abstract

The brain-derived neurotropic growth factor (BDNF) gene has been linked to dementia, inflammation, and Apolipoprotein E (APOE) ɛ4 status. We used cerebrospinal fluid (CSF) amyloid-β (Aβ)42 and phosphorylated tau (p-tau) to investigate associations with BDNF polymorphisms and modifications by APOE ɛ4 or inflammation in a memory clinic population (n = 114; subjective cognitive decline, mild cognitive impairment, Alzheimer’s disease). We found distinct pathways to Alzheimer’s disease pathology: Val-Met displayed lower CSF-Aβ42 in APOE ɛ4+ carriers, independent of p-tau, while Val-Val displayed greater p-tau at higher IL-6 and sub-threshold Aβ42. This may contribute to resolving some inconsistencies in the BDNF literature and provide possible inroads to specific Aβ and tau interventions depending on BDNF polymorphism.

Published
2022

46. Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline

Author

Bos, Isabelle, Verhey, Frans R., Ramakers, Inez H.G.B., Jacobs, Heidi I. L., Soininen, Hilkka, Freund-Levi, Yvonne, Hampel, Harald, Tsolaki, Magda, Wallin, Åsa K., van Buchem, Mark A., Oleksik, Ania, Verbeek, Marcel M., Olde Rikkert, Marcel, van der Flier, Wiesje M., Scheltens, Philip, Aalten, Pauline, Visser, Pieter Jelle, and Vos, Stephanie J. B.

Published
2017
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48. Systematic review of the body of evidence for the use of biomarkers in the diagnosis of dementia

Author

Noel-Storr, Anna H., Flicker, Leon, Ritchie, Craig W., Nguyen, Giang Huong, Gupta, Tarun, Wood, Phillip, Walton, Josephine, Desai, Meera, Solomon, Danielle Fraser, Molena, Emma, Worrall, Rosemary, Hayen, Anja, Choudhary, Prateek, Ladds, Emma, Lanctôt, Krista L., Verhey, Frans R., McCleery, Jenny M., Mead, Gillian E., Clare, Linda, Fioravanti, Mario, Hyde, Chris, Marcus, Sue, and McShane, Rupert

Published
2013
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49. Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum

Author

Jansen, Willemijn J, Janssen, Olin, von Arnim, Christine, Marquié, Marta, Martinez-Lage, Pablo, Maserejian, Nancy, Mattsson, Niklas, de Mendonça, Alexandre, Meyer, Philipp T, Miller, Bruce L, Minatani, Shinobu, Mintun, Mark A, Mok, Vincent C T, Baiardi, Simone, Molinuevo, Jose Luis, Morbelli, Silvia Daniela, Morris, John C, Mroczko, Barbara, Na, Duk L, Newberg, Andrew, Nobili, Flavio, Nordberg, Agneta, Olde Rikkert, Marcel G M, de Oliveira, Catarina Resende, Baldeiras, Ines, Olivieri, Pauline, Orellana, Adela, Paraskevas, George, Parchi, Piero, Pardini, Matteo, Parnetti, Lucilla, Peters, Oliver, Poirier, Judes, Popp, Julius, Prabhakar, Sudesh, Barthel, Henryk, Rabinovici, Gil D, Ramakers, Inez H, Rami, Lorena, Reiman, Eric M, Rinne, Juha O, Rodrigue, Karen M, Rodríguez-Rodriguez, Eloy, Roe, Catherine M, Rosa-Neto, Pedro, Rosen, Howard J, Bateman, Randall J, Rot, Uros, Rowe, Christopher C, Rüther, Eckart, Ruiz, Agustín, Sabri, Osama, Sakhardande, Jayant, Sánchez-Juan, Pascual, Sando, Sigrid Botne, Santana, Isabel, Sarazin, Marie, Van Berckel, Bart, Scheltens, Philip, Schröder, Johannes, Selnes, Per, Seo, Sang Won, Silva, Dina, Skoog, Ingmar, Snyder, Peter J, Soininen, Hilkka, Sollberger, Marc, Sperling, Reisa A, Binette, Alexa Pichet, Spiru, Luisa, Stern, Yaakov, Stomrud, Erik, Takeda, Akitoshi, Teichmann, Marc, Teunissen, Charlotte E, Thompson, Louisa I, Tomassen, Jori, Tsolaki, Magda, Vandenberghe, Rik, Blennow, Kaj, Verbeek, Marcel M, Verhey, Frans R J, Villemagne, Victor, Villeneuve, Sylvia, Vogelgsang, Jonathan, Waldemar, Gunhild, Wallin, Anders, Wallin, Åsa K, Wiltfang, Jens, Wolk, David A, Boada, Merce, Yen, Tzu-Chen, Zboch, Marzena, Zetterberg, Henrik, Boecker, Henning, Tijms, Betty M, Bottlaender, Michel, den Braber, Anouk, Brooks, David J, Van Buchem, Mark A, Camus, Vincent, Carill, Jose Manuel, Cerman, Jiri, Chen, Kewei, Chételat, Gaël, Chipi, Elena, Vos, Stephanie J B, Cohen, Ann D, Daniels, Alisha, Delarue, Marion, Didic, Mira, Drzezga, Alexander, Dubois, Bruno, Eckerström, Marie, Ekblad, Laura L, Engelborghs, Sebastiaan, Epelbaum, Stéphane, Ossenkoppele, Rik, Fagan, Anne M, Fan, Yong, Fladby, Tormod, Fleisher, Adam S, Van der Flier, Wiesje M, Förster, Stefan, Fortea, Juan, Frederiksen, Kristian Steen, Freund-Levi, Yvonne, Frings, Lars, Visser, Pieter Jelle, Frisoni, Giovanni B, Fröhlich, Lutz, Gabryelewicz, Tomasz, Gertz, Hermann-Josef, Gill, Kiran Dip, Gkatzima, Olymbia, Gómez-Tortosa, Estrella, Grimmer, Timo, Guedj, Eric, Habeck, Christian G, Group, Amyloid Biomarker Study, Hampel, Harald, Handels, Ron, Hansson, Oskar, Hausner, Lucrezia, Hellwig, Sabine, Heneka, Michael, Herukka, Sanna-Kaisa, Hildebrandt, Helmut, Hodges, John, Hort, Jakub, Aarsland, Dag, Huang, Chin-Chang, Iriondo, Ane Juaristi, Itoh, Yoshiaki, Ivanoiu, Adrian, Jagust, William J, Jessen, Frank, Johannsen, Peter, Johnson, Keith A, Kandimalla, Ramesh, Kapaki, Elisabeth N, Alcolea, Daniel, Kern, Silke, Kilander, Lena, Klimkowicz-Mrowiec, Aleksandra, Klunk, William E, Koglin, Norman, Kornhuber, Johannes, Kramberger, Milica G, Kuo, Hung-Chou, Van Laere, Koen, Landau, Susan M, Altomare, Daniele, Landeau, Brigitte, Lee, Dong Young, de Leon, Mony, Leyton, Cristian E, Lin, Kun-Ju, Lleó, Alberto, Löwenmark, Malin, Madsen, Karine, Maier, Wolfgang, Marcusson, Jan, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Laboratory Medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, APH - Personalized Medicine, APH - Methodology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and Psychiatrie & Neuropsychologie

Subjects
Male, MILD COGNITIVE IMPAIRMENT, epidemiology [Cognitive Dysfunction], positron emission tomography, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], epidemiology [Alzheimer Disease], Neuroscience(all), diagnostic imaging [Cognitive Dysfunction], Amyloidogenic Proteins, tau Proteins, cerebrospinal fluid [Amyloid beta-Peptides], DIAGNOSIS, cerebrospinal fluid, Apolipoproteins E, Alzheimer Disease, Prevalence, Humans, Amyloid, Alzheimer, PET, Cognitive Dysfunction, ddc:610, cerebrospinal fluid [Peptide Fragments], Aged, Amyloid beta-Peptides, neurology, DEMENTIA, Correction, ASSOCIATION, Amyloidosis, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], health care planning, clinical trial design, Peptide Fragments, cerebrospinal fluid [Alzheimer Disease], PET, DRIFT, Cross-Sectional Studies, cerebrospinal fluid [Biomarkers], cerebrospinal fluid [tau Proteins], Radiology Nuclear Medicine and imaging, Positron-Emission Tomography, genetics [Apolipoproteins E], Female, Neurology (clinical), diagnostic imaging [Alzheimer Disease], cerebral amyloid aggregation, Biomarkers
Abstract

Importance: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.Objective: To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.Design, Setting, and Participants: This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Exposures: Alzheimer disease biomarkers detected on PET or in CSF.Main Outcomes and Measures: Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Results: Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P = .18).Conclusions and Relevance: This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.

Published
2022

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