21 results on '"Lehtisalo, Jenni"'
Search Results
2. Dementia prevention: The potential long-term cost-effectiveness of the FINGER prevention program.
- Author
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Wimo A, Handels R, Antikainen R, Eriksdotter M, Jönsson L, Knapp M, Kulmala J, Laatikainen T, Lehtisalo J, Peltonen M, Sköldunger A, Soininen H, Solomon A, Strandberg T, Tuomilehto J, Ngandu T, and Kivipelto M
- Subjects
- Humans, Aged, Male, Female, Finland, Aged, 80 and over, Dementia prevention & control, Dementia economics, Cost-Benefit Analysis, Quality-Adjusted Life Years, Markov Chains
- 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., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
- Published
- 2023
- Full Text
- View/download PDF
3. Third follow-up of the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) cohort investigating determinants of cognitive, physical, and psychosocial wellbeing among the oldest old: the CAIDE85+ study protocol.
- Author
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Barbera M, Kulmala J, Lisko I, Pietilä E, Rosenberg A, Hallikainen I, Hallikainen M, Laatikainen T, Lehtisalo J, Neuvonen E, Rusanen M, Soininen H, Tuomilehto J, Ngandu T, Solomon A, and Kivipelto M
- Subjects
- Activities of Daily Living, Aged, 80 and over, Cognition, Finland, Follow-Up Studies, Heart Disease Risk Factors, Humans, Risk Factors, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cognitive Dysfunction, Dementia diagnosis, Dementia epidemiology
- Abstract
Background: The oldest old is the fastest growing age group worldwide and the most prone to severe disability, especially in relation to loss of cognitive function. Improving our understanding of the predictors of cognitive, physical and psychosocial wellbeing among the oldest old can result in substantial benefits for the individuals and for the society as a whole. The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study investigated risk factors and determinants of cognitive impairment in a population-based longitudinal cohort, which was first examined between 1972 and 1992, when individuals were in their midlife, and re-assessed in 1998 and 2005-2009. Most of the study participants are currently aged 85 years or older. We aim to re-examine the cohort's survivors and gain further insights on the mechanisms underlying both cognitive and overall healthy ageing at old age., Methods: CAIDE85+ is the third follow-up of the CAIDE study participants. All individuals still alive and living in the Kuopio and Joensuu areas of Eastern Finland, from the original CAIDE cohort (two random samples, N = 2000 + ~ 900), will be invited to a re-examination. The assessment includes self-reported data related to basic demographics and lifestyle, as well as psychosocial and physical health status. Cognitive and physical evaluations are also conducted. Blood biomarkers relevant for dementia and ageing are assessed. Primary outcomes are the measurements related to cognition and daily life functioning (CERAD, Trail Making Test-A, Letter-Digit Substitution Test, Clinical Dementia Rating and Activities of Daily Living). Secondary endpoints of the study are outcomes related to physical health status, psychosocial wellbeing, as well as age-related health indicators., Discussion: Through a follow-up of more than 40 years, CAIDE85+ will provide invaluable information on the risk and protective factors that contribute to cognitive and physical health, as well as ageing and longevity., Study Registration: The present study protocol has been registered at https://clinicaltrials.gov/ (registration nr NCT03938727 , date 03.05.2019).
- Published
- 2020
- Full Text
- View/download PDF
4. World-Wide FINGERS Network: A global approach to risk reduction and prevention of dementia.
- Author
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Kivipelto M, Mangialasche F, Snyder HM, Allegri R, Andrieu S, Arai H, Baker L, Belleville S, Brodaty H, Brucki SM, Calandri I, Caramelli P, Chen C, Chertkow H, Chew E, Choi SH, Chowdhary N, Crivelli L, Torre R, Du Y, Dua T, Espeland M, Feldman HH, Hartmanis M, Hartmann T, Heffernan M, Henry CJ, Hong CH, Håkansson K, Iwatsubo T, Jeong JH, Jimenez-Maggiora G, Koo EH, Launer LJ, Lehtisalo J, Lopera F, Martínez-Lage P, Martins R, Middleton L, Molinuevo JL, Montero-Odasso M, Moon SY, Morales-Pérez K, Nitrini R, Nygaard HB, Park YK, Peltonen M, Qiu C, Quiroz YT, Raman R, Rao N, Ravindranath V, Rosenberg A, Sakurai T, Salinas RM, Scheltens P, Sevlever G, Soininen H, Sosa AL, Suemoto CK, Tainta-Cuezva M, Velilla L, Wang Y, Whitmer R, Xu X, Bain LJ, Solomon A, Ngandu T, and Carrillo MC
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- Clinical Trials as Topic, Cognition physiology, Humans, Research Design, Risk Reduction Behavior, Alzheimer Disease prevention & control, Dementia prevention & control, Exercise Therapy, Life Style
- Abstract
Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)
- Published
- 2020
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5. Adherence to multidomain interventions for dementia prevention: Data from the FINGER and MAPT trials.
- Author
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Coley N, Ngandu T, Lehtisalo J, Soininen H, Vellas B, Richard E, Kivipelto M, and Andrieu S
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- Aged, Clinical Trials as Topic, Dementia diet therapy, Dementia drug therapy, Exercise Therapy, Female, Finland, Humans, Outcome Assessment, Health Care, Risk Factors, Cognitive Behavioral Therapy, Dementia prevention & control, Fatty Acids, Omega-3 administration & dosage, Life Style
- Abstract
Introduction: Multidomain interventions, targeting multiple risk factors simultaneously, could be effective dementia prevention strategies, but may be burdensome and not universally acceptable., Methods: We studied adherence rates and predictors in the Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability and Multidomain Alzheimer Preventive Trial prevention trials, for all intervention components (separately and simultaneously). Finnish Geriatric Intervevntion Study to Prevent Cognitive Impairment and Disability participants received a 2-year multidomain lifestyle intervention (physical training, cognitive training, nutritional counseling, and cardiovascular monitoring). Multidomain Alzheimer Preventive Trial participants received a 3-year multidomain lifestyle intervention (cognitive training, physical activity counseling, and nutritional counseling) with either an omega-3 supplement or placebo., Results: Adherence decreased with increasing intervention complexity and intensity: it was highest for cardiovascular monitoring, nutritional counseling, and the omega-3 supplement, and lowest for unsupervised computer-based cognitive training. The most consistent baseline predictors of adherence were smoking and depressive symptoms., Discussion: Reducing participant burden, while ensuring that technological tools are suitable for older individuals, maintaining face-to-face contacts, and taking into account participant characteristics may increase adherence in future trials., (Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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6. Healthy Dietary Changes in Midlife Are Associated with Reduced Dementia Risk Later in Life.
- Author
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Sindi S, Kåreholt I, Eskelinen M, Hooshmand B, Lehtisalo J, Soininen H, Ngandu T, and Kivipelto M
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- Aged, Body Mass Index, Dementia diagnosis, Dietary Fiber administration & dosage, Exercise, Female, Follow-Up Studies, Humans, Male, Phytochemicals administration & dosage, Risk Factors, Self Report, Socioeconomic Factors, Vitamins administration & dosage, Aging, Dementia prevention & control, Diet, Healthy
- Abstract
Diet is an important modifiable lifestyle factor related to dementia risk. Yet, the role of midlife dietary changes is unclear. The goal is to investigate whether midlife healthy dietary changes are associated with late-life dementia risk. Data were collected within the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) population-based cohort study ( n = 2000) (mean baseline age = 56 years). Participants returned for two late-life re-examinations (mean age = 70 and 78 years). Self-reported midlife diet was measured in a sub-sample ( n = 341) (mean total follow-up = 16.8 years). Changes in specific dietary components (fats, vegetables, sugar, salt) were measured in midlife. Dementia diagnoses were ascertained with detailed examinations. Analyses adjusted for potential confounders. Total midlife healthy dietary changes (improving quality of fats, increasing vegetables, decreasing sugar and salt) were associated with a reduced risk of dementia (fully adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) = 0.20⁻0.85). In contrast, when each factor was assessed individually, associations were not significant. This study is the first to show that beneficial midlife dietary changes are associated with a reduced dementia risk later in life. The results highlight the importance of targeting dietary patterns, where various food items may have synergistic effects.
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- 2018
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7. Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: The FINGER trial.
- Author
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Rosenberg A, Ngandu T, Rusanen M, Antikainen R, Bäckman L, Havulinna S, Hänninen T, Laatikainen T, Lehtisalo J, Levälahti E, Lindström J, Paajanen T, Peltonen M, Soininen H, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Solomon A, and Kivipelto M
- Subjects
- Aged, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control, Cognition, Cognitive Behavioral Therapy, Cognitive Dysfunction epidemiology, Dementia epidemiology, Exercise Therapy, Female, Humans, Male, Middle Aged, Risk Factors, Socioeconomic Factors, Treatment Outcome, Cognitive Dysfunction prevention & control, Dementia prevention & control, Healthy Lifestyle
- Abstract
Introduction: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition., Methods: The FINGER recruited 1260 people from the general Finnish population (60-77 years, at risk for dementia). Participants were randomized 1:1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z-score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed-model repeated-measures analyses., Results: Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini-Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P-values for interaction > .05)., Conclusions: The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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8. Nutrition guidance within a multimodal intervention improves diet quality in prodromal Alzheimer’s disease: Multimodal Preventive Trial for Alzheimer’s Disease (MIND-ADmini)
- Author
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Levak, Nicholas, Lehtisalo, Jenni, Thunborg, Charlotta, Westman, Eric, Andersen, Pia, Andrieu, Sandrine, Broersen, Laus M., Coley, Nicola, Hartmann, Tobias, Irving, Gerd Faxén, Mangialasche, Francesca, Ngandu, Tiia, Pantel, Johannes, Rosenberg, Anna, Sindi, Shireen, Soininen, Hilkka, Solomon, Alina, Wang, Rui, and Kivipelto, Miia
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- 2024
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- View/download PDF
9. Nutrition guidance within a multimodal intervention improves diet quality in prodromal Alzheimer's disease: Multimodal Preventive Trial for Alzheimer's Disease (MIND-ADmini).
- Author
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Levak, Nicholas, Lehtisalo, Jenni, Thunborg, Charlotta, Westman, Eric, Andersen, Pia, Andrieu, Sandrine, Broersen, Laus M., Coley, Nicola, Hartmann, Tobias, Irving, Gerd Faxén, Mangialasche, Francesca, Ngandu, Tiia, Pantel, Johannes, Rosenberg, Anna, Sindi, Shireen, Soininen, Hilkka, Solomon, Alina, Wang, Rui, and Kivipelto, Miia
- Subjects
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ALZHEIMER'S disease , *NUTRIENT density , *NUTRITIONAL status , *ALZHEIMER'S patients , *FOOD consumption - Abstract
Background: Multimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer's disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them. Method: A 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records. Results: The dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake. Conclusion: These results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density. Trial registration: ClinicalTrials.gov NCT03249688, 2017–07-08. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
10. Nutrition guidance within a multimodal intervention improves diet quality in prodromal Alzheimer's disease: Multimodal Preventive Trial for Alzheimer's Disease (MIND-ADmini).
- Author
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Levak, Nicholas, Lehtisalo, Jenni, Thunborg, Charlotta, Westman, Eric, Andersen, Pia, Andrieu, Sandrine, Broersen, Laus M., Coley, Nicola, Hartmann, Tobias, Irving, Gerd Faxén, Mangialasche, Francesca, Ngandu, Tiia, Pantel, Johannes, Rosenberg, Anna, Sindi, Shireen, Soininen, Hilkka, Solomon, Alina, Wang, Rui, and Kivipelto, Miia
- Subjects
ALZHEIMER'S disease ,NUTRIENT density ,NUTRITIONAL status ,ALZHEIMER'S patients ,FOOD consumption - Abstract
Background: Multimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer's disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them. Method: A 6-month MIND-AD
mini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records. Results: The dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake. Conclusion: These results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density. Trial registration: ClinicalTrials.gov NCT03249688, 2017–07-08. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
11. Alzheimer's disease genetic risk score and neuroimaging in the FINGER lifestyle trial.
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Saadmaan, Gazi, Dalmasso, Maria Carolina, Ramirez, Alfredo, Hiltunen, Mikko, Kemppainen, Nina, Lehtisalo, Jenni, Mangialasche, Francesca, Ngandu, Tiia, Rinne, Juha, Soininen, Hilkka, Stephen, Ruth, Kivipelto, Miia, and Solomon, Alina
- Abstract
INTRODUCTION: We assessed a genetic risk score for Alzheimer's disease (AD‐GRS) and apolipoprotein E (APOE4) in an exploratory neuroimaging substudy of the FINGER trial. METHODS: 1260 at‐risk older individuals without dementia were randomized to multidomain lifestyle intervention or health advice. N = 126 participants underwent magnetic resonance imaging (MRI), and N = 47 positron emission tomography (PET) scans (Pittsburgh Compund B [PiB], Fluorodeoxyglucose) at baseline; N = 107 and N = 38 had repeated 2‐year scans. RESULTS: The APOE4 allele, but not AD‐GRS, was associated with baseline lower hippocampus volume (β = −0.27, p = 0.001), greater amyloid deposition (β = 0.48, p = 0.001), 2‐year decline in hippocampus (β = −0.27, p = 0.01), total gray matter volume (β = −0.25, p = 0.01), and cortical thickness (β = −0.28, p = 0.003). In analyses stratified by AD‐GRS (below vs above median), the PiB composite score increased less in intervention versus control in the higher AD‐GRS group (β = −0.60, p = 0.03). DISCUSSION: AD‐GRS and APOE4 may have different impacts on potential intervention effects on amyloid, that is, less accumulation in the higher‐risk group (AD‐GRS) versus lower‐risk group (APOE). Highlights: First study of neuroimaging and AD genetics in a multidomain lifestyle intervention.Possible intervention effect on brain amyloid deposition may rely on genetic risk.AD‐GRS and APOE4 allele may have different impacts on amyloid during intervention. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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12. Dementia prevention: The potential long‐term cost‐effectiveness of the FINGER prevention program.
- Author
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Wimo, Anders, Handels, Ron, Antikainen, Riitta, Eriksdotter, Maria, Jönsson, Linus, Knapp, Martin, Kulmala, Jenni, Laatikainen, Tiina, Lehtisalo, Jenni, Peltonen, Markku, Sköldunger, Anders, Soininen, Hilkka, Solomon, Alina, Strandberg, Timo, Tuomilehto, Jaakko, Ngandu, Tiia, and Kivipelto, 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
13. Occupational complexity and cognition in the FINGER multidomain intervention trial.
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Rydström, Anders, Darin‐Mattsson, Alexander, Kåreholt, Ingemar, Ngandu, Tiia, Lehtisalo, Jenni, Solomon, Alina, Antikainen, Riitta, Bäckman, Lars, Hänninen, Tuomo, Laatikainen, Tiina, Levälahti, Esko, Lindström, Jaana, Paajanen, Teemu, Havulinna, Satu, Peltonen, Markku, Sindi, Shireen, Soininen, Hilkka, Neely, Anna Stigsdotter, Strandberg, Timo, and Tuomilehto, Jaakko
- Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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14. Development of the First WHO Guidelines for Risk Reduction of Cognitive Decline and Dementia: Lessons Learned and Future Directions.
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Stephen, Ruth, Barbera, Mariagnese, Peters, Ruth, Ee, Nicole, Zheng, Lidan, Lehtisalo, Jenni, Kulmala, Jenni, Håkansson, Krister, Chowdhary, Neerja, Dua, Tarun, Solomon, Alina, Anstey, Kaarin J., and Kivipelto, Miia
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NON-communicable diseases ,DISEASE risk factors ,COGNITION disorders ,SYMPTOMS ,DEMENTIA ,GENETICS - 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-middle income countries. In conclusion, the evidence from the first WHO guidelines for risk reduction of cognitive decline and dementia indicated that "one size does not fit all," and multidomain approaches adaptable to different populations and individuals are likely to be the most effective. Harmonization in trial design, the use of appropriate outcome measures, and sustainability in large at-risk populations in the context of other chronic disorders also emerged as key elements. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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15. Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: The FINGER trial
- Author
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Rosenberg, Anna, Ngandu, Tiia, Rusanen, Minna, Antikainen, Riitta, Backman, Lars, Havulinna, Satu, Hanninen, Tuomo, Laatikainen, Tiina, Lehtisalo, Jenni, Levalahti, Esko, Lindstrom, Jaana, Paajanen, Teemu, Peltonen, Markku, Soininen, Hilkka, Stigsdotter Neely, Anna, Strandberg, Timo, Tuomilehto, Jaakko, Solomon, Alina, Kivipelto, Miia, Clinicum, Department of Public Health, University of Helsinki, Timo Strandberg / Principal Investigator, Department of Medicine, Hjelt Institute (-2014), and HUS Internal Medicine and Rehabilitation
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PROTOCOL ,Male ,Geriatrik ,Clinical Neurology ,Intervention ,EXERCISE ,3124 Neurology and psychiatry ,Cognition ,Risk Factors ,COMPLAINTS ,Humans ,CORONARY-HEART-DISEASE ,Cognitive Dysfunction ,Healthy Lifestyle ,OLDER-ADULTS ,Aged ,Science & Technology ,Cognitive Behavioral Therapy ,Prevention ,3112 Neurosciences ,1103 Clinical Sciences ,Alzheimer's disease ,RANDOMIZED CONTROLLED-TRIAL ,IMPAIRMENT ,Middle Aged ,Lifestyle ,Multidomain ,Exercise Therapy ,ALZHEIMERS-DISEASE ,FINNISH GERIATRIC INTERVENTION ,Cognitive impairment ,Treatment Outcome ,Socioeconomic Factors ,Randomized controlled trial ,Cardiovascular Diseases ,Geriatrics ,3121 General medicine, internal medicine and other clinical medicine ,Dementia ,Female ,Neurosciences & Neurology ,PRIMARY PREVENTION ,1109 Neurosciences ,Life Sciences & Biomedicine ,DIABETES PREVENTION ,CLINICAL-TRIALS ,tervention - Abstract
Introduction: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition. Methods: The FINGER recruited 1260 people from the general Finnish population (60-77 years, at risk for dementia). Participants were randomized 1: 1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z-score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed-model repeated-measures analyses. Results: Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini-Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P-values for interaction > .05). Conclusions: The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia. (C) 2017 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
- Published
- 2017
16. Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial.
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Sindi, Shireen, Solomon, Alina, Kåreholt, Ingemar, Hovatta, Iiris, Antikainen, Riitta, Hänninen, Tuomo, Levälahti, Esko, Laatikainen, Tiina, Lehtisalo, Jenni, Lindström, Jaana, Paajanen, Teemu, Peltonen, Markku, Khalsa, Dharma Singh, Wolozin, Benjamin, Strandberg, Timo, Tuomilehto, Jaakko, Soininen, Hilkka, Ngandu, Tiia, Kivipelto, Miia, and Group, FINGER Study
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CLINICAL trials ,TELOMERES ,DEMENTIA ,OLDER people ,APOLIPOPROTEIN E - 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. [ABSTRACT FROM AUTHOR]- Published
- 2021
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17. Diabetes, glycaemia, and cognitiona secondary analysis of the Finnish Diabetes Prevention Study
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Lehtisalo, Jenni, Lindstrom, Jaana, Ngandu, Tiia, Kivipelto, Miia, Ahtiluoto, Satu, Ilanne-Parikka, Pirjo, Keinanen-Kiukaanniemi, Sirkka, Eriksson, Johan G., Uusitupa, Matti, Tuomilehto, Jaakko, Luchsinger, Jose A., Finnish Diabet Prevention Study DP, Clinicum, Department of Public Health, Johan Eriksson / Principal Investigator, and Department of General Practice and Primary Health Care
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dysglycaemia ,cognition ,DECLINE ,DEMENTIA ,WOMEN ,DYSFUNCTION ,3142 Public health care science, environmental and occupational health ,ALZHEIMERS-DISEASE ,MELLITUS ,IMPAIRED GLUCOSE-TOLERANCE ,RISK-FACTOR ,3121 General medicine, internal medicine and other clinical medicine ,LIFE-STYLE ,type 2 diabetes ,OLDER-ADULTS - Abstract
BackgroundType 2 diabetes is linked with cognitive dysfunction and dementia in epidemiological studies, but these observations are limited by lack of data on the exact timing of diabetes onset. We investigated diabetes, dysglycaemia, and cognition in the Finnish Diabetes Prevention Study, in which the timing and duration of diabetes are well documented. MethodsThe Finnish Diabetes Prevention Study comprised middle-aged, overweight participants with impaired glucose tolerance but no diabetes at baseline (n=522), randomized to lifestyle intervention or a control group. After an intervention period (mean duration 4years) and follow-up (additional 9years), cognitive assessment with the CERAD test battery and Trail Making Test A (TMT) was executed twice within a 2-year interval. Of the 364 (70%) participants with cognitive assessments, 171 (47%) had developed diabetes. ResultsCognitive function did not differ between those who developed diabetes and those who did not. Lower mean 2-h glucose at an oral glucose tolerance test (OGTT) and HbA(1C) during the intervention period predicted better performance in the TMT (p=0.012 and 0.024, respectively). Those without diabetes or with short duration of diabetes improved in CERAD total score between the two assessments (p=0.001) whereas those with long duration of diabetes did not (p=0.844). ConclusionsBetter glycemic control among persons with baseline impaired glucose tolerance predicted better cognitive performance 9years later in this secondary analysis of the Finnish Diabetes Prevention Study population. In addition, learning effects in cognitive testing were not evident in people with long diabetes duration. Copyright (c) 2015 John Wiley & Sons, Ltd.
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- 2016
18. Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: The FINGER trial.
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Rosenberg, Anna, Ngandu, Tiia, Rusanen, Minna, Antikainen, Riitta, Bäckman, Lars, Havulinna, Satu, Hänninen, Tuomo, Laatikainen, Tiina, Lehtisalo, Jenni, Levälahti, Esko, Lindström, Jaana, Paajanen, Teemu, Peltonen, Markku, Soininen, Hilkka, Stigsdotter‐Neely, Anna, Strandberg, Timo, Tuomilehto, Jaakko, Solomon, Alina, and Kivipelto, Miia
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Introduction: The 2‐year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition. Methods: The FINGER recruited 1260 people from the general Finnish population (60–77 years, at risk for dementia). Participants were randomized 1:1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z‐score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed‐model repeated‐measures analyses. Results: Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini–Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P‐values for interaction >.05). Conclusions: The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia. Highlights: The FINGER intervention benefits cognition regardless of participants' characteristics.Sociodemographics, vascular risk, or MMSE do not modify response to intervention.Intervention can be implemented in a large elderly population at risk for dementia. [ABSTRACT FROM AUTHOR]
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- 2018
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19. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): Study design and progress.
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Kivipelto, Miia, Solomon, Alina, Ahtiluoto, Satu, Ngandu, Tiia, Lehtisalo, Jenni, Antikainen, Riitta, Bäckman, Lars, Hänninen, Tuomo, Jula, Antti, Laatikainen, Tiina, Lindström, Jaana, Mangialasche, Francesca, Nissinen, Aulikki, Paajanen, Teemu, Pajala, Satu, Peltonen, Markku, Rauramaa, Rainer, Stigsdotter-Neely, Anna, Strandberg, Timo, and Tuomilehto, Jaakko
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Abstract: Background: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland. Materials: Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score ≥6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures. Results: Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle–related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014. Conclusions: The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia. [Copyright &y& Elsevier]
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- 2013
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20. Associations of Depressive Symptoms and Cognition in the FINGER Trial: A Secondary Analysis of a Randomised Clinical Trial.
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Neuvonen, Elisa, Lehtisalo, Jenni, Ngandu, Tiia, Levälahti, Esko, Antikainen, Riitta, Hänninen, Tuomo, Laatikainen, Tiina, Lindström, Jaana, Paajanen, Teemu, Soininen, Hilkka, Strandberg, Timo, Tuomilehto, Jaakko, Kivipelto, Miia, and Solomon, Alina
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MENTAL depression , *SECONDARY analysis , *CLINICAL trials , *COGNITION disorders , *EXECUTIVE function , *VASCULAR dementia , *UNHEALTHY lifestyles , *SELF-monitoring (Psychology) - 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. [ABSTRACT FROM AUTHOR]
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- 2022
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21. New insights on the genetic etiology of Alzheimer’s and related dementia
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Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris, Andrade, Victor, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C., Grenier-Boley, Benjamin, Campos-Martin, Rafael, Holmans, Peter A., Boland, Anne, Kleineidam, Luca, Damotte, Vincent, van der Lee, Sven J., Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C., Yaqub, Amber, Prokic, Ivana, Costa, Marcos R, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Boada, Mercè, Aarsland, Dag, García-González, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J., Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Belén Pastor, Ana, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizzarro, Alessandra, Alcolea, Daniel, Blesa, Rafael, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bresner, Catherine, Brookes, Keeley J., Brusco, Luis Ignacio, Bûrger, Katharina, Bullido, María J., Burholt, Vanessa, Bush, William S., Calero, Miguel, Dufouil, Carole, Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chillotti, Caterina, Brodaty, Henry, Ciccone, Simona, Claassen, Jurgen A.H.R., Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D., Debette, Stéphanie, Deckert, Jürgen, del Ser, Teodoro, Denning, Nicola, DeStefano, Anita, Dichgans, Martin, Diehl-Schmid, Janine, Diez-Fairen, Mónica, Rossi, Paolo Dionigi, Djurovic, Srdjan, Duron, Emmanuelle, Düzel, Emrah, Engelborghs, Sebastiaan, Escott-Price, Valentina, Espinosa, Ana, Buiza-Rueda, Dolores, Ewers, Michael, Tagliavini, Fabrizio, Nielsen, Sune Fallgaard, Farotti, Lucia, Fenoglio, Chiara, Fernández-Fuertes, Marta, Hardy, John, Ferrari, Raffaele, Ferreira, Catarina B, Ferri, Evelyn, Fin, Bertrand, Fischer, Peter, Fladby, Tormod, Fließbach, Klaus, Fortea, Juan, Fostinelli, Silvia, Fox, Nick C., Franco-Macías, Emlio, Frank-García, Ana, Froelich, Lutz, Galimberti, Daniela, García-Alberca, Jose Maria, Garcia-Madrona, Sebastian, García-Ribas, Guillermo, Chene, Geneviève, Ghidoni, Roberta, Giegling, Ina, Giaccone, Giorgio, Goldhardt, Oliver, González-Pérez, Antonio, Graff, Caroline, Grande, Giulia, Green, Emma, Grimmer, Timo, Grünblatt, Edna, Guetta-Baranes, Tamar, Haapasalo, Annakaisa, Hadjigeorgiou, Georgios, Haines, Jonathan L., Hamilton-Nelson, Kara L., Hampel, Harald, Hanon, Olivier, Hartmann, Annette M., Hausner, Lucrezia, Harwood, Janet, Heilmann-Heimbach, Stefanie, Helisalmi, Seppo, Heneka, Michael T., Hernández, Isabel, Herrmann, Martin J., Hoffmann, Per, Holmes, Clive, Holstege, Henne, Vilas, Raquel Huerto, Hulsman, Marc, Humphrey, Jack, Biessels, Geert Jan, Johansson, Charlotte, Kehoe, Patrick G., Kilander, Lena, Ståhlbom, Anne Kinhult, Kivipelto, Miia, Koivisto, Anne, Kornhuber, Johannes, Kosmidis, Mary H., Kuksa, Pavel P., Kunkle, Brian W., Lage, Carmen, Laukka, Erika J, Lauria, Alessandra, Lee, Chien-Yueh, Lehtisalo, Jenni, Satizabal, Claudia L., Lerch, Ondrej, Lleó, Alberto, Lopez, Rogelio, Lopez, Oscar, de Munain, Adolfo Lopez, Love, Seth, Löwemark, Malin, Luckcuck, Lauren, Macías, Juan, MacLeod, Catherine A., Maier, Wolfgang, Mangialasche, Francesca, Spallazzi, Marco, Marquié, Marta, Marshall, Rachel, Martin, Eden R., Martín Montes, Angel, Rodríguez, Carmen Martínez, Masullo, Carlo, Mayeux, Richard, Mead, Simon, Mecocci, Patrizia, Medina, Miguel, Meggy, Alun, Mendoza, Silvia, Menéndez-González, Manuel, Mir, Pablo, Periñán, Maria Teresa, Mol, Merel, Molina-Porcel, Laura, Montrreal, Laura, Morelli, Laura, Moreno, Fermín, Morgan, Kevin, Nöthen, Markus M., Muchnik, Carolina, Nacmias, Benedetta, Ngandu, Tiia, Nicolas, Gael, Nordestgaard, Børge G., Olaso, Robert, Orellana, Adelina, Orsini, Michela, Ortega, Gemma, Padovani, Alessandro, Caffarra, Paolo, Papenberg, Goran, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Pérez-Cordón, Alba, Pérez-Tur, Jordi, Pericard, Pierre, Peters, Oliver, Pijnenburg, Yolande A.L., Pineda, Juan A, Piñol-Ripoll, Gerard, Pisanu, Claudia, Polak, Thomas, Popp, Julius, Posthuma, Danielle, Priller, Josef, Puerta, Raquel, Quenez, Olivier, Quintela, Inés, Thomassen, Jesper Qvist, Rábano, Alberto, Rainero, Innocenzo, Ramakers, Inez, Real, Luis M, Reinders, Marcel J.T., Riedel-Heller, Steffi, Riederer, Peter, Rodriguez-Rodriguez, Eloy, Rongve, Arvid, Allende, Irene Rosas, Rosende-Roca, Maitée, Royo, Jose Luis, Rubino, Elisa, Rujescu, Dan, Sáez, María Eugenia, Sakka, Paraskevi, Saltvedt, Ingvild, Sanabria, Ángela, Sánchez-Arjona, María Bernal, Sanchez-Garcia, Florentino, Mehrabian, Shima, Sánchez-Juan, Pascual, Sánchez-Valle, Raquel, Sando, Sigrid B, Scamosci, Michela, Scarmeas, Nikolaos, Scarpini, Elio, Scheltens, Philip, Scherbaum, Norbert, Scherer, Martin, Schmid, Matthias, Schneider, Anja, Schott, Jonathan M., Selbæk, Geir, Sha, Jin, Shadrin, Alexey A, Skrobot, Olivia, Snijders, Gijsje J. L., Soininen, Hilkka, Solfrizzi, Vincenzo, Solomon, Alina, Sorbi, Sandro, Sotolongo-Grau, Oscar, Spalletta, Gianfranco, Spottke, Annika, Squassina, Alessio, Tartari, Juan Pablo, Tárraga, Lluís, Tesí, Niccolo, Thalamuthu, Anbupalam, Tegos, Thomas, Traykov, Latchezar, Tremolizzo, Lucio, Tybjærg-Hansen, Anne, Uitterlinden, Andre, Ullgren, Abbe, Ulstein, Ingun, Valero, Sergi, Van Broeckhoven, Christine, van der Lugt, Aad, Van Dongen, Jasper, van Rooij, Jeroen, van Swieten, John, Vandenberghe, Rik, Verhey, Frans, Vidal, Jean-Sébastien, Vogelgsang, Jonathan, Vyhnalek, Martin, Wagner, Michael, Wallon, David, Wang, Li-San, Wang, Ruiqi, Weinhold, Leonie, Wiltfang, Jens, Windle, Gill, Woods, Bob, Yannakoulia, Mary, Zhao, Yi, Zulaica, Miren, Serrano-Rios, Manuel, Seripa, Davide, Stordal, Eystein, Farrer, Lindsay A., Psaty, Bruce M., Ghanbari, Mohsen, Raj, Towfique, Sachdev, Perminder, Mather, Karen, Jessen, Frank, Ikram, M. Arfan, de Mendonça, Alexandre, Hort, Jakub, Tsolaki, Magda, Pericak-Vance, Margaret A., Amouyel, Philippe, Williams, Julie, Frikke-Schmidt, Ruth, Clarimon, Jordi, Deleuze, Jean-François, Rossi, Giacomina, Seshadri, Sudha, Andreassen, Ole A., Ingelsson, Martin, Hiltunen, Mikko, Sleegers, Kristel, Schellenberg, Gerard D., van Duijn, Cornelia M., Sims, Rebecca, van der Flier, Wiesje M., Ruiz, Agustín, Ramirez, Alfredo, and Lambert, Jean-Charles
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0303 health sciences ,Microglia ,Amyloid ,business.industry ,Disease ,medicine.disease ,Bioinformatics ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Genetic etiology ,Medicine ,Dementia ,Egfr signaling ,business ,Gene ,030217 neurology & neurosurgery ,030304 developmental biology ,Genetic association - Abstract
Alzheimer’s disease (AD) is a severe and incurable neurodegenerative disease, and the failure to find effective treatments suggests that the underlying pathology remains poorly understood. Due to its strong heritability, deciphering the genetic landscape of AD and related dementia (ADD) is a unique opportunity to advance our knowledge. We completed a meta-analysis of genome-wide association studies (39,106 clinically AD-diagnosed cases, 46,828 proxy-ADD cases and 401,577 controls) with the most promising signals followed-up in 25,392 independent AD cases and 276,086 controls. We report 75 risk loci for ADD, including 42 novel ones. Pathway-enrichment analyses confirm the involvement of amyloid/Tau pathways, highlight the role of microglia and its potential interaction with APP metabolism. Numerous genes exhibited differential expression or splicing in AD-related conditions and gene prioritization implies EGFR signaling and TNF-α pathway through LUBAC complex. We also generated a novel polygenic risk score strongly associated with the risk of future dementia or progression from mild cognitive impairment to dementia. In conclusion, by more than doubling the number of loci associated with ADD risk, our study offers new insights into the pathophysiological processes underlying AD and offers additional therapeutic entry-points and tools for translational genomics.
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