Journal Article

DZNE-2026-00177

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Alzheimer and cardiovascular genetic scores and cognition: the FINGER randomized controlled trial.

Saadmaan, G. ; Dalmasso, M. C. ; Maria, M. ; Lehtisalo, J. ; Hiltunen, M. ; Kaikkonen, M. U. ; Levälahti, E. ; Mangialasche, F. ; Perola, M. ; Ramirez, A.DZNE* ; Stephen, R. ; Ngandu, T. ; Kivipelto, M. ; Solomon, A.

2026
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/brain/awaf277

Abstract: Alzheimer's disease and coronary artery disease are common late-life chronic conditions and share multiple risk factors, including the apolipoprotein E (APOE) ε4 allele. A meta-analysis of two multidomain lifestyle intervention trials found greater cognitive benefits in APOE4 carriers compared with non-carriers. This study investigated the impact of genetic risk scores for Alzheimer's disease and coronary artery disease (AD-GRS, CAD-GRS) on cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) randomized controlled trial. FINGER included 1259 at-risk individuals without dementia from the general population, aged 60-77 years. Participants were randomized 1:1 to a 2-year multidomain lifestyle intervention or regular health advice. The primary outcome was change in cognition based on a modified Neuropsychological Test Battery (14 tests). Previous comprehensive AD-GRS and CAD-GRS were calculated using genome-wide association study data (1177 participants, with 585 in the control and 592 in the intervention groups, exploratory analysis). The intervention-control difference in annual overall cognition change (95% confidence interval) for participants with AD-GRS above/below the median (i.e. higher/lower risk) was 0.032 (0.002-0.063) versus 0.017 (-0.011 to 0.045), and for CAD-GRS above/below the median was 0.031 (0.002 to 0.059) versus 0.016 (-0.012 to 0.044). AD-GRS or CAD-GRS were not significantly related to the intervention effect overall (P > 0.46), but for AD-GRS there were differences between females and males (P = 0.024). The intervention-control difference in annual overall score change was 0.045 (0.004 to 0.087) for higher-risk females, 0.003 (-0.040 to 0.047) for lower-risk females, 0.019 (-0.026 to 0.064) for higher-risk males, and 0.027 (-0.009 to 0.064) for lower-risk males. People with genetic susceptibility for Alzheimer's disease/dementia or coronary artery disease can benefit from multidomain lifestyle interventions. Although the findings for the AD-GRS and CAD-GRS risk groups were similar to APOE4 carrier status, with additional gender differences for AD-GRS, these exploratory findings need to be verified across several multidomain lifestyle trials to ensure adequate statistical power and inclusion of genetically diverse populations.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Female (MeSH) ; Aged (MeSH) ; Middle Aged (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: psychology (MeSH) ; Cognition: physiology (MeSH) ; Neuropsychological Tests (MeSH) ; Coronary Artery Disease: genetics (MeSH) ; Coronary Artery Disease: psychology (MeSH) ; Apolipoprotein E4: genetics (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Genome-Wide Association Study (MeSH) ; Cognitive Dysfunction: genetics (MeSH) ; Risk Factors (MeSH) ; Finland (MeSH) ; Life Style (MeSH) ; Alzheimer’s disease ; cognition ; genetic risk scores ; multidomain intervention ; randomized controlled trial ; Apolipoprotein E4

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Contributing Institute(s):

1. Patient Studies (Bonn) (Patient Studies (Bonn))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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