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000285053 0247_ $$2ISSN$$a1460-2156
000285053 037__ $$aDZNE-2026-00177
000285053 041__ $$aEnglish
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000285053 1001_ $$00000-0002-0925-7609$$aSaadmaan, Gazi$$b0
000285053 245__ $$aAlzheimer and cardiovascular genetic scores and cognition: the FINGER randomized controlled trial.
000285053 260__ $$aOxford$$bOxford Univ. Press$$c2026
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000285053 520__ $$aAlzheimer'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.
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000285053 650_7 $$2Other$$aAlzheimer’s disease
000285053 650_7 $$2Other$$acognition
000285053 650_7 $$2Other$$agenetic risk scores
000285053 650_7 $$2Other$$amultidomain intervention
000285053 650_7 $$2Other$$arandomized controlled trial
000285053 650_7 $$2NLM Chemicals$$aApolipoprotein E4
000285053 650_2 $$2MeSH$$aHumans
000285053 650_2 $$2MeSH$$aMale
000285053 650_2 $$2MeSH$$aFemale
000285053 650_2 $$2MeSH$$aAged
000285053 650_2 $$2MeSH$$aMiddle Aged
000285053 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000285053 650_2 $$2MeSH$$aAlzheimer Disease: psychology
000285053 650_2 $$2MeSH$$aCognition: physiology
000285053 650_2 $$2MeSH$$aNeuropsychological Tests
000285053 650_2 $$2MeSH$$aCoronary Artery Disease: genetics
000285053 650_2 $$2MeSH$$aCoronary Artery Disease: psychology
000285053 650_2 $$2MeSH$$aApolipoprotein E4: genetics
000285053 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000285053 650_2 $$2MeSH$$aGenome-Wide Association Study
000285053 650_2 $$2MeSH$$aCognitive Dysfunction: genetics
000285053 650_2 $$2MeSH$$aRisk Factors
000285053 650_2 $$2MeSH$$aFinland
000285053 650_2 $$2MeSH$$aLife Style
000285053 7001_ $$aDalmasso, Maria Carolina$$b1
000285053 7001_ $$aMaria, Maleeha$$b2
000285053 7001_ $$00000-0002-8818-0848$$aLehtisalo, Jenni$$b3
000285053 7001_ $$aHiltunen, Mikko$$b4
000285053 7001_ $$00000-0001-6294-0979$$aKaikkonen, Minna U$$b5
000285053 7001_ $$aLevälahti, Esko$$b6
000285053 7001_ $$aMangialasche, Francesca$$b7
000285053 7001_ $$00000-0003-4842-1667$$aPerola, Markus$$b8
000285053 7001_ $$0P:(DE-2719)2812825$$aRamirez, Alfredo$$b9
000285053 7001_ $$aStephen, Ruth$$b10
000285053 7001_ $$00000-0002-3698-2021$$aNgandu, Tiia$$b11
000285053 7001_ $$aKivipelto, Miia$$b12
000285053 7001_ $$aSolomon, Alina$$b13
000285053 773__ $$0PERI:(DE-600)1474117-9$$a10.1093/brain/awaf277$$gVol. 149, no. 2, p. 644 - 652$$n2$$p644 - 652$$tBrain$$v149$$x0006-8950$$y2026
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