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@ARTICLE{Saadmaan:285053,
author = {Saadmaan, Gazi and Dalmasso, Maria Carolina and Maria,
Maleeha and Lehtisalo, Jenni and Hiltunen, Mikko and
Kaikkonen, Minna U and Levälahti, Esko and Mangialasche,
Francesca and Perola, Markus and Ramirez, Alfredo and
Stephen, Ruth and Ngandu, Tiia and Kivipelto, Miia and
Solomon, Alina},
title = {{A}lzheimer and cardiovascular genetic scores and
cognition: the {FINGER} randomized controlled trial.},
journal = {Brain},
volume = {149},
number = {2},
issn = {0006-8950},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DZNE-2026-00177},
pages = {644 - 652},
year = {2026},
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.},
keywords = {Humans / Male / Female / Aged / Middle Aged / Alzheimer
Disease: genetics / Alzheimer Disease: psychology /
Cognition: physiology / Neuropsychological Tests / Coronary
Artery Disease: genetics / Coronary Artery Disease:
psychology / Apolipoprotein E4: genetics / Genetic
Predisposition to Disease / Genome-Wide Association Study /
Cognitive Dysfunction: genetics / Risk Factors / Finland /
Life Style / Alzheimer’s disease (Other) / cognition
(Other) / genetic risk scores (Other) / multidomain
intervention (Other) / randomized controlled trial (Other) /
Apolipoprotein E4 (NLM Chemicals)},
cin = {Patient Studies (Bonn)},
ddc = {610},
cid = {I:(DE-2719)1011101},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40747850},
doi = {10.1093/brain/awaf277},
url = {https://pub.dzne.de/record/285053},
}