%0 Journal Article
%T Alzheimer's disease genetic risk score and neuroimaging in the FINGER lifestyle trial.
%A Saadmaan G
%A Dalmasso MC
%A Ramirez A
%A Hiltunen M
%A Kemppainen N
%A Lehtisalo J
%A Mangialasche F
%A Ngandu T
%A Rinne J
%A Soininen H
%A Stephen R
%A Kivipelto M
%A Solomon A
%J Alzheimers Dement
%V 20
%N 6
%D 2024 Jun 22
%M 38647197
%F 16.655
%R 10.1002/alz.13843
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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).<BR><B>CONCLUSIONS: </B>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).<BR><B>CONCLUSIONS: </B>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.