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.
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This post is Copyright: Gazi Saadmaan,
Maria Carolina Dalmasso,
Alfredo Ramirez,
Mikko Hiltunen,
Nina Kemppainen,
Jenni Lehtisalo,
Francesca Mangialasche,
Tiia Ngandu,
Juha Rinne,
Hilkka Soininen,
Ruth Stephen,
Miia Kivipelto,
Alina Solomon | April 22, 2024