Journal Article

Alzheimer's disease genetic risk score and neuroimaging in the FINGER lifestyle trial

Dalmasso, Maria Carolina, Mangialasche, Francesca, Kivipelto, Miia, Kemppainen, Nina, Solomon, Alina, Saadmaan, Gazi, Hiltunen, Mikko, Lehtisalo, Jenni, Ramirez, Alfredo, Ngandu, Tiia, Stephen, Ruth, Rinne, Juha, Soininen, Hilkka

2024

Overview

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.

• Publisher: John Wiley and Sons Inc
• Subject: Alzheimer's disease / APOE4 / clinical trial / dementia / genetic risk score / neuroimaging biomarker / Short Report / Short Reports