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

Abstract

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. 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. 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). 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). 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.