A brain‐wide risk score of Alzheimer’s disease based on multimodal neuroimaging predicts cognition in large N>37000 population data

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is the most frequent age‐related dementia impairing memory, thinking, and social skills. Much research has been conducted in recent years to investigate the genetic risk of AD, but little effort has been made to find a brain imaging‐based AD risk evaluation. Here, we proposed a multimodal neuroimaging‐based measure of AD risk, called brain‐wide risk score (BRS).MethodFunctional network connectivity (FNC) and voxelwise gray matter (GM) from the Open Access Series of Imaging Studies (OASIS)‐3 (N = 1302 samples) cohort was used as a reference dataset to define mild cognitive impairment (MCI) and control (CN)group to evaluate individuals in the UK Biobank (N = 37,784) dataset. We calculated the mean of FNC and GM of MCI and CN. Next, we removed the mean FNC and GM from each sample FNC and GM of the target dataset. Then, we calculated the distance between the target dataset and CN (i.e., dist_CN) and MCI (i.e., dist_MCI) of the reference dataset using Euclidian distance. Finally, we calculated Δdiff = dist_CN‐dist_MCI as a BRS of AD, where the positive values are associated with higher AD BRS. Using two BRSs estimated based on FNC and GM for target dataset, we identified four AD biotypes. Samples with two negative Δdist represent low AD risk (Biotype1), samples with two positive Δdist represent high AD risk (Biotype4), and samples with one negative and one positive Δdist represent moderate AD risk (Biotype2/3). Next, we compared cognitive scores including fluid intelligence (FI) and reaction time (RT) across four biotypes.ResultFig.1 shows the 2D histogram of two BRS estimated from FNC and GM. We identified 11704 participants as biotype1, 10910 as biotype2, 7804 as biotype3 and 7366 as biotype4. We also found that Biotype1, with lower AD BRS, significantly shows a higher FI score than Biotype3 and Biotype4 (Fig.2, FI panel). Additionally, Biotype 4, with the highest BRS, had the most increased RT among all four AD biotypes (Fig.2, RT panel).ConclusionWe develop a new multimodal neuroimaging‐based BRS based which we identified four AD biotypes. We found that BRS predict cognitive scores in the identified biotypes.