Association of APOE rs405509 (-219 T/G) with multidimensional cognitive function, brain structure, and resting-state...

The effects of the APOE rs405509 (-219 T/G) polymorphism on cognition, lipid profiles, gray matter volume (GMV), and resting-state networks (RSNs) in older Chinese adults remain unclear.

A total of 123 community-dwelling elderly individuals were divided into G allele carriers (n = 68) and TT homozygotes (n = 55). Participants underwent neuropsychological assessments and lipid detection; 111 received MRI. Multivariate linear regression analyzed genotype-cognition associations, with stratified analyses by demographics and APOE ε4 status. Structural images were processed using CAT12 for GMV, and independent component analysis identified RSNs.

In the full sample, G allele carriers showed worse performance in the Auditory Verbal Learning Test (AVLT), Rey-Osterrieth Complex Figure (ROCF) copy, and Boston Naming Test (BNT), with deficits remaining stable across stratified subgroups. However, in the neuroimaging subsample (n = 111), deficits remained significant only for AVLT and BNT, likely due to reduced statistical power. No significant group differences were found in lipid profiles or CAT12-derived GMV. Conversely, significant group differences emerged in resting state functional connectivity (rsFC) within auditory, language, and visual networks, where altered rsFC of auditory network positive correlated with cognitive performance.

The APOE rs405509 G allele is associated with cognitive decline, particularly in memory and naming. These deficits appear independent of gross GMV alterations but may be mediated by disrupted functional network integration, suggesting functional changes might precede structural atrophy.