# Genetic Prοpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population

## TL;DR

This study explores how genetic factors linked to dementia pathology are associated with cognitive decline in older adults.

## Contribution

The study reveals that genetic predisposition to amyloid-beta and white matter hyperintensities affects global and memory-specific cognitive decline differently across subgroups.

## Key findings

- Higher PRS for Aβ42 and WMH were associated with faster global cognitive decline.
- The effect of PRS on memory decline varied by age, sex, and education level.
- Genetic associations with global decline were consistent across subgroups.

## Abstract

In the present study, we investigated the association of genetic predisposition with specific dimensions of dementia pathophysiology for global and domain-specific cognitive decline in older adults. The sample was drawn from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study, comprising 512 cognitively normal individuals over 64 years of age, with a mean follow-up of 2.9 years. Cognitive function was evaluated through a neuropsychological test battery, while genetic predisposition was assessed based on two distinct Polygenic Risk Scores (PRS) for amyloid-beta 42 (Aβ42) and white matter hyperintensities (WMH). The association of each PRS with the cognitive decline rate was examined using generalized estimating equation models. In the whole sample, higher PRSs Aβ42 (β = −0.042) and WMH (β =−0.029) were associated with a higher rate of global cognitive decline per year, an association which remained significant in age, sex, and education subgroups. Moreover, higher PRSs Aβ42 and WMH were related to significant memory decline only in females, older, and highly educated participants. Thus, while the association of both PRSs with global cognitive decline over time was independent of age, sex, or education, the relationship of the specific PRSs with the memory decline rate appeared to vary depending on these factors.