A New Tool for Predicting Late-Onset Alzheimer's

A higher polygenic risk (PGR) score may predict late-onset Alzheimer's disease (LOAD), new research shows.

Investigators found a higher PGR was significantly linked to smaller hippocampal volume and poorer executive function in physically and cognitively healthy adults.

The study was published online October 7 in Neuropsychopharmacology.

PGR scoring is a way to estimate an individual's genetic risk of inheriting a trait or disease. There's evidence that using such scoring can improve prediction of AD.

The new analysis included 32,790 nondemented individuals with a mean age of 63 years from the UK Biobank.

Researchers conducted genotyping to arrive at a PGR score. To do this, they took summary data from a genome-wide association study (GWAS), an approach that identifies genetic variants associated with a particular disease.

Results showed LOAD-PGR was associated with left hippocampal volume in the fully adjusted model (β = −0.118, P = .002).

Two measures related to executive function were significantly associated with PGR in the fully adjusted model. These included fluid intelligence (β = −0.080, P = .002) and matrix completion (β = −0.102, P = .003).

The new findings suggest genetic risk variants for AD may pick up the earliest signs of pathology prior to cognitive problems.

The authors note the study findings are not generalizeable to populations other than those with White European ancestry.

This study, carried out in a large population, suggests that using a specific algorithm that combines brain imaging results and cognitive abilities with known risk genes for Alzheimer's may be a useful tool to identify individuals with early Alzheimer's-related brain changes. However, more research is needed in larger, more diverse populations over a longer period of time to fully understand these links.