Polygenic Risk Score for Alzheimer’s and Cognitive Decline in Type 2 Diabetes: No Relationship Found

Published on August 30, 2022

Imagine a team of researchers trying to find a connection between genes associated with Alzheimer’s disease and cognitive decline in older adults with type 2 diabetes. They analyzed the polygenic risk score (PRS) for late-onset Alzheimer’s disease (LOAD) in a group of Jewish participants. The PRS is like adding up all the little pieces of genetic information that contribute to the likelihood of developing Alzheimer’s. After meticulous analysis and adjusting for various factors, they discovered that the PRS did not have any significant association with overall cognitive functioning or decline in different cognitive domains. However, this doesn’t mean that there are no connections at all! There might be other pathways and genetic factors that play a role in the link between Alzheimer’s and cognitive decline. To dive deeper into this fascinating research and learn more about the intricate relationship between genes and cognitive health, check out the full article!

ObjectivesMultiple risk loci for late-onset Alzheimer’s disease (LOAD) have been identified. Type 2 diabetes (T2D) is a risk factor for cognitive decline, dementia and Alzheimer’s disease (AD). We investigated the association of polygenic risk score (PRS) for LOAD with overall cognitive functioning and longitudinal decline, among older adults with T2D.MethodsThe study included 1046 Jewish participants from the Israel Diabetes and Cognitive Decline (IDCD) study, aged ≥ 65 years, diagnosed with T2D, and cognitively normal at baseline. The PRS included variants from 26 LOAD associated loci (at genome-wide significance level), and was calculated with and without APOE. Outcome measures, assessed in 18 months intervals, were global cognition and the specific domains of episodic memory, attention/working memory, executive functions, and language/semantic categorization. Random coefficient models were used for analysis, adjusting for demographic variables, T2D-related characteristics, and cardiovascular factors. Additionally, in a subsample of 202 individuals, we analyzed the association of PRS with the volumes of total gray matter, frontal lobe, hippocampus, amygdala, and white matter hyperintensities. Last, the association of PRS with amyloid beta (Aβ) burden was examined in 44 participants who underwent an 18F-flutemetamol PET scan.ResultsThe PRS was not significantly associated with overall functioning or decline in global cognition or any of the specific cognitive domains. Similarly, following correction for multiple testing, there was no association with Aβ burden and other brain imaging phenotypes.ConclusionOur results suggest that the cumulative effect of LOAD susceptibility loci is not associated with a greater rate of cognitive decline in older adults with T2D, and other pathways may underlie this link.

Read Full Article (External Site)

Leave a Reply

Your email address will not be published. Required fields are marked *

You may use these HTML tags and attributes:

<a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>