Investigating the Association Between Polygenic Risk Scores for Alzheimer's Disease With Cognitive Performance and...

Area of Science:

• Neuroscience
• Genetics
• Cognitive Psychology

Background:

• Alzheimer's disease (AD) pathology begins years before clinical symptoms, necessitating early detection for prevention.
• Untreated AD dementia highlights the critical need for understanding early-stage pathology and genetic predispositions.
• Identifying at-risk individuals early is crucial for developing targeted, disease-modifying treatments.

Purpose of the Study:

• To investigate the association between genetic predisposition to AD and intrinsic functional connectivity in asymptomatic individuals.
• To examine the relationship between genetic risk and cognitive performance in healthy adults.
• To explore potential biomarkers for early AD risk assessment.

Main Methods:

• 136 cognitively healthy adults (younger and older groups) were assessed.
• Resting-state functional magnetic resonance imaging (fMRI) was used to evaluate brain connectivity.
• DNA genotyping for polygenic risk scores (PRS) and comprehensive neuropsychological testing were performed.

Main Results:

• Higher polygenic risk scores (PRS) were significantly associated with lower working memory scores in older adults (>60 years).
• No significant modulation of posterior cingulate cortex (PCC) functional connectivity was observed in relation to PRS.
• Genetic risk did not significantly alter intrinsic functional connectivity in the examined brain regions.

Conclusions:

• Genetic polymorphisms may influence the impact of other AD risk factors.
• Further research is warranted to explore these modulations, especially in cognitively healthy populations.
• Early identification of genetic predisposition may aid in developing preventative strategies for Alzheimer's disease.