Association of Alzheimer's Disease Polygenic Risk Score with Concussion Severity and Recovery Metrics

Area of Science:

• Neuroscience
• Genetics
• Sports Medicine

Background:

• Investigating genetic links between Alzheimer's disease (AD) and concussion is crucial for understanding elevated dementia risk post-injury.
• Previous research on AD genetic risk factors and their association with concussion outcomes has yielded mixed and limited results.

Purpose of the Study:

• To examine the association between AD polygenic risk scores (PRS) and APOE genotypes with concussion severity and recovery.
• To investigate if genetic predisposition to AD influences concussion outcomes in collegiate athletes.

Main Methods:

• Utilized the NCAA-DoD Grand Alliance CARE Consortium dataset with 931 participants.
• Assessed six concussion outcomes including recovery time (days to asymptomatic, return to play) and severity (SAC, BESS, symptom scores).
• Calculated AD PRS and employed multiple linear regression, ANOVAs, t-tests, and chi-square tests to analyze genetic associations with outcomes.

Main Results:

• A preliminary association was found between higher AD PRS and longer return to play (RTP) time in a subgroup with normal RTP (<24 days).
• This association (9.89 hours increase in RTP per SD increase in PRS) lost statistical significance after adjusting for covariates.
• No other consistent significant associations were observed between AD genetic risk factors and concussion severity or recovery measures.

Conclusions:

• Current findings suggest that high genetic risk for AD is not associated with more severe concussions or poorer recovery in young adults.
• Replication in larger, diverse cohorts with extended follow-up is recommended to validate these results.