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

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BACKGROUND: Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed. OBJECTIVE: We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset. METHODS: We assessed six concussion outcomes in 931 participants, including two recovery measures (number of days to asymptomatic and to return to play (RTP)) and four severity measures (scores on SAC and BESS, SCAT symptom severity and total number of symptoms). We calculated the PRS using a published score and performed multiple linear regression to assess the relationship of the PRS with outcomes. We also used ANOVAs, t-tests, and chi-square tests to examine outcomes by APOE genotype. RESULTS: Higher PRS was associated with longer injury to RTP time in the normal RTP (< 24 days) subgroup (p = 0.024). A one standard deviation increase in the PRS resulted in a 9.89 hour increase to RTP time. This result was no longer significant after inclusion of covariates. There were no other consistently significant effects. CONCLUSIONS: Our findings suggest high AD genetic risk is not associated with more severe concussions or poor recovery in young adults. Future studies should attempt to replicate these findings in larger samples with longer follow-up using PRS calculated from diverse populations.

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