Alzheimer’s Disease Genetic Risk Influences Recovery Among Individuals Receiving Traumatic Brain Injury Rehabilitation

Evidence supports the role of traumatic brain injury (TBI) as a risk factor for Alzheimer’s disease (AD), and it has been shown that some individuals with TBI experience post-injury cognitive decline; however, it is currently not clear whether genetic risk for AD may influence TBI recovery. This study investigated the association of AD genetic risk with TBI recovery, assessed with the Functional Independence Measure (FIM) at 1-year post-injury, in the TBI Model Systems cohort ( N = 176). AD genetic risk was calculated using an AD polygenic risk score (PRS) measuring 37 SNPs previously shown to be associated with AD risk independently of Apolipoprotein E (APOE) genotype, the major known risk factor for late-onset AD. A linear regression model predicting FIM score at 1-year follow-up, including AD PRS, FIM score at hospital discharge, three genetic ancestry components, sex, age and education at follow-up, and APOE e4 allele carrier status, was significant ( F (2,154) = 12.729, p < 0.001); the model showed that higher AD PRS predicted worse FIM outcome scores (beta = −0.167, t = 2.226, p = 0.027). Post-hoc testing showed similar though less significant effects for the FIM motor and cognitive subscales. These preliminary findings highlight the need for larger-scale investigations of genetic factors and fluid biomarkers as additional predictors of recovery following TBI, as well as risk for cognitive decline.