A pilot study on Alzheimer’s disease‐related biological and cognitive markers in dementia and history of mild traumatic brain injury

Abstract

AbstractBackgroundMild traumatic brain injury (mTBI) has been associated with a higher risk for developing dementia later in life. Several mechanisms have been proposed, with most relating to TBI accelerating AD‐linked pathological changes or decreasing neuronal and/or cognitive reserve. The purpose of this study was to compare AD‐linked biomarkers and measures of neuronal and cognitive functioning in AD participants with and without a history of mTBI.MethodThe Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset was used to identify participants with dementia due to AD and a history of mTBI (n = 10),compared with a group of AD patients without TBI (n = 20) similar in gender, age (±5 years), education (± 3 years), and apolipoprotein ε4 status. Baseline cerebrospinal fluid (CSF)‐derived markers of amyloid and tau, and FDG PET glucose metabolism for three regions of interest (angular, temporal, and posterior cingulate), along with neuropsychological measures (i.e., Alzheimer’s Disease Assessment Scale–Cognitive Subscale 13 items, Rey Verbal Learning Test, Wechsler Memory Scale Logical Memory, Trail Making Test), were compared between groups.ResultAD mTBI and control groups did not significantly differ in glucose metabolism using PET across regions often reduced in AD (p=0.53). CSF‐derived markers of amyloid formation also did not differ between the groups (p=0.76), though interestingly, there was a trend for higher phosphorylated tau (p=0.07) and total tau (0.08) markers in the mTBI group (Mptau=41.0, SD=15.0; Mttau=409.9, SD=133.7) relative to the control group (Mptau=31.5, SD=9.8; Mttau=319.5, SD=93.4). The groups were similar across neuropsychological measures (p’s=0.16 – 0.90).ConclusionA history of mTBI was not associated with greater markers of amyloid formation, lower cerebral glucose metabolism, or worse cognitive functioning in those with AD dementia. While not statistically significant, AD participants with mTBI did have a trend for higher tau levels compared to those with no history of TBI in this preliminary study. The findings may indicate a link between mTBI and greater accumulation of tau in some individuals that needs further evaluation in future studies with larger samples.