Lifetime TBI and cognitive domain deficits in late life: The PROTECT-TBI cohort study

This is the author accepted manuscript.Data sharing statement: Deidentified participant data and data dictionary for the PROTECT study is available on request from the PROTECT study team at the University of Exeter (support.protect@exeter.ac.uk). Access is available after approval of a proposal and a signed data access agreement.TBI causes cognitive impairment but it remains contested which cognitive domains are most affected. Further, moderate-severe TBI is known to be deleterious, but studies of mild TBI (mTBI) show a greater mix of negative and positive findings . This study examines the longerterm cognitive effects of TBI severity and number of mild TBI in later life. We examined a subset (n=15,764) of the PROTECT study, a cohort assessing risk factors for cognitive decline (ages between 50 and 90). Participants completed cognitive assessments annually for four years. Cognitive tests were grouped using a Principal Components Analysis (PCA) into working memory, episodic memory, attention, processing speed and executive function. Lifetime TBI severity and number were retrospectively recalled by participants using the Brain Injury Screening Questionnaire (BISQ). Linear Mixed Models examined the effect of severity of head injury (non-TBI head strike, mild TBI (mTBI) and moderate-severe TBI) and number of mTBI at baseline and over time. mTBI was considered as a continuous and categorical variable (groups: 0 mTBI, 1 mTBI, 2 mTBIs, 3 mTBIs and 4+ mTBIs). Of the participants 5,725 (36.3%) reported at least one mild TBI and 510 (3.2%) at least one moderate-severe TBI, while 3,711 (23.5%) had suffered at worst a non-TBI head strike and 5,818 (32.9%) reported no head injuries. The participants had suffered their last reported head injury an average (SD) of 29.6 (20.0) years prior to the study. Regarding outcomes, there was no worsening in longitudinal cognitive trajectories over the study duration but at baseline there were significant cognitive deficits associated with TBI. At baseline, compared to those without head injury, individuals reporting at least one moderate-severe TBI had significantly poorer attention (B=-0.163, p<0.001), executive scores (B=-0.151, p=0.004) and processing speed (B=-0.075, p=0.033). Those who had suffered at least a single mTBI also demonstrated significantly poorer attention scores at baseline compared to the no head injury group (B=-0.052, p=0.001). Compared to those with no mTBI, those in the 3 mTBI group manifested poorer baseline executive function (B=-0.149, p=0.025) and attention scores (B=-0.085, p=0.015). At baseline, those who had suffered 4 or more mild TBIs demonstrated poorer attention (B=-0.135, p