Lifetime Traumatic Brain Injury and Cognitive Domain Deficits in Late Life: The PROTECT-TBI Cohort Study

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.Traumatic brain injury (TBI) causes cognitive impairment but it remains contested regarding 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 longer-term cognitive effects of TBI severity and number of mTBIs 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 years). Participants completed cognitive assessments annually for 4 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 (LMMs) examined the effect of severity of head injury (non-TBI head strike, 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 5725 (36.3%) reported at least one mTBI and 510 (3.2%) at least one moderate-severe TBI, whereas 3711 (23.5%) had suffered at worst a non-TBI head strike and 5818 (32.9%) reported no head injuries. The participants had suffered their last reported head injury an average (standard deviation, 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 with 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 with the no head injury group (B = −0.052, p = 0.001). Compared with 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 four or more mTBIs demonstrated poorer attention (B = −0.135, p < 0.001), processing speed (B = −0.072, p = 0.009), and working memory (B = −0.052, p = 0.036), compared with those reporting no mTBI. TBI is associated with fixed, dose, and severity-dependent cognitive deficits. The most sensitive cognitive domains are attention and executive function, with approximately double the effect compared with processing speed and working memory. Post-TBI cognitive rehabilitation should be targeted appropriately to domain-specific effects. Significant long-term cognitive deficits were associated with three or more lifetime mTBIs, a critical consideration when counseling individuals post-TBI about continuing high-risk activities.This paper represents an independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. This research was also supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula