Neuroimaging and Clinical Findings in Healthy Middle-Aged Adults With Mild Traumatic Brain Injury in the PREVENT Dementia Study
Authors: Low Audrey , McKiernan Elizabeth , Prats-Sedano Maria A. , Carter Stephen F. , Stefaniak James D. , Su Li , Dounavi Maria-Eleni , Muniz-Terrera Graciela , Jenkins Natalie , Bridgeman Katie , Ritchie Karen , Lawlor Brian , Naci Lorina , Malhotra Paresh , Mackay Clare , Koychev Ivan , Thayanandan Tony , Raymont Vanessa , Ritchie Craig W. , Stewart William , O’Brien John T. ,   PREVENT Dementia Investigators, Bridgeman Katie , Chouliaras Leo , Coleman Siobhan , Darwin Hannah , Dounavi Maria-Eleni , Deng Feng , Dudas Robert , Gregory Sarah , Koychev Ivan , Lawlor Brian , Low Audrey , Mackay Clare , Mak Elijah , Malhotra Paresh , Muniz-Terrera Graciela , Naci Lorina , O’Brien John , Raymont Vanessa , Ritchie Craig , Su Li , Swann Peter , Thayanandan Tony , Williams Guy 
Published: August 2024

Importance

Traumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI.

Objective

To assess whether TBI are associated with and interact with midlife changes in neuroimaging and clinical features in otherwise healthy individuals.

Design, Setting, and Participants

This cross-sectional analysis used baseline data from the PREVENT Dementia program collected across 5 sites in the UK and Ireland between 2014 and 2020. Eligible participants were cognitively healthy midlife adults aged between 40 and 59 years. Data were analyzed between January 2023 and April 2024.

Exposure

Lifetime TBI history was assessed using the Brain Injury Screening Questionnaire.

Main Outcomes and Measures

Cerebral microbleeds and other markers of cerebral small vessel disease (white matter hyperintensities [WMH], lacunes, perivascular spaces) were assessed on 3T magnetic resonance imaging. Clinical measures were cognition, sleep, depression, gait, and cardiovascular disease (CVD) risk, assessed using Computerized Assessment of Information Processing (COGNITO), Pittsburgh Sleep Quality Index, Center for Epidemiologic Studies Depression Scale, clinical interviews, and the Framingham Risk Score, respectively.

Results

Of 617 participants (median [IQR] age, 52 [47-56] years; 380 female [61.6%]), 223 (36.1%) had a history of TBI. TBI was associated with higher microbleed count (β = 0.10; 95% CI, 0.01-0.18; P = .03), with a dose-response association observed with increasing number of TBI events (β = 0.05; 95% CI, 0.01-0.09; P = .03). Conversely, TBI was not associated with other measures of small vessel disease, including WMH. Furthermore, TBI moderated microbleed associations with vascular risk factors and clinical outcomes, such that associations were present only in the absence of TBI. Importantly, observations held when analyses were restricted to individuals reporting only mild TBI.

Conclusions and Relevance

In this cross-sectional study of healthy middle-aged adults, detectable changes in brain imaging and clinical features were associated with remote, even mild, TBI in the general population. The potential contribution of vascular injury to TBI-related neurodegeneration presents promising avenues to identify potential targets, with findings highlighting the need to reduce TBI through early intervention and prevention in both clinical care and policymaking.