The Relationship Between Age, Brain Structure, and Cognition in Chronic Traumatic Brain Injury

Background The long-term impact of traumatic brain injury (TBI) on ageing remains poorly understood without controlled studies. Objective Cross-sectionally examine how chronic moderate–severe TBI and advancing age interact to affect brain structure and related cognition in adults aged 40 to 90 years who received compensated inpatient rehabilitation in Australia. Methods Cross-sectional magnetic resonance imaging (MRI) and neuropsychological data were collected from 123 individuals with chronic moderate–severe TBI (6-33 years post-injury; M age = 59.64) and age- and gender-matched to 74 non-TBI controls (M age = 62.10). Analyses examined cortical thickness, subcortical volume, and white matter microstructural integrity using tract-based analysis. Results Ageing and TBI were independently associated with reduced structural integrity in multiple regions. However, age moderated the effect of TBI on both fornix integrity and left thalamic volume, such that TBI-related reductions were present in adults in their 40s to 70s and 40s to 60s, respectively, but attenuated in the oldest age groups (80+ and 70+, respectively) relative to controls. Fornix and thalamic reductions correlated with poorer cognitive function, with the largest effects in verbal memory and processing speed. Conclusions While TBI and ageing were independently associated with changes in brain structure, their interaction manifested distinctly in the bilateral fornix and left thalamus, with TBI-related structural losses in middle-age that diminished in later life as controls experienced typical age-related declines. In adults who received inpatient rehabilitation, moderate–severe TBI may result in initial structural alterations that do not accelerate age-related declines or compound with ageing processes long-term. Age-dependent fornix and thalamic structural changes were strongly associated with cognitive performance, particularly in verbal memory and processing speed.