Distinct patterns of neurodegeneration after TBI and in Alzheimer’s disease

Abstract Background Traumatic brain injury (TBI) is an established risk factor for dementia, with Alzheimer’s disease reportedly more prevalent post‐injury. Experimental injury models relate axonal injury to the generation of toxic proteinopathies including amyloid and hyperphosphorylated tau, but epidemiological data relating brain injury and Alzheimer’s disease specifically are inconsistent. Using longitudinal volumetric MRI, it is possible to assess commonalities and differences between chronic post‐traumatic neurodegeneration, Alzheimer’s disease and ageing in vivo, to better understand the long‐term consequences of TBI. Method Serial volumetric T1‐weighted MRI was performed on two occasions a year apart in 55 patients after moderate‐severe TBI, a group of 23 age‐matched healthy volunteers, a group of 15 older healthy controls (healthy ageing group), as well as 45 patients with Alzheimer’s disease alongside 23 age‐matched controls comprising the MIRIAD dataset. Jacobian determinant (JD) brain atrophy rates in white, grey matter and CSF were quantified, spatial patterns defined and systematically compared between the groups. Diffusion imaging was acquired in TBI patients at baseline, facilitating the generation of the fractional anisotropy metric of axonal integrity via diffusion tensor imaging. Result Atrophy rates were significantly increased in white matter only after TBI (P<0.01), in contrast to increases in both white matter and grey matter in Alzheimer’s disease (P<0.001). Common subcortical white matter regions showed atrophy in both Alzheimer’s disease and TBI, but deep white matter atrophy was TBI‐specific, and cortical atrophy Alzheimer’s disease‐specific. Post‐TBI atrophy patterns were distinct from ageing, which more closely resembled Alzheimer’s disease, and were predicted by the extent of axonal injury on diffusion tensor imaging at baseline (P<0.05). Conclusion Neurodegeneration after moderate‐severe TBI is distinct in location from both ageing and Alzheimer’s disease, with a characteristic central white matter predominance. This likely reflects the underlying spatial distribution of traumatic axonal injury, and may represent ongoing chronic Wallerian degeneration, and/or toxic proteinopathy‐driven neurodegeneration.