Atrophic changes observed with MRI on autopsies of those with chronic traumatic encephalopathy could be a disease marker in living patients
A number of atrophic changes detected with magnetic resonance imaging (MRI) in patients with chronic traumatic encephalopathy (CTE) could be an important marker of the disease if observed in living patients. This was the tentative conclusion of a study by a team from the Framingham Heart Study, Boston University School of Medicine, Boston, US.
CTE is defined as a progressive neurodegenerative disorder linked to repetitive traumatic brain injury from head impacts and is a common finding in deceased, retired American football players. The pathognomonic lesion of CTE is an abnormal accumulation of hyper-phosphorylated tau protein (p-tau) within neurons and a definitive diagnosis can only be made by post-mortem examination of brain tissue. Furthermore, CTE has been categorised into four pathological stages of CTE, stages I (mild) to IV(severe), based on the density and regional deposition of p-tau.
Although imaging studies in living patients at a higher risk of CTE such as former American football players have revealed some changes, these studies could not definitively characterise the specific in vivo structural MRI patterns of CTE.
For the present study, the US researchers turned to MRI scans of patients with autopsy confirmed CTE together with a brain samples obtained from patients with normal cognition to compare atrophic changes. The researchers were interested in testing the associations between p-tau severity in those with CTE with atrophy changes seen on MRI. The neuropathological evaluations were undertaken by three neurologists, blinded to clinical data from the participants and who rated regional atrophy changes on a scale of 0 (none) to 4 (severe) in 14 different regions. In addition, the presence of cavum septum pellucidum (CPS), which is a common neuropathological feature of chronic traumatic encephalopathy, was recorded on a binary (absent/present) scale. For their analysis, the researchers used linear regression models to compare the brains of those with CTE and normal cognition donors. For those with CTE, the regression models examined the association between p-tau severity and atrophy changes seen on MRI.
A total of 55 donors with CTE and 31 men (11 who were deceased) with normal cognition were included in the analysis. The mean age at the time of the scan was 71 years for donors with CYE and 76 for those with normal cognition. In the majority of cases (65%), the MRI scan had been requested in CTE donors because of dementia or neurodegenerative disease. Among those with normal cognition, requests for the scans were for a wider range of conditions including cardiovascular causes (22.6%) and memory complaints (16.1%).
Compared to those with normal cognition, CTE donors had greater mean differences in atrophic changes in a number of areas. For example, orbital-frontal atrophy (mean difference, MD = 1.29, p = 0.009), dorsolateral frontal (MD = 1.31, p = 0.013), superior frontal (MD = 1.05, p = 0.046) and anterior temporal (MD = 1.57, p = 0.009). There were no differences for posterior atrophy or microvascular disease. In addition, among donors with CTE, there was a 6-fold increased odds of CSP (Odds ratio, OR = 6.7, p < 0.05) and a greater degree of tau severity across the different regions of the brain which was associated with a greater total brain atrophy on the MRI scan.
The authors concluded that in men with autopsy-confirmed CTE, there was more severe atrophy changes and more severe p-tau pathology. They suggested that if validated with prospective studies, their findings could support the use of structural MRI as a valuable tool to support a diagnosis of CTE during life.
Alosco ML et al. Structural MRI profiles and tau correlates of atrophy in autopsy-confirmed CTE. Alzheimers Res 2021 Ther