Comparison of Structural MRI Profiles Between Autopsy-Confirmed Chronic Traumatic Encephalopathy and Alzheimer’s Disease
Sydney Mosaheb1, Asim Mian2, Chad Farris2, Karen Buch3, Breton Asken4, Gil Rabinovici5, Madeline Uretsky1, Yorghos Tripodis2, Brett Martin2, Joseph Palmisano2, Neil Kowall2, Bertrand Huber2, Robert Stern1, Ronald Killiany2, Thor Stein6, Ann McKee6, Jesse Mez1, Michael Alosco1
1Neurology, Boston University Chobanian & Avedisian School of Medicine, 2Boston University Chobanian & Avedisian School of Medicine, 3Massachusetts General Hospital, 4University of Florida, 5UCSF Memory & Aging Center, 6VA Boston Healthcare System
Objective:
To compare visually-rated macrostructural features on MRIs between autopsy-confirmed CTE and participants with AD.
Background:
Biomarkers that can accurately detect the neurodegenerative disease chronic traumatic encephalopathy (CTE) do not yet exist. Structural MRI is an integral component to the in vivo detection of Alzheimer’s disease (AD) and related disorders but currently unclear usefulness in identifying CTE. MRI features of CTE have been previously characterized through comparison to participants with normal cognition. The specificity of those findings to CTE (versus alternative neurodegenerative diseases) is uncertain due to lack of disease comparison groups like AD.
Design/Methods:
The sample included 63 brain donors with autopsy-confirmed CTE and 35 participants with AD (7 autopsy-confirmed, 28 AD dementia). Participants were all males, >60 years. MRIs were obtained through medical records. Three neuroradiologists used visual rating scales (0=absent, 4=severe) to rate atrophy on T1 and microvascular disease on T2-FLAIR. Cavum septum pellucidum (CSP) presence was rated. Majority rating was used; median was used in the absence of majority. Analysis of covariance controlling for age at MRI compared groups on atrophy and microvascular disease ratings. Binary logistic regression was used for absent/present CSP.
Results:
Of the 63 with CTE, 56 had high stage and donors with CTE were four years younger than AD (71.51, SD=7.7 vs 75.6, SD=7.4). Compared with AD, CTE had higher anterior temporal lobe atrophy ratings (mean diff=1.01, 95%CI=0.08-1.94) and a 5.2X (95% CI=1.02-26.90) increase odds for having a CSP. There were statistical trends for greater dorsolateral frontal atrophy (mean diff=0.88, 95%CI=-0.06-1.81), larger third ventricle (mean diff=0.46, 95%CI=-0.07-0.99), and greater periventricular (mean diff=0.39, 95% CI=-0.05-0.83) and deep white matter hyperintensities (mean diff=0.42, 95%CI=-0.05-0.89) in CTE. There were no effects for parietal-occipital and medial temporal lobes, lateral ventricles, corpus callosum, or microbleeds (p>0.10).
Conclusions:
Frontotemporal atrophy and CSP on MRI might facilitate differential diagnosis of CTE from AD.