Comparison of Structural MRI Profiles Between Autopsy-Confirmed Chronic Traumatic Encephalopathy and Alzheimer's Disease

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. Disclosure: Miss Mosaheb has nothing to disclose. Dr. Mian has received personal compensation for serving as an employee of Boston Imaging Core Lab. Dr. Mian has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Biogen. Dr. Mian has stock in Boston Imaging Core Lab. Dr. Mian has received intellectual property interests from a discovery or technology relating to health care. Mr. Farris has nothing to disclose. Karen Buch, MD has nothing to disclose. Breton Asken has nothing to disclose. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eisai. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GE Healthcare. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Joihnson. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. The institution of Dr. Rabinovici has received research support from NIH. The institution of Dr. Rabinovici has received research support from American College of Radiology. The institution of Dr. Rabinovici has received research support from Alzheimer’s Association. The institution of Dr. Rabinovici has received research support from Rainwater Charitable Foundation. The institution of Dr. Rabinovici has received research support from Genentech. Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Topic Chair, Course Director and teacher with AAN. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Grant reviewer with NIH. Madeline Uretsky has nothing to disclose. Yorghos Tripodis, 5406 has nothing to disclose. Brett Martin has nothing to disclose. Joseph Palmisano has nothing to disclose. Dr. Kowall has received publishing royalties from a publication relating to health care. Bertrand Huber has nothing to disclose. Robert Stern, PhD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Robert Stern, PhD has received research support from Eisai. The institution of Robert Stern, PhD has received research support from Lilly. The institution of Robert Stern, PhD has received research support from ATRI/NIA. Robert Stern, PhD has received publishing royalties from a publication relating to health care. Robert Stern, PhD has a non-compensated relationship as a Member with NFLPA Mackey-White Committee that is relevant to AAN interests or activities. Dr. Killiany has nothing to disclose. Dr. Stein has nothing to disclose. Dr. McKee has nothing to disclose. The institution of Dr. Mez has received research support from NIH, DOD. The institution of Michael Alosco, PHD has received research support from NIH.