An important first step
The investigators also examined ventricle size. The lateral ventricles in the CTE group were significantly larger (mean difference, 1.72; 95% CI, .62-2.82; P = .01), as was the third ventricle (mean difference, .80; 95% CI, .26-1.35; P = .01).
When neuropathologists rated tau severity and atrophy at autopsy, they found that more severe p-tau pathology was associated with greater atrophy among those with CTE (beta = .68; P < .01).
Dr. Alosco called the finding “exciting,” noting that it suggests “this tau is a precipitant for neurodegeneration.”
He noted that, although some researchers have used positron emission tomography (PET) tau tracers to uncover a CTE pattern, MRI is relatively inexpensive and routinely used as part of dementia assessment.
While the new study is “an important first step” in using MRI to diagnose CTE, larger sample sizes are needed, Dr. Alosco said. “We also need to look at other disease groups and really nail down the difference with CTE in terms of patterns” (vs. Alzheimer’s disease and vs. frontotemporal lobar degeneration), he added.
“Once those differences are cleared, we will be ready to be more confident when we interpret these images.”.
‘Not unexpected’
Commenting on the research, neurologist and concussion expert Francis X. Conidi, DO, director, Florida Center for Headache and Sports Neurology, Port St. Lucie, said that, although the study was “well thought out and interesting,” the results were “not completely unexpected.”
Frontal and anterior temporal lobe atrophy and prominent third ventricles are very common in patients with traumatic brain injury (TBI), which is “a prerequisite to develop CTE,” said Dr. Conidi, who was not involved with the research.
The current study’s findings mirror observations found in a National Football League cohort he and his colleagues are following – and in his patients with TBI in general.
Dr. Conidi noted that there is a “significant subjective component” to the study results because they relied on the opinion of neuroradiologists. He is not convinced MRI findings of frontotemporal and medial temporal lobe atrophy necessarily represent CTE and not TBI. In fact, he noted that patients with TBI have a significantly greater chance of not developing a neurodegenerative disorder.
Dr. Conidi added that he doesn’t think MRI will ever be the gold standard for diagnosing or even assessing risk of developing CTE. “That lies in tau PET imaging,” he said.
Overstated conclusion?
Also commenting on the research findings, Kristen Dams-O’Connor, PhD, professor, vice chair of research, and director, Brain Injury Research Center, Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai in New York, said the sensitivity analyses, particularly those designed to clarify contributions of Alzheimer’s disease and other neuropathological contributions to associations between p-tau and atrophy, “increase our confidence” in the findings.
“What’s exciting about this paper is that it provides very preliminary support for adding another tool to our arsenal as we try to establish a constellation of in vivo diagnostic markers that, together, will help us rule in a post-traumatic neurodegenerative process and rule out other brain diseases.”
A possible study limitation is that the MRI scans were from low-field strength magnets, although that makes the study more “ecologically valid”, said Dr. Dams-O’Connor. “Many clinical scanners are built around a 1.5T magnet, so what the researchers see in this study is what a radiologist may see in the clinic.”
The conclusion that frontal-temporal atrophy is an MRI marker of CTE is “an overstatement” as this pattern of atrophy is not specific to CTE, said Dr. Dams-O’Connor. “The association of p-tau with atrophy is unsurprising and doesn’t bring us much closer to understanding how, or whether, the patterns of p-tau accumulation observed in CTE contribute to the clinical expression of symptoms.”
Dr. Alosco and Dr. Conidi report no relevant financial relationships. Disclosures for the other study authors are listed in the original journal article. The study was funded by grants from the National Institute on Aging, the National Institute on Neurological Disorders and Stroke, National Institute of Aging Boston University AD Center, Department of Veterans Affairs Merit Award, the Nick and Lynn Buoniconti Foundation, and BU-CTSI.