Memory and executive function symptoms more accurate for predicting CTE than mood, behavior

(Boston)–Diagnosing Chronic Traumatic Encephalopathy (CTE) during life is crucial for developing therapies and for determining how common the disease is among individuals exposed to repetitive head impacts from contact sports, military service and physical violence.

While the ability to diagnose CTE prior to death has remained elusive, researchers from Boston University School of Medicine (BUSM) for the first time have shown that progressive memory loss and issues with executive function, the ability to focus, follow directions, and problem-solve, are more useful for predicting CTE pathology than mood and behavior symptoms.

CTE is a progressive brain disease. Clinically, impulsivity, explosivity, depression, memory impairment and executive dysfunction have been reported to occur in the disease.

“This study significantly advances our understanding of how to diagnose CTE in life, suggesting progressive memory and executive function symptoms are particularly valuable for predicting CTE pathology,” explained corresponding author Jesse Mez, MD, MS, director of the Boston University (BU) Alzheimer’s Disease Center Clinical Core and a BU CTE Center Investigator.

In 2014, criteria for traumatic encephalopathy syndrome (TES) were proposed for use in clinical research settings to diagnose CTE in life. In an effort to assess the reliability and diagnostic validity of TES criteria, a team of clinicians interviewed family members of 336 brain donors exposed to repetitive head impacts from contact sports, military service and/or physical violence who were at risk for CTE. Neuropathologists then evaluated the brains for CTE pathology. An expert panel of clinicians then determined whether (TES) criteria (i.e. proposed criteria to diagnose CTE in life) were met. They found when individual TES criteria components were assessed, cognitive symptoms, but not mood/behavior or motor symptoms, were significantly associated with CTE pathology.

According to Mez, this study moves the field closer to being able to diagnose CTE in life rather than exclusively after death, as is currently the case. “Our study provides doctors with information about which symptoms are most predictive of CTE pathology,” he adds.

While having reliable and valid criteria to diagnose CTE in life will improve patient care and accelerate the development of effective therapies, Mez points out that the criteria did not perform well enough to be immediately moved to the clinic. However, these findings were used by an international team of experts to develop improved TES criteria.

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These findings appear online in

Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association

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This work was supported by the National Institute of Neurological Disorders and Stroke (U01NS086659, U01NS093334, U54NS115266, R01NS078337, R56NS078337, K23NS102399), National Institute of Aging (P30AG13846; supplement 0572063345, R01AG057902, R01AG061028, K23AG046377, R01AG1649, R01AG062348, R21HD089088, F32NS096803), National Center for Advancing Translational Sciences (1UL1TR001430), Department of Veterans Affairs (I01 CX001135, CSP 501, B6796-C, I01CX001038), Department of Defense (W81XWH-13-2-0095, W81XWH-13-2-0064, W81XWH1810580, PRARP-13267017), Canadian Institutes of Health Research (CIHR), Fonds de Recherche du Québec – Santé (FRQS), the Alzheimer’s Association (NIRG-15-362697, NIRG-305779), the National Operating Committee on Standards for Athletic Equipment (NOCSAE), the Nick and Lynn Buoniconti Foundation, the Concussion Legacy Foundation, the Andlinger Foundation, the WWE, and the NFL.

Note to Editors:

Dr. Goldstein is a paid consultant to Johnson & Johnson, Janssen Research & Development LLC, and Rebiscan Inc and has received funding from the WWE (World Wrestling Entertainment) and Ivivi Health Sciences.

Dr. Nowinski is the Co-Founder and Chief Executive Officer of the Concussion Legacy Foundation, and serves as an advisor for Oxeia Biopharmaceuticals.

Dr. Stern is a paid consultant to Biogen, is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association, receives royalties for published neuropsychological tests from Psychological Assessment Resources Inc, is a member of the Board of Directors of King-Devick Technologies, and reported grants from the National Institutes of Health during the conduct of the study.

Dr. Cantu is a paid consultant to the National Football League Head Neck and Spine Committee, a vice president and chair of the scientific advisory committee of the National Operating Committee on Standards for Athletic Equipment, and a consultant to the Concussion Legacy Foundation; he also receives royalties from Houghton Mifflin Harcourt and compensation for expert legal opinion to the National Collegiate Athletic Association and National Hockey League and is a member of the Mackey-White Committee of the National Football League Players Association.

Dr. McKee is a member of the Mackey-White Committee of the National Football League Players Association and reports receiving grants from the National Institutes of Health and Department of Veteran Affairs and other funding from Buoniconti Foundation during the conduct of the study.

Dr. Alosco reported grants from National Institutes of Health/National Institute of Neurological Disorders and Stroke during the conduct of the study.

Dr. Katz reported grants from Boston University School of Medicine Department of Neurology during the conduct of the study, receives royalties from Springer/Demos Publishing for a text book on brain injury, serves as an expert witness in legal cases involving brain injury and concussion; receives a stipend from Encompass Health as program medical director for brain injury and chair of the annual Neurorehabilitation conference; has received honoraria for a keynote address for the HealthSouth annual Medical Directors meeting.

Dr. Mez reported grants from the National Institutes of Health, Department of Defense, Alzheimer’s Association, and Concussion Legacy Foundation during the conduct of the study.