Link Found Between Traumatic Brain Injury and Late-Life Parkinson’s, but Not Alzheimer’s Disease
Traumatic brain injury (TBI) with a loss of consciousness (LOC) may be associated with later development of Parkinson’s disease but not Alzheimer’s disease or incident dementia, according to a study conducted at the Icahn School of Medicine at Mount Sinai and the University of Washington School of Medicine. The research, published today in JAMA Neurology, contradicts common assumptions about the relationship between TBI and Alzheimer’s disease as found in other high-profile studies.
There is great interest in the late effects of TBI and the widespread public health implications. The Centers for Disease Control and Prevention estimates that more than 1.3 million Americans visit an emergency department each year because of a TBI-related injury.
The research team studied head injury data from 7,130 older adults – the largest study ever on this topic – as part of three prospective cohort studies that performed annual or biennial cognitive and clinical testing. Of this group, 865 people had suffered TBI with LOC at some point before the study began. Of the 865, 142 had been unconscious for more than one hour. The researchers evaluated associations between TBI and late-life clinical outcomes, such as dementia, Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease and change in parkinsonian signs. Roughly 23 percent of the study group had brain autopsies, and in that group researchers searched for any link between TBI and neuropathological findings. Neuropathology is considered the gold standard for diagnosing neurodegenerative disease.
No statistically significant relationship between TBI with LOC and dementia risk was discovered when the group with TBI with LOC was compared with the 1,537 patients who developed dementia during the study. Results for Alzheimer’s disease (diagnosed in 1,322 study participants) were similar. However, regression data showed a strong association between TBI with LOC greater than an hour and Parkinson’s disease (117 cases during the study). Neuropathological findings at autopsy (1,652 autopsy cases) showed no association between TBI with LOC and beta amyloid plaques or neurofibrillary tangles, the hallmark indicators of Alzheimer’s disease. However, the autopsies found an increased risk for Lewy bodies (abnormal aggregates of protein) in TBI with LOC less than an hour and an increased risk of cerebral microinfarcts (microscopic stroke) in TBI with LOC more than an hour.
“The results of this study suggest that some individuals with a history of TBI are at risk for late-life neurodegeneration but not Alzheimer’s disease,” says Kristen Dams-O’Connor, PhD, Co-Director of the Brain Injury Research Center and Associate Professor in the Department of Rehabilitation Medicine at the Icahn School of Medicine at Mount Sinai. “We want to identify and treat post-TBI neurodegeneration while people are still alive, but to do this, we need to first understand the disease. Prospective TBI brain donation studies can help us characterize post-TBI neurodegeneration, identify risk factors, and develop effective treatments.”
These findings suggest that clinicians may be misdiagnosing late-life TBI-related neurodegeneration as Alzheimer’s disease, and therefore treatment targeting Alzheimer’s would be ineffective in helping late-life decline among patients who experienced TBI. Further work is needed to characterize post-TBI neurodegeneration.
The lead investigator for this study is Paul Crane, MD, MPH, Professor in the Department of Medicine at the University of Washington School of Medicine. Cleveland Clinic, University of Utah, Rush University Medical Center and Group Health Research Institute also contributed to this research.
The National Institutes of Health and the Paul Allen Family Foundation provided funding for the study.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in 4 out of 10 pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.