Summary: According to a new study, people with a history of TBI are at an increased risk for developing some neurodegenerative diseases later in life. However, TBI’s don’t appear to be linked to a higher risk for Alzheimer’s disease.
Source: Mount Sinai Hospital.
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 Brian Injury Research Center and Associate Professor in the Department of Rehabilitative 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.
Funding: The National Institutes of Health and the Paul Allen Family Foundation provided funding for the study.
Source: Matt Kozar – Mount Sinai Hospital
Image Source: This NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings” by Paul K. Crane, MD, MPH; Laura E. Gibbons, PhD; Kristen Dams-O’Connor, PhD; Emily Trittschuh, PhD; James B. Leverenz, MD; C. Dirk Keene, MD, PhD; Joshua Sonnen, MD; Thomas J. Montine, MD, PhD; David A. Bennett, MD; Sue Leurgans, PhD; Julie A. Schneider, MD, MS; and Eric B. Larson, MD, MPH in JAMA Neurology. Published online July 11 2016 doi:10.1001/jamaneurol.2016.1948
[cbtabs][cbtab title=”MLA”]Mount Sinai Hospital. “Study Finds Link Between TBI and Parkinson’s, But Not Alzheimer’s.” NeuroscienceNews. NeuroscienceNews, 11 July 2016.
<https://neurosciencenews.com/parkinsons-tbi-neurology-4651/>.[/cbtab][cbtab title=”Mount Sinai Hospital”]Mount Sinai Hospital. (2016, July 11). Study Finds Link Between TBI and Parkinson’s, But Not Alzheimer’s. NeuroscienceNews. Retrieved July 11, 2016 from https://neurosciencenews.com/parkinsons-tbi-neurology-4651/[/cbtab][cbtab title=”Chicago”]Mount Sinai Hospital. “Study Finds Link Between TBI and Parkinson’s, But Not Alzheimer’s.” https://neurosciencenews.com/parkinsons-tbi-neurology-4651/ (accessed July 11, 2016).[/cbtab][/cbtabs]
Abstract
Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings
Importance The late effects of traumatic brain injury (TBI) are of great interest, but studies characterizing these effects are limited.
Objective To determine whether TBI with loss of consciousness (LOC) is associated with an increased risk for clinical and neuropathologic findings of Alzheimer disease (AD), Parkinson disease (PD), and other dementias.
Design, Setting, and Participants This study analyzed data from the Religious Orders Study (ROS), Memory and Aging Project (MAP), and Adult Changes in Thought study (ACT). All ROS and MAP participants and a subset of ACT participants consent to autopsy. Studies performed annual (ROS and MAP) or biennial (ACT) cognitive and clinical testing to identify incident cases of dementia and AD. The 7130 participants included members of a Seattle-area health care delivery system (ACT), priests and nuns living in orders across the United States (ROS), and Chicago-area adults in retirement communities (MAP). Of these, 1589 underwent autopsy. Primary hypothesis was that TBI with LOC would be associated with increased risk for AD and neurofibrillary tangles. Data were accrued from 1994 to April 1, 2014.
Exposures Self-reported TBI when the participant was free of dementia, categorized as no more than 1 vs more than 1 hour of LOC.
Main Outcomes and Measures Clinical outcomes included incident all-cause dementia, AD, and PD in all studies and incident mild cognitive impairment and progression of parkinsonian signs in ROS and MAP. Neuropathologic outcomes included neurofibrillary tangles, neuritic plaques, microinfarcts, cystic infarcts, Lewy bodies, and hippocampal sclerosis in all studies.
Results Of 7130 participants (2879 [40.4%] men; overall mean [SD] age, 79.9 [6.9] years), 865 reported a history of TBI with LOC. In 45 190 person-years of follow-up, 1537 incident cases of dementia and 117 of PD were identified. No association was found between TBI with LOC and incident dementia (ACT: HR for TBI with LOC ≤1 hour, 1.03; 95% CI, 0.83-1.27; HR for TBI with LOC >1 hour, 1.18; 95% CI, 0.77-1.78; ROS and MAP: HR for TBI with LOC ≤1 hour, 0.87; 95% CI, 0.58-1.29; HR for TBI with LOC >1 hour, 0.84; 95% CI, 0.44-1.57) or AD (findings similar to those for dementia). Associations were found for TBI with LOC and incident PD in ACT (HR for TBI with LOC >1 hour, 3.56; 95% CI, 1.52-8.28) and progression of parkinsonian signs in ROS and MAP (odds ratio [OR] for TBI with LOC ≤1 hour, 1.65; 95% CI, 1.23-2.21; OR for TBI with LOC >1 hour, 2.23; 95% CI, 1.16-4.29). Traumatic brain injury with LOC was associated with Lewy bodies (any Lewy body in ACT: RR for TBI with LOC >1 hour, 2.64; 95% CI, 1.40-4.99; Lewy bodies in substantia nigra and/or locus ceruleus in ACT: RR for TBI with LOC >1 hour, 3.30; 95% CI, 1.71-6.38; Lewy bodies in frontal or temporal cortex in ACT: RR for TBI with LOC >1 hour, 5.73; 95% CI, 2.18-15.0; ROS and MAP: RR for TBI with LOC ≤1 hour, 1.64; 95% CI, 1.00-2.70; pooled RR for TBI with LOC ≤1 hour, 1.59; 95% CI, 1.06-2.39) and microinfarcts (any cortical microinfarct in ROS and MAP: RR for TBI with LOC >1 hour, 2.12; 95% CI, 1.12-4.01; pooled RR for TBI with LOC >1 hour, 1.58; 95% CI, 1.06-2.35).
Conclusions and Relevance Pooled clinical and neuropathologic data from 3 prospective cohort studies indicate that TBI with LOC is associated with risk for Lewy body accumulation, progression of parkinsonism, and PD, but not dementia, AD, neuritic plaques, or neurofibrillary tangles.
“Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings” by Paul K. Crane, MD, MPH; Laura E. Gibbons, PhD; Kristen Dams-O’Connor, PhD; Emily Trittschuh, PhD; James B. Leverenz, MD; C. Dirk Keene, MD, PhD; Joshua Sonnen, MD; Thomas J. Montine, MD, PhD; David A. Bennett, MD; Sue Leurgans, PhD; Julie A. Schneider, MD, MS; and Eric B. Larson, MD, MPH in JAMA Neurology. Published online July 11 2016 doi:10.1001/jamaneurol.2016.1948
