By Nitin K. Sethi, MD

Associate Professor of Neurology, Weill Cornell Medical College

Dr. Sethi reports no financial disclosures relevant to this field of study.

SYNOPSIS: This study analyzed pooled clinical and neuropathological data of older adults free of dementia from three prospective cohort studies and found that traumatic brain injury with loss of consciousness was associated with risk for Lewy body accumulation, Parkinson’s disease, and progression of Parkinsonism, but not dementia, Alzheimer’s disease, neuritic plaques, or neurofibrillary tangles.

SOURCE: Crane PK, Gibbons LE, Dams-O’Connor K, et al. Association of traumatic brain injury with late-life neurodegenerative conditions and neuropathologic findings. JAMA Neurol 2016; Jul 11. doi: 10.1001/jamaneurol.2016.1948. [Epub ahead of print].

Traumatic brain injuries (TBI) are common and occur both in the civilian and military setting. Short- and long-term sequelae of TBI include motor and sensory deficits as well as neuropsychiatric disorders. There is growing concern that repeated TBI, even milder forms (concussion), can lead to chronic traumatic encephalopathy. Concern also has been raised about an increased risk of Alzheimer’s disease (AD), Parkinson’s disease (PD), and other dementias following TBI. Crane et al pooled clinical and neuropathological data from three prospective cohort studies (Religious Orders Study [ROS], Memory and Aging Project [MAP], and Adult Changes in Thought [ACT] study) to determine whether TBI with loss of consciousness (LOC) was associated with an increased risk for clinical and neuropathological findings of AD, PD, and other dementias. The ROS study enrolled older religious clergy from more than 40 groups across the United States; MAP enrolled older residents from Chicago-area retirement facilities and subsidized housing, church groups, and social service agencies; and ACT enrolled older Seattle-area Group Health members. Of 7,130 participants (2,879 [40%] men; overall mean [SD] age, 79.9 years), 865 reported a history of TBI with LOC. In 45,190 person-years of follow up, 1,537 incident cases of dementia and 117 cases of PD were identified. TBI with LOC was not associated with incident dementia or AD. TBI with LOC > 1 hour was associated with incident PD (ACT study). TBI with any LOC was associated with progression of parkinsonian signs (ROS and MAP studies). Neuropathological findings revealed an association of TBI with the presence of Lewy bodies (either in the substantia nigra and/or locus ceruleus or in the frontal or temporal cortex) and also cortical microinfarcts. The authors did not find associations between TBI with LOC and neurofibrillary degeneration or neuritic plaques. APOE genotype status did not affect the results of the study. Limitations of the study included lack of an ethnically diverse study population and failure to account for potential confounders, such as occupational history, smoking, physical activity, body mass index, risk taking, and alcohol intake.


Physicians evaluating and treating patients with TBI frequently are asked to predict both short-term and long-term sequelae. The lack of a reliable and reproducible TBI biomarker (serum or CSF) and its association with well-defined clinical and neuropathological measures of outcome makes the task more difficult. Recent studies have raised concern about the association of multiple concussions (mild TBI) with the development of chronic traumatic encephalopathy, especially in young, fit athletes competing in contact sports, such as boxing and football. The effect of TBI with LOC on the aging brain is less well known, with recent studies raising concern for neurodegenerative disorders such as AD, PD, as well as certain psychiatric disorders. Future well-designed studies should assess the association of TBI with LOC against well-defined clinical and neuropathological measures of outcome at different points post-injury. A better understanding of the pathophysiological process and individual traits that increase susceptibility to neurodegenerative diseases following TBI are needed.1


  1. Young JS, Hobbs JG, Bailes JE. The impact of traumatic brain injury on the aging brain. Curr Psychiatry Rep 2016;18:81. doi: 10.1007/s11920-016-0719-9.