Association between Traumatic Brain Injury and Late Life Neurodegenerative Conditions and Neuropathological Findings

Abstract

IMPORTANCE

There is great interest in the late effects of traumatic brain injury (TBI).

OBJECTIVE

To determine whether TBI with loss of consciousness (LOC) is associated with increased risk for clinical and neuropathological findings of Alzheimer’s disease, Parkinson’s disease, and other dementias. Our primary hypothesis was that TBI with LOC would be associated with increased risk for Alzheimer’s disease and neurofibrillary tangles.

DESIGN

Prospective cohort studies which follow all participants (Religious Orders Study and the Memory and Aging Project, ROS and MAP) or all consenting participants (Adult Changes in Thought, ACT) to autopsy. Studies performed annual (ROS and MAP) or biennial (ACT) cognitive and clinical testing to identify incident cases of dementia and Alzheimer’s disease.

SETTING

Members of a Seattle-area healthcare delivery system (ACT); priests and nuns living in orders across the US (ROS), and Chicago-area adults in retirement communities (MAP).

PARTICIPANTS

7,130 older adults; 1,589 came to autopsy.

EXPOSURE

Self reported TBI reported when free of dementia, categorized as <1 hour vs. > 1 hour of LOC.

MAIN OUTCOMES AND MEASURES

Clinical: incident all-cause dementia, Alzheimer’s disease, and Parkinson’s disease (all studies), and incident mild cognitive impairment and progression of parkinsonian signs (ROS and MAP). Neuropathology: neurofibrillary tangles, neuritic plaques, microinfarcts, cystic infarcts, Lewy bodies, and hippocampal sclerosis (all studies).

RESULTS

865 participants reported a history of TBI with LOC. In >45,000 person-years of follow-up, there were 1,537 incident dementia and 117 incident Parkinson’s disease cases. There was no association between TBI with LOC and incident dementia or Alzheimer’s disease. There were associations between TBI with LOC and incident Parkinson’s disease and progression of parkinsonian signs. There was no association between TBI with LOC and neurofibrillary tangles or neuritic plaques. There was an association between TBI with LOC and Lewy bodies, and with microinfarcts, though numbers of people with these findings were small.

CONCLUSIONS AND RELEVANCE

Pooled clinical and neuropathology data from three prospective cohort studies indicate that TBI with LOC is associated with risk of Lewy body accumulation, progression of parkinsonism, and Parkinson’s disease, but not dementia, Alzheimer’s disease, neuritic plaques, or neurofibrillary tangles.