Research Reports - 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

Crane PK(1), Gibbons LE(1), Dams-O'Connor K(2), Trittschuh E(3), Leverenz JB(4),
Keene CD(5), Sonnen J(6), Montine TJ(7), Bennett DA(8), Leurgans S(8), Schneider
JA(9), Larson EB(10).

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. 

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