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2016 ; 73
(9
): 1062-9
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Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions
and Neuropathologic Findings
#MMPMID27400367
Crane PK
; Gibbons LE
; Dams-O'Connor K
; Trittschuh E
; Leverenz JB
; Keene CD
; Sonnen J
; Montine TJ
; Bennett DA
; Leurgans S
; Schneider JA
; Larson EB
JAMA Neurol
2016[Sep]; 73
(9
): 1062-9
PMID27400367
show ga
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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