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P2–222: Alzheimer's disease, Lewy body disease and TDP43 proteinopathy following a single TBI
Author(s) -
Daneshvar Daniel,
Katz Douglas,
Stein Thor,
Alvarez Victor,
McKee Ann
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.868
Subject(s) - dementia , medicine , traumatic brain injury , atrophy , pallor , chronic traumatic encephalopathy , amnesia , cerebral atrophy , neurofibrillary tangle , autopsy , senile plaques , disease , psychology , pathology , alzheimer's disease , pediatrics , psychiatry , poison control , concussion , injury prevention , environmental health
TDP-43 pathologywas investigated in the amygdala, hippocampus, entorhinal, frontal and temporal cortices, and a summary measure was created by adding the semi-quantitative severity scores across the regions. Brains were also evaluated for neurofibrillary tangle (NFT) density and average amyloid-beta burden across multiple brain regions, neocortical Lewy bodies (LB), gross and microscopic cerebral infarcts, and hippocampal sclerosis (HS). Results: TDP-43 pathology was identified in 46% of subjects and was associated with amyloid (r1⁄40.23, p1⁄40.007), NFT (r1⁄40.35, p <0.001), and HS (c 2 [1] 1⁄4 2.38, p 1⁄4 0.001) but not LB or infarcts. After controlling for amyloid, NFT, and HS, TDP-43 pathology was associated with more rapid cognitive decline, accounting for 8% of variability in rates of global cognitive decline compared to 10% for NFT. TDP-43 pathology was related to a distinct profile (decline in episodic and working memory but not semantic memory or perceptual speed) and was associated with dementia but not mild cognitive impairment. Next we investigated the role of TDP-43 in terminal decline. A composite measure of global cognition (baseline mean 1⁄4 0.014, SD 1⁄4 0.517) declined a mean of 0.032-unit per year (95% confidence interval [CI]: -0.048, -0.017) until 3.24 years (mean) before death (95% CI: -3.72, -2.78) when the rate increased to 0.353 unit (95% CI: -0.430, -0.281). TDP-43 pathology was associated with faster preterminal decline (estimate 1⁄4 -0.025, 95% CI: -0.041, -0.009); and earlier onset (estimate 1⁄4 -0.057, 95% CI: -0.95, -0.17), and faster rate of terminal decline (estimate 1⁄4 0.071, 95% CI: -0.127, -0.016). NFT were associated with preterminal (estimate 1⁄4 -0.032, 95% CI: -0.062, -0.002) but not terminal (estimate 1⁄4 -0.022, 95%CI: -0.087, 0.042) decline. Conclusions: These results suggest that TDP-43 pathology plays a central role in age-related cognitive decline, terminal decline and dementia.