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P1‐414: ASSOCIATION OF BRAIN MICROSTRUCTURE AND AMYLOID‐β WITH COGNITIVE DECLINE IN EARLY ALZHEIMER'S DISEASE
Author(s) -
Reas Emilie T.,
Hagler Donald J.,
White Nathan,
Kuperman Joshua,
Bartsch Hauke,
Wierenga Christina,
Galasko Douglas R.,
Dale Anders M.,
Banks Sarah Jane,
Mcevoy Linda,
Brewer James B.
Publication year - 2019
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.2019.06.1019
Subject(s) - cognitive decline , cognition , dementia , amyloid (mycology) , white matter , psychology , alzheimer's disease , effects of sleep deprivation on cognitive performance , cerebral amyloid angiopathy , pittsburgh compound b , medicine , neuroscience , pathology , disease , magnetic resonance imaging , cognitive impairment , radiology
Background: Amyloid-b accumulates in early stages of Alzheimer’s disease (AD) and is thought to contribute to neurodegenerative processes leading to cognitive impairment. Microstructural compromise to gray and white matter, measurable with diffusion imaging, correlates with cognitive decline in AD, though the role of amyloid in the microstructural events contributing to cognitive impairment is uncertain. We used the advanced diffusionMRI technique restriction spectrum imaging (RSI) to examine associations of amyloid-b and brain microstructure with longitudinal cognitive decline in early AD. Methods: Thirty-six participants, including 23 healthy controls and seven individuals with mild cognitive impairment and six with mild AD, aged 63-91 years, completed cognitive assessment and RSI from 2013-2016 and returned for cognitive re-evaluation an average of 3.5 years later. Participants underwent lumbar puncture to measure CSF amyloid-b-42 and amyloid-b-40, and individuals were classified as amyloid-positive (N 1⁄4 23; amyloid-b-42 < 0.30 ng/ml) or amyloid-negative (N 1⁄4 13). Partial correlations were computed between amyloid-b and cognitive tests scores, or annualized cognitive change scores. Linear regressions tested whether amyloid-b or RSI measures predicted cognitive function or rates of decline. Partial correlations, stratified by amyloid status, were computed between RSI and cognitive measures, or cognitive change scores. Results: Lower amyloid-b-42 levels correlated with worse global cognitive function and delayed recall, and greater dementia severity, and amyloid-positive individuals demonstrated impairment in these measures. Amyloid-b-42 positively correlated with restricted isotropic diffusion in several white matter tracts. Restricted diffusion and isotropic free water diffusion better predicted cognitive function and longitudinal cognitive decline than amyloid-b. RSI measures more strongly correlated with cognitive function and rates of cognitive decline for amyloid-positive than amyloid-negative individuals. Conclusions: This study suggests that cognitive decline in early AD is more strongly linked to microstructural compromise than amyloid-b, and that the association between brain microstructural changes and cognitive impairment is stronger for individuals with elevated amyloid-b accumulation. RSI measures of brain microarchitecture may be valuable indicators of future cognitive decline, particularly for individuals in preclinical AD. Future research will help to clarify the modulating role of amyloid-b on microstructural compromise precipitating AD progression.