Associations Between Microstructure, Amyloid, and Cognition in Amnestic Mild Cognitive Impairment and Dementia.

Published on Jan 1, 2020in Journal of Alzheimer's Disease3.909
· DOI :10.3233/JAD-190871
Emilie T. Reas13
Estimated H-index: 13
(UCSD: University of California, San Diego),
Donald J. Hagler88
Estimated H-index: 88
(UCSD: University of California, San Diego)
+ 7 AuthorsJames B. Brewer50
Estimated H-index: 50
(UCSD: University of California, San Diego)
BACKGROUND: Although amyloid-beta (Abeta) and microstructural brain changes are both effective biomarkers of Alzheimer's disease, their independent or synergistic effects on cognitive decline are unclear. OBJECTIVE: To examine associations of Abeta and brain microstructure with cognitive decline in amnestic mild cognitive impairment and dementia. METHODS: Restriction spectrum imaging, cerebrospinal fluid Abeta, and longitudinal cognitive data were collected on 23 healthy controls and 13 individuals with mild cognitive impairment or mild to moderate Alzheimer's disease. Neurite density (ND) and isotropic free water diffusion (IF) were computed in fiber tracts and cortical regions of interest. We examined associations of Abeta with regional and whole-brain microstructure, and assessed whether microstructure mediates effects of Abeta on cognitive decline. RESULTS: Lower ND in limbic and association fibers and higher medial temporal lobe IF predicted baseline impairment and longitudinal decline across multiple cognitive domains. ND and IF predicted cognitive outcomes after adjustment for Abeta or whole-brain microstructure. Correlations between microstructure and cognition were present for both amyloid-positive and amyloid-negative individuals. Abeta correlated with whole-brain, rather than regional, ND and IF. CONCLUSION: Abeta correlates with widespread microstructural brain changes, whereas regional microstructure correlates with cognitive decline. Microstructural abnormalities predict cognitive decline regardless of amyloid, and may inform about neural injury leading to cognitive decline beyond that attributable to amyloid.
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