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- Title
Association Between Amyloid-β, Small-vessel Disease, and Neurodegeneration Biomarker Positivity, and Progression to Mild Cognitive Impairment in Cognitively Normal Individuals.
- Authors
Nadkarni, Neelesh K; Tudorascu, Dana; Campbell, Elizabeth; Snitz, Beth E; Cohen, Annie D; Halligan, Edye; Mathis, Chester A; Aizenstein, Howard J; Klunk, William E
- Abstract
<bold>Background: </bold>We estimated the prevalence and incidence of amyloid-β deposition (A), small-vessel disease (V), and neurodegeneration (N) biomarker positivity in community-dwelling cognitively normal individuals (CN). We determined the longitudinal association between the respective biomarker indices with progression to all-cause mild cognitive impairment (MCI) and its amnestic and nonamnestic subtypes.<bold>Methods: </bold>CN participants, recruited by advertising, underwent brain [C-11]Pittsburgh Compound-B (PiB)-positron emission tomography (PET), magnetic resonance imaging, and [F-18]fluoro-2-deoxy-glucose (FDG)-PET, and were designated as having high or low amyloid-β (A+/A-), greater or lower white matter hyperintensities burden (V+/V-) and diminished or normal cortical glucose metabolism (N+/N-). MCI was adjudicated using clinical assessments. We examined the association between A, V, and N biomarker positivity at study baseline and endpoint, with progression to MCI using linear regression, Cox proportional hazards and Kaplan-Meier analyses adjusted for age and APOE-ε4 carrier status.<bold>Results: </bold>In 98 CN individuals (average age 74 years, 65% female), A+, V+, and N+ prevalence was 26%, 33%, and 8%, respectively. At study endpoint (median: 5.5 years), an A+, but not a V+ or N+ scan, was associated with higher odds of all-cause MCI (Chi-square = 3.9, p = .048, odds ratio, 95% confidence interval = 2.6 [1.01-6.8]). Baseline A+, V+, or N+ were not associated with all-cause MCI, however, baseline A+ (p = .018) and A+N+ (p = .049), and endpoint A+N+ (p = .025) were associated with time to progression to amnestic, not nonamnestic, MCI.<bold>Conclusion: </bold>Longitudinal assessments clarify the association between amyloid-β and progression to all-cause MCI in CN individuals. The association between biomarker positivity indices of amyloid-β and neurodegeneration, and amnestic MCI reflects the underlying pathology involved in the progression to prodromal Alzheimer's disease.
- Subjects
MILD cognitive impairment; NEURODEGENERATION; MAGNETIC resonance imaging; POSITRON emission tomography; OXYGENATORS
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2019, Vol 74, Issue 11, p1753
- ISSN
1079-5006
- Publication type
journal article
- DOI
10.1093/gerona/glz088