Brain Amyloid Deposition and Longitudinal Cognitive Decline in Nondemented Older Subjects: Results from a Multi-Ethnic Population

Gu, Yian; Zahodne, Laura B.; Razlighi, Qolamreza R.; Janicki, Sarah Christine; Ichise, Masanori; Manly, Jennifer J.; Devanand, Devangere P.; Brickman, Adam M.; Schupf, Nicole; Mayeux, Richard Paul; Stern, Yaakov

Objective: We aimed to whether the abnormally high amyloid-β (Aβ) level in the brain among apparently healthy elders is related with subtle cognitive deficits and/or accelerated cognitive decline. Methods: A total of 116 dementia-free participants (mean age 84.5 years) of the Washington Heights Inwood Columbia Aging Project completed 18F-Florbetaben PET imaging. Positive or negative cerebral Aβ deposition was assessed visually. Quantitative cerebral Aβ burden was calculated as the standardized uptake value ratio in pre-established regions of interest using cerebellar cortex as the reference region. Cognition was determined using a neuropsychological battery and selected tests scores were combined into four composite scores (memory, language, executive/speed, and visuospatial) using exploratory factor analysis. We examined the relationship between cerebral Aβ level and longitudinal cognition change up to 20 years before the PET scan using latent growth curve models, controlling for age, education, ethnicity, and Apolipoprotein E (APOE) genotype. Results: Positive reading of Aβ was found in 41 of 116 (35%) individuals. Cognitive scores at scan time was not related with Aβ. All cognitive scores declined over time. Aβ positive reading (B = -0.034, p = 0.02) and higher Aβ burden in temporal region (B = -0.080, p = 0.02) were associated with faster decline in executive/speed. Stratified analyses showed that higher Aβ deposition was associated with faster longitudinal declines in mean cognition, language, and executive/speed in African-Americans or in APOE ε4 carriers, and with faster memory decline in APOE ε4 carriers. The associations remained significant after excluding mild cognitive impairment participants. Conclusions: High Aβ deposition in healthy elders was associated with decline in executive/speed in the decade before neuroimaging, and the association was observed primarily in African-Americans and APOE ε4 carriers. Our results suggest that measuring cerebral Aβ may give us important insights into the cognitive profile in the years prior to the scan in cognitively normal elders.


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Taub Institute
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December 14, 2015