Bischof G, Rodrigue K, Kennedy K, Devous M, Rieck J, Park D.
Beta-Amyloid Deposition and White Matter Hyperintensities Both Contribute To Age-Related Decline in Cognition in Healthy Adults.
Human Amyloid Imaging Abstract. 2012 Jan 1;
White matter hyperintensities (WMH) increase with age and are an important marker of cerebrovascular health. Beta amyloid (AB) deposition also increases with age and is a key biomarker of Alzheimer’s disease (AD) pathology. Surprisingly,0% of cognitively-normal adults show significant AB deposition.
In this study, we examined the effect of WMH and AB burden on a range of cognitive tasks in a large sample of healthy adults (N=89; aged0-89;1.16±11.44) from the Dallas Lifespan Brain Study (DLBS). Participants underwent) high-resolution T1 MRI scanning,) FLAIR imaging and) a18F-Florbetapir PET scan. Mean cortical AB was computed by extracting AB counts across ROIs, normalized to cerebellum. WMH were reliably traced. Additionally, we traced hippocampal volume (HCV), which has been hypothesized to be negatively affected later in the cascade of AD-related neuropathology. We applied stepwise regression to examine the effects of WMH, AB and HCV (in that order) on domains of cognition including processing speed, working memory, executive functioning, reasoning and episodic memory.
Results show that both WMH and AB deposition make independent negative contributions in explaining variance associated with age-related declines in measures of processing speed, working memory, and executive function. Reasoning and episodic memory were primarily affected by WMH but not AB. After controlling for AB and WMH, HCV affected only executive function.
The findings suggest that WMH burden is a strong predictor of age-related variance in cognition. Furthermore, AB burden predicts processing speed, working memory and executive function. Memory and reasoning were less sensitive to the effects of AB and suggest that this may be related to buffering effects of knowledge on higher order cognition. We conclude that it is important to measure both WMH and AB burden in individuals as differential sources of cognitive decline with varying implications for intervention.
Supported in part by NIH grantsR37AG-006265-25,R37 AG-006265-25S1, and Alzheimer’s Association grant IIRG-09-135087. Radiotracer was generously provided to the study by Avid Radiopharmaceuticals.