Effect of white matter hyperintensities and amyloid on neurodegenerative change and cognitive trajectory in cognitively unimpaired older adults

Abstract

AbstractBackgroundOverwhelming evidence of association between amyloidosis and neurodegeneration, particularly in the hippocampus, has been reported. However, the recognition of cerebrovascular disease (CVD), the most common comorbidity in elderly patients with dementia2, as a contributor to neurodegeneration process has remained modest. The objective of this study is to investigate the contributions of amyloidosis, as measured by amyloid PET, and CVD, as reflected by white matter hyperintensity (WMH), on neurodegenerative change and how their combination impacts cognitive trajectory in cognitively unimpaired (CU) individuals.Method139 CU participants from the University of California, Davis Alzheimer’s Disease Research Center diversity cohort received at least two cognitive assessments and underwent a PET exam at baseline, and baseline and follow‐up MRI imaging (Table 1). Z‐score measures of DVR19 and SUVR20 values were used as measure of baseline amyloid beta (Aβ) burden. Baseline WMH volume was log‐transformed and regressed against intracranial volume (TCV). Four markers of neurodegeneration were used, including hippocampal volume (regressed against TCV), mean cortical GM thickness and two cognitive‐related signature region of interest (sROI), including episodic memory and executive function. We used structural equation modeling (SEM) analyses (Figure 1) to investigate associations between cognitive performance trajectories (∼6 years), including episodic memory and executive function, and baseline Aβ, baseline WMH and change in the four neurodegeneration markers.ResultSEM analysis revealed significant effects of increased baseline Aβ and greater baseline WMH on accelerated decrease in neurodegeneration marker measures in all models (Figure 2). Increased baseline amyloid and WMH, but not neurodegenerative change measures, were also associated with accelerated decline in episodic memory performance (pvalues<0.05, Figure 2, panels A‐C‐E). Finally, increased baseline Aβ and accelerated decreased in cortical GM and sROI thickness were found to be associated with accelerated decline in executive function (pvalues<0.05, Figure 2, panels B‐D‐F).ConclusionOur findings suggest that both CVD and amyloidosis simultaneously impact neurodegenerative change and that these pathologies are associated with cognitive trajectories, but the dynamics of these trajectory are different for executive and memory, suggesting different early path of vulnerability for these domains and emphasizing the need to thoroughly understand the interaction between amyloidosis, CVD, and neurodegeneration.