Cerebral Blood Flow and Amyloid-β Interact to Affect Memory Performance in Cognitively Normal Older Adults

Cerebral blood flow (CBF) alterations and amyloid-beta (A beta) accumulation have been independently linked to cognitive deficits in older adults at risk for dementia. Less is known about how CBF and A beta may interact to affect cognition in cognitively normal older adults. Therefore, we examined potential statistical interactions between CBF and A beta status in regions typically affected in Alzheimer's disease (AD) within a sample of older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Sixty-two cognitively normal participants (mean age = 72 years) underwent neuroimaging and memory testing. Arterial spin labeling magnetic resonance imaging was used to quantify CBF and florbetapir PET amyloid imaging was used to measure A beta deposition. A beta status (i.e., positivity versus negativity) was determined based on established cutoffs (Landau et al., 2013). The Rey Auditory Verbal Learning Test was used to assess memory. Linear regression models adjusted for age, education, and sex, demonstrated significant interactions between CBF and A beta status on memory performance. Among A positive older adults, there were significant negative associations between higher CBF in hippocampus, posterior cingulate, and precuneus and poorer memory performance. In contrast, among A beta negative older adults, there were no significant associations between CBF and cognition. Our findings extend previous CBF studies of dementia risk by reporting interactions between A beta status and CBF on memory performance in a sample of well-characterized, cognitively normal older adults. Results suggest that differential CBF-cognition associations can be identified in healthy, asymptomatic A beta positive older adults relative to A beta negative individuals. Associations between higher CBF and poorer memory among A beta positive older adults may reflect a cellular and/or vascular compensatory response to pathologic processes whereby higher CBF is needed to maintain normal memory abilities. Findings indicate that CBF and its associations with cognition may have utility as a reliable marker of brain function early in the AD process when interventions are likely to be beneficial.