Date of Award

2017

Degree Type

Thesis

Department

Interdisciplinary Studies

First Advisor

Peter J. Snyder

Abstract

The objective of this thesis was to determine the association among a cardiac workload marker (the rate pressure product [RPP]), working memory, and cortical amyloid-β (Aβ) burden in 63 cognitively normal midlife adults (average age = 62.8 years-old) at risk for Alzheimer’s disease (AD).

All subjects were recruited on the basis of reporting a first-degree family history of AD as well as significant subjective memory complains. Each subjects underwent 18F-florbetapir PET imaging to measure neocortical Aβ aggregation. The PET standardized uptake values (SUV) of neocortical Aβ were summed and normalized to the whole cerebellum SUV, resulting in a region-to-cerebellum ratio (SUVr). Blood pressure and heart rate data were collected during an initial baseline visit with subjects at rest. All assessments occurred between 0800 and 0900. After the collection of these measures, all subjects completed the Groton Maze Learning Test (GMLT; www.cogstate.com). The GMLT is an iPad-administered hidden maze learning test that differentially measures both spatial working memory and reasoning/problem solving cognitive functions.

The results show a moderate positive correlation between cardiac workload (at rest) and cognitive impairment as measured by the GMLT; however, this result only holds for the 15 subjects with evidence of substantial neocortical amyloid aggregation (SUVr PET scan) (R2 = 0.30; p = .034). By comparison, no such relationship was observed for the 48 subjects without any evidence of cortical Aβ plaque burden (R2 = .02). With all 63 subjects considered together, there is a small-to-moderate relationship between neocortical Aβ burden and RPP (r = 0.261, ρ = .039), with increasing cardiac workload at rest associated with greater neocortical amyloidosis. This relationship remained significant after statistical control for body mass index (r = 0.262, ρ = .040) and age (r = .258, ρ = .043).

These results show a small-to-moderate relationship between increasing myocardial oxygen use (at rest) and neocortical amyloidosis in individuals at the preclinical stage of AD.

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