ORCID

http://orcid.org/0000-0003-2279-4510

Date of Award

Winter 12-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

The overall goal of this dissertation is to gain a better understanding of how Alzheimer disease relates to normal aging and cerebrovascular disease to impact neuroimaging measures in a clinically meaningful way. Both aging and cerebrovascular disease are known to influence measures of Alzheimer disease, making it difficult to separate what changes are attributable specifically to Alzheimer disease. We hypothesize that a better understanding of these relationships will allow future studies to appropriately take these factors into account. In Chapters 2 and 3 we attempt to separate out the influences of normal aging and Alzheimer disease on measures of atrophy. In Chapter 2 we show that non-linear, region-specific patterns of atrophy occur with aging, but we are not able to detect additional atrophy occurring in preclinical Alzheimer disease. Thus, preclinical Alzheimer disease is likely not confounding aging research so long as careful cognitive screening of the participants is done. In Chapter 3 we show that controlling for the age-related atrophy we describe in Chapter 2 does not improve volumetric prediction of symptomatic Alzheimer disease, likely because age-related atrophy contributes to symptoms. Despite this, volumetric predictions were still useful in detecting symptomatic Alzheimer disease in research cohorts and in patient populations. In Chapters 4 and 5 we change focus to vascular dementia, examining if cerebrovascular disease develops independently or synergistically with Alzheimer disease. In Chapter 4 we find that preclinical Alzheimer disease is not more prevalent, and thus is not a risk factor, in stroke nor in post-stroke dementia. Finally, in Chapter 5 we find that patterns of white matter hyperintensities, as a reflection of small vessel disease, have greater volumes in symptomatic Alzheimer disease relative to normal aging and preclinical Alzheimer disease. However, white matter hyperintensities could not distinguish normal aging from preclinical Alzheimer disease, leaving it unclear if white matter hyperintensities develop as a later part of Alzheimer disease or simply co-occur and have an additive effect on cognition.

Language

English (en)

Chair and Committee

Tammie LS Benzinger

Committee Members

Joshua S. Shimony

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