Graduation Year

2021

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

School of Aging Studies

Major Professor

Brent J. Small, Ph.D.

Committee Member

Victor A. Molinari, Ph.D.

Committee Member

John A. Schinka, Ph.D.

Committee Member

Zahinoor Ismail, Ph.D.

Committee Member

Ross Andel, Ph.D.

Keywords

cognition, dementia, neuropsychiatric symptoms, older adults, risk factors

Abstract

Older age is associated with an increased risk for cognitively impairing diseases such as dementia. Despite significant research to find ways to cure this disease, there has been little success. However, a critical need when an intervention is discovered is a need to find ways to identify people who are at the greatest risk of developing dementia earlier in the disease process so that interventions can be implemented at that time. This could potentially lessen their risk or delay when they are diagnosed. Using longitudinal data from the National Alzheimer’s Coordinating Center (NACC), the aims of this current dissertation were to examine cognitive, neuropsychiatric, and neurostructural risk factors for dementia, as well as how lifestyle can mitigate this risk.

The first research question examined cross-sectional differences and longitudinal changes in cognitive performance based on the presence mild behavioral impairment (MBI), or the late-life onset of neuropsychiatric symptoms. Cognition was examined in over 17,000 participants through a battery of neuropsychological tasks that assessed one’s attention, episodic memory, executive function, language, visuospatial ability, and processing speed. Results indicated that older adults with MBI, regardless of whether they were cognitively healthy or diagnosed with Mild Cognitive Impairment (MCI), performed significantly worse at baseline on all tasks of cognition and exhibited greater longitudinal declines on tasks of episodic memory, language, and processing speed. Specifically, cognitively healthy older adults with MBI performed significantly worse on tasks of processing speed across time, and older adults with mild cognitive impairment (MCI) and MBI performed significantly worse on executive function, visuospatial ability, and processing tasks across time. Overall, MBI was related to poorer cognitive performance cross-sectionally and longitudinally.

For the second research question, the interaction between volumes of various brain regions and MBI and performance on cognitive tasks was evaluated. The brain regions examined in almost 2,000 participants included total brain gray matter, total brain white matter, total cerebrum brain, total cerebrum gray matter, total cerebrum white matter, frontal lobe, parietal lobe, temporal lobe, occipital lobe, hippocampal, parahippocampal, entorhinal cortex, caudal anterior cingulate cortex, and rostral anterior cingulate cortex volumes. There were significant differences in cognitive performance found based on one’s MBI and MCI status, as well as the volumes of a specific brain region. The results for these analyses indicated that cognitively healthy participants with MBI performed worse on attention tasks because of the volume of the rostral ACC. They also suggested that older adults with MCI, but no MBI performed worse on processing speed tasks due to total brain white matter and total cerebrum white matter volumes. These participants were also found to perform worse on executive function tasks due to total brain white matter volumes.

Finally, in the third research question, we examined risk for dementia, Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) based on one’s MBI and MCI status. Results of these analyses suggest that there is an increased risk for dementia, and each of the diagnoses, in people who have MBI. Further, participants who are cognitively healthy with MBI are at the greatest risk for FTD, where those with MCI and MBI are at the greatest risk DLB. In this research question we also examined how one’s lifestyle can influence risk. Here, we found that unhealthy lifestyles increase the risk for dementia and AD, but not for DLB or FTD.

Overall, the findings from this dissertation suggest that MBI significantly influences multiple aspects of cognition and increases the risk for dementia. Further, the results suggest that lifestyle plays an important role in risk for AD, but not DLB or FTD. Future research should continue to examine how MBI influences cognition over time, how MBI is related to various brain structures, and how each of these factors influences risk for dementia. Further, research should examine how identifying people with MBI could be utilized in practice to identify people in the prodromal stages of dementia. Finally, future research should examine interventions that could be utilized to improve one’s lifestyle in an attempt to mitigate risk for dementia.

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