Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)


Healthcare Genetics

Committee Chair/Advisor

Sara M. Sarasua

Committee Member

Jane M. DeLuca

Committee Member

Nicole J. Davis

Committee Member

Chang-En Yu

Committee Member

Stephen M. Thielke


Objectives: Alzheimer’s disease-related dementia is a devastating neurodegenerative disease that affects millions of people. The goal of this work is to investigate biological mechanisms such as weight loss and mitochondrial function that can serve as prognostic factors for dementia, healthy aging, and longevity.

Methodologies: This work consists of two separate systematic literature reviews, and an investigational study. The first review examined existing studies on weight trends in dementia. The second review investigated the role of mitochondria and its associated gene TOMM40 in aging. The third paper included a nested case control analysis of weight change patterns before and after diagnosis with dementia while controlling for genetic risk factors.

Results: The first literature review revealed that weight loss can be detected at least a decade prior to a diagnosis of dementia, and weight loss continued after diagnosis. The second review on genetic variants in the TOMM40 gene found associations with longevity, cognitive function, and body mass index. A statistical analysis of 11,000 participants from the Health and Retirement Study revealed that people who lost weight in middle to late age had a two-fold increased risk of developing dementia even after adjusting for APOE gene variants, and genetic predictors for longevity and body mass index.

Conclusions: Although the review suggested that polymorphisms in genes APOE and TOMM40 are associated with changes in cognition, BMI, and longevity; the analysis suggested that weight loss in dementia is an independent biological process. Pre-dementia weight loss may be useful for predicting future incidence of cognitive decline.

Author ORCID Identifier




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