Date of Award

Summer 8-18-2023

Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)




Fayeza Ahmed

Second Committee Member

Emily Haigh

Third Committee Member

Bruce Hermann

Additional Committee Members

Rebecca MacAulay

Michael Robbins


Dementia is defined as gradual, progressive loss of cognitive functioning, greater than what is expected of normal aging, resulting in functional impairment. There are several types of dementia clinical syndromes that are accompanied by unique patterns of cognitive dysfunction and neuropathological changes. Alzheimer’s disease (AD) is the most common type of clinical dementia syndrome, accounting for approximately 60-70% of cases. Neuropathological mechanisms associated with AD include the disruption of the cholinergic system, accumulation of amyloid-beta plaques and hyperphosphorylated tau, as well as vascular pathology. Vascular pathology complicates the characterization of clinical and neuropathic changes in AD, as there becomes significant overlap with vascular dementia clinical presentation and pathology. Furthermore, many people with dementia have “mixed dementia,” or brain changes associated with more than one cause of dementia. This may contribute to the difficulty establishing effective pharmacological interventions to reverse or prevent future neurodegeneration. As a result, research examining modifiable risk factors to prevent neuropathological changes associated with dementia, including AD, has become of interest. Modifiable risk factors include physical activity, sleep, alcohol and tobacco use, and nutrition. Diet has been proposed to reduce risk of AD via neuroinflammatory mechanisms, oxidative stress, and by reducing risk for other comorbid medical conditions (e.g., vascular disease, diabetes, hypertension). There is limited research in the examination of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and cognition, longitudinally, in a middle-aged sample, as well as the potential moderating effect of APOE genotype, of which the e4 allele confers increased risk for AD. The current proposal provides a literature review of AD, including cognitive and neuropathological changes, as well as AD vascular factors, and diet as a modifiable risk factor.

The proposed study aimed to examine the longitudinal effects of nonmodifiable risk factors (age, gender, APOE genetic status) and modifiable risk factors (MIND diet adherence and physical health) on cognition; furthermore, to determine if APOE genetic status modifies the relationship between MIND diet and cognition, longitudinally. Participants included middle-aged adults with a family history of AD enrolled in the Wisconsin Register for Alzheimer’s Prevention (WRAP) study. Latent Growth Curve (LGC) modeling was conducted to examine aims, assessing change across three visits (Visit 4 through Visit 6). Cognitive outcomes included previously established WRAP cognitive composite and factor scores. Upon examination of initial hypothesized models, empirical cognitive factor scores had significantly poorer model fit, and therefore, theoretically derived composite outcomes were used for structural modeling. Regarding physical health, waist-to-hip ratio (WHR) significantly reduced structural model fit across all cognitive outcomes, and therefore, WHR as a predictor of cognition was removed from analyses. Nonparametric correlations revealed, as expected, that WHR was negatively correlated with all cognitive outcomes (theoretical and empirical cognitive outcomes). Regarding diet, MIND diet adherence had unexpected significant negative effects on Theoretical Executive Functioning (TEF) growth over time; however, APOE risk scores did not significantly moderate this relationship. Improving the understanding of causative relationships among underlying hypothesized mechanisms of dietary benefits on cognition and AD risk is crucial to reduce the burden of AD. The null findings highlighted important gaps in the literature that warrant additional investigation, including further examination of these relationships in cognitively and demographically diverse individuals and exploration of cognitive phenotypes associated with APOE risk.