Date of Award

2025

Document Type

Thesis

Publisher

Edith Cowan University

Degree Name

Doctor of Philosophy

School

School of Medical and Health Sciences

First Supervisor

Warnakulasuriya Mary Ann Dipika Binosha Fernando

Second Supervisor

Ralph Martins

Third Supervisor

Samantha Gardener

Fourth Supervisor

Stephanie Rainey-Smith

Abstract

Diet has been shown to impact both depression and Alzheimer’s disease (AD), while depression itself is comorbid with AD and increases future risk of developing the disease. Therefore, further elucidating this intricate relationship and determining how diet influences AD, as well as symptoms of depression and anxiety, is of great importance, particularly for older adults. Following a critical narrative review (Chapter 2), the first aim of this thesis was to examine whether diet moderates the relationship between symptoms of depression and anxiety, and cognitive performance cross-sectionally (Chapter 3). This was explored across three dietary patterns: Mediterranean Diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), and Western diet. The results showed that in males with low to moderate MeDi adherence, greater depressive symptoms were associated with poorer attention and processing performance. Similarly, in males with high Western diet adherence, greater anxiety symptoms were associated with poorer performance on a Preclinical Alzheimer's Cognitive Composite (PACC).

The second and third aims of this thesis were to investigate dietary patterns as potential moderators of the relationship between symptoms of depression and anxiety, and AD-related neuroimaging and blood-based biomarkers (Chapter 4 and 5, respectively). The results of Chapter 4 revealed that among individuals with lower DASH diet adherence, greater depressive and anxiety symptoms were associated with higher brain amyloid-β (Aβ) load, a hallmark of AD pathogenesis. Notably, the anxiety association was observed both in the cohort as a whole and in Apolipoprotein E (APOE) ε4 allele carriers, a genetic risk factor for AD. Chapter 5 showed that in males with mean MeDi adherence, depressive symptoms were associated with higher plasma neurofilament light (NfL) levels, a blood-based biomarker of neurodegeneration. Additionally, in APOE ε4 non-carriers with below mean and mean MeDi adherence, depressive symptoms were associated with higher plasma NfL levels.

The final aim of this thesis investigated dietary patterns as moderators of the relationship between depression and anxiety symptomology, and cognition, over time (Chapter 6). In males with mean or below mean MeDi adherence, increasing depressive symptoms were associated with faster cognitive decline, as measured by PACC. Furthermore, APOE ɛ4 carriers with mean MeDi adherence showed greater decline in language with increasing depressive symptoms. Below mean DASH adherence was associated with greater decline in PACC scores as anxiety symptoms increased, in APOE ɛ4 non-carriers. Moreover, in males, higher Western diet adherence was associated with greater cognitive decline as depressive symptoms increased.

Collectively, the results presented in this thesis highlight dietary patterns as potential moderators of the relationship between symptoms of depression and anxiety, cognition, and AD biomarkers. The findings also highlight the need for considering dietary approaches to mental health and AD prevention that are tailored to the individual on the basis of APOE genotype and sex. Chapter 7 of this thesis discusses the implications of these findings in greater detail, as well as considering future research directions.

DOI

10.25958/88cb-h728

Access Note

Access to this thesis is embargoed until 16th January 2029

Available for download on Tuesday, January 16, 2029

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