Preventive potential of diet in the pre-clinical phase of Alzheimer’s disease symptomatology

Projections estimate 131.5 million will be living with dementia by the year 2050. Alzheimer’s disease is the leading cause of dementia, accounting for 60-70% of all cases and is a global public health priority. Alzheimer’s disease (AD) risk increases with age and lacks efficacious drugs. Pharmacological treatment is failing, leading to a growing body of research investigating the preventative potential of modifiable lifestyle risk factors, such as diet. Summaries of the existing evidence reveal an association between Mediterranean-style diet adherence and reduced AD incidence; however, no review has investigated this relationship with respect to the hallmark AD biomarkers that manifest decades prior to clinical symptomatology. Amassed evidence indicates associations between diet and Alzheimer’s disease may occur through biomarker pathways such as amyloid-β; however, very few studies have investigated dietary/ amyloid-β relationships and prior to this thesis, no study has investigated this relationship in a female only cohort. Chapters 1 and 2 examined the current literature regarding diet-AD relationship. Previous evidenc from systematic review suggests a relationship between dietary adherence and Alzheimer’s risk; however, this thesis provided the first meta-analytic evidence of this relationship extending to the prodromal phase of neuropathological change. A comprehensive systematic review and meta analysis into diet and Alzheimer’s biomarkers found a small but significant effect of diet on AD biomarkers. This review supported the notion that diet and nutrition display therapeutic potential for non-pharmacological lifestyle intervention. Chapters 4 and 5 investigated the changing nutritional and dietary habits of Australian ageing women over time. Participants from the longitudinal Women’s Healthy Ageing Project completed assessments, including a validated food frequency questionnaire, at two time-points 14 years apart (1998 and 2012). Energy intake significantly decreased over time, whilst energy-adjusted total fat, saturated fat, monounsaturated fat and cholesterol intakes all significantly increased. Three dietary patterns were identified at both time points; two ‘healthy-type’ patterns as well as a third less healthy pattern. In these women, although some participant’s dietary pattern remained largely stable over time, the majority of women underwent dietary pattern change over this time in their lives. Chapter 6 presented a cross-sectional analysis of the relationship between dietary pattern adherence and beta-amyloid deposition in participants of the Women’s Healthy Ageing Project. Adherence to the Junk Food dietary pattern was found to be a significant predictor of cerebral amyloid-β deposition, highlighting the importance of diet as a potentially modifiable lifestyle risk factor in the preclinical phase of Alzheimer’s disease. This thesis presented the first systematic review and meta analysis analysing diet-Alzheimer’s relations in the preclinical, neuropathological stage of disease progression. Given accumulated evidence of a diet-Alzheimer’s pathway in the hallmark biomarkers of this disease, this thesis was the first to examine this relationship in a female only cohort, at a much greater risk than their male counterparts. The results of this thesis, in concert with previous literature, suggest diet has a substantial role in preclinical Alzheimer’s disease progression and displays significant therapeutic potential as a low-cost, accessible and effective modifiable lifestyle risk factor. However; it is clear that the complex connection between diet and brain health requires further research to elucidate the underlying mechansisms governing this relationship