The influence of diet and metabolism on hippocampus and hypothalamus connectivity across the lifespan

Thesis

The high prevalence of unhealthy dietary patterns, obesity, and related brain disorders such as dementia emphasise the importance of research that examines the effect of dietary and metabolic factors on brain health. Using magnetic resonance imaging (MRI) to assess brain grey matter functional connectivity (FC) and volumes, this thesis aimed to examine the relationship between measures of diet and metabolism and the brain over the adult lifespan.

First, a systematic review was conducted, to examine the relationship between dietary and metabolic health in relation to a wide range of brain MRI markers. The reviewed evidence suggested that lower dietary and metabolic health quality was related to reduced brain volume and connectivity, especially in the default mode network and the frontal and temporal lobes, although there were contrasting trends for each of these associations.

To address the gaps identified by the review, we examined the association between dietary and metabolic health in relation to the hippocampus and hypothalamus FC and volumes in the cross-sectional Human Connectome Project cohort of 400 younger adults and in the longitudinal Whitehall II cohort of 775 midlife-older aged adults. The Whitehall cohort had longitudinal measures of diet/metabolic markers collected every 5 years throughout their midlife (40-70 years old).

First, we note that different dietary and metabolic markers have unique patterns of longitudinal trajectories from mid-to-old-age. Our findings supported the hypothesis that better dietary and metabolic health is associated with volumetric and FC differences of the hippocampus and the hypothalamus both in younger and older cohorts. Specifically, dietary and metabolic health was linked to (1) hippocampal FC with the frontal lobe, precentral gyrus, and occipital lobe and (2) hypothalamic FC with the brainstem and the basal forebrain. These findings contribute to a growing understanding of the brain networks associated with dietary and metabolic health.

The thesis provides insights into when in life dietary and metabolic health measures are related to brain health. Our findings indicated that in order to promote brain health in older age, some metabolic factors may be better targeted in midlife (e.g., cholesterol, diet, abdominal fat), while other factors should be targeted as early as possible (blood pressure, body composition/BMI). This may have implications for preventative lifestyle interventions to reduce the risk of developing dementia and to maintain overall brain health.

Authors: Jensen, DEA

• DOI: 10.5287/ora-kom4pjjj5
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: big data; hypothalamus; ageing; MRI; hippocampus; diet; connectivity