Fatih, Nasrtullah;
(2024)
Sex differences in the relationship between
glycaemic traits and brain and cognitive health.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Evidence shows that diabetes is a risk factor for dementia.1 But how diabetes-related mechanisms affect brain health in the general population is still poorly understood. Answering this entails examining whether glycaemia and its related markers are associated with specific brain changes (e.g., Alzheimer’s disease-like pathology, damage to the brain’s microvasculature) or cognitive impairments. In line with the growing evidence highlighting important sex differences in metabolic and neurological health, these associations were examined separately in males and females. To combine different scientific approaches (e.g., using genetics and time-sensitive mediation analysis) when examining these relationships, two different samples with unique characteristics and phenotyping, National Survey of Health and Development and UK Biobank, were used. In National Survey of Health and Development, poorer glycaemia and insulin resistance were associated with lower brain volume measures in females but not in males. This relationship was not mediated by systemic inflammation. In the UK Biobank sample, glycaemia-brain volume associations appeared to be non-linear with both low and high glycaemia being associated with smaller brain volumes. There were some suggestions of increased susceptibility in these relationships for females although analysis was complicated by the non-linear associations observed. A polygenic risk score for glycaemia was not convincingly associated with imaging markers of brain health, although the weakness of the genetic instrument limited the conclusions that could be drawn. There were no convincing associations between glycaemia and cognitive outcomes in either sample.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Sex differences in the relationship between glycaemic traits and brain and cognitive health |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10196381 |
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