Brief Description of the Project
Title: Infection-Related Hospitalisation, Leukocyte Telomere Length, and Dementia: A Causal Mediation Analysis
Overview:
This project investigates whether leukocyte telomere length (TL) mediates the association between infection-related hospitalisation and dementia risk. Previous research has linked infection-related hospitalisation to an increased risk of dementia, yet the biological mechanisms remain unclear. Telomere attrition, an indicator of biological aging and immune senescence, is hypothesised as a mediator in this relationship.
Objectives:
1. Infection-Related Hospitalisation and TL: Examine whether severe infections requiring hospitalisation influence TL and attrition over time.
2. TL and Dementia Risk: Assess whether shorter TL is associated with a higher risk of developing dementia.
3. Mediation Analysis: Determine whether TL mediates the effect of infection-related hospitalisation on dementia onset.
Methods:
The study will utilise longitudinal data from the National Survey of Health and Development (NSHD) and UK Biobank, both of which contain linked hospitalisation records and TL measurements. Three sub-studies will be conducted:
* Study 1: A retrospective cohort study assessing infection-related hospitalisation and TL.
* Study 2: A retrospective cohort study on TL and dementia incidence.
* Study 3: A mediation analysis quantifying the indirect effect of infection-related hospitalisation on dementia via TL.
Statistical methods will include linear regression, Cox proportional hazards models, and counterfactual mediation analysis.
Expected Outcomes:
This research will clarify the role of TL in dementia pathogenesis and help identify at-risk individuals earlier. Findings may inform interventions targeting telomere preservation to mitigate dementia risk.
