Integrated investigation of dementia risk factors : insights from geography, record linkage, and individual participant meta-analysis
Russ, Thomas Charles
Dementia is a public health priority and its importance is projected to increase in coming decades, particularly in low-to middle-income countries. A description of the methodological challenges of observational studies and the limitations of previous attempts to combine the published literature leads me to discuss ascertainment of dementia cases and the suitability of dementia mortality as an outcome. I report the findings of a memory clinic study where 71.5% of 502 deceased individuals with probable Alzheimer dementia had dementia correctly recorded on their death certificate, which is an improvement on similar results from two decades earlier. I review the evidence for geographical variation in dementia and discuss the implication that such variation might point towards potentially modifiable risk or protective factors for dementia. I have attempted to overcome the methodological challenges alluded to above by only examining within-study comparisons. A metaanalysis of rural-urban comparisons reveals some evidence of increased prevalence (odds ratio; 90% confidence interval (CI): 1.11; 0.79, 1.57) and incidence (1.20; 0.84, 1.71) of dementia in rural areas. These associations were stronger for Alzheimer dementia and particularly so in studies which identified early life rural residence (prevalence 2.22; 1.19, 4.16; incidence 1.64; 1.08, 2.50). Since there are no effective treatments, there is an obvious need to focus on prevention and an urgent need to improve our understanding of the aetiology of dementia in order to attempt to prevent or delay its onset. However, it is clear that prevention must begin sufficiently early in life to have an effect – intervening in later life might be too late. I describe a body of work using the Health Survey for England cohort studies examining the association between a series of risk factors and later dementiarelated death, including cardiovascular disease risk factors, psychological distress, and socioeconomic status. For example, there is a dose-response relationship between increasing psychological distress and dementia death (12-item General Health Questionnaire score 1-3 vs 0 age- and sex-adjusted hazard ratio; 95% CI: 1.44; 1.17, 1.78; score 4-12 vs 0: 1.74; 1.36, 2.22). I conclude by summarising the contribution these publications have made to the field of dementia epidemiology and by outlining ongoing and future projects building on the work presented in this thesis.