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Lifestyle factors, metabolic dysfunction and dementia

Dementia is a highly disabling syndrome characterized by progressive decline in cognitive functions, including memory, abstract thinking and judgment. In later stages dementia results in total dependency, frailty and eventually death. Alzheimer’s disease (AD) is the dominant subtype of dementia accounting for more than 60% of all cases, followed by vascular dementia (10-20%) and mixed type dementia. 

Currently, more than 800,000 people in the UK live with dementia. As well as the huge personal cost, dementia costs the UK economy £23 billion per year, which is more than cancer and heart disease combined. Additionally, 25 million people in the UK have a family member or a close friend with dementia. 

As population rates of older people are increasing and if prevention and treatment strategies remain unchanged, it is estimated that 42 million worldwide will suffer from dementia by 2020. However, if we manage to delay the onset of Alzheimer’s disease by just 5 years, we could then cut the prevalence rates in half. Therefore, the identification of potentially modifiable risk factors becomes a priority and it will have substantial impact on the clinical, social and economic level.

Increasing age is the main risk factor for the development of dementia. A number of risk factors have been examined including physical activity, smoking, obesity and diabetes. Other lifestyle and metabolic factors may be particularly important in dementia risk, but findings are not entirely consistent and there is a shortage of high quality syntheses on these topics, including both systematic reviews and meta-analyses. Also, evidence from large well-designed cohort studies may aid our understanding and clarify associations with dementia. Research has identified three risk factors with promising results in previous studies, but either no systematic reviews have been published to synthesize and evaluate this evidence or additional evidence from large cohorts to support existing literature is needed before we draw any conclusions.

These potentially modifiable risk factors are:

  • Adherence to a Mediterranean diet
  • Parathyroid hormone
  • Total cholesterol levels

To fill this gap in the literature and as a main objective of the PhD, two systematic reviews will be conducted to investigate the potential association between dementia and Mediterranean diet and parathyroid hormone.  Each systematic review will be followed by a meta-analysis where data allow it.  Additionally, two prospective analyses using data from large cohort studies will investigate further the relationship of total cholesterol levels and parathyroid hormone to dementia risk.  A secondary objective is to address the methodological challenges that often arise from the comparison of different measures of outcome in cognitive decline and dementia. For example, a variety of tools have been used in cognitive assessment due both to varying disciplinary approaches and to scientific and theoretical developments over time. 

The first systematic review examined the association between adherence to Mediterranean diet and cognitive function or dementia. More information can be found here.

Ilianna Lourida
Supervised by: Dr David Llewellyn, Dr Jo Thompson-Coon, Prof Chris Dickens

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