Determining the causal effects of lipid levels on risk of dementia: a triangulation of the available evidence and individual participant data meta-analysis
Award Number
DRF-2018-11-ST2-048Award Type
Doctoral Research FellowshipProgramme
NIHR FellowshipsStatus / Stage
CompletedDates
1 January 2019 -31 December 2021
Duration (calculated)
02 years 11 monthsFunder(s)
NIHRFunding Amount
£293,307.00Funder/Grant study page
NIHRContracted Centre
University of BristolPrincipal Investigator
Mr Luke McGuinnessPI ORCID
0000-0001-8730-9761WHO Catergories
High quality epidemiological dataUnderstanding Underlying Disease
Disease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 111 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Award Number | DRF-2018-11-ST2-048 |
|---|---|
| Status / Stage | Completed |
| Start Date | 20190101 |
| End Date | 20211231 |
| Duration (calculated) | 02 years 11 months |
| Funder/Grant study page | NIHR |
| Contracted Centre | University of Bristol |
| Funding Amount | £293,307.00 |
Abstract
In the UK, an estimated 800000 people are currently living with dementia and this number is expected to double by 2040. Despite the number of dementia cases and decades of research, there remains much unknown about the pathogenesis and progression of the disease, and, at present, no effective treatment exists to arrest or reverse the cognitive decline associated with the condition. In this context, identification of causal relationships between modifiable targets and dementia risk is central to the development of evidence-based prevention strategies and will be critically important in maintaining the long-term health of the ageing public. Blood lipid levels have been implicated in the aetiology of dementia by genetic linkage and functional cell biology studies, but current epidemiological evidence has yet to reach a consensus on their role in dementia risk. To identify, assess and integrate all available epidemiological evidence relevant to determining the causal effects of lipid levels on dementia risk, and to identify whether specific groups of individuals are more likely to benefit from modification of lipid levels than others.Methods A systematic review of the published and grey literature will be used to identify and critically assess all evidence examining lipid levels as a risk factor for incident dementia. A collaboration between existing prospective cohorts, including those reported in published studies identified through the systematic review and those containing relevant unanalysed data (e.g. the Caerphilly Prospective Study), will be established as part of this project. Using the individual participant data (IPD) from these cohorts, a two-stage IPD meta-analysis will be performed to identify patient-level characteristics that may modify the effect of lipid levels on dementia risk. Concurrently to the IPD analysis, a novel triangulation framework for aetiological epidemiology, which incorporates summary statistics from diverse methodological approaches, will be used to integrate evidence for or against a causal link between lipid levels and incident dementia. The framework will incorporate novel evidence produced as part of this project, in the form a two-sample MR study conducted using the MR-Base platform.Anticipated impact and dissemination In the absence of a cure, identification of lipid levels as modifiable risk factor with causal links to dementia would benefit NHS patients by providing an effective way of reducing their dementia risk. A preventative measure against dementia would also benefit the NHS, reducing the burden of care that is associated with the increasing prevalence of dementia. Increasing the strength of evidence for or against a causal link will also impact funding bodies. If a link is demonstrated, then funding for much need longer term RCTS of lipid-modifying treatments should be made available. If no link is found, then valuable resources can be directed towards other promising avenues of dementia research. The outputs of this study will also impact future research. An exhaustive list of studies examining lipids as a risk factor for dementia will be made available, while researchers will be able to apply for access to the collaborative IPD database established as part of the project.
Aims
To identify, assess and integrate all available epidemiological evidence relevant to determining the causal effects of lipid levels on dementia risk, and to identify whether specific groups of individuals are more likely to benefit from modification of lipid levels than others.