Currently, there is no targeted treatment available for vascular dementia, the second most common type of dementia, leading to a pressing need to prevent vascular dementia. People with vascular dementia usually have other complex health conditions, and this contributes to them having a shorter life expectancy compared to people with Alzheimer's.
Recent studies from the US and China suggest thiazolidinediones (TZDs), a class of diabetes drugs, have the potential to reduce the chances of developing all types of dementia in people with type 2 diabetes. However, previous studies are limited because they did not consider underlying health conditions and treatments for vascular dementia and only studied limited populations. Therefore, results cannot be applied to a broader population.
Therefore, we hypothesise that TZDs can protect the brain by preventing vascular disease and thereby prevent vascular dementia. We will use new methods to investigate the association between TZD use and the chance of developing vascular dementia in people with type 2 diabetes identified using the GP records, CPRD Aurum. Then, we will evaluate how changes in diabetes treatments and their dose over time are related to risks for developing vascular dementia.
Our project is expected to discover whether existing antidiabetic drugs can be used to prevent other diseases that they were not originally intended to use. The evidence may support future clinical studies testing the impacts of TZD on people with cognitive function and/or vascular dementia. Consequently, this research can lead to quicker and less expensive drug development to prevent vascular dementia.
Background: Vascular dementia is the second most common type of dementia that has no targeted treatments available, and its complex underlying cardiovascular and cerebrovascular comorbidities contribute to a shorter lifespan than those with Alzheimer's disease. TZDs, a class of oral antihyperglycemic agents, have shown a reduced risk of all-cause dementia and vascular dementia in people with type 2 diabetes mellitus (T2DM). However, existing evidence on TZD use and vascular dementia is limited by methodological issues in assessing drug exposure, comorbidities and treatments driving vascular dementia, and results have limited generalisability.
Aims: This study aims to investigate (1) the association between baseline TZD use and the incidence of vascular dementia among people with T2DM and (2) how changes in antidiabetic treatments and their dose over time (e.g., TZDs and metformin) associated with subsequent risk of vascular dementia in T2DM.
Methods: We will perform a retrospective cohort study using the UK CPRD Aurum database. This project will include adults (ageā„18 years) with a new onset T2DM without dementia between 01/01/2003 and 31/12/2023. The primary outcome will be incident vascular dementia, with secondary outcomes being mixed dementia and Alzheimer's disease. We will analyse objective (1) using flexible parametric survival models that account for competing events (e.g., death obtained from linked data), preventing vascular dementia from onset. We will subsequently assess medications every six months and analyse objective (2) using a landmark model. This original work will provide more robust evidence of the link between TZD use and the risk of vascular dementia.
Expected outcome: We will build a fundamental theoretical knowledge underpinning the development of drug repurposing, which may foster cost-effective and fast-track drug development. The evidence may support further randomised clinical trials testing the clinical and cost-effectiveness of TZD on cognitive and/or vascular dementia outcomes in people with T2DM.
Incident vascular dementia; Incident mixed dementia; Incident Alzheimer's disease
Joyce (Yun-Ting) Huang - Chief Investigator - University of Manchester
Joyce (Yun-Ting) Huang - Corresponding Applicant - University of Manchester
- Collaborator -
David Jenkins - Collaborator - University of Manchester
Li-Chia Chen - Collaborator - University of Manchester
Martin Rutter - Collaborator - University of Manchester
ONS Death Registration Data;Patient Level Index of Multiple Deprivation