Life course aetiology of dementia and cognitive decline: improving causal inference
Award Number
MR/P014437/1Award Type
FellowshipProgramme
Research GrantStatus / Stage
ActiveDates
1 June 2017 -31 May 2020
Duration (calculated)
02 years 11 monthsFunder(s)
MRC (UKRI)Funding Amount
£315,800.64Funder/Grant study page
MRC UKRIContracted Centre
University of BristolContracted Centre Webpage
Principal Investigator
Emma AndersonPI Contact
Emma.Louise.Anderson@bristol.ac.ukPI ORCID
0000-0002-1508-0598WHO Catergories
Understanding risk factorsUnderstanding Underlying Disease
Disease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 252 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Award Number | MR/P014437/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20170601 |
| End Date | 20200531 |
| Duration (calculated) | 02 years 11 months |
| Funder/Grant study page | MRC UKRI |
| Contracted Centre | University of Bristol |
| Contracted Centre Webpage | |
| Funding Amount | £315,800.64 |
Abstract
Existing evidence for modifiable risk factors for dementia is inconsistent. This is perhaps unsurprising given the , such as the potential for reverse causation and selection bias. The overall aim of the proposed work is to improve understanding of the causal determinants of, and mechanistic pathways to, dementia and cognitive decline, using novel analytical approaches and cross-cohort comparisons. I will improve causal inference in Mendelian randomisation studies of dementia by using simulation analyses to investigate and apply methods for dealing with selection bias. I will assess whether people at increased genetic risk of Alzheimer’s (based on a polygenic risk score) have different life course trajectories of cognitive capability than people not at increased genetic risk. I will use novel statistical methods (such as Mendelian randomisation, offspring instrumental variable analysis and bivariate multilevel modelling) to identify causal risk factors for dementia and cognitive decline across the life course and use novel mediation methods (such as network Mendelian randomisation, counterfactual, decomposition and G computation) to assess possible mediation by circulating metabolites. The triangulation of research findings across different analytical methods and across cohorts in different settings is novel and will increase confidence in my findings. I will use data from cohorts within Dementias Platform UK, the Avon Longitudinal Study of Parents And Children (UK), EPIPorto (Portugal) and The HUNT Study. This work has the potential to inform preventive strategies, which is important given the rising economic burden of the ageing population and because current treatments are unable to delay the onset of, or cure, dementia.
Aims
My project aims to characterise if and how people at increased genetic risk of dementia differ in terms of their cognitive capability across the whole life course. For example, do people with increased genetic risk of dementia achieve lower grades at school and achieve a lower cognitive peak in early life? Do they start to decline cognitively at an earlier age, or at a faster rate than people who are not at increased genetic risk of dementia? My project also aims to identify causal risk factors for dementia by employing state of the art analytical approaches and by studying many different groups of people (cohorts).