Life course aetiology of dementia and cognitive decline: improving causal inference

Award Number
Award Type
Research Grant
Status / Stage
1 June 2017 -
31 May 2020
Duration (calculated)
02 years 11 months
Funding Amount
Funder/Grant study page
Contracted Centre
University of Bristol
Contracted Centre Webpage
Principal Investigator
Emma Anderson
PI Contact
WHO Catergories
Understanding risk factors
Understanding Underlying Disease
Disease Type
Dementia (Unspecified)

CPEC Review Info
Reference ID252
ResearcherReside Team


Award NumberMR/P014437/1
Status / StageActive
Start Date20170601
End Date20200531
Duration (calculated) 02 years 11 months
Funder/Grant study pageMRC UKRI
Contracted CentreUniversity of Bristol
Contracted Centre Webpage
Funding Amount£315,800.64


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.


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).