Principal Investigator: Professor John Gallacher
Institution: University of OxfordTags: 15697, cognition, Dementia, Lifestyle Ageing, neurodegeneration
1) University of Cambridge, Public Health and Primary Care, Forvie Site, Robinson Way, Cambridge, CB2 0SR, United Kingdom
2) University of Edinburgh, Centre for Clinical Brain Sciences, Chancellor’s Building (room FU303), 49 Little France Crescent, Edinburgh, EH16 4SB, United Kingdom
3) University College London, Dementia Research Centre, NHNN, 8-11 Queen Square, London, WC1N 3BG, United Kingdom
4) Cardiff University, Psychological Medicine, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, United Kingdom
5) Imperial College London, Division of Brain Sciences, Department of Medicine, Hammersmith Hospital, DuCane Road, London, W12 0NN, United Kingdom
6) Swansea University, College of Medicine, Singleton Park, Swansea, SA2 8PP, United Kingdom
1a: The MRC Dementias Platform UK (DPUK) is a multi-cohort collaboration. This proposal is to use UKB data alongside that of other cohorts to investigate the determinants of dementia. To do this we will need to compare cognitive and lifestyle data in those with and without dementia. We will need to take account of co-morbidities, family history, genetics imaging and biomarkers.
1b: Dementia is a major public health problem and one of the chronic diseases that UKB was established to investigate
1c: We will compare risk factors for dementia prevalence and incidence within cohorts and between cohorts. This is a statistical analysis of existing data.
UKB will be used to generate hypotheses which will be tested in confirmatory analyses using other DPUK cohorts.
1d: full cohort
We will use standard regression techniques to investigate how lifestyle (alcohol, diet, smoking exercise, deprivation) are related to cognitive decline and dementia. These analyses will require access to a broad range of covariates to adjust for confounding and identify mediating variables.
Genetic data will be used in two ways. First as a means of identifying genotype associations between lifestyle and cognitive decline. Second, as a instrumental variables for testing mechanistic hypotheses through Mendelian randomisation. Imaging data will be used to compare structural brain changes with cognitive changes and relate these changes back to lifestyle and genetics exposures.
The programme of research will develop over the next 4 years as more data become available. For this specific proposal we will focus on the impact of smoking, alcohol and exercise on dementia and cognitive function. This proposal does not require participant recontact or access to bio-samples. Not applicable The analysis will involve using the strengths and limitations of different datasets to scientific advantage. For example, using ?flat? data from UK Biobank e.g. baseline and follow-up data alongside derived imaging and genetic data to identify putative causal determinants of cognitive decline and dementia. The limitation of the UKB dataset is the short follow-up time, and so confirmatory analyses will be conducted in DPUK datasets that, although less extensive, have longer follow-up periods. Comparison cohorts include the Whitehall study and the Caerphilly study.
Similarly analyses will be conducted in DPUK cohorts, such as Whitehall and Caerphilly, to identify risks for cognitive decline and dementia. The limitations in these datasets are narrow breadth of measurement and lack of statistical power. Confirmatory analyses will conducted in the UKB dataset as it has a wide range of variables and substantial statistical power.
- Obtain UKB data (M1-6)
- Analyse UKB data (6-12)
- Access other DPUK cohort data (M13-18)
- Confirmatory analyses (M19-24)
Where previously our scope stated: “how lifestyle (alcohol, diet, smoking exercise, deprivation) “, we would like to include early brain injury, abuse and sleep within these examples.
Selected analyses will be conducted on raw brain image files within the scope of the project, e.g,
- APOE status, brain volume, diurnal variation and dementia outcomes
- APOE status, brain activity, sleep disturbances, cognitive decline
3. Deprivation, brain volume, mental health, cognition and dementia outcomes
Last updated Jun 10, 2019