Both dementia and diabetes are increasingly common, costly, disabling conditions with increased mortality risk. It is well-established that diabetes confers an increased risk of dementia. Some of this link may be explained by the co-occurrence of circulation-related risk factors in diabetes (e.g. hypertension, high cholesterol and obesity) and diabetes-related complications, each of which is an independent risk factor for dementia. However, to what extent the control of blood glucose, blood pressure and cholesterol levels during the course of Type 2 diabetes (T2D) modulates this relationship is to date largely unclear. Furthermore, the temporal association between the onset of dementia and the presence of diabetes-related complications affecting small and large blood vessels is not well studied. The aim of this study is to characterise temporal changes in blood glucose, blood pressure and cholesterol during a 12-year follow-up of people with T2D, and compare metabolic changes in people who did and did not develop dementia. We also aim to determine the association between blood glucose levels, other vascular risk factors, complications of diabetes and the occurrence of dementia and its outcomes using a large national database. We will use the data to explore whether these associations differ by age, gender and ethnicity.
This study will be a retrospective open cohort study of adults with Type 2 Diabetes from the CPRD. Dementia-free adults with Type 2 Diabetes over the age of 45 years will be followed up from 1 April 2004 to 30 September 2016. The primary outcome if interest will be the diagnosis of dementia (categorised as vascular dementia, Alzheimer's dementia or other dementia). We will characterise the retrospective trajectories of glycated haemoglobin, cholesterol and blood pressure among patient who develop and those who do not develop dementia during the study period. Multilevel growth models will be utilised to compare trajectories of the metabolic parameters in the dementia and non-dementia groups. Patients will be categorised according to HbA1c, SBP, DBP and lipid measure segments and we will use survival analyses to estimate the risk of dementia by levels of metabolic parameters. Survival analyses will be used to assess the link between microvascular (retinopathy, nephropathy, neuropathy) and macrovascular disease (AMI, stroke, TIA and death due to acute CVD events) and the development of dementia. We will further assess the association between these parameters and survival after the diagnosis of dementia. Subgroup analyses by ethnicity, socio-economic deprivation, sex and the presence of hypertension will be performed.
Dementia - To ascertain the development of dementia during the study period in the initially dementia-free cohort of patients with T2D, the presence of diagnostic read codes for vascular dementia, Lewy body dementia, Alzheimer's dementia and other non-vascular forms of dementia will be identified using 1. Diagnostic read codes from primary care records; 2. Prescription data from primary care records; 3. HES data including primary and secondary diagnostic codes on admission; 4. ONS mortality data; 5. MMSE scores using primary care data. Death - Date and cause of death. Diagnostic codes will be used to triangulate dementia diagnosis. In survival analyses death-censored outcome of dementia will be examined as well as death as a competing outcome to dementia.
Christopher Millett - Chief Investigator - Imperial College London
Eszter P Vamos - Corresponding Applicant - Imperial College London
Alex Bottle - Collaborator - Imperial College London
Azeem Majeed - Collaborator - Imperial College London
Ben Griffiths - Collaborator - Imperial College London
Heidi Lai - Collaborator - Imperial College London
Lefkos Middleton - Collaborator - Imperial College London
Mahsa Mazidi - Collaborator - Imperial College London
Mansour Taghavi Azar Sharabiani - Collaborator - Imperial College London
HES Admitted Patient Care;HES Admitted Patient Care;ONS Death Registration Data;ONS Death Registration Data;Practice Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation