Dementia impacts adversely on the quality of life of affected individuals and their families. On average, people worry more about cognitive decline and dementia than any other condition as they age. There is currently no reliable restorative medical treatment for cognitive impairment, which means there is substantial interest in finding preventive and tractable solutions to lower risk of dementia, and delay age of onset.
Cardiometabolic and cardiac conditions (e.g. diabetes and atrial fibrillation, respectively) have each been associated with increased risk of dementia, however it is rare to have large enough data samples to ask key questions with any degree of confidence, such as: if you have one of each, is the added risk more than the sum of their individual, added parts? (i.e. ‘synergistic’). Is the added risk different depending on individual demographics such as age at onset/duration/severity of conditions, sex, deprivation, mental health conditions, or historic medications like statins? Is the effect independent of shared physical health/dementia risk factors, including aspects of lifestyle like smoking?
This work has the potential to benefit people with cardiometabolic and/or cardiac conditions, and health service providers by increasing our understanding of how different medical characteristics and multimorbidity impacts people’s risk of dementia. In the absence of restorative ‘curing’ treatments for dementia, the public health focus should be on prevention and delaying of cognitive impairment. This information may assist health practitioners to better target services, support and interventions for patients with poor physical and/or cognitive health.
Dementia is a public health priority. It is a condition with no current ameliorative treatments and the focus is therefore prevention and delaying onset. Cardiometabolic conditions such as diabetes, hypertension and high cholesterol, as well as cardiac conditions such as heart failure and atrial fibrillation, are generally known independent risk factors. This is probably due to a variety of mechanisms including but not limited to atherosclerosis limiting blood flow to the brain; increased promotion/decreased clearance of characteristic Alzheimer’s disease amyloid beta plaques; increased neuroinflammation and ‘leakage’ of the blood-brain barrier (i.e. microhaemorrhages). There is also likely some confounding where shared risk factors underlie both physical and cognitive health.
The aim of the proposed study is to test for associations between cardiometabolic and/or cardiac health and risk of dementia; the extent to which these associations are statistically independent of other risk factors such as smoking, obesity, deprivation, medications and mental health conditions, and whether people with both cardiometabolic and cardiac conditions (vs. one alone) show synergistically vs. additively increased risk. For this population-based study, we will use primary care records, derived from general practice information systems, linked anonymously with secondary care data from Hospital Episode Statistics Admitted Patient Care data. We plan to use the linkage of these data provided by the Clinical Practice Research Datalink (CPRD) Gold and Aurum datasets.
This research will include nested case-control study of the prevalence of dementia (defined a priori by read-codes) in patients with and without cardiometabolic and cardiac conditions, investigating the relationship between baseline conditions, potential confounders (e.g. medications; mental health; deprivation) and dementias. We will use linear and conditional logistic regressions to these for these associations and interactions, similar to prior independent CPRD/dementia studies.
• Exposure: frequencies of cardiometabolic (e.g. hypertension; type-2 diabetes; high cholesterol) and/or cardiac (e.g. atrial fibrillation; heart failure) conditions (see appendix for full list).
• Outcome: dementia, categorised/derived into:
o Late-onset Alzheimer’s disease [AD; index age ≥65 years]
o Vascular dementia (any age)
o All-cause dementia(excluding read codes pertaining to familial early-onset AD).
Diagnosis/indexing of dementia will be defined as the presence in the patient’s record of any CPRD read codes for dementia as a diagnosis, symptom, or referral, or prescription for a cognitive-type medication (memantine, donepezil, rivastigmine, galantamine, or tacrine) if a code for a diagnosis of dementia was recorded within 12 months (where index date will be considered date of that prescription).
Donald Lyall - Chief Investigator - University of Glasgow
Donald Lyall - Corresponding Applicant - University of Glasgow
Bhautesh Jani - Collaborator - University of Glasgow
Claire Hastie - Collaborator - University of Glasgow
Daniel Mackay - Collaborator - University of Glasgow
Frederick Ho - Collaborator - University of Glasgow
Jill Pell - Collaborator - University of Glasgow
Jim Lewsey - Collaborator - University of Glasgow
Jordan Canning - Collaborator - University of Glasgow
Kathryn Richardson - Collaborator - University of East Anglia
Naveed Sattar - Collaborator - University of Glasgow
Terence Quinn - Collaborator - University of Glasgow
HES Admitted Patient Care;Practice Level Index of Multiple Deprivation