Dementia is a common cause of disability, dependency, and death among older people. It affects approximately 50million people globally, with nearly 10 million new cases every year.
Previous studies have shown that individuals who take a certain class of medication, known as anticholinergics, for a long period of time, have a higher risk of developing memory decline and dementia. A strong link was found in those who used the sub-class of anticholinergics commonly used to treat a bladder symptom, known as overactive bladder (OAB), in older people. Whilst anticholinergics are the first-line drug treatment for overactive bladder, small-scale research studies suggest that there may be differences between the drugs in the extent to which they affect individuals’ risk of dementia. There is a need for a large-scale study to find out if there are indeed differences in dementia risk associated with the different drugs.
To address this important research gap, the proposed research aims to assess the link between different anticholinergic drugs used to treat overactive bladder, and the risk of dementia. Using records from CPRD, individuals with dementia will be matched with individuals of similar age, sex and general practice, without dementia. These individuals will be assessed for differences in their use of different bladder anticholinergics, as well as a non-anticholinergic overactive bladder medication. This will enable us to assess the risk of dementia associated with different anticholinergics prescribed for overactive bladder, and help doctors make safer prescribing decisions when prescribing anticholinergics to treat overactive bladder.
Background:
Anticholinergic drugs, commonly used to treat symptoms of overactive bladder (OAB) in older adults, have been found to be associated with dementia risk (1, 2). Evidence suggests that some bladder anticholinergic medication are safer than others in relation to dementia risk, but differences in the long-term effects of these drugs on dementia risk are not well defined.
Aim: To assess the association between different anticholinergic OAB drugs and risk of dementia
Design: Nested case-control study
Setting: General practices in England providing data to CPRD GOLD and Aurum databases, with linkage to secondary care records in Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records.
Study population:
Cases: Individuals aged over 55 years, with documented diagnosis of dementia and/or those with prescriptions for drugs used specifically to treat dementia (acetylcholinesterase inhibitors).
Controls: Each patient with dementia will be matched with five individuals without dementia by age, sex, general practice and calendar time using incidence density sampling.
The index date for controls will be the date of diagnosis for their matched case.
Exposure:
The primary exposure will include anticholinergic OAB drugs: darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine and trospium, and a non-anticholinergic OAB drug mirabegron, for comparison.
Covariates: Risk factors for dementia, conditions associated with anticholinergic drug use and exposure to non-bladder anticholinergic drugs, will be included as covariates in multivariable models.
Statistical analyses:
• Descriptive analyses of individuals with dementia and their matched non-dementia controls, trends over time of prescribing bladder anticholinergics, and variation in prescribing between practices and by patient characteristics.
• Conditional logistic regression analyses to estimate the odds ratios for dementia associated with different anticholinergic OAB drugs and mirabegron.
• Sensitivity analyses to assess dementia risk associated with anticholinergic exposure over different time windows, and subgroup analyses in case patients with different dementia subtypes.
• Dementia risk associated with anticholinergic OAB drugs and mirabegron
• Prescribing trends of anticholinergic OAB drugs
Barbara Iyen - Chief Investigator - University of Nottingham
Barbara Iyen - Corresponding Applicant - University of Nottingham
Anthony Avery - Collaborator - University of Nottingham
Brian Bell - Collaborator - University of Nottingham
Carol Coupland - Collaborator - University of Nottingham
Darren Ashcroft - Collaborator - University of Manchester
Delia Bishara - Collaborator - King's College London (KCL)
Martin Orrell - Collaborator - University of Nottingham
Tom Dening - Collaborator - University of Nottingham
Yana Vinogradova - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation