Overactive bladder is increasingly common as people age and can severely affect quality of life. It is often treated with medications called ‘anticholinergics’ or ‘antimuscarinics’, but some studies have associated these with memory problems and a higher risk dementia if used for a long time.
However, we don’t know whether these medications actually cause this increased risk or are simply used more often in people already at risk of dementia. We also don’t know how the risk varies among different patient groups or types of anticholinergics.
Data from medical records are increasingly used for dementia research, but there are challenges in their use. Dementia diagnoses can be delayed, not made at all, or not promptly communicated across healthcare services, so this needs careful analysis.
We will analyse the general practitioner (GP) and hospital records of >700,000 patients aged ≥50 years in England prescribed bladder anticholinergics. We will examine whether, all other factors being equal, patients taking long-term bladder anticholinergics develop dementia more often than patients with only a single prescription. We will then estimate how this risk varies by duration of treatment, for specific patient groups, and for specific bladder drugs. As we also don’t fully understand how these medications affect the brain, we will also examine whether delirium or fractures are more common with longer term use of bladder anticholinergics.
This study will help patients and doctors to make more informed choices regarding treatments for bladder problems, balancing the benefits that they experience with any risks there might be.
Previous studies suggest that long-term overactive bladder (OAB) anticholinergic use may increase dementia risk, however studies suffer from residual confounding and protopathic bias. This topic requires more detailed investigation and as identified by the National Institute of Health and Care Excellence.
Aims
1. To describe OAB medication prescriptions trends in England between 2000-2019, by sex and age group.
2. To test whether recurrent OAB anticholinergic prescriptions are associated with increased dementia incidence versus receiving one prescription (separately in men and women). In particular to test whether associations vary by a) cumulative dose, b) specific drugs (compared to oxybutynin), and c) in certain patient groups (e.g. age group, comorbidity).
As secondary analyses, to examine whether recurrent OAB anticholinergic prescription is associated with increased risks of:
2d. dementia compared to recurrent prescription of alpha-blockers in men and vaginal oestrogens in women (as active comparators)
2e. stroke (as a negative control outcome)
2f. motor vehicle accidents (to examine confounding by OAB severity)
3&4. To examine whether OAB anticholinergic use is associated with delirium and functional decline
Exposure
Prescriptions for OAB anticholinergics (oxybutynin, tolterodine, solifenacin, darifenacin, fesoterodine, propiverine, or trospium) within the first 12 months of therapy.
Methods
New user design cohort studies of patients in England prescribed OAB medications since 1998. Dementia incidence (using Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics mortality data) will be compared after applying a 3-year lag period between patients receiving a second OAB prescription to those only receiving one prescription using Cox regression with age as the time-scale. We are using a triangulation approach, hence performing various analyses to see if the findings are consistent with causality and examine confounding and selection biases. This includes additionally examining the outcomes of delirium, fractures and stroke (primarily with exposure as time-varying and no lag period).
Primary: dementia; Secondary: delirium; fracture; stroke; motor vehicle accident
Kathryn Richardson - Chief Investigator - University of East Anglia
Kathryn Richardson - Corresponding Applicant - University of East Anglia
Chris Fox - Collaborator - University of East Anglia
Duncan Edwards - Collaborator - University of Cambridge
Irene Petersen - Collaborator - University College London ( UCL )
Jalesh Panicker - Collaborator - National Hospital for Neurology and Neurosurgery
Katharina Mattishent - Collaborator - University of East Anglia
Louise Robinson - Collaborator - Newcastle University
Nicholas Steel - Collaborator - University of East Anglia
Oby Enwo - Collaborator - University of East Anglia
Stuart Irving - Collaborator - Norfolk and Norwich University Hospitals
Yoon Loke - Collaborator - University of East Anglia
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation