Long-term use of anticholinergic medications for Parkinson’s disease, bladder conditions, and depression was associated with an increased risk for dementia, a case-control study found.
For drugs previously associated with delirium, the highest odds were seen with anticholinergic drugs for Parkinson’s (adjusted OR 1.29, 95% CI 1.11-1.50, P<0.01) and bladder conditions (adjusted OR 1.18, 95% CI 1.13-1.23, P<0.01), reported George Savva, Ph.D., of the University of East Anglia in Norwich, England, and colleagues.
The association was also seen with antidepressants (adjusted OR 1.11, 95% CI 1.08-1.14, P<0.01), they wrote in The BMJ.
“Many of the treatment options for these conditions involve medication with anticholinergic effects,” said Savva.
Frequently prescribed anticholinergic drugs include procyclidine (Kemadrin) for Parkinson’s; tolterodine, oxybutynin, and solifenacin (Vesicare) for urological conditions such as overactive bladder or incontinence; and amitriptyline, dosulepin, and paroxetine for depression.
“We found that people who had been diagnosed with dementia were up to 30% more likely to have been prescribed specific classes of anticholinergic medications,” said Savva in a statement. “And the association with dementia increases with greater exposure to these types of medication.”
For drugs with an anticholinergic cognitive burden (ACB) score of 3, the adjusted OR increased from 1.07 (95% CI 1.02-1.12, P<0.01) for patients with 14 to 89 daily doses of these drugs to 1.31 (95% CI 1.22-1.41, P<0.01) for those with over 1,460 daily doses.
“We already have strong evidence that anticholinergics cause confusion and in the short-term will potentially worsen the symptoms of dementia,” said co-author Ian Maidment, Ph.D., of Aston University in Birmingham, England, in a statement. “This study shows that some anticholinergics may cause long-term harm in addition to short-term harm.”
Savva’s group studied the medical records of 40,770 patients, ages ≥65, who were diagnosed with dementia, comparing them with 283,933 controls. They looked at those with new diagnoses and what anticholinergic medication they were prescribed in the 4 to 20 years prior, identifying 14,453 (35%) patients with dementia and 86,403 (30%) controls who had been prescribed at least one anticholinergic drug with an ACB score of 3.
The adjusted OR for any anticholinergic drug with an ACB score of 3 being associated with dementia was 1.11 (95% CI 1.08-1.14, P<0.01), but drugs for gastrointestinal and respiratory conditions were not linked with dementia risk.
ACB scores were defined as:
- 1: possibly anticholinergic, but without known clinically relevant negative cognitive effects (e.g., antihistamines)
- 2: definitely anticholinergic, with established and clinically relevant anticholinergic effects based on blood-brain penetration
- 3: same as 2 but with reported associations of delirium (e.g., tricyclic antidepressants)
Savva cautioned that the study only revealed an association and not cause. “It could be that these medications are being prescribed for very early symptoms indicating the onset of dementia,” he said. “But because our research shows that the link goes back up to 15 or 20 years before someone is eventually diagnosed with dementia, it suggests that reverse causation, or confounding with early dementia symptoms, probably isn’t the case.”
Other than antidepressants, no drugs with an ACB score of 1 were associated with an increased risk of dementia.