Cumulative Use of Strong Anticholinergic Medications and Incident Dementia
By S. Gray, Melissa L. Anderson, S. Dublin, J. Hanlon, R. Hubbard, Rod L. Walker, Onchee Yu, Paul K. Crane, E. Larson. JAMA Internal Medicine, 2015
1,033 citations recorded by the source corpus.
IMPORTANCE Many medications have anticholinergic effects. The general view is that anticholinergic-induced cognitive impairment is reversible upon medication discontinuation. However, a few studies suggest that anticholinergic medications may be associated with increased dementia risk. OBJECTIVE To examine whether cumulative anticholinergic medication use is associated with a higher risk of incident dementia. DESIGN Prospective population-based cohort study using data from the Adult Changes in Thought Study. SETTING Group Health, an integrated health-care delivery system, Seattle, Washington PARTICIPANTS 3,434 participants aged 65 and older with no dementia at study entry. Initial recruitment occurred between 1994 and 1996 or 2000 and 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants received follow-up every two years. EXPOSURE Using computerized pharmacy dispensing data, cumulative anticholinergic exposure was defined as the total standardized daily doses (TSDD) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was time-varying. MAIN OUTCOMES AND MEASURES Incident dementia and Alzheimer’s disease using standard diagnostic criteria. Statistical analyses used Cox proportional hazards models, adjusted for demographic, health behaviors and health status including comorbidities. RESULTS The most common anticholinergic drug classes used were tricyclic antidepressants, first generation antihistamines and bladder antimuscarinics. Over a mean follow-up of 7.3 years, 797 participants (23%) developed dementia (637 developed Alzheimer’s). A 10-year cumulative dose-response relationship was observed for both dementia and Alzheimer’s disease (test for trend, p<0.001). For dementia, adjusted hazard ratios (HRs) and 95% confidence interval (CI) for cumulative anticholinergic use was 0.92 (95% CI, 0.74-1.16) for 1-90 TSDD; 1.19 (CI, 0.94-1.51) for 91-365 TSDD; 1.23 (CI, 0.94-1.62) for 366-1095 TSDD; and 1.54 (95% CI, 1.21-1.96) for >1095 TSDD, compared to non-use. A similar pattern of results was noted for Alzheimer’s disease. Results were robust to secondary, sensitivity and post-hoc analyses. CONCLUSION AND RELEVANCE Higher cumulative anticholinergic medication use is associated with an increased risk for dementia. Efforts to increase awareness among health professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.
Subfields: Critical Care and Intensive Care Medicine, Geriatrics and Gerontology, Psychiatry and Mental health
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Citations in the corpus
- American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (2015, background): “Use of anticholinergic medications remains a concern because it is associated with impaired cognitive and physical function and risk of dementia.(29,30) These criteria continue to be useful and necessary as a clinical and public health tool to improve medication safety in older adults and to increas”
- The Epidemiology of Alzheimer's Disease Modifiable Risk Factors and Prevention (2021, neutral): “Over a long period of 4 years, excess use of anticholinergics was considered as a risk for AD (HR 1.63, 95% CI 1.24-2.14) (115).”
- The cholinergic system in the pathophysiology and treatment of Alzheimer's disease. (2018, background): “Thus, higher estimates of cumulative exposure to anticholinergic therapies were associated with a greater risk for incident dementia or Alzheimer’s disease dementia than were lower levels of cumulative anticholinergic exposure (Gray et al., 2015).”