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Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB.
“Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study”.
JAMA Intern Med. 2015 Mar 03;175(3):401-7.
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Abstract
MPORTANCE
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.
Key Words: dementia, Alzheimer disease, pharmacoepidemiology, cohort study, anticholinergic medication use, aged
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