Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Mar;175(3):401-7.
doi: 10.1001/jamainternmed.2014.7663.

Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study

Affiliations
Free PMC article

Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study

Shelly L Gray et al. JAMA Intern Med. .
Free PMC article

Abstract

Importance: Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia.

Objective: To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia.

Design, setting, and participants: Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses.

Exposures: Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) 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 updated as participants were followed up over time.

Main outcomes and measures: Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities.

Results: The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses.

Conclusions and relevance: Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.

Conflict of interest statement

Disclosures: Dr. Dublin received a Merck/American Geriatrics Society New Investigator Award. Dr. Larson receives royalties from UpToDate. Rod Walker has received funding as a biostatistician from a research grant awarded to Group Health Research Institute from Pfizer. Onchee Yu has received funding as a biostatistician from a research grant awarded to Group Health Research Institute from Amgen. All other authors have no conflicts to disclose.

Comment in

Similar articles

See all similar articles

Cited by 158 articles

See all "Cited by" articles

Publication types

MeSH terms

Substances

Feedback