Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study.
Level 3 - non-randomized controlled study
Prospective non-randomized population-based cohort study
PubMed 25621434 · doi:10.1001/jamainternmed.2014.7663
What was done
A prospective population-based cohort study followed 3,434 participants aged 65 years or older with no dementia at baseline from the Adult Changes in Thought study in Seattle, Washington (mean follow-up 7.3 years). Cumulative anticholinergic exposure was measured from computerized pharmacy dispensing records as total standardized daily doses (TSDDs) over the past 10 years, excluding the most recent 12 months to avoid prodromal confounding. Cox proportional hazards regression models adjusted for demographics, health behaviors, and comorbidities evaluated incident dementia and Alzheimer disease.
What was found
During follow-up, 797 participants (23.2%) developed dementia, of whom 637 (79.9%) had Alzheimer disease. A significant 10-year cumulative dose-response relationship was observed for both all-cause dementia and Alzheimer disease (test for trend, P < .001). Adjusted hazard ratios for incident dementia compared with nonuse were 0.92 (95% CI, 0.74–1.16) for 1 to 90 TSDDs, 1.19 (95% CI, 0.94–1.51) for 91 to 365 TSDDs, 1.23 (95% CI, 0.94–1.62) for 366 to 1095 TSDDs, and 1.54 (95% CI, 1.21–1.96) for greater than 1095 TSDDs.
Why it matters
This study shows that high cumulative exposure to strong anticholinergics is associated with an increased risk of dementia, suggesting that anticholinergic-associated cognitive impairment may not be completely reversible upon medication discontinuation.
Limits
The observational design cannot exclude residual confounding by indication for conditions treated with anticholinergics (such as depression or urinary incontinence). Exposure was based on pharmacy dispensing data rather than confirmed pill ingestion or adherence, over-the-counter anticholinergic use could not be fully captured, and the cohort was limited to a single regional healthcare system.
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