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Anticholinergics Strongly Linked to Dementia and Alzheimer’s

February 20, 2015

Anticholinergics, excluding tricyclic antidepressants, are included on the 2012 Beers Criteria of inappropriate medications in older adults. The recommendation to avoid anticholinergics in older adults is based on the rationale that they have reduced clearance in older adults, and tolerance develops when used as a hypnotic.1 Also, these agents carry risk of confusion, xerostomia, constipation, and other effects. Previous studies have reported that anticholinergics increase the risk of cognitive decline in elderly persons, but that this risk decreases over time upon discontinuing the agent.2  However, a new study published by Gray and colleagues3 in JAMA Internal Medicine reports that high cumulative use of anticholinergics significantly increases the risk for dementia in older adults.
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The prospective population-based cohort study utilized data from the Adult Changes in Thought study in Group Health, a Seattle-based integrated healthcare delivery system. A total of 3434 adults aged 65 years and older with no dementia at baseline were included in the study and followed every 2 years from 1994 through September 2012. Investigators looked at total standardized daily doses (TSDDs) of anticholinergics within a 10-year period and incident dementia, which was defined according to standard diagnostic criteria.

The results showed that during a mean follow-up of 7.3 years, 23.2% of patients (n=797) developed dementia, almost 80% of which were Alzheimer’s disease. The most common anticholinergic classes in these patients were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. Over a 10-year period, a significant 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% confidence interval [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. The results were similar for Alzheimer’s disease and were as robust in secondary, post-hoc, and sensitivity analyses.

Based on these results, the investigators concluded that prescribers should be more aware of this risk and minimize anticholinergic use over time.

-Allison Musante


  1. Campanelli CM. American Geriatrics Society Updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60(4):616-631.
  2. Carriere I, Fourrier-Reglat A, Dartigues J-F, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009;169(14):1317-1324.
  3. Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. Published online ahead of print January 26, 2015.
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