Cumulative Anticholinergic Exposure Is Associated with Poor Memory and Executive Function in Older Men

Authors

  • Ling Han MD, PhD,

    1. From the *Program on Aging, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; and Clinical Epidemiology Research Center, Department of Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
    Search for more papers by this author
  • Joseph V. Agostini MD,

    1. From the *Program on Aging, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; and Clinical Epidemiology Research Center, Department of Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
    Search for more papers by this author
  • Heather G. Allore PhD

    1. From the *Program on Aging, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; and Clinical Epidemiology Research Center, Department of Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
    Search for more papers by this author

Address correspondence to Ling Han, MD, PhD, Yale University Department of Internal Medicine, Program on Aging, 300 George Street Suite 775, New Haven, CT 06511. E-mail: ling.han@yale.edu

Abstract

OBJECTIVES: To examine the longitudinal relationship between cumulative exposure to anticholinergic medications and memory and executive function in older men.

DESIGN: Prospective cohort study.

SETTING: A Department of Veterans Affairs primary care clinic.

PARTICIPANTS: Five hundred forty-four community-dwelling men aged 65 and older with diagnosed hypertension.

MEASUREMENTS: The outcomes were measured using the Hopkins Verbal Recall Test (HVRT) for short-term memory and the instrumental activity of daily living (IADL) scale for executive function at baseline and during follow-up. Anticholinergic medication use was ascertained using participants' primary care visit records and quantified as total anticholinergic burden using a clinician-rated anticholinergic score.

RESULTS: Cumulative exposure to anticholinergic medications over the preceding 12 months was associated with poorer performance on the HVRT and IADLs. On average, a 1-unit increase in the total anticholinergic burden per 3 months was associated with a 0.32-point (95% confidence interval (CI)= 0.05–0.58) and 0.10-point (95% CI=0.04–0.17) decrease in the HVRT and IADLs, respectively, independent of other potential risk factors for cognitive impairment, including age, education, cognitive and physical function, comorbidities, and severity of hypertension. The association was attenuated but remained statistically significant with memory (0.29, 95% CI=0.01–0.56) and executive function (0.08, 95% CI=0.02–0.15) after further adjustment for concomitant non-anticholinergic medications.

CONCLUSION: Cumulative anticholinergic exposure across multiple medications over 1 year may negatively affect verbal memory and executive function in older men. Prescription of drugs with anticholinergic effects in older persons deserves continued attention to avoid deleterious adverse effects.

Ancillary