Cumulative Anticholinergic Exposure Is Associated with Poor Memory and Executive Function in Older Men
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.
et al. Adverse drug reactions associated with global cognitive impairment in elderly persons.
Ann Intern Med
1987; 107: 169–173.
Drug-induced cognitive impairment. Defining the problem and finding solutions.
1993; 3: 349–357.
Adverse drug events in elderly patients receiving home health services following hospital discharge.
1999; 33: 1147–1153.
et al. Impact of inappropriate drug use on mortality and functional status in representative community dwelling elders.
2002; 40: 166–176.
et al. Anticholinergic drugs and physical function among frail elderly population.
Clin Pharmacol Ther
2007; 81: 235–241.
The problems of anticholinergic adverse effects in older patients.
1993; 3: 335–348.
Acetylcholine and delirium.
Dement Geriatr Cogn Dis
1999; 10: 342–344.
et al. Modeling dementia: Effects of scopolamine on memory and attention.
1988; 26: 685–700.
Patterns of memory failure after scopolamine treatment: Implications for cholinergic hypotheses of dementia.
Behav Neur Biol
1986; 45: 196–211.
Anticholinergic drug-induced delirium: Experimental modification, quantitative EEG, and behavioral correlations.
J Nerv Ment Dis
1966; 143: 492–507.
et al. Central anticholinergic hypersensitivity in aging.
J Geriatr Psychiat Neurol
1992; 5: 72–77.
Polypharmacy: The cure becomes the disease.
J Gen Intern Med
1993; 8: 278–283.
et al. Impact of inappropriate drug use among hospitalized older adults.
Eur J Clin Pharmacol
2005; 61: 453–459.
et al. The risk of anticholinergic toxicity in the elderly: A study of prescribing practices in two populations.
1983; 38: 31–35.
et al. Serum anticholinergic activity in a community-based sample of older adults: Relationship with cognitive performance.
Arch Gen Psychiatry
2003; 60: 198–203.
et al. Drugs with anticholinergic properties and cognitive performance in the elderly: Results from the Paquid Study.
Br J Clin Pharmacol
2005; 59: 143–151.
et al. A drug burden index to define the functional burden of medications in older people.
Arch Intern Med
2007; 167: 781–787.
et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: Longitudinal cohort study.
2006; 332: 455–459.
Chronic exposure to anticholinergic medications adversely affects the course of Alzheimer disease.
Am J Geriatr Psychiatry
2003; 11: 458–461.
et al. Effects of statin use on muscle strength, cognition, and depressive symptoms in older adults.
J Am Geriatr Soc
2007; 55: 420–425.
Joint National Committee.
The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
Arch Intern Med
1997; 157: 2413–2446.
The Hopkins Verbal Learning Test: Development of a new memory test with six equivalent forms.
1991; 5: 125–142.
et al. Detecting dementia with the Hopkins Verbal Learning Test and the Mini-Mental State Examination.
Arch Clin Neuropsychol
2004; 19: 89–104.
Multidimensional Functional Assessment of Older Adults: The Duke Older Americans Resources and Services Procedures. Hillsdale, NJ: Lawrence Erlbaum Associates, Inc., 1988.
et al. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients.
Arch Intern Med
2001; 161: 1099–1105.
et al. Anticholinergic effects of drugs commonly prescribed for the elderly: Potential means for assessing risk of delirium.
Am J Psychiatry
1992; 149: 1393–1394.
Snipping the thread of life. Antimuscarinic side effects of medications in the elderly.
Arch Intern Med
1989; 149: 2414–2420.
et al. The relationship of an anticholinergic rating scale with serum anticholinergic activities in elderly nursing home residents.
2002; 36: 14–19.
et al. The anticholinergic scale as a measure of drug-related anticholinergic burden: Association with serum anticholinergic activity.
J Clin Pharmacol
2006; 46: 1481–1486.
et al. Methods for assessing drug-related anticholinergic activity. [Review].
2005; 25: 1592–1601.
American Society of Hospital Pharmacists.
American Hospital Formulary Service. Drug information. Bethesda, MD: American Society of Hospital Pharmacists, 1994.
The treatment of hypertension in older people and its effect on cognitive function [Review].
1997; 51: 208–212.
et al. Neuropsychological effects of antihypertensive drugs.
1987; 5: 689–701.
et al. Benzodiazepine use as a cause of cognitive impairment in elderly hospital inpatients.
J Gerontol Biol Sci Med Sci
1995; 50A: M99–M106.
The CES-D scale: A self-report depression scale for research in the general population.
Appl Psychol Meas
1977; 1: 385–401.
et al. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation.
J Chronic Dis
1987; 40: 373–383.
Bias and confounding in pharmacoepidemiology. In: BL Strom, ed. Pharmacoepidemiology. New York: John Wiley & Sons, 2000, pp
et al. SAS System for Mixed Models. Cary, NC: SAS Institute Inc., 1996.
Applied Multiple Regression—Correlation Analysis for the Behavioral Sciences. Mahwah, NJ: Lawrence Erlbaum Associates, Inc., 2003.