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Chronic Anticholinergic Use and Dementia Risk

Summary and Comment |
December 1, 2009

Chronic Anticholinergic Use and Dementia Risk

  1. David L. Bachman, MD

A longitudinal study in community-dwelling elders suggests that chronic anticholinergic use may not only produce short-term cognitive effects but may also increase the risk for dementia.

  1. David L. Bachman, MD

Does chronic anticholinergic use, long recognized as causing cognitive impairment in older people, increase the long-term risk for dementia, particularly Alzheimer disease (AD)? And do patients who have discontinued anticholinergic medications have the same risk for dementia as chronic users?

To find out, researchers conducted an observational study in community-dwelling adults aged 65 and older. The study was partially funded by a manufacturer of anticholinergic drugs. Of the original 9077 dementia-free participants at study inception, data were available on 6912. Participants had follow-up examinations at 2 years and most also at 4 years (mean follow-up duration, 3.5 years). Cognitive measures included a word list generation task, Trail Making Tests A and B, and the Mini-Mental State Examination. A preliminary diagnosis of dementia according to DSM-IV criteria was validated by an independent panel. Anticholinergic use was assessed by means of drug-list interview for all prescription and over-the-counter medications and validated by direct inspection of prescriptions or medications whenever possible.

Of the 6912 participants, 86.4% did not report anticholinergic use at any time during the study, 2.5% reported use only at baseline (discontinuing group), and 4.6% reported use at baseline and at the 2-year follow-up or longer (continuous group). (Intermittent use was not considered.) Men and women in the continuous group had greater cognitive decline than the never-users, even after adjustments for comorbid factors (e.g., depression and Parkinson disease). Cognitive function did not differ significantly between the discontinuing group and never-users.

Among the 7123 participants included in the analysis for dementia, 221 had newly diagnosed dementia; 143 of these diagnoses were for AD. Continuous, but not discontinued, anticholinergic use was associated with increased dementia risk (hazard ratio, 1.65; P=0.05). The authors conclude that continuous anticholinergic medication use in elders may place them at increased risk for dementia or AD.

Comment

The acute risk of anticholinergic medication use in elders with or without preexisting dementia is well known. The Beers List of “potentially inappropriate medications” particularly highlights anticholinergic medications (Arch Intern Med 2003; 163:2716), which produce not only delirium and other cognitive effects but also adverse effects particularly troubling to older individuals, such as constipation and bladder retention. Despite the potential for these adverse effects, anticholinergic medications continue to be prescribed to older individuals with surprising frequency. In the present study, 14.6% of these community-dwelling participants received prescription or over-the-counter anticholinergic medications at some time during a 4-year period.

The authors raise an important concern as to whether chronic use of anticholinergic medications can increase the risk for dementia or AD, in addition to the known acute effects. They acknowledge that misdiagnosis of dementia may occur in patients taking chronic anticholinergic medication. However, chronic anticholinergic exposure may genuinely increase the long-term risk for dementia, perhaps through an effect on trophic factors or cholinergic system regulation. If so, anticholinergic medications may join late-life hormone therapy in women as iatrogenic factors that may contribute to dementia.

Dr. Bachman is Professor of Neuroscience, Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston.

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Reader Comments (1)

Nichol T Iverson

These drugs have anticholinergic effects. Are they likely to increase the risk for progression to AD?

Competing interests: None declared

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