Anticholinergic Drugs May Increase Cognitive Decline

Susan Jeffrey

April 18, 2008

April 18, 2008 (Chicago, Illinois) — A new study finds that the use of drugs with anticholinergic activity is associated with a more rapid decline in cognitive performance in older individuals.

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The findings suggest that physicians should take this possible effect into account when prescribing anticholinergic medication or drugs that have anticholinergic properties, said lead author Jack Tsao, MD, DPhil, associate professor of neurology at Uniformed Services University, in Bethesda, Maryland.

Dr. Tsao presented the results here at the American Academy of Neurology 60th Annual Meeting.

Anticholinergic Properties

Their study arose from experience with a patient seen by study coauthor Kenneth Heilman, MD, from the University of Florida at Gainesville, Dr. Tsao told Medscape Neurology & Neurosurgery. The woman had come in with memory complaints and hallucinations. However, Dr. Tsao said, "Her cognitive testing was essentially normal except for the memory issues, so she didn't fit the diagnosis of Alzheimer's-type dementia."

This patient had just begun treatment with tolterodine (Detrol, Pfizer) a drug to treat overactive-bladder problems. "Because Dr. Heilman had seen a previous case of another woman who had memory complaints that reversed after stopping her bladder medicine, we did the same for this lady, and her memory improved," he said. "This prompted us to ask the question of whether anticholinergic medicines or medicines that have anticholinergic properties actually can impair thinking in normal individuals."

Anticholinergic drugs range from the overactive-bladder agents and the Parkinson's-disease agents that are known to be strongly anticholinergic, to drugs such as warfarin, furosemide (Lasix, Sanofi-Aventis), hydrochlorothiazide, and ranitidine (Zantac, GlaxoSmithKline), an antireflux drug, that have weaker anticholinergic properties, Dr. Tsao said.

"When we actually looked through the literature, a lot of medicines that are not advertised as anticholinergic in nature actually have anticholinergic properties in vitro," he said.

To look more closely at this potential problem in a wider population, they used data from the Rush Religious Orders Study, a longitudinal cohort study enrolling older Catholic nuns and clergy without known dementia at enrollment. Of these, 870 had at least 1 follow-up evaluation.

During baseline and annual clinical evaluations, medication and supplement use was determined by direct observation of pill bottles, and global cognitive function was measured using a 21-item neuropsychological battery.

They divided subjects into those who had taken any of the drugs on the list they had compiled of those with anticholinergic properties (n = 679); subjects who had never taken any of these agents (n = 191) were used as the reference group.

The subjects were observed for a mean of 7.8 person-years, the authors note. In piecewise-regression models adjusted for age, sex, and education, the level and annual rate of cognitive decline for individuals before and after starting an anticholinergic drug werecompared with the intercept and slope for the reference group.

Dr. Tsao and colleagues report that the level and annual rate of change were not significantly different between the medication and reference groups prior to the use of an anticholinergic agent. However, compared with the reference group, the rate of cognitive decline after anticholinergic use was 0.045 units/year more rapid (P = .0044), the authors write.

"As all subjects were cognitively normal at the time of entry into the Religious Order Study and none were taking medications with anticholinergic effects, we conclude that initiation of medications with anticholinergic activity is associated with a more rapid decline in cognitive performance," the authors conclude.

In future work, they plan to stratify these agents on the basis of the relative potency of their anticholinergic effects to see whether more potent drugs may have a greater effect on memory compared with those that are less potent, Dr. Tsao concluded. "We're also going to try to see whether those subjects who might have mild cognitive impairment fare worse."

The study was supported by a grant from the American Philosophical Society and the National Institute on Aging. Dr. Tsao reports that he has received personal compensation for activities with CME LLC as an independent reviewer; holds stock and/or stock options in Amgen; and has received research support from Defense Spinal Cord and Column Injury Program, Uniformed Services University, and the Comprehensive Neuroscience Program. Disclosures for coauthors appear in the abstract.

American Academy of Neurology 60th Annual Meeting: Abstract S51.001. Presented April 17, 2008.

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