Reassuring Findings on Anticholinergics in Dementia Patients

Megan Brooks

October 04, 2011

October 4, 2011 — Taking medication with a low level of anticholinergic activity does not appear to cause further cognitive impairment or more rapid cognitive decline in patients with established Alzheimer's disease (AD), a new study shows.

"We hope that this will provide some reassurance to families and carers of those with dementia," Chris Fox, MD, from the University of East Anglia Norwich School of Medicine in the United Kingdom, noted in a prepared statement.

However, Dr. Fox said, "we remain concerned" about the effect on frail older people who have no signs or mild signs of impaired cognition before they start a drug with anticholinergic activity.

The concern stems in part from an earlier study the team conducted. In that study of roughly 13,000 older adults, use of anticholinergic drugs appeared to increase the risk for both cognitive impairment and death after adjustment for age, sex, baseline mental status, education, income level, number of nonanticholinergic medications, and health conditions.

"We feel more work is needed in this population," Dr. Fox told Medscape Medical News.

The results were published online September 18 in Age and Ageing.

The Laser-AD Study Cohort

Anticholinergics affect the brain by blocking the neurotransmitter acetylcholine. Older adults are particularly sensitive to anticholinergic effects, and they are at high risk for exposure to such medications because of multiple illnesses that prompt frequent use of prescription and over-the-counter medications.

It's estimated that up to half of patients with dementia in the United States take at least 1 prescription or over-the-counter medication with anticholinergic activity for a variety of conditions, including psychiatric disorders, cardiac disease, or bladder illnesses.

In their latest study, Dr. Fox and colleagues looked at the effect of "anticholinergic burden" on cognitive impairment and deterioration in 224 patients with AD enrolled in the London and South East Region AD (Laser-AD) study.

Each participant's "anticholinergic burden" was calculated by using the Anticholinergic Burden scale (ABS), previously developed by the study team.

"The scale was developed through a systematic review of the literature to identify drugs with documented anticholinergic activity," they explain in their report. "The ABS scale focuses on central effects of medication with anticholinergic actions derived from reported serum anticholinergic assays and systematic evidence review of studies developed."

The study participants had a mean age of 81 years; 150 were living at home and 74 were living in a nursing home. Cognitive function was measured at baseline and 6 and 18 months later using the Mini-Mental State Exam, the Severe Impairment Battery, and the Alzheimer's Disease Assessment Battery, Cognitive subsection.

'Weak' Anticholinergic Blockers Seem Safe in AD

Of the 224 participants, 167 (74.6%) completed follow-up at 18 months, 48 (21.4%) died during the study period, 8 (3.6%) dropped out, and 1 (0.4%) moved away.

During the study period, the average number of medications taken was 3.6 and the average anticholinergic load was 1.1 (range, 0 - 7). Psychotropics were the most common group of medications with anticholinergic effects used by study participants.

According to the investigators, there was no significant correlation between the anticholinergic burden expressed as the ABS score and cognition on any of the 3 tests at baseline, 6 months, or 18 months.

At baseline, 47% of participants were receiving cholinesterase inhibitors; at 18 months, the percentage had grown to 57%. Use of cholinesterase inhibitors had no effect on the cognitive test results.

This study "suggests that using weak anticholinergic blocking drugs [is] not associated with a deterioration in cognition," Dr. Fox told Medscape Medical News. "We need more studies on the impact of more potent anticholinergic drugs on cognition in Alzheimer's dementia," he noted.

Decreased Sensitivity

The lack of an effect of anticholinergic burden noted in this study, the investigators say, could be due to "the decreased sensitivity of patients with more advanced cognitive impairment."

Lawrence Tune, MD, professor of psychiatry and behavioral sciences, Emory University School of Medicine, Atlanta, Georgia, who was not involved in the study, agrees. "The authors correctly note that their patient population is quite advanced; that might explain the negative result that goes against other published studies," he told Medscape Medical News.

It's also possible that because participants had taken anticholinergic medication for significant time periods, any effect on cognitive function had occurred before enrollment in the study.

This is supported by the fact that the group of patients in the study who had a "clinically meaningful" anticholinergic burden at baseline had lower cognition sores on the Mini-Mental State Exam and Severe Impairment Battery at baseline.

It's also possible that medications with anticholinergic effects "may not be as damaging to cognition as first thought in established dementia." In patients with AD, Dr. Fox explained, "there could be too much damage to the cholinergic pathways already or it could be that mild anticholinergic medicines don't affect cognition."

The investigators note that their study of patients with AD contrasts with findings from a smaller but similar study of 69 patients with AD published in 2003.

In this study, MMSE scores at 2 years were significantly worse for patients receiving anticholinergic medications than for those not receiving anticholinergics. The study team concluded that long-term exposure to anticholinergics may have adverse effects on the clinical course of AD.

Clearly more research is needed, the researchers conclude.

The original source of funding for the study was Lundbeck Pharmaceuticals. Several of the authors have received honoraria and educational grant support from the pharmaceutical industry. Dr. Tune has disclosed no relevant financial relationships.

Age Ageing. Published online September 18, 2011. Abstract.

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