Anti-Cholinergic Drugs Linked to Cognitive Impairment in Elderly

Anti-Cholinergic Drugs Linked to Cognitive Impairment in Elderly

The use of anti-cholinergic drugs by older patients has been linked with mild cognitive impairment, according to a new study in France.

Results of the study were published online on BMJ.com and reported by MedPage Today on February 1, 2006.

An anti-cholinergic drug is one that opposes or blocks the action of the neurotransmitter acetylcholine. Drugs with anti-cholinergic effects include some bronchodilators, antihistamines, analgesics, anti-hypertensives, antidepressants, antiparkinsonian agents and corticosteroids.

Elderly patients taking any of these drugs may consequently experience "significant deficits in cognitive functioning," according to Marie Ancelin, PhD, a senior research fellow at the French national health research unit.

Patients who experience these deficits as a result of taking anti-cholinergic drugs are "highly likely to be classified as mildly cognitively impaired," Dr Ancelin and colleagues reported. A further complicating factor is that these people, once diagnosed with mild cognitive impairment, may receive prescriptions for acetylcholinesterase inhibitors, which inhibit breakdown of acetylcholine.

The researchers therefore advised that physicians prescribing for this patient population should assess the cholinergic effects of their current drug regimen before prescribing an acetylcholinesterase inhibitor.

Clinical Study

Dr Ancelin and colleagues conducted a longitudinal cohort study in the Montpellier region, east of Marseilles. The trial involved 372 participants over age 60 years who showed no signs of dementia when recruited.

The researchers then analyzed each participant's cholinergic burden of drugs, administered annual tests and conducted a neurological assessment at eight years on the participants remaining in the study.

The results showed that 297 participants had taken no anti-cholinergic drugs either at baseline or in the following year, while 30 participants had continually taken at least one anti-cholinergic drug. Other participants had either stopped or started taking these drugs during the year and were excluded.

The results also showed that:

• 80% of the continual anti-cholinergic drug users had mild cognitive impairment, compared with 35% of non-users.
• Anti-cholinergic drug use was a strong predictor of mild cognitive impairment (after adjusting for age, sex, education, treated hypertension and untreated depression).
• Participants who continually used anti-cholinergic drugs performed worse on reaction time, attention, delayed non-verbal memory, narrative recall, visuospatial construction and language tasks, but not on tasks of reasoning, immediate and delayed recall of word lists and implicit memory.
• At the eight-year follow-up point, all participants had a similar risk of developing dementia: 16% for continual anti-cholinergic drug users versus 14% for non-users.

Dr Ancelin and colleagues noted that, in research into mild cognitive impairment, pro-cholinergic drugs such as Aricept (donepezil) or Reminyl (galantamine) are often used to slow the progress to dementia.

"People with mild cognitive impairment due to anti-cholinergic drugs could be in the absurd situation of receiving pro-cholinergic drugs to counteract the effects of anti-cholinergic agents," the researchers reportedly said.

Sources:
Drug Side Effects Can Befuddle Elderly Brains, MedPage Today, February 1, 2006.
Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. Ancelin ML et al, British Medical Journal, 2006.

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