Anticholinergic drugs, which block the neurotransmitter acetylcholine in the central or peripheral nervous system, are indicated for the treatment of depression, gastrointestinal disorders, Parkinson's disease, urinary incontinence, epilepsy, and allergies. Prolonged exposure to these drugs has been linked to cognitive decline and dementia, but it isn't known whether the elevated risk is specific to the anticholinergic action itself. A recent case-control study was the first to estimate the effect of different classes of anticholinergic drugs on the incidence of dementia.

Patients with a new diagnosis of dementia were identified, and their use of anticholinergic drugs four to 20 years before diagnosis was compared with that of matched controls without dementia. All drugs prescribed during the drug-exposure period were classified according to the Anticholinergic Cognitive Burden (ACB) scale, with scores ranging from 1 to 3 (1 representing possible cognitive [as opposed to gastrointestinal, for example] anticholinergic effects, based on laboratory testing, and 3 representing established clinically relevant cognitive anticholinergic effects). The study sample included nearly 41,000 cases and nearly 284,000 controls (median age, 83 years; 63% women). The median drug-exposure period was seven years.

During the drug-exposure period, 35% of cases and 30% of controls were prescribed at least one anticholinergic drug with an ACB score of 3. A positive and significant association was found between the prescription of any anticholinergic drug and dementia, and a dose response was seen with drugs with an ACB score of 2 or 3.

Dementia incidence was significantly associated with the prescription of antidepressant, antiparkinson, and urological drugs with an ACB score of 3, even 15 to 20 years before diagnosis of dementia. No such association was found with antispasmodics, antipsychotics, or antihistamines with a score of 3.

The study authors advise clinicians to consider the risk of long-term cognitive effects when weighing the risks and benefits of anticholinergic drugs.-KR

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