Heavy use of anticholinergics, including OTC treatments, seems to increase the likelihood of developing Alzheimer’s disease (AD), new research shows. The study suggests, for example, “that a person taking an anticholinergic, such as oxybutynin chloride 5mg/d or doxepin hydrochloride 10mg/d, for more than three years, would have a greater risk for dementia”.

Researchers ascertained cumulative exposure to anticholinergics for 3,434 people aged 65 years or older without dementia, expressed as total standardised daily doses (TSDDs) dispensed in the past 10 years. They excluded the most recent 12 months to avoid confounding from treatment of AD’s prodromal symptoms, such as depression, but updated cumulative exposure during follow-up.

The most commonly used anticholinergics were tricyclic antidepressants (63.1 per cent of TSDDs), first-generation antihistamines (17.2 per cent) and bladder antimuscarinics (10.5 per cent). During the mean follow-up of 7.3 years, 797 people (23.2 per cent) developed dementia and, of those, 79.9 per cent were diagnosed with possible or probable AD. AD risk rose with cumulative anticholinergic exposure.

People with the highest exposure (TSDD >1095) were 54 per cent more likely to be diagnosed with dementia and 63 per cent more likely to be diagnosed with AD than nonusers. People with the next highest exposure (TSDD, 366- 1095) had a slightly increased risk of dementia and AD (23 and 30 per cent respectively) although neither was statistically significant.

The link remained after accounting for the potential use of anticholinergics in prodromal dementia and was consistent across anticholinergics: high users of first-generation antihistamines and bladder antimuscarinics were more likely to develop AD.

Antidepressants, commonly used in early undiagnosed dementia, do not account for the link. The authors suggest that healthcare professionals should consider alternatives to anticholinergics for older patients or, if there is no alternative, use the lowest effective dose and discontinue ineffective therapy.

They suggest educating patients about the potential risks as some anticholinergics are available OTC, and call for additional studies to confirm these findings and understand the mechanisms. (JAMA Intern Med doi:10.1001/ jamainternmed.2014.7663)