No causal ties between anticholinergic drug use and dementia, cognitive decline

Observational studies have reported that long-term use of anticholinergic drugs carries an increased hazard of developing dementia or cognitive decline, but no causal link can be inferred due to the nature of the studies and considerable risk of bias, according to a meta-analysis.

Researchers searched multiple online databases for randomized controlled trials or observational studies evaluating the effects of anticholinergic drug exposure in relation to dementia, mild cognitive impairment (MCI), or cognitive decline over ≥12 weeks of follow-up.

Twenty-six cohort and case-control studies (mean study duration, 73 months) met the inclusion criteria. The total population comprised 621,548 participants (mean age, 74 years; 60 percent female). These studies were conducted in Europe, North America, and Taiwan and were mostly community based, except for three studies that involved outpatients and two studies of care home residents. The meta-analysis included 19 studies.

Pooled data revealed that anticholinergic drug use was associated with greater odds of developing dementia (odds ratio [OR], 1.20, 95 percent confidence interval [CI] 1.09–1.32), with substantial heterogeneity among studies (I², 86 percent). This association was seen among both short-term users (OR, 1.23, 95 percent CI, 1.17–1.29; I², 2 percent) and long-term users (OR, 1.50, 95 percent CI, 1.22–1.85; I², 90 percent).

Any anticholinergic use was also associated with cognitive decline (standardized mean difference, 0.15, 95 percent CI, 0.09–0.21; I², 3 percent) but not with MCI (OR, 1.24, 95 percent CI, 0.97–1.59; I², 0 percent).

The researchers underscored the need for stronger evidence from high-quality studies to guide the management of long-term use of anticholinergic drugs.