Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis

Abstract

Background the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear. Methods we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I. Results twenty-six studies (including 621,548 participants) met our inclusion criteria. ‘Any’ anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09–1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17–1.29, I2 = 2%; and OR 1.50, 95% CI 1.22–1.85, I2 = 90%). ‘Any’ anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09–0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97–1.59, I2 = 0%). Conclusions anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.

The effects of anticholinergic medications on cognition in children: a systematic review and meta-analysis

“…We quantified the effects of anticholinergic medications on cognition in children systematically across the literature. We report that, unlike older adult samples [7][8][9] , anticholinergic medications are not associated with cognitive impairments in children. This finding was regardless of the classification approach used: drug class, potency, duration of use, and cognitive domain.…”

“…Interestingly, all study designs included in this review were experimental, whereas those included in reviews of older adults are typically longitudinal epidemiological cohort studies [7][8][9] . Standards of reporting cognitive www.nature.com/scientificreports/ performance also differ between children and adults.…”

“…Anticholinergic medications are commonly prescribed 1 – 3 yet a growing body of evidence has demonstrated that their use is associated with a higher risk of incident cognitive impairment 4 – 6 . This literature has been reviewed multiple times in older adults, whereby anticholinergic medications have been consistently associated with cognitive decline and dementia 7 – 9 . There has been no systematic synthesis of the cognitive effects of anticholinergic medications in children.…”

Risk of anticholinergic burden in adults with intellectual disabilities: a Scottish retrospective cohort study of n = 17 220

“…2017; Pieper et al . 2020), the latter being associated with high anticholinergic burden 15–20 years before diagnosis (Richardson et al . 2018).…”

The role of sex, age and genetic polymorphisms of CYP enzymes on the pharmacokinetics of anticholinergic drugs

“…Further to general prescribing guidelines 1,2 which caution against anticholinergic medication use in older adults, two academic groups (5th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 3 and the Lancet Commission 4 ) have recently identified anticholinergic medications among potential risk factors for developing dementia. Subsequent to the publication of these guidelines, several new studies have identified exposure to anticholinergic agents as risk factors for mild cognitive impairment and dementia 5–7 . Clinical experience and research demonstrate an increased risk of adverse drug events, 8–12 cognitive impairment, 13–18 and mortality 12 related to the use of anticholinergic drugs in older adults.…”