Association between anticholinergic (atropinic) drug exposure and cognitive function in longitudinal studies among individuals over 50 years old: a systematic review

Purpose With increasing age, adults are often exposed to anticholinergic drugs and are prone to potential adverse drug reaction, among which cognitive impairment. If the short-term cognitive effects of anticholinergic drugs are well established, their long-term cognitive effects have less been studied. Objective To provide a systematic review of longitudinal studies which assessed the effect of anticholinergic exposure on cognition in individuals over 50 years. Materials We searched the MEDLINE database for studies with a minimal 6-month follow-up, assessing anticholinergic exposure through a biological measure or a clinical list and reporting at least one cognitive outcome. We used the modified Newcastle-Ottawa scale and additional criteria regarding the anticholinergic exposure to assess studies’ methodological quality. Given the heterogeneity of the studies, we performed a systematic review. Results Among the 1574 references retrieved, 25 studies were included. Anticholinergic medications were mostly defined through the Anticholinergic Cognitive Burden Scale ( n = 14/25). Six studies evaluated baseline drug collection, 14 used longitudinal aggregated measure, and 5 multiple drug exposure measures over time. Seventeen studies assessed anticholinergic burden. Cognitive function was assessed by mild cognitive impairment/dementia incidence ( n = 15) or neuropsychological tests ( n = 14). Most studies were of poor quality and retrieved discordant results. However, studies with good quality ( n = 4) suggested a relationship between anticholinergic drug exposure and/or burden and cognitive function. Conclusion Our review suggests a deleterious effect of anticholinergic exposure on mid/long-term cognitive function but should be confirmed in studies with improved methodology. Meanwhile, prescription of anticholinergic drugs should remain cautious.