Anticholinergic exposure and cognitive decline in older adults: Effect of anticholinergic exposure definitions in a 3-year analysis of the Multidomain Alzheimer Preventive Trial (MAPT) study.

AIM: To assess the association between anticholinergic (atropinic) burden and cognitive decline in older adults over 3 years.

METHODS: We used data from Multidomain Alzheimer Preventive Trial (MAPT) study participants aged ≥70 years and at risk of cognitive decline. Cognitive function was assessed with a composite score (Mini Mental State Examination orientation, Free and Cued Selective Reminding Test, Category Naming Test, Digit Symbol Substitution Test) at 12, 24 and 36 months. Participants declining by more than 0.236 points on the composite score (representing the lowest quintile of 1-year cognitive change) during any 1-year period were considered to have undergone cognitive decline. Anticholinergic exposure was defined by 4 methods for each of 4 anticholinergic scales (Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, Anticholinergic Risk Scale, Durán). The association between cognitive decline and time-varying anticholinergic exposure (primary analysis using Durán list and maximal anticholinergic score (0,1 or 3) was assessed using Cox proportional hazards models. Other cognitive decline definitions were used in sensitivity analyses.

RESULTS: At baseline, among 1,396 patients included, 7.4 to 23.5% were exposed to anticholinergics depending on the anticholinergic scale used. 64% of participants experienced cognitive decline during follow-up. Regardless of the anticholinergic scale/exposure measurement used, no significant association was observed with cognitive decline (primary analysis: compared to non-anticholinergic users, Hazard ratio (HR)=1.14(95%Confidence Interval (CI)=[0.95-1.38] for anticholinergic score=1; HR=0.92(95%CI=[0.65;1.30] for score=3). Results were stable in sensitivity analyses.

CONCLUSION: We did not find any significant association between anticholinergic exposure and cognitive decline in older adults using anticholinergic scales and definitions of exposure.