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

Abstract

Aim: The aim of the present study was to assess the association between anticholinergic (atropinic) burden and cognitive decline in older adults over the course of 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 (MMSE) 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 four methods for each of four anticholinergic scales (Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, Anticholinergic Risk Scale, the Durán list). The association between cognitive decline and time-varying anticholinergic exposure [primary analysis using the 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 1396 patients included, 7.4-23.5% were exposed to anticholinergic agents, depending on the anticholinergic scale used. Sixty-four per cent 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 with non-anticholinergic agent 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 found no significant association between anticholinergic exposure and cognitive decline in older adults using anticholinergic scales and definitions of exposure.

Keywords: adverse drug reactions; elderly; neurodegeneration; pharmacoepidemiology.

Figure 1

Flow chart of the included subjects

Figure 2

Anticholinergic exposure by cognitive decline status [defined by the quintile definition (−0.236 points)] during follow‐up (number of subjects = 1396). (A) Baseline anticholinergic burden (maximal score); (B) Incident anticholinergic drug users during follow‐up; (C) Baseline anticholinergic drug users; (D) Baseline anticholinergic burden (sum of scores). ACB, Anticholinergic Cognitive Burden; ADS, Anticholinergic Drug Scale; ARS, Anticholinergic Risk Scale

Figure 3

Risk of cognitive decline [defined by the quintile definition (−0.236 points)] during follow‐up by anticholinergic exposure defined by the Durán list in Kaplan–Meier analyses (number of subjects = 1396). (A) Anticholinergic burden (maximal score); (B) Anticholinergic burden (sum of scores); (C) Anticholinergic drug users; (D) Prevalent anticholinergic drug users at baseline ^† Considered as a time‐varying variable in the analysis

Figure 4

Cognitive decline status [defined by the quintile definition (−0.236 points)] risk at any time according to anticholinergic exposure defined by the Anticholinergic Drug Scale in Kaplan–Meier analyses (number of subjects = 1396). (A) Anticholinergic burden (maximal score); (B) Anticholinergic burden (sum of scores); (C) Anticholinergic drug users; (D) Prevalent anticholinergic drug users at baseline ^† Considered as a time‐varying variable in the analysis

Figure 5

Cognitive decline status [defined by the quintile definition (−0.236 points)] risk at any time, according to anticholinergic exposure defined by the Anticholinergic Cognitive Burden in Kaplan–Meier analyses (number of subjects = 1396). (A) Anticholinergic burden (maximal score); (B) Anticholinergic burden (sum of scores); (C) Anticholinergic drug users; (D) Prevalent anticholinergic drug users at baseline ^† Considered as time‐varying variable in the analysis

Figure 6

Cognitive decline status [defined by the quintile definition (−0.236 points)] risk at any time according to anticholinergic exposure defined by the Anticholinergic Risk Scale in Kaplan–Meier analyses (number of subjects = 1396). (A) Anticholinergic burden (maximal score); (B) Anticholinergic burden (sum of scores); (C) Anticholinergic drug users; (D) Prevalent anticholinergic drug users at baseline ^† Considered as time‐varying variable in the analysis