In the longitudinal logistic regression analyses, decline in cognitive performance was defined as a decrease from baseline of at least 6 points on the Isaacs Set Test total score or at least 2 points on the BVRT and the MMSE (lowest quintiles). For the TMT, cognitive decline was defined as an increase from baseline of at least 16 (TMT A) or 35 seconds (TMT B) (Table 2). In women, univariate logistic regression adjusted for age, educational level, center, and baseline cognitive score (model 0) indicated a significant association between anticholinergic use and decline in Isaacs Set Test total score (OR, 1.47; 95% confidence interval [CI], 1.16-1.86; P = .002) and in the MMSE (OR, 1.26; 95% CI, 1.00-1.60; P = .05). No significant association was observed for the BVRT (P = .33) and the TMT A (P = .73) or TMT B (P = .88). In men, anticholinergic use was significantly associated with decline in the BVRT (OR, 1.70; 95% CI, 1.13-2.56; P = .01) but was not significantly associated in the TMT B (OR, 1.61; 95% CI, 0.98-2.64; P = .06) in the Isaacs Set Test or the TMT A. In multivariate logistic regression (model 1), the same associations were observed with significant cognitive decline in the Isaacs Set Test in women (P = .003) and in the BVRT in men (P = .01). These associations persisted in the complete model (model 2) further adjusted for other confounders such as disease associated with anticholinergic prescription (depression, ischemic diseases, Parkinson disease, and hypertension). The OR was 1.41 (95% CI, 1.11-1.79; P = .006) for decline on the Isaacs Set Test total score in women. This effect seemed related to the early retrieval phase (OR, 1.27; 95% CI, 0.99-1.62; P = .06), whereas no notable association was found for the late retrieval phase (data not shown). In men, the OR was 1.63 (95% CI, 1.08-2.47; P = .02) for decline in the BVRT test. However, the association with decline in the TMT B in men was not significant in model 2 (P = .14), as well as for the MMSE in women (P = .10). For women specifically, an interaction was observed on the MMSE between anticholinergic use and age (risk increasing with age; P = .002) and apolipoprotein E (the risk being significantly increased only for APOE*E4 carriers; OR, 2.05; 95% CI, 1.24-3.40; P = .005 vs OR, 1.07; 95% CI, 0.81-1.40; P = .65 in non–APOE*E4 carriers). There was also an interaction between anticholinergic use and HT on early retrieval on the Isaacs Set Test; the risk of cognitive decline in those using anticholinergics was increased for those who had never used HT (OR, 1.44; 95% CI, 1.07-1.94; P = .02) in contrast with current HT users (OR, 0.51; 95% CI, 0.25-1.05; P = .07).