BACKGROUND: Despite the high intake of medications with anticholinergic properties by community-dwelling elderly persons, the effects on cognitive decline and dementia have rarely been evaluated. METHODS: Participants were 4128 women and 2784 men 65 years or older from a population-based cohort recruited from 3 French cities. Cognitive performance, clinical diagnosis of dementia, and anticholinergic use were evaluated at baseline and 2 and 4 years later. RESULTS: A total of 7.5% of the participants reported anticholinergic drug use at baseline. Multivariate-adjusted logistic regression indicated that women reporting use of anticholinergic drugs at baseline showed greater decline over 4 years in verbal fluency scores (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.11-1.79) and in global cognitive functioning (OR, 1.22; 95% CI, 0.96-1.55) than women not using anticholinergic drugs. In men, an association was found with decline in visual memory (OR, 1.63; 95% CI, 1.08-2.47) and to a lesser extent in executive function (OR, 1.47; 95% CI, 0.89-2.44). Notable interactions were observed in women between anticholinergic use and age, apolipoprotein E, or hormone therapy. A 1.4- to 2-fold higher risk of cognitive decline was observed for those who continuously used anticholinergic drugs but not for those who had discontinued use. The risk of incident dementia over the 4-year follow-up period was also increased in continuous users (hazard ratio [HR], 1.65; 95% CI, 1.00-2.73) but not in those who discontinued the use of anticholinergic drugs (HR, 1.28; 95% CI, 0.59-2.76). CONCLUSIONS: Elderly people taking anticholinergic drugs were at increased risk for cognitive decline and dementia. Discontinuing anticholinergic treatment was associated with a decreased risk. Physicians should carefully consider prescription of anticholinergic drugs in elderly people, especially in the very elderly and in persons at high genetic risk for cognitive disorder.