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The 3-City Study

Isabelle Carrière, PhD; Annie Fourrier-Reglat, PhD; Jean-François Dartigues, MD; Olivier Rouaud, MD; Florence Pasquier, MD; Karen Ritchie, PhD; Marie-Laure Ancelin, PhD

Arch Intern Med. 2009;169(14):1317-1324.

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.

Author Affiliations: Inserm, U888, Université Montpellier 1, Montpellier, France (Drs Carrière, Ritchie, and Ancelin); Inserm, U657 (Dr Fourrier-Reglat), and Inserm, U897 (Dr Dartigues), Université Bordeaux 2, Bordeaux, France; Department of Neurology, Centre Hospitalier Universitaire Dijon, Dijon, France (Dr Rouaud); and Department of Neurology, Centre Hospitalier Universitaire Lille, Lille, France (Dr Pasquier).

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