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The neuroprotective effects of caffeine

A prospective population study (the Three City Study)

K. Ritchie, PhD, I. Carrière, PhD, A. de Mendona, MD, PhD, F. Portet, MD, PhD, J. F. Dartigues, MD, PhD, O. Rouaud, MD, P. Barberger-Gateau, MD, PhD and M. L. Ancelin, PhD

From INSERM U888 (K.R., I.C., F.P., A.d.M., M.L.A.), Montpellier; INSERM U593 (J.F.D., P.B.-G.), Bordeaux University 2; INSERM U708 (O.R.), University of Paris, France; and Department of Neurology and Laboratory of Neurosciences (A.d.M.), University of Lisbon, Portugal.

Address correspondence and reprint requests to Dr. Karen Ritchie, INSERM U888 Nervous System Pathologies: Epidemiological and Clinical Research, La Colombière Hospital, 34093 Montpellier Cedex 5, France ritchie{at}montp.inserm.fr

Objective: To examine the association between caffeine intake, cognitive decline, and incident dementia in a community-based sample of subjects aged 65 years and over.

Methods: Participants were 4,197 women and 2,820 men from a population-based cohort recruited from three French cities. Cognitive performance, clinical diagnosis of dementia, and caffeine consumption were evaluated at baseline and at 2 and 4 year follow-up.

Results: Caffeine consumption is associated with a wide range of sociodemographic, lifestyle, and clinical variables which may also affect cognitive decline. Multivariate mixed models and multivariate adjusted logistic regression indicated that women with high rates of caffeine consumption (over three cups per day) showed less decline in verbal retrieval (OR = 0.67, CI = 0.53, 0.85), and to a lesser extent in visuospatial memory (OR = 0.82, CI = 0.65, 1.03) over 4 years than women consuming one cup or less. The protective effect of caffeine was observed to increase with age (OR = 0.73, CI = 0.53, 1.02 in the age range 65 to 74; OR = 0.3, CI = 0.14, 0.63 in the range 80+). No relation was found between caffeine intake and cognitive decline in men. Caffeine consumption did not reduce dementia risk over 4 years.

Conclusions: The psychostimulant properties of caffeine appear to reduce cognitive decline in women without dementia, especially at higher ages. Although no impact is observed on dementia incidence, further studies are required to ascertain whether caffeine may nonetheless be of potential use in prolonging the period of mild cognitive impairment in women prior to a diagnosis of dementia.

*These authors contributed equally to this work.

The 3C Study is conducted under a partnership agreement among INSERM, the Victor Segalen–Bordeaux II University, and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and first phase of the study. The 3C-Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, the Institut de la Longévité, Agence Franaise de Sécurité Sanitaire des Produits de Santé, the regional governments of Aquitaine, Bourgogne, and Languedoc-Roussillon, and the Fondation de France, the Ministry of Research-INSERM Programme "Cohorts and collection of biological material." The Lille Génopôle received an unconditional grant from Eisai.

Disclosure: The authors report no conflicts of interest.

Received November 30, 2006. Accepted in final form March 5, 2007.

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