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Effectiveness of the Combination of Memantine Plus Vitamin D on Cognition in Patients With Alzheimer Disease: A Pre-Post Pilot Study

Annweiler, Cédric MD, PhD*,†,‡; Herrmann, François R. MD, MPH§; Fantino, Bruno MD, PhD†,‡; Brugg, Bernard PhD; Beauchet, Olivier MD, PhD*,†,‡

Cognitive and Behavioral Neurology: September 2012 - Volume 25 - Issue 3 - p 121–127
doi: 10.1097/WNN.0b013e31826df647
Original Studies

Objective: To determine whether treatment with memantine plus vitamin D is more effective than memantine or vitamin D alone in improving cognition among patients with Alzheimer disease (AD).

Methods: We studied 43 white outpatients (mean 84.7±6.3 years; 65.1% women) with a new diagnosis of AD, who had not taken anti-dementia drugs or vitamin D supplements. We prescribed memantine alone (n=18), vitamin D alone (n=17), or memantine plus vitamin D (n=8) for an average of 6 months. We assessed cognitive change with the Mini-Mental State Examination (MMSE). We used age, sex, pre-treatment MMSE score, and duration of treatment as covariables.

Results: Before treatment, the 3 groups had comparable MMSE scores. At 6 months, participants taking memantine plus vitamin D increased their MMSE score by 4.0±3.7 points (P=0.034), while participants taking memantine alone remained stable (change of 0.0±1.8 points; P=0.891), as did those taking vitamin D alone (−0.6±3.1 points; P=0.504). Treatment with memantine plus vitamin D was associated with improvement in the MMSE score compared to memantine or vitamin D alone after adjustment for covariables (P<0.01). Mixed regression analysis showed that the visit by combined treatments (memantine plus vitamin D) interaction was significant (P=0.001), while memantine or vitamin D alone showed no effect.

Conclusions: Patients with AD who took memantine plus vitamin D for 6 months had a statistically and clinically relevant gain in cognition, underlining possible synergistic and potentiating benefits of the combination.

*Department of Neuroscience, Division of Geriatric Medicine, Angers University Hospital, Angers, France

University Memory Clinic, Angers, France

UPRES EA 2646, University of Angers, UNAM, Angers, France

§Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland

UPMC Université Paris 6, UMR 7102 NPA, Paris, France

The concept of combining memantine with vitamin D in the prevention and treatment of Alzheimer disease and related disorders was patented by Angers University Hospital and the University of Angers.

No funding was received to support this study. None of the authors have a personal financial interest in this research. The staff members of the Angers Memory Clinic were not compensated for their services to the study.

C.A. has full access to the study data and takes responsibility for the integrity of the data and the accuracy of the data analysis. C.A. and O.B. conceived of and designed the study; acquired, analyzed, and interpreted the data; drafted the manuscript; and provided administrative, technical, and material support. O.B. supervised the study. C.A. and F.R.H. provided statistical expertise. B.F., F.R.H., and B.B. provided critical revisions to the manuscript.

Reprints: Cédric Annweiler, MD, PhD, Department of Neuroscience, Division of Geriatric Medicine, Angers University Hospital, 49933 Angers Cedex 9, France (e-mail:

Received December 21, 2011

Accepted April 27, 2012

© 2012 Lippincott Williams & Wilkins, Inc.