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Am J Neurodegener Dis 2012;1(3):280-291

Original Article
Therapeutic application of melatonin in mild cognitive impairment

Daniel P Cardinali, Daniel E Vigo, Natividad Olivar, María F Vidal, Analía M Furio, Luis I Brusco

Departamento de Docencia e Investigación, Facultad de Ciencias Médicas, Pontificia Universidad Católica
Argentina, Buenos Aires, Argentina; Centro de Neuropsiquiatría y Neurología de la Conducta, Hospital de
Clínicas “José de San Martín”, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

Received August 30, 2012; Accepted October 11, 2012; Epub November 18, 2012; Published November 30, 2012

Abstract: Mild cognitive impairment (MCI) is an etiologically heterogeneous syndrome defined by cognitive impairment
in advance of dementia. We previously reported in a retrospective analysis that daily 3 - 9 mg of a fast-release
melatonin preparation given p. o. at bedtime for up to 3 years significantly improved cognitive and emotional
performance and daily sleep/wake cycle in MCI patients. In a follow up of that study we now report data from another
series of 96 MCI outpatients, 61 of who had received daily 3 - 24 mg of a fast-release melatonin preparation p. o. at
bedtime for 15 to 60 months. Melatonin was given in addition to the standard medication prescribed by the attending
psychiatrist. Patients treated with melatonin exhibited significantly better performance in Mini–Mental State Examination
and the cognitive subscale of the Alzheimer’s disease Assessment Scale. After application of a neuropsychological
battery comprising a Mattis´ test, Digit-symbol test, Trail A and B tasks and the Rey´s verbal test, better performance
was found in melatonin-treated patients for every parameter tested. Abnormally high Beck Depression Inventory scores
decreased in melatonin-treated patients, concomitantly with the improvement in the quality of sleep and wakefulness.
The comparison of the medication profile in both groups of MCI patients indicated that 9.8% in the melatonin group
received benzodiazepines vs. 62.8% in the non-melatonin group. The results further support that melatonin can be a
useful add-on drug for treating MCI in a clinic environment. (AJND1208001).

Keywords: Mild cognitive impairment, Alzheimer´s disease, melatonin, benzodiazepines, neuropsychological tests,
retrospective study


Address all correspondence to:
Dr. Cardinali DP
Departamento de Docencia e Investigación
Facultad de Ciencias Médicas, UCA, Av. Alicia Moreau de Justo
1500, 4º piso. C1107AFD Buenos Aires, ARGENTINA.
Tel: 54 11 43590200, int 2310; Fax: 54 1143590200, int 2310
E-mail: danielcardinali@uca.edu.ar or danielcardinali@fibertel.com.ar