Therapeutic application of melatonin in mild cognitive impairment

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.

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

Figure 1

Retrospective analysis of 96 outpatients complaining of MCI symptoms, 61 of which received daily 3 to 24 mg of a fast-release melatonin preparation p.o. at bedtime for 15 to 60 months. Melatonin was given in addition to the individual standard medication prescribed by the attending psychiatrist. The other 35 subjects selected received the medication prescribed by the attending psychiatrist which did not include melatonin. Initial and final neuropsychological evaluation including the MMSE, ADAS-Cog, Mattis´ test and Digit-symbol task are depicted. See Methods for further experimental details. Shown are the means ± SD. P values denote the differences between groups of changes in neuropsychological evaluation before and after the follow-up period (Mann-Whitney U test). Z values are depicted in Table 2.

Figure 2

Retrospective analysis of 96 outpatients complaining of MCI symptoms, 61 of which received daily 3 to 24mg of a fast-release melatonin preparation p.o. at bedtime for 15 to 60 months. For details see Legend to Figure 1.Initial and final neuropsychological evaluation of trail A and trail B tasks, and Rey´s verbal test are depicted. Shownare the means ± SD. P values denote the differences between groups of changes in neuropsychological evaluationbefore and after the follow-up period (Mann-Whitney U test). Z values are depicted in Table 2.

Figure 3

Retrospective analysis of 96 outpatients complaining of MCI symptoms, 61 of which received daily 3 to 24mg of a fast-release melatonin preparation p.o. at bedtime for 15 to 60 months. For details see Legend to Figure 1.Initial and final neuropsychological evaluation of Beck Depression Inventory and a global assessment of wakefulnessand sleep quality are depicted. Shown are the means ± SD. P values denote the differences between groups ofchanges in neuropsychological evaluation before and after the follow-up period (Mann-Whitney U test). Z values aredepicted in Table 2.