Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial

Jun 28, 2014Clinical interventions in aging

Adding prolonged-release melatonin to improve thinking and sleep in mild to moderate Alzheimer's disease: a 6-month controlled trial

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Abstract

Patients treated with (PRM) had significantly better cognitive performance compared to those on placebo after 24 weeks.

Cognitive performance improvements were measured using the Instrumental Activities of Daily Living (IADL) and Mini-Mental State Examination (MMSE), with significant results (P=0.004 and P=0.044, respectively).
Sleep efficiency, assessed by the Pittsburgh Sleep Quality Index (PSQI), was better in the PRM group (P=0.017).
In patients with comorbid insomnia, PRM treatment led to significant improvements in IADL (P=0.032), MMSE score (P=0.0177), and sleep efficiency (P=0.04).
Median values for the Assessment Scale-Cognition (ADAS-Cog) showed significant improvement with PRM compared to placebo (P=0.045).
PRM was well tolerated, with adverse events comparable to those observed with placebo.

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PURPOSE: A link between poor sleep quality and (AD) has recently been suggested. Since endogenous melatonin levels are already reduced at preclinical AD stages, it is important to ask whether replenishing the missing hormone would be beneficial in AD and whether any such effects would be related to the presence of sleep disorder in patients.

PATIENTS AND METHODS: The effects of add-on (PRM) (2 mg) to standard therapy on cognitive functioning and sleep were investigated in 80 patients (men [50.7%], women [49.3%], average age 75.3 years [range, 52-85 years]) diagnosed with mild to moderate AD, with and without insomnia comorbidity, and receiving standard therapy (acetylcholinesterase inhibitors with or without memantine). In this randomized, double-blind, parallel-group study, patients were treated for 2 weeks with placebo and then randomized (1:1) to receive 2 mg of PRM or placebo nightly for 24 weeks, followed by 2 weeks placebo. The AD Assessment Scale-Cognition (ADAS-Cog), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE), sleep, as assessed by the Pittsburgh Sleep Quality Index (PSQI) and a daily sleep diary, and safety parameters were measured.

RESULTS: Patients treated with PRM (24 weeks) had significantly better cognitive performance than those treated with placebo, as measured by the IADL (P=0.004) and MMSE (P=0.044). Mean ADAS-Cog did not differ between the groups. Sleep efficiency, as measured by the PSQI, component 4, was also better with PRM (P=0.017). In the comorbid insomnia (PSQI ≥6) subgroup, PRM treatment resulted in significant and clinically meaningful effects versus the placebo, in mean IADL (P=0.032), MMSE score (+1.5 versus -3 points) (P=0.0177), and sleep efficiency (P=0.04). Median ADAS-Cog values (-3.5 versus +3 points) (P=0.045) were significantly better with PRM. Differences were more significant at longer treatment duration. PRM was well tolerated, with an adverse event profile similar to that of placebo.

CONCLUSION: Add-on PRM has positive effects on cognitive functioning and sleep maintenance in AD patients compared with placebo, particularly in those with insomnia comorbidity. The results suggest a possible causal link between poor sleep and cognitive decline.

Key numbers

1.5

Increase in MMSE Score

Mean MMSE score change in insomnia subgroup after 24 weeks.

-3.5

Decrease in ADAS-Cog Score

Median ADAS-Cog score change in insomnia subgroup after 24 weeks.

0.04

Improvement in Sleep Efficiency

P-value for PSQI component measuring sleep efficiency in the insomnia subgroup.

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Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial

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