Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease

Abstract

Objectives: To test whether the addition of melatonin to bright-light therapy enhances the efficacy in treating rest-activity (circadian) disruption in institutionalized patients with Alzheimer's disease (AD).

Design: Randomized, controlled trial.

Setting: Two nursing homes in San Francisco, California.

Participants: Fifty subjects (mean age 86) with AD.

Intervention: Experimental subjects received 1 hour of morning light exposure (> or = 2,500 lux in gaze direction) Monday to Friday for 10 weeks and 5 mg melatonin (LM, n=16) or placebo (LP, n=17) in the evening. Control subjects (n=17) received usual indoor light (150-200 lux).

Measurements: Nighttime sleep variables, day sleep time, day activity, day:night sleep ratio, and rest-activity parameters were determined using actigraphy.

Results: Linear mixed models were employed to test the primary study hypotheses. No significant differences in nighttime sleep variables were found between groups. At the end of the intervention, the LM group showed significant improvement in daytime somnolence as indicated by a reduction in the duration of daytime sleep, an increase in daytime activity, and an improvement in day:night sleep ratio. The LM group also evidenced a significant increase in rest-activity rhythm amplitude and goodness of fit to the cosinor model.

Conclusion: Light treatment alone did not improve nighttime sleep, daytime wake, or rest-activity rhythm. Light treatment plus melatonin increased daytime wake time and activity levels and strengthened the rest-activity rhythm. Future studies should resolve the question of whether these improvements can be attributed to melatonin or whether the two zeitgebers interact to amplify efficacy.

Figure 1

Rest–activity rhythm acrophase and amplitude. ● Baseline, ○ End of Intervention. These polar plots provide a visual representation of the individual subject’s acrophase (time of peak activity) and amplitude relative to the 24-hour day at baseline and end of intervention. Position on the circular axis corresponds to 24-hour clock time, with midnight represented as 0 on the far right, 6:00 a.m. on the top, noon on the left, and 6:00 p.m. at the bottom. Position on the radial axis corresponds to rhythm amplitude, smaller amplitudes are closer to the center, and larger amplitudes are more distal.

Figure 2

Hourly activity counts according to group. Mean (5-day, 4-night) hourly natural log (ln) activity counts by time of day and group at baseline and end of intervention. C = control, LP = light and placebo, LM = light and melatonin. The absolute and relative change in the position of the solid line from baseline to end of intervention graphically illustrate the increase in daytime activity in the LM group.