Circadian disturbances are well documented in AD patients, and studies suggest that light therapy improves behavior and sleep patterns (see, e.g., Mishima et al., 1994 and Dowling et al., 2007), but this is the first multicenter, randomized clinical trial to address the treatment. First author Rixt Riemersma-van der Lek and colleagues used a 2 x 2 design to randomize 189 patients at 12 care group facilities into placebo, melatonin, light, and light plus melatonin groups. Patients receiving the light treatment lived in care facilities that had constant whole-day bright light (1,000 lux—about three to five times the intensity of a typical living room), while those receiving melatonin were given 2.5 mg each evening. The treatments lasted for as long as 3.5 years.

Riemersma-van der Lek and colleagues found that the light treatment alone attenuated cognitive decline on the Mini-Mental State Exam (MMSE) by 0.9 points (or 5 percent), reduced depression as assessed by the Cornell Scale for Depression in Dementia (CSDD) by 19 percent, and slowed the gradual deterioration in activities of daily living (nurse-informant activities of daily living scale) by about half. Melatonin helped patients fall asleep faster and increased their amount of sleep by nearly half an hour. The combination of light and melatonin reduced aggressive behavior by 9 percent, increased sleep efficiency, and improved nocturnal restlessness. The only downside appears to be that melatonin by itself increased withdrawn behavior and had bad outcomes on mood, lowering scores on positive mood scales and increasing negative ones. Van Someren told ARF that this might be because the dose selected was too high. When the researchers examined plasma melatonin, they found that daytime levels were elevated, which may contribute to the behavioral problems (melatonin is naturally released only during the dark period). “It may be that in older adults, metabolism becomes so slow that some melatonin leaks into fat tissue and then leaks out again during the day when it should not be available,” Van Someren said. He suggested that a lower dose of the hormone might be just as good while having fewer side effects, but cautioned that it will need to be tested.

Van Someren stressed that this is not a cure for AD. “I don’t want to give people false hope by making the suggestion that we have something to cure AD. We definitely do not,” he said. Then how does strengthening the circadian rhythm help? Van Someren made a comparison between a shift-working AD patient with jet-lag who has had a terrible night’s sleep and the same patient on vacation with no jet-lag who had a great night’s sleep. The first patient will be more irritable and perform more poorly in a cognitive test. “Light helps the biological clock to enforce better rhythms on the brain so you sleep better during the night, you are more alert during the day, and you feel better and function better even though the [pathological] decline is going on,” he said.—Tom Fagan.

Reference:
Riemersma-van der Lek R, Swaab DF, Twisk J, Hol EM, Hoogendijk WJG, Van Someren EJW. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities. JAMA 2008, June 11; 299:2642-2655. Abstract