June 12, 2008 — A new study finds that a strategy as simple as increasing levels of daytime lighting in care facilities may improve a variety of cognitive and noncognitive symptoms in patients with dementia.

Researchers carried out a randomized trial using a factorial design to study the effects of light and melatonin, both of which modulate circadian rhythm, or the combination of both light and melatonin among patients with dementia living in 12 group care facilities in the Netherlands.

They found that increasing levels of daytime lighting in the facility had a "modest" benefit in improving some symptoms of disturbed cognition, mood, behavior, functional abilities, and sleep.

"Melatonin improved sleep, but its long-term use by elderly individuals can only be recommended in combination with light to suppress adverse effects on mood," the researchers, with first author Rixt F. Riemersma-van der Lek, MD, from the Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, conclude. "The long-term application of whole-day bright light did not have any adverse effects, on the contrary, and could be considered for use in care facilities for elderly individuals with dementia."

The study is published in the June 11 issue of the Journal of the American Medical Association.

Moderating the Circadian Clock

In addition to cognitive decline, elderly patients with dementia frequently have disturbances of mood, behavior, sleep, and activities of daily living, the study authors write. These symptoms increase caregiver burden and increase the risk for institutionalization for the patient.

Changes in the "circadian pacemaker" of the brain, found in the hypothalamic suprachiasmatic nucleus, may contribute to these disturbances in cognition, behavior, mood, and sleep, they note. This system, though, is "highly sensitive" to the effects of environmental light and the hormone melatonin and may not function optimally when light exposure and melatonin are reduced.

"To our knowledge, no previous studies in humans have applied long-term combined stimulation of the circadian timing system with daily light and melatonin," the study authors write. "We hypothesized that long-term treatment would attenuate cognitive decline and depression, as the primary and secondary outcomes, respectively, and would moreover ameliorate behavioural, functional, and sleep disturbances."

The present study is a multicenter, double-blind, randomized, placebo-controlled trial of these strategies, alone or combined, in 189 residents of 12 group-care facilities in the Netherlands. The mean age of the residents was 85.8 years, 90% were women, and 87% had dementia.

Randomization to light therapy was by institution and to melatonin or placebo by resident. Residents were randomized in a 2 x 2-factorial design to a facility with whole day bright light (± 1000 lux) or dim (± 300 lux) and to 2.5 mg/day of melatonin or placebo, given for a mean of 15 months to a maximum of 3.5 years.

Light exposure was manipulated by installation of a large number of ceiling-mounted fixtures with acrylic glass diffusers containing fluorescent bulbs in the common living room of the group-care facilities. In the facilities randomized to dim light, the same number of fixtures was installed but with half the number of bulbs and with fixtures farther away from eye level.

Subjects were evaluated every 6 months with use of standardized scales for cognitive and noncognitive symptoms, activities of daily living, and any adverse effects.

The results showed that light therapy attenuated cognitive deficits by 5%, the study authors report, "without decelerating the progressive cognitive worsening (as is also the case for acetylcholinesterase inhibitors)." It also reduced symptoms of depression and attenuated the increase in functional limitations with time.

Table. Primary and Secondary Outcomes With Light Therapy vs No Light Therapy

Melatonin, on the other hand, had no effect on depression ratings but adversely affected caregiver ratings of withdrawn behavior and mood expression. "We suspect that the long-term daily application of 2.5 mg of melatonin may have induced supraphysiological daytime levels, which are associated with sleepiness and dysphoria," they write. They suggest that for practical application, a lower dose in combination with light therapy be considered.

However, melatonin did have some beneficial effects, reducing sleep onset latency by 8.2 minutes (19%), increasing total sleep duration by 27 minutes (6%), and increasing the mean duration of uninterrupted sleep periods by 25%. In combination with bright light, melatonin also improved sleep efficiency, reduced nocturnal restlessness, and reduced the average duration of brief nocturnal awakenings.

It is interesting to note that these effects increased over time with treatment, the study authors note.

"If effects were sustained over time," they write, "prolonged combined treatment could help maintain sleep efficiency above 85%, which has been regarded as a cut-off for clinically relevant disturbed sleep. Our novel finding that some melatonin effects develop slowly and/or only in combination with light treatment may explain the lack of effects in some of the previous short-term studies."

The study was funded by the Netherlands Organization for Health Research, the Hague; the Stichting De Drie Lichten, Leiden; Zeist; Japan Foundation for Aging and Health; Hersenstichting Nederland; and Internationale Stichting Alzheimer Onderzoek. Philips Lighting BV, Braun, and Cambridge Neurotechnology supplied material for the study at a reduced cost. Three of the study authors have obtained funding. The other study authors have disclosed no relevant financial relationships.

JAMA. 2008;299:2642-2655.

Clinical Context

Study Highlights

• Included were 189 residents (170 women, 19 men; mean age, 85.8 years) from 12 different residential homes providing assisted care, where residents lived in their own apartments but spent the day in a common living room.
• Facilities were randomized to either melatonin or bright light alone, the combination of both (6 facilities; n = 98), or placebo (6 facilities; n = 91).
• Excluded were patients using monoamine oxidase inhibitors or nonsteroidal anti-inflammatory drugs or patients with liver or kidney dysfunction or aphakia.
• The diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria.
• 63% met criteria for probable Alzheimer's disease, 11% for vascular dementia, and 13% for other dementia such as frontal-type and Lewy-body dementia.
• Facilities were rated on the Therapeutic Environment Screening Scale for conditions such as lighting, design, maintenance, and staff interactions.
• Light exposure was manipulated by ceiling-mounted fixtures with acrylic glass diffusers in the common living room.
• The light treatment group received ± 1000 lux between 9 AM and 6 PM, whereas the placebo light group received ± 300 lux.
• The melatonin group received 2.5 mg of intermediate-release melatonin at bedtime administered by nursing staff.
• Patients were observed for up to 3.5 years for a mean of 15 months, between 0.5 and 3.5 years across facilities.
• Tests were administered 6 weeks before and 6 weeks after the start of treatment and every 6 months after.
• Cognitive performance, mood (depression and anxiety), behaviors (agitation, withdrawn behavior, distress), and daily functioning were assessed by neuropsychologists and caregivers.
• Estimates of sleep were obtained by 14 days of actigraphy recording with use of the Actiwatch (Cambridge Neurotechnology, Cambridge, England) and accompanying software.
• Sleep parameters included bedtime and wake time, quantity of sleep and wakefulness, restlessness, and sleep structure.
• Light treatment ameliorated the cognitive decline of participants overall by 0.9 points or a relative 5% (P = .04) with a fixed difference at all time points.
• Light treatment ameliorated symptoms of depression by 1.5 points or a relative 19% (P= .02).
• Melatonin adversely affected mood by lowering positive ratings by 0.5 points (5%) and increasing negative ratings by 0.8 points (14%; P = .02).
• Exposure to bright light compensated for the negative effects of melatonin on mood.
• Melatonin aggravated the withdrawn behavior rating by 1.02 points (7%; P = .02), but combined light and melatonin ameliorated the negative effect of melatonin on agitated behavior by 3.9 points or a relative 9% (P = .01).
• Light treatment attenuated the gradual increase in functional limitation by 1.8 points or a relative 53%.
• Combined treatment improved sleep efficiency by 3.5% (P = .01) and ameliorated nocturnal restlessness by 1 minute per hour each year (9%; P = .01).
• Melatonin improved sleep duration by 27 minutes (6%) and, with light treatment, by an additional 10 minutes per year (2%).
• Combined treatment significantly reduced sleep fragmentation by reducing brief nocturnal awakenings by 0.5 minutes per year or a relative 12%.
• Melatonin improved average duration of uninterrupted sleep by 5.8 minutes or a relative 25%.
• Light, melatonin, or the combination of both did not affect medication use.
• The authors concluded that exposure to light reduced the decline in cognitive and functional deficits in patients with dementia and that melatonin combined with light improved sleep quality, but melatonin alone had adverse effects on mood, which were compensated for by light exposure.

Pearls for Practice

• Exposure to bright light in older patients with dementia is associated with a reduction in cognitive decline and improvement in daily functioning.
• Melatonin in older patients with dementia is associated with negative effects on mood, which are ameliorated by light treatment, and positive effects on sleep.

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