Cognitive/Non-cognitive Function in Elderly Patients

Abstract & Commentary

By Donal P. O'Mathuna, PhD. Dr. O'Mathuna is a lecturer in Health Care Ethics, School of Nursing, Dublin City University, Ireland; he reports no financial relationships relevant to this field of study.

Source: Riemersma-van der Lek RF, et al. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA. 2008;299:2642-2655.

Cognitive decline, mood, behavioral and sleep disturbances, and limitations of activities of daily living commonly burden elderly patients with dementia and their caregivers. Circadian rhythm disturbances have been associated with these symptoms.

Objective: To determine whether the progression of cognitive and non-cognitive symptoms may be ameliorated by individual or combined long-term application of the two major synchronizers of the circadian timing system: bright light and melatonin.

Design, Setting, and Participants: A long-term, double-blind, placebo-controlled, 2x2 factorial, randomized trial performed from 1999 to 2004 with 189 residents of 12 group care facilities in the Netherlands; mean (SD) age, 85.8 (5.5) years; 90% were female and 87% had dementia.

Interventions: Random assignment by facility to long-term daily treatment with whole-day bright (±1000 lux) or dim (±300 lux) light and by participant to evening melatonin (2.5 mg) or placebo for a mean (SD) of 15 (12) months (maximum period of 3.5 years).

Main Outcome Measures: Standardized scales for cognitive and non-cognitive symptoms, limitations of activities of daily living, and adverse effects assessed every six months.

Results: Light attenuated cognitive deterioration by a mean of 0.9 points (95% confidence interval [CI], 0.04-1.71) on the Mini-Mental State Examination or a relative 5%. Light also ameliorated depressive symptoms by 1.5 points (95% CI, 0.24-2.70) on the Cornell Scale for Depression in Dementia or a relative 19%, and attenuated the increase in functional limitations over time by 1.8 points per year (95% CI, 0.61-2.92) on the nurse-informant activities of daily living scale or a relative 53% difference. Melatonin shortened sleep onset latency by 8.2 minutes (95% CI, 1.08-15.38) or 19% and increased sleep duration by 27 minutes (95% CI, 9-46) or 6%. However, melatonin adversely affected scores on the Philadelphia Geriatric Centre Affect Rating Scale, both for positive affect (-0.5 points; 95% CI, -0.10 to -1.00) and negative affect (0.8 points; 95% CI, 0.20-1.44). Melatonin also increased withdrawn behavior by 1.02 points (95% CI, 0.18-1.86) on the Multi Observational Scale for Elderly Subjects scale, although this effect was not seen if given in combination with light. Combined treatment also attenuated aggressive behavior by 3.9 points (95% CI, 0.88-6.92) on the Cohen-Mansfield Agitation Index or 9%, increased sleep efficiency by 3.5% (95% CI, 0.8%-6.1%), and improved nocturnal restlessness by 1.00 minute per hour each year (95% CI, 0.26-1.78) or 9% (treatment X time effect).

Conclusions: Light has a modest benefit in improving some cognitive and non-cognitive symptoms of dementia. To counteract the adverse effect of melatonin on mood, it is recommended only in combination with light.

Trial Registration: controlled-trials.com/isrctn Identifier: ISRCTN93133646

Commentary

As the population ages, the number of people in residential homes is increasing. More women than men become residents in these homes for a variety of reasons, something reflected in the gender make-up of this study: 90% of the participants were female. This limits the generalizability of the findings, however. When age-related dementia develops, cognitive decline is often accompanied by sleep and mood disturbances. These affect quality of life, functional abilities, and the burden on those caring for residents.

When sleep is disturbed, the body's circadian pacemaker can become desynchronized. This system is highly sensitive to both environmental light and the hormone melatonin. The body's production of melatonin cycles during the day, influenced by light and darkness. Production also changes with age. Jet lag develops as a result of desynchronization of the circadian rhythms, which has led to much interest in supplemental melatonin to relieve the symptoms of jet lag. While earlier studies were encouraging, more recent studies have not found benefit for jet lag.1 At the same time, use of melatonin to treat various sleep disorders has been receiving much attention.2 The study by Riemersma-van der Lek et al is the first to examine the long-term efficacy of both bright light and melatonin on cognitive and non-cognitive functions associated with sleep disturbances.

The study recruited participants from 12 facilities in the Netherlands where residents have their own apartments but spend much of their time in common living areas supervised by caregivers. The majority of participants (87%) had dementia. The homes were randomly assigned to deliver bright light or normal light. For the bright light group, sufficient fluorescent lights were installed in the common living areas to deliver approximately 1000 lux. Similar fixtures, but with fewer lights, were installed in the homes in the placebo light group. The participants were randomized a second time to receive either melatonin (2.5 mg 1 hour before bedtime) or placebo tablets. The participants were then monitored for up to 3.5 years, with assessments conducted six weeks after enrollment and every six months subsequently.

A total of 13 different outcome measurements were made: four mood scales, four functional status scales, one functional limitations scale, and three estimates of sleep quality. While a large number of measures has advantages, it can also increase the chances of finding spurious positive results. It can lead to situations, as with this study, where some results are positive and others negative, making straight-forward recommendations difficult.

However, the results of this study did show several significant benefits from bright light. Based on these findings, the use of whole-day bright light in residential homes for the elderly can be recommended. However, the benefits were very modest and, while statistically significant, it would be difficult to determine their clinical significance. For example, baseline sleep efficiency ranged between 70% and 76%. Combined treatment with bright light and melatonin led to an average improvement of 3.5%. This remains short of the 85% efficiency that is often used as a cut-off for overcoming sleep disturbances. In addition, the cost of installing and running the additional lights was not calculated.

The findings for melatonin were not as clear-cut. While positive changes were found for some sleep parameters, other outcomes were negatively affected (see the summary above for details). Those receiving both melatonin and bright light had more beneficial changes. The strength of the changes increased over time. This may offer insight into some of the variability found in previous melatonin studies, as they may not have been conducted over a sufficiently long period to allow changes to develop. Of concern is the finding that those receiving melatonin showed more withdrawn behaviors and mood deterioration. The researchers suspected that this may have been due to the long-term administration of a dose of 2.5 mg. Melatonin has been associated with day-time sleepiness. The researchers recommended a lower dose for older people. In general, melatonin was tolerated well. No serious adverse events were reported by the physicians caring for the participants. The daughter of one participant suspected the study treatments led to her mother's increased restlessness and falls. She was withdrawn from the study and found to have been in the double placebo group.

Overall, the study found some limited benefits for whole-day bright light in residential homes. It also demonstrated the feasibility of conducting a rigorous clinical trial of combination complementary therapies.3

References

1. Buscemi N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ. 2006;332:385-393.

2. Pandi-Perumal SR, et al. Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs. 2007;21:995-1018.

3. Chan E. Quality of efficacy research in complementary and alternative medicine. JAMA. 2008;299: 2685-2686.