The Corpus Callosum

A study published in title="Journal of the American Medical Association">JAMA
indicates that treatment with bright light alone (1,000 href="http://en.wikipedia.org/wiki/Lux">lux), or
bright light combined with href="http://en.wikipedia.org/wiki/Melatonin">melatonin,
can improve symptoms in patients with dementia.  Melatonin
alone appeared to have a slight adverse effect.

This already has been reported by href="http://www.time.com/time/health/article/0,8599,1813396,00.html">Time,
the BBC,
href="http://www.modernmedicine.com/modernmedicine/Neurology/Bright-Light-Can-Help-Treat-Dementia-Symptoms/ArticleNewsFeed/Article/detail/523025?contextCategoryId=40224">Modern
Medicine, href="http://psychcentral.com/news/2008/06/11/bright-light-helps-elderly-with-dementia/2442.html">PsychCentral,
href="http://www.medgadget.com/archives/2008/06/bright_lights_help_dementia_sufferers.html">MedGadget,
and Medical
News Today
.  As I start to write it, though, I can
find only href="http://paxalles.blogs.com/paxalles/2008/06/dementia-slowed.html">one
blog that mentions it, so it is worth mentioning here.
 

This was a long-term study of a medium number of elderly patients with
dementia, all of whom lived in a  group setting.  It
was a randomized, double-blind study.  Specifically, it
included 189 patients who were followed for a mean of 15 months.
 

The effect size was not great, but it was statistically significant.
 Moreover, there were improvements in mood, functional, and
behavioral measures.  Cognitive function on the href="http://en.wikipedia.org/wiki/Mini-mental_state_examination">Mini-Mental
State Exam (a measure of cognitive function) declined by 0.9
points less in the group that received bright light.  Scores
on the href="http://siq.air.org/ResourceDetail.aspx?source=CMS&ResourceID=349">Cornell
Scale for Depression in Dementia were better by 19%.
 Bright light also reduced the increase in functional
limitations over time by 1.8 points per year on the Nurse-informant
Activities of Daily Living Scale (a relative 53% difference).
 Combined treatment reduced aggressive behavior by 9%
on the Cohen-Mansfield
Agitation Index
.

href="http://jama.ama-assn.org/cgi/content/short/299/22/2642">Effect
of Bright Light and Melatonin on Cognitive and Noncognitive Function in
Elderly Residents of Group Care Facilities

Rixt F. Riemersma-van der Lek, MD; Dick F. Swaab, MD,
PhD; Jos Twisk, PhD; Elly M. Hol, PhD; Witte J. G. Hoogendijk, MD, PhD;
Eus J. W. Van Someren, PhD

JAMA. 2008;299(22):2642-2655.

Context  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 noncognitive symptoms may be ameliorated
by individual or combined long-term application of the 2 major
synchronizers of the circadian timing system: bright light and
melatonin.

Design, Setting, and Participants  A
long-term, double-blind, placebo-controlled, 2 x 2 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 noncognitive symptoms, limitations of
activities of daily living, and adverse effects assessed every 6 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 noncognitive symptoms of dementia. To
counteract the adverse effect of melatonin on mood, it is recommended
only in combination with light.

Note that no one is saying that the treatment(s) had any effect on the
underlying disease process.  Rather, the treatment(s) had an
effect on symptoms.  Even so, the findings are clinically
important.  Specifically, the reduction in aggression, and the
slower decline in loss of ADL function, could improve quality of life.
 Those differences also could reduce caregiver burden.

There are limitations to the study.  Owing to the nature of
the population being studied, there was a lot of missing data.
 People died, or transferred to other facilities.
 Some facilities stopped participating.  There are
statistical ways of adjusting for this, but is still is a limitation.
 Also, the study was carried out in the Netherlands.
 This is not a flaw or limitation, per se, but it may affect
the generalizability of the outcome.  Amsterdam is at latitude
52°N, as compared to, say, New York City, at 40°N, or Mexico City at
19°N.  Would the effect be the same in a less northern
location?  Probably, since the indoor lighting conditions may
not be that much different; but, you don’t know until you do the study.
 

Of course the biggest limitation is that studies such as these need to
be replicated elsewhere, before any firm conclusion can be drawn.
 

So what is going on in the brain?  Ageing is known to affect
the function of the circadian timing system (biological clock) in the
part of the brain known as the href="http://en.wikipedia.org/wiki/Suprachiasmatic_nucleus">suprachiasmatic
nucleus.  Melatonin and bright light help to correct
the alterations in this functioning.  It is not clear how this
improves cognitive function, aggressive behavior, and activities of
daily living.  The positive effect on mood is understood a
little better, as href="http://scienceblogs.com/clock/2008/04/seasonal_affective_disorder_th_2.php">Coturnix
explains.

In vague terms, it seems likely that boosting the function of the
circadian timing system helps to optimize a variety of physiological
functions.  This may be how the treatment helps with the other
symptoms.  This explanation is not very helpful, though, as it
does not explain the divergence in findings between melatonin alone,
bright light alone, and combined treatment.  Like most of
these studies, it generates a lot more questions than it answers.
 

There are a few more interesting points to consider.  Note
that bright light and melatonin both are inexpensive.  The
benefits from these interventions are href="http://psychiatry.jwatch.org/cgi/content/full/2008/610/1">comparable
in size to those seen from patented (expensive) medications.
 Plus, if the caregiver burden is decreased, the cost of
providing care could actually go down, while the quality of life goes
up.  It’s hard to beat that, from a cost-effectiveness
standpoint.

Comments

  1. #1 Mark P
    June 12, 2008

    Now that’s interesting. We are currently going through the mental and physical decline of my father in law. He spends his days sitting in a dark room (the kind that “den” seems to fit really well). I wonder if it’s worthwhile to have his wife simply turn on a damned light …

  2. #2 Joseph j7uy5
    June 12, 2008

    Possibly, although few households will get to 1,000 Lux brightness without adding some more lights. It seems simple enough, and can’t hurt. Some people find that once they get used to it, they like the extra light.

  3. #3 Mike
    June 12, 2008

    They had that infrared hat for alzheimer’s in the news a couple of months ago. Maybe a combination of that hat with melatonin would lead to an even greater symptom resolution.

    I’m somewhat skeptical of this study myself. All too often these alzheimer’s studies merely offer patients and families false hope.

    “The benefits from these interventions are comparable in size to those seen from patented (expensive) medications.”
    Thats good news. I wonder if you combined this treatment with drugs that increase acetylcholine if you would get an even greater benefit. Or maybe they have overlapping mechanism with negligible added effect. That’s the problem with polypharmacy, there are so many variables that can effect the study outcome that it’s difficult to optimize treatment.

    By the way, check out my neuroscience and neurotechnology blog. It might have some stuff that would interest you.

  4. #4 ebohlman
    June 12, 2008

    I wonder if the mechanism behind this effect is related to the “sundowning” phenomenon where dementia symptoms tend to worsen in the late afternoon/early evening (depending on the season and location) as the sun starts to go down.

  5. #5 stumpy
    June 12, 2008

    Regarding Mark P.’s comment, above: My understanding is that the bright light (10,000lux) used to treat seasonal depression works best if it’s full-spectrum, not the fragmented spectrum most domestic lights provide. It might be worth checking into the specs of the lights used here. Also, it’s interesting that the participants in this study were exposed to whole-day bright light, rather than just early-morning bright light, as is recommended for seasonal depression. Makes me wonder if the bright light treatment is really only providing a nonspecific benefit, maybe offsetting sensory deprivation? It also makes me wonder if the bright light treatment was really treating depression that somehow wasn’t recognized. I’m sure the authors would’ve controlled for this, but still… guess I’ll have to read the entire article.

  6. #6 Mark P
    June 17, 2008

    Another comment from a physician regarding my father in law was that some recent studies (or as far as I know, perhaps only one recent study) indicated that vitamin D deficiency was indicated in dementia problems of the elderly. He said my father in law should be outside in bright sun on a regular basis. I wonder if D deficiency the culprit in both cases.

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