Research Abstracts

Prior Clinical Studies

Light therapy of patients with parkinsonism

Artemenko AR, Levin VI | Zh Nevrol Psikhiatr Im S S Korsakova

Summary: Light therapy was applied over a 6 month period in an effort to provide relief to PD patients experiencing depression. Investigators also wanted to see if light would reduce the need for polypharmacy.

Findings: After implementing a “drug holiday,” bradykinesia was improved, although no effect was seen with tremor. Depression and sleep improved and motor performance on a computer based test improved. Drug dose after 6 months in patients receiving light was lower than in patients receiving drug alone.

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The effect of sleep deprivation on motor impairment and retinal adaptation in Parkinson's disease

Reist C, Sokolski KN, Chen CC, Coskinas E, Demet EM | Prog Neuropsychopharmacol Biol Psychiatry

Summary: Total sleep deprivation (TSD) was applied in PD patients that displayed chronic depression. During the procedure TSD patients were exposed to well-lit environments for periods of 24 hours.

Findings: A strong anti-depressant effect and a reduction in bradykinesia, rigidity and tremor were observed. While several mechanisms were postulated, the authors could not rule out the prolonged exposure to ambient light during the extended waking period as the basis for the therapeutic effect.

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Summary: Case series study where patients were exposed to bright light therapy for 1 hour in the evening over several months. The dose of exposure was ≈ 1500 lux.

Findings: Bradykinesia improved as did depression and insomnia. Tremor was not affected by the light therapy. Reduction in anti-Parkinsonian medication, antidepressants, and anxiolytic and soporific drugs was achieved.

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Bright light therapy in Parkinson's disease: a pilot study

Paus S, Schmitz-Hübsch T, Wüllner U, Vogel A, Klockgether T, Abele T | Mov Disord

Summary: Double-blind study with 36 PD patients using bright light (7,500 lux) vs. placebo (950 lux) for 30 minutes in the morning.

Findings: Although the trial only lasted 15 days and differences were small, improvement was found in tremor and depression in PD patients but not bradykinesia or sleep. This was the first double-blind study in PD, and results warranted a larger study.

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Summary: The long-term effect of evening bright light therapy in 129 PD patients was examined. 98 light therapy patients were compared to 31 early leavers from the program. These groups were also compared with a group of patients on light therapy which had other neurological diseases.

Findings: Bright light therapy not only improved the primary and secondary symptoms of PD gradually over several years but these patients were maintained on lower doses of drug. Those that stayed in the program did not show progression of the disease compared to patients that dropped out of the program.

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Summary: Random, blind trial with 3 arms and 18 subjects over a 6 week period. Arm 1: light+CBT+sleep hygiene. Arm 2: Doxepin. Arm 3: Placebo light+CBT+sleep hygiene.

Findings: Sleep improved but no improvement was seen on the UPDRS. Light was applied in the morning or evening depending on loosely defined chronotype. No control was used on drug dosing. The study was poorly designed and controlled but still showed that sleep improved.

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Animal Studies

Summary: Applied various sensory stimuli including high intensity light to induce stimulus bound recovery in experimental PD produced by lesions of the lateral hypothalamus in rats.

Findings: Of all the stimuli applied only a 20-minute pulse of light induced intense movement and returned sleep EEG to normal.

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Summary: Applied bright ambient light in the presence of various stimulants, which affect the dopamine system and movement.

Findings: The hypermotility produced by amphetamines was enhanced further by exposure to intense environmental light. In further studies this was found to be related to the function of midbrain dopamine systems.

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Melatonin modulates apomorphine-induced rotational behaviour

Burton S, Daya S, Potgieter B| Experientia

Summary: Injected melatonin into rats with unilateral 6-OHDA lesioned rats to determine if melatonin aided recovery.

Findings: While melatonin did not alter movement in this model of PD, they incidentally applied high intensity light which repaired rotation after only 20-minutes of exposure.

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REM sleep deprivation in an experimental model of Parkinson's disease

Andrade LA, Lima JG, Tufik S, Bertolucci PH, Carlini EA | Arq Neuropsiquiatr

Summary: An experimental model of total sleep deprivation (TSD) was used in rats with PD.

Findings: While the methodology employed was not precise, TSD involves exposing animals and man to environments (usually well lit) to prolong wakefulness, and this lessened the severity of experimental PD.

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Summary: Experimental PD was produced by bilateral 6- OHDA. Constant environmental melatonin and constant light were applied while measuring recovery.

Findings: While melatonin administered daily by the I.P. route worsened motor performance in experimental PD, 24-hour light exposure improved it and enhanced recovery.

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Summary: Investigators injected L-dopa or ML-23 (a melatonin antagonist) into the vitreous in minute doses to observe the effects upon motor function.

Findings: L-dopa improved motor function during the day while using ML-23 to block melatonin receptors at night did the same. This is the first work which describes the chemistry of melanocytes which is responsible for the behavioral effects of light therapy; a definition which has been missing from the SAD work.

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Retrospective Studies and Reviews

Summary: This article is a comprehensive review of the relationship between visual / circadian function and PD.

Findings: Melatonin is neurotoxic to photoreceptors. Retinal, nigral and pineal cells all contain melanocytes and are all functionally similar and susceptible to the neurotoxic effects of melatonin. Melatonin and DA exist in functional opposition. This relationship is out of balance in PD. Light therapy is effective in PD across many preclinical and clinical models. The mechanism by which this occurs is defined.

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Bright light therapy in Parkinson’s disease: An overview of the background and evidence

Rutten S, Vriend C, van den Heuvel OA, Smit JH, Berendse HW, van der Werf YD | Parkinsons Dis

Summary: Review article on sleep, circadian function and Parkinson’s disease and the use of light.

Findings: This review examined the importance of circadian function in sleep and reviewed published literature about utilizing bright light therapy in the treatment of Parkinson’s disease. The number and types of studies were examined in depth, with recommendations on the most efficacious application of light. It concluded that enough preliminary work had been done to warrant more clinical trials.

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Sleep deprivation therapy in depressive illness and Parkinson's disease

Demet EM, Chicz-Demet A, Fallon JH, Sokolski KN | Prog Neuropsychopharmacol Biol Psychiatry

Summary: Although TSD aggravates sleep problems in PD, it improves other features such as depression. Reports also suggest improvements in tremor, rigidity and bradykinesia.

Findings: An attempt to explain the mechanism of action in TSD; it may be that cholinergic activity, which is overexpressed in both PD and depression, may be suppressed by TSD. Light exposure is associated with the effect of TSD.

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Epidemiological Studies and Reviews

A prospective study of night shift work, sleep duration, and risk of Parkinson's disease

Chen H, Schermhammer E, Schwarzchild MA, Ascherio A. | Am J Epidemiol

Summary: This study examined the incidence of PD in 84,794 nurses working the nightshift.

Findings: The incidence of PD dropped by 50% in nurses exposed to light in the nursing station while working night shift. Also related, the incidence of cancer was increased and was associated with circadian disruption caused by shiftwork. The involvement of melatonin was discussed. Sleep duration was also positively associated with Parkinson's disease risk; those with long sleep profiles were at greater risk for PD.

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Summary: Review of studies associating melatonin levels to Parkinson’s disease as well as to cancer.

Findings: Studies show higher morning melatonin levels in PD patients than in healthy controls. Sleep disorders in PD may be associated with variations in melatonin levels. Animal models show increased melatonin causes increased PD, while reduction of melatonin (also with bright light) aids recovery. Longer years of working night shifts is associated with a reduced risk of PD, whereas longer hours of sleep appear to increase their risk. In sum, while lower melatonin concentrations may predict a higher cancer risk, there is also some evidence that they may be associated with a lower risk of PD.

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Parkinson's disease incidence: magnitude, comparability, time trends

de Pedro Cuesta J, Stawiarz L. | Acta Neurol Scand

Summary: Incidence of PD was studied in Iceland, Turku Finland and Rochester Minnesota (USA).

Findings: Compared to the higher latitudes, a statistically significant 56% decrease in the incidences of Parkinsonism onsets was found.

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Studies of the prevalence of paralysis agitans by tracer methodology

de Pedro Cuesta J | Acta Neurol Scand Suppl

Summary: The prevalence of Parkinson’s is related to latitude and population density.

Findings: Parkinson’s increases with higher latitude.

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