Rhythmic Light Therapy for Alzheimer's Disease Patients

Study Overview
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Brief Summary
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The investigator will investigate how light delivering 40 hertz (Hz) affects subjective sleep and cognition in a controlled laboratory study. A lab study will allow the collection of electroencephalogram (EEG) data, perform cognitive tests, and observe the response in those with mild cognitive impairment (MCI) compared to a healthy control group (HC). Participants will attend two study sessions over the course of two weeks. During both sessions, all participants will experience 10 minutes of a low-level light, followed by a data collection period which involves a sleepiness rating, an electroencephalogram (EEG) recording, and a computerized memory test. Participants will then experience either a RL or a placebo RL condition for one hour, after which there will be a second data collection.

Detailed Description
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The investigator will demonstrate the effect of 40 hertz (Hz) rhythmic light (RL) to promote gamma wave entrainment (rhythmic light [RL]) on: brain response (electroencephalography [EEG]); cognitive performance (working memory task); and subjective sleepiness (questionnaires). The study will recruit 20 adult mild cognitive impairment (MCI) patients and 20 healthy, age-matched controls (HC) to participate in this study. Sessions will initiate with a 10-minute adaptation period to a low-level ambient light providing illuminance of 15 lux at participants' eye level on a vertical plane, followed by a pre-exposure data collection period, including Karolinska Sleepiness Scale (KSS), EEG, and a working memory task. Participants will experience either 40 Hz RL or placebo RL conditions for a duration of 1 hour, followed by the second data collection period. On the second data collection day, participants will experience the other condition, so that all participants experience both lighting conditions. The experimental sessions will start at 14:00 on each experimental day which will be separated by 1 week.

Official Title
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Phase 1 - The Use of Rhythmic Light Therapy to Entrain Gamma Oscillations and the Circadian System in Patients With Alzheimer's Disease

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Device: Tailored Rhythmic Lighting Intervention
* Device: Placebo Rhythmic Lighting Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be diagnosed with amnestic mild cognitive impairment or mild Alzheimer's disease, as defined by a Montreal Cognitive Assessment (MoCA) score between 17 and 25 For the age-matched healthy controls, participants must not be diagnosed with mild cognitive impairment or Alzheimer's disease related dementias (MoCA score above 25). Participants must score a 5 or less in the Pittsburgh Sleep Quality Index (PSQI) Exclusion Criteria: All participants must not be taking sleeping medication or oral melatonin Presence of another brain disease that fully explains the dementia (extensive brain vascular disease, Parkinson's disease, dementia with Lewy bodies, traumatic brain injury, or multiple sclerosis) residence in a skilled nursing facility or long-term care Major organ failure (e.g., kidney failure) Uncontrolled generalized disorders such as hypertension or diabetes Obstructing cataracts, macular degeneration, and blindness Severe sleep apnea or restless leg syndrome History of epilepsy

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Tailored Rhythmic Lighting<br>1 hour intervention period where active lighting is experienced by participants. | Device: Tailored Rhythmic Lighting Intervention<br>* 40 hertz (Hz) rhythmic lighting (RL) for a duration of 1 hour. The flicker frequency of the 40 Hz RL will be 40 Hz and the stimulation will be a square wave with a 50 % duty cycle (i.e., 12.5 milliseconds light- on and 12.5 milliseconds light-off). The RL will provide a 30 lux of red light on a vertical plane at the eye level.<br>|
| Placebo Comparator: Inactive Placebo Rhythmic Lighting<br>1 hour intervention period where an inactive, placebo lighting condition is experienced by participants. | Device: Placebo Rhythmic Lighting Intervention<br>* Placebo rhythmic light (RL) for a duration of 1 hour. In the placebo RL condition, the duty cycle will be delivered with a random interval determined by a Poisson process with an average interval of 40 hertz (Hz). The placebo RL conditions will provide a 30 lux of red light on a vertical plane at the eye level.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electroencephalography (EEG) power at 40 hertz (Hz) | Electroencephalography (EEG) recordings, lasting 3-minutes each, will occur 2 times per experimental session. The power at 40 hertz (Hz), 4-8 Hz (theta), and 30-55 Hz (low gamma) frequency ranges will be calculated at each electrode site. Entrainment to the 40 Hz rhythmic stimulation will be assessed in terms of increases in power at 40 Hz. | baseline | 
| Electroencephalography (EEG) power at 40 hertz (Hz) | Electroencephalography (EEG) recordings, lasting 3-minutes each, will occur 2 times per experimental session. The power at 40 hertz (Hz), 4-8 Hz (theta), and 30-55 Hz (low gamma) frequency ranges will be calculated at each electrode site. Entrainment to the 40 Hz rhythmic stimulation will be assessed in terms of increases in power at 40 Hz. | 1 hour after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Sleepiness using the Karolinska Sleepiness Scale (KSS) | The Karolinska Sleepiness Scale (KSS) outcome prompts participants to rate how sleepy or alert they are feeling on a scale ranging from 1 to 9, where 1 = very alert, 3 = rather alert, 5 = neither alert nor sleepy, 7 = sleepy, but no difficulty remaining awake, and 9 = very sleepy, fighting sleep, an effort to remain awake. | baseline | 
| Subjective Sleepiness using the Karolinska Sleepiness Scale (KSS) | The Karolinska Sleepiness Scale (KSS) outcome prompts participants to rate how sleepy or alert they are feeling on a scale ranging from 1 to 9, where 1 = very alert, 3 = rather alert, 5 = neither alert nor sleepy, 7 = sleepy, but no difficulty remaining awake, and 9 = very sleepy, fighting sleep, an effort to remain awake. | 1 hour after intervention | 
| Cognition using a working memory task | Participants view a serial visual display of letters and math problems. They are asked to hold the letters in memory while simultaneously determining if the simple math problems are correct (e.g., 7+5=13). Performance is assessed in percent correct and by measuring accuracy and Reaction Time (RT). | baseline | 
| Cognition using a working memory task | Participants view a serial visual display of letters and math problems. They are asked to hold the letters in memory while simultaneously determining if the simple math problems are correct (e.g., 7+5=13). Performance is assessed in percent correct and by measuring accuracy and Reaction Time (RT). | 1 hour after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Light Treatment, Circadian Rhythms, Gamma Wave Entrainment, Rhythmic Light, Mild Alzheimer's Disease, Sleep, Memory, Electroencephalogram