Rhythmic Light Therapy for Alzheimer's Disease Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Device: Tailored Rhythmic Lighting Intervention; Device: Placebo Rhythmic Lighting Intervention

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Menands, New York, United States, 12204
      • Light and Health Research Center
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Tailored Rhythmic Lighting then Inactive Placebo Rhythmic Lighting; hour intervention period where active lighting is experienced by participants. then 1 hour intervention period where an inactive, placebo lighting condition is experienced by participants.; sessions, 1 week apart	Device: Tailored Rhythmic Lighting Intervention; 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.
Placebo Comparator: Inactive Placebo Rhythmic Lighting then Active Tailored Rhythmic Lighting; hour intervention period where an inactive, placebo lighting condition is experienced by participants. then 1 hour intervention period where active lighting is experienced by participants.; sessions, 1 week apart	Device: Placebo Rhythmic Lighting Intervention; Placebo rhythmic light (RL) for a duration of 1 hour. In the placebo RL condition, the duty cycle will be delivered at randomly varying frequencies of 20 Hz and 50 Hz, specifically avoiding the frequency of 40 Hz. The placebo RL conditions will provide a 30 lux of red light on a vertical plane at the eye level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Electroencephalography (EEG) Power at 40 Hertz (Hz)	Electroencephalography (EEG) recordings - the change in 40 Hz gamma power, computed by calculating the difference between the average gamma power at baseline (T1) and during the light intervention (T2). This difference was obtained by subtracting baseline 40 Hz power from the intervention 40 Hz power to assess acute neural effects	baseline and during the light intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in 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 and 1 hour after intervention (intervention is 2 hours)
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 (intervention is 2 hours)

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Mariana Figueiro, PhD, ICAHN School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• Akerstedt T, Gillberg M. Subjective and objective sleepiness in the active individual. Int J Neurosci. 1990 May;52(1-2):29-37. doi: 10.3109/00207459008994241.
• Buysse DJ, Reynolds CF 3rd, Monk TH, Hoch CC, Yeager AL, Kupfer DJ. Quantification of subjective sleep quality in healthy elderly men and women using the Pittsburgh Sleep Quality Index (PSQI). Sleep. 1991 Aug;14(4):331-8. Erratum In: Sleep 1992 Feb;15(1):83.
• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x. Erratum In: J Am Geriatr Soc. 2019 Sep;67(9):1991. doi: 10.1111/jgs.15925.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2022
• Primary Completion (Actual): July 12, 2023
• Study Completion (Actual): July 12, 2023

Study Registration Dates

• First Submitted: August 12, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Sleep; Electroencephalogram; Memory; Circadian Rhythms; Mild Alzheimer's Disease; Light Treatment; Gamma Wave Entrainment; Rhythmic Light
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease
• Other Study ID Numbers: GCO 21-0378-01; 5R01AG072762 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No