Physiological Effect of Non-invasive Photobiomodulation on Cognition and Mood in Older Adults With Subjective Cognitive Impairment

Overview

Subjective cognitive impairment (SCI) is a non-clinical condition manifesting as a self-reported decline in cognitive function without objective clinical evidence, and is prevalent among older adults and strongly associated with declining mood. This study explores the potential of photobiomodulation (PBM) as a therapeutic intervention for SCI. PBM, using near-infrared light, is a non-invasive neuromodulation approach that has shown promise in improving neuronal function, blood flow, and reducing inflammation in both healthy adults and patients with neurological conditions, including dementia and depression. This study proposes investigating the potential of forehead (tPBM), intranasal (iPBM) and vagal (vPBM) PBM to enhance mood and cognitive function in individuals with SCI as a proof of concept for the future use of PBM as therapy for cognitive decline in general. This study will recruit approximately 80 participants with SCI for the study, and the total expected duration of the participant\'s participation in the study is 5 weeks. The active and sham Neuro 5T device consisting of a headset with a built-in controller, nasal and neck applicators will be used. The nasal and neck applicators each contains a single LED and will be placed into the nostril or neck and secured into place. The headset contains multiple LEDs in a wearable applicator and may be adjusted. The Neuro 5T also contains telemetry features to allow documentation of patient usage of the device. LEDs are semiconductor electronic components that emit light. Participants will be given PBM devices for in-home usage, 2 times a day, 7 days a week, for 5 weeks. Participants will undergo EEG, MRI, cognitive and nasal microbiome assessments before and after the 5-week period.

Detailed description

This study will recruit approximately 80 participants with SCI for the study, and the total expected duration of the participant's participation in the study is 5 weeks. The active and sham Neuro 5T device consisting of a headset with a built-in controller, nasal and neck applicators will be used. The nasal and neck applicators each contains a single LED and will be placed into the nostril or neck and secured into place. The headset contains multiple LEDs in a wearable applicator and may be adjusted. The Neuro 5T also contains telemetry features to allow documentation of patient usage of the device. LEDs are semiconductor electronic components that emit light. Participants will be given PBM devices for in-home usage, 2 times a day, 7 days a week, for 5 weeks. Participants will undergo EEG, MRI, cognitive and nasal microbiome assessments before and after the 5-week period.

Interventions

• Other Photobiomodulation
  the application of red and near-infrared light
• Other Sham (No Treatment)
  Control intervention; no photobiomodulation

Primary outcome measures

• Geriatric Depression Scale (Short Form) [Time frame: The first assessment will take place before participants receive treatment, and another session no more than 2 weeks after their final treatment session.]
• Montreal Cognitive Assessment [Time frame: The first assessment will take place before participants receive treatment, and another session no more than 2 weeks after their final treatment session.]

Secondary outcome measures (4)

• EEG signal metrics and spatial-temporal pattern [Time frame: Two sessions, to be completed no more than 2 weeks before the start of the treatment sessions and then no more than 2 weeks after the conclusion of all treatment sessions]
• Alpha diversity [Time frame: Two nasal swab samples collected; one before the administration of the first treatment session, and one after the last treatment session.]
• Resting-state fMRI [Time frame: Two scans, to be completed no more than 2 weeks before the start of the first treatment session and no more than 2 weeks after the conclusion of the last treatment session.]
• Beta diversity [Time frame: Two nasal swab samples collected; one before the administration of the first treatment session, and one after the last treatment session.]

Eligibility criteria

Inclusion criteria

• Affirmative responses to two questions on a self-report questionnaire: "Do you feel your memory is becoming worse?" "If so, are you concerned?"

Exclusion criteria

• Presence of clinically diagnosed dementia, mild cognitive impairment, depression, post-traumatic stress disorder, obsessive-compulsive disorder, eating disorder(s), schizophrenia, or other psychiatric disorders.
• History of a manic, hypomanic, or mixed depressive episode.
• Treatment with electroconvulsive therapy, intravenous and/or intranasal ketamine in the 6-weeks prior to study enrolment.
• History of substance-use disorder in the past 12 months.
• Presence of current alcohol-use disorder.
• A positive urine toxicology screen for non-prescribed substance use.
• A positive pregnancy test at screening.
• A history of major medical or neurological illness.
• A history of traumatic brain injury, stroke, seizures, or previous brain surgery.
• Current use of anti-coagulants.
• Contraindications to magnetic resonance imaging (MRI) scanning.
• Being currently involved in other intervention studies.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Rotman Research Institute — Toronto

Publications

• Zomorrodi R, Loheswaran G, Pushparaj A, Lim L. Pulsed Near Infrared Transcranial and Intranasal Photobiomodulation Significantly Modulates Neural Oscillations: a pilot exploratory study. Sci Rep. 2019 Apr 19;9(1):6309. doi: 10.1038/s41598-019-42693-x. PMID 31004126
• Zollinger I, Bauer A, Blotenberg I, Brettschneider C, Buchholz M, Czock D, Dohring J, Escales C, Fankhaenel T, Frese T, Hoffmann W, Kaduszkiewicz H, Konig HH, Luppa M, Oey A, Pabst A, Sanftenberg L, Thyrian JR, Weiss J, Wendel F, Wiese B, Riedel-Heller SG, Gensichen J. Associations of Depressive Symptoms with Subjective Cognitive Decline in Elderly People-A Cross-Sectional Analysis from the AgeWel PMID 37629244
• Wang X, Tian F, Reddy DD, Nalawade SS, Barrett DW, Gonzalez-Lima F, Liu H. Up-regulation of cerebral cytochrome-c-oxidase and hemodynamics by transcranial infrared laser stimulation: A broadband near-infrared spectroscopy study. J Cereb Blood Flow Metab. 2017 Dec;37(12):3789-3802. doi: 10.1177/0271678X17691783. Epub 2017 Feb 9. PMID 28178891
• Van Lankveld, H., Chen, J.X., Zhong, X.Z., Chen, J.J., 2025. Consistent and real-time BOLD fMRI response to pulsed transcranial and intranasal photobiomodulation. , in: OHBM 2025 Annual Meeting. Presented at the OHBM 2025 Annual meeting.
• Thompson SL, O'Leary GH, Austelle CW, Gruber E, Kahn AT, Manett AJ, Short B, Badran BW. A Review of Parameter Settings for Invasive and Non-invasive Vagus Nerve Stimulation (VNS) Applied in Neurological and Psychiatric Disorders. Front Neurosci. 2021 Jul 13;15:709436. doi: 10.3389/fnins.2021.709436. eCollection 2021. PMID 34326720
• Schiffer F, Johnston AL, Ravichandran C, Polcari A, Teicher MH, Webb RH, Hamblin MR. Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety. Behav Brain Funct. 2009 Dec 8;5:46. doi: 10.1186/1744-9081-5-46. PMID 19995444
• Saltmarche AE, Naeser MA, Ho KF, Hamblin MR, Lim L. Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report. Photomed Laser Surg. 2017 Aug;35(8):432-441. doi: 10.1089/pho.2016.4227. Epub 2017 Feb 10. PMID 28186867
• Salehpour F, Majdi A, Pazhuhi M, Ghasemi F, Khademi M, Pashazadeh F, Hamblin MR, Cassano P. Transcranial Photobiomodulation Improves Cognitive Performance in Young Healthy Adults: A Systematic Review and Meta-Analysis. Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):635-643. doi: 10.1089/photob.2019.4673. Epub 2019 Sep 24. PMID 31549906

Identifiers

NCT: NCT07445945 · REB 25-12

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗