Effects of Photobiomodularion on Brain Connectivity and Cognitive Function in Cognitive Impairment

NCT ID: NCT07287527

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-30

Study Completion Date

2026-10-31

Brief Summary

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The goal of this clinical trial is to learn if transcranial photobiomodulation (t-PBM), a light-based brain therapy, can help improve memory and cognitive skills in older adults with amnestic mild cognitive impairment (aMCI). This condition involves memory problems that are greater than normal aging and may increase the chance of developing Alzheimer's disease.

The main questions this study aims to answer are:

1. Does t-PBM, when used together with cognitive training, improve memory and cognitive skills?
2. Does t-PBM change how certain brain areas communicate with each other, especially in the default mode network (DMN)?

Researchers will compare:

t-PBM plus cognitive training to sham (inactive) t-PBM plus the same cognitive training to see if the active light treatment leads to better cognitive improvement and healthier brain activity.

Participants will:

* Provide a blood sample so the research team can create a genetic profile;
* Complete cognitive tests before and after the 4-week program;
* Meet with a dietitian before and after the program so the research team can make sure diet stays consistent and does not influence brain results;
* Have a brain fMRI scan before and after treatment to measure brain connectivity changes;
* Take part in eight sessions of cognitive training;
* Receive either active t-PBM or sham t-PBM during these sessions.

Detailed Description

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Amnestic mild cognitive impairment (aMCI) is associated with early disruptions in large-scale brain networks, including the default mode network (DMN), which often shows inefficient or abnormally high connectivity in individuals at increased risk for Alzheimer's disease. Human studies examining the impact of transcranial photobiomodulation (t-PBM) on DMN connectivity and cognitive performance in aMCI remain limited, and few controlled trials have assessed Group × Time interaction effects. This study was designed to address this gap by evaluating whether t-PBM produces measurable changes in resting-state functional connectivity and cognitive outcomes when combined with cognitive rehabilitation.

The trial uses a randomized, sham-controlled, pretest-posttest design. Participants with aMCI were randomly assigned to receive either active t-PBM paired with a cognitive rehabilitation program or sham t-PBM with the same cognitive rehabilitation. The intervention was delivered across eight sessions. Cognitive assessments and resting-state fMRI scans were conducted before the first session and after the final session to evaluate changes in cognitive performance and DMN connectivity. The experimental model allows for the direct evaluation of treatment-related neural changes while accounting for natural variation and practice effects.

To minimize confounding factors, dietary stability was monitored. All participants completed a dietitian visit at baseline and follow-up to document eating habits and reduce the influence of diet-related changes on cognitive or imaging outcomes. In addition, peripheral venous blood samples were collected at baseline for genetic analysis. Genotyping targeted APOE alleles (rs429358, rs7412) and the COMT Val158Met (rs4680) polymorphism. DNA extraction followed silica membrane-based protocols, and allelic discrimination was performed using TaqMan-based real-time PCR. Quality assurance included blinded laboratory processing, random duplicates, call rate thresholds (\>95%), and Hardy-Weinberg equilibrium criteria. These genetic data were incorporated into exploratory models to examine whether genotype moderated baseline brain connectivity or response to the intervention.

Neuroimaging was conducted using a GE SIGNA Hero 3.0 Tesla MRI system. High-resolution T1-weighted structural images were acquired using an axial MPRAGE sequence (TR = 2745 ms, TE = 3.01 ms, TI = 1020 ms, flip angle = 8°, 1 mm slice thickness, voxel size 0.44 × 0.44 × 1 mm, 225 slices). Resting-state functional MRI data were collected using an axial multiband echo-planar imaging sequence (TR = 2000 ms, TE = 22 ms, flip angle = 20°, voxel size 3.125 × 3.125 × 3 mm, 45 slices, matrix 64 × 64, 200 volumes; approximately 6 minutes 40 seconds). Participants were instructed to remain still, keep their eyes closed, and avoid focused mental activity during the scan. These data enable reliable estimation of DMN functional connectivity before and after the intervention.

The study integrates cognitive rehabilitation outcomes, functional neuroimaging, dietary monitoring, and genetic profiling to explore neurobiological and behavioral effects of t-PBM in aMCI. By evaluating network-level changes and potential individual differences in treatment response, the trial aims to improve understanding of whether t-PBM can serve as a network-targeted adjunctive intervention for individuals with early cognitive impairment.

Conditions

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AMCI - Amnestic Mild Cognitive Impairment

Keywords

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t-PBM aMCI fMRI Cognitive Rehabilitation functional connectivity APOE COMT

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Participants and their caregivers were masked to whether they received active t-PBM or sham stimulation. The clinician who diagnosed and referred participants into the study was also masked to group assignment. The sham procedure produced the same visual cues and procedures as active t-PBM but delivered no therapeutic light. The device operator was aware of assignment due to technical requirements. The researcher responsible for data collection and analysis was not masked. Participants and caregivers were informed of their group assignment only after the study was completed.

Study Groups

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Intervention Arm: Active Treatment

Participants in this arm will receive active transcranial photobiomodulation delivered at gamma frequency while simultaneously participating in a structured cognitive rehabilitation session. The photobiomodulation device will be placed on the participant's head and will operate continuously for 20 minutes during each session. Cognitive rehabilitation tasks will be administered throughout the stimulation period to enhance cognitive engagement. This combined intervention will be applied across all scheduled treatment sessions.

Group Type EXPERIMENTAL

Active transcranial Photobiomodulation

Intervention Type DEVICE

The active intervention consists of transcranial photobiomodulation (t-PBM) delivered while the device is placed on the participant's head and operating at gamma-frequency. The device provides active near-infrared light output throughout the 20-minute session. Active intervention is administered for a total of 8 sessions.

Cognitive Rehabilitation

Intervention Type BEHAVIORAL

The cognitive rehabilitation program consists of 8 sessions, each lasting 20 minutes, delivered simultaneously with either active or sham transcranial photobiomodulation (t-PBM). The program is a pen-and-paper-based cognitive exercise protocol targeting attention, memory, executive functions, and language. Each session includes structured tasks with predefined difficulty levels. Task difficulty increases progressively by 0.5 points from Session 1 onward, ensuring gradual cognitive challenge and adaptation across all eight sessions. The rehabilitation protocol is identical for both study arms.

Control Arm: Sham/Placebo

Participants in this arm will receive sham transcranial photobiomodulation while completing the same cognitive rehabilitation session provided to the experimental group. The device will be placed on the participant's head and will appear to operate normally; however, no active light output will be delivered. Each session lasts 20 minutes, during which participants complete standardized cognitive rehabilitation tasks. Session frequency, duration, and rehabilitation procedures are identical to the experimental arm to maintain blinding and ensure comparable conditions.

Group Type SHAM_COMPARATOR

sham transcranial Photobiomodulation

Intervention Type DEVICE

The sham intervention uses the same transcranial photobiomodulation (t-PBM) device and head placement as the active intervention; however, no therapeutic near-infrared light output is delivered. The device's external indicators remain active to mimic real stimulation and maintain participant blinding. Each session lasts 20 minutes. The sham intervention is administered for a total of 8 sessions.

Cognitive Rehabilitation

Intervention Type BEHAVIORAL

The cognitive rehabilitation program consists of 8 sessions, each lasting 20 minutes, delivered simultaneously with either active or sham transcranial photobiomodulation (t-PBM). The program is a pen-and-paper-based cognitive exercise protocol targeting attention, memory, executive functions, and language. Each session includes structured tasks with predefined difficulty levels. Task difficulty increases progressively by 0.5 points from Session 1 onward, ensuring gradual cognitive challenge and adaptation across all eight sessions. The rehabilitation protocol is identical for both study arms.

Interventions

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Active transcranial Photobiomodulation

The active intervention consists of transcranial photobiomodulation (t-PBM) delivered while the device is placed on the participant's head and operating at gamma-frequency. The device provides active near-infrared light output throughout the 20-minute session. Active intervention is administered for a total of 8 sessions.

Intervention Type DEVICE

sham transcranial Photobiomodulation

The sham intervention uses the same transcranial photobiomodulation (t-PBM) device and head placement as the active intervention; however, no therapeutic near-infrared light output is delivered. The device's external indicators remain active to mimic real stimulation and maintain participant blinding. Each session lasts 20 minutes. The sham intervention is administered for a total of 8 sessions.

Intervention Type DEVICE

Cognitive Rehabilitation

The cognitive rehabilitation program consists of 8 sessions, each lasting 20 minutes, delivered simultaneously with either active or sham transcranial photobiomodulation (t-PBM). The program is a pen-and-paper-based cognitive exercise protocol targeting attention, memory, executive functions, and language. Each session includes structured tasks with predefined difficulty levels. Task difficulty increases progressively by 0.5 points from Session 1 onward, ensuring gradual cognitive challenge and adaptation across all eight sessions. The rehabilitation protocol is identical for both study arms.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* Age 55 years or older
* Diagnosis of amnestic Mild Cognitive Impairment (aMCI)

Exclusion Criteria

* Presence of a neurological disorder
* Presence of a severe psychiatric disorder
* Having a pacemaker or other implanted medical device that is not MRI-compatible
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Uskudar University

OTHER

Sponsor Role lead

Responsible Party

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Baris Metin

Prof. Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Baris Metin, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Uskudar University

Locations

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NPIstanbul Brain Hospital

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

Uskudar University, Faculty of Medicine

Istnabul, , Turkey (Türkiye)

Site Status RECRUITING

Countries

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Turkey (Türkiye)

Central Contacts

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Shams Farhad, PhD

Role: CONTACT

Phone: +905528566917

Email: [email protected]

Facility Contacts

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Shams Farhad, PhD

Role: primary

[email protected] Farhad, PhD candidate

Role: primary

References

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Chan AS, Lee TL, Hamblin MR, Cheung MC. Photobiomodulation Enhances Memory Processing in Older Adults with Mild Cognitive Impairment: A Functional Near-Infrared Spectroscopy Study. J Alzheimers Dis. 2021;83(4):1471-1480. doi: 10.3233/JAD-201600.

Reference Type BACKGROUND
PMID: 33998541 (View on PubMed)

Other Identifiers

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UUBAYP-2024-003

Identifier Type: -

Identifier Source: org_study_id