An interventional study of Active transcranial Photobiomodulation and sham transcranial Photobiomodulation in AMCI - Amnestic Mild Cognitive Impairment, sponsored by Uskudar University. Recruiting at 2 sites in Turkey (Türkiye). Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2025-12-17.
Sponsored by Uskudar University · Not applicable, Interventional, and Treatment
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:
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:
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.
Uskudar University is the lead sponsor of 164 studies on the registry; 35 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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.
Device: Active transcranial Photobiomodulation · Behavioral: Cognitive Rehabilitation
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.
Device: sham transcranial Photobiomodulation · Behavioral: Cognitive Rehabilitation
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.
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.
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.
Change in Default Mode Network (DMN) Functional Connectivity Measured by Resting-State fMRI
Time frame: Baseline and after completion of the 8-session intervention (approximately 4 weeks)
Change in Montreal Cognitive Assessment (MoCA) Total Score
Baseline and post-intervention cognitive performance will be compared using the Montreal Cognitive Assessment (MoCA), a standardized cognitive screening instrument. Score range: 0 to 30 points (higher scores indicate better cognitive performance).
Time frame: From baseline to post-intervention assessment following 8 sessions
Genotype-Based Comparison of Treatment Outcomes
This outcome measure evaluates group-based comparisons of treatment-related changes in cognitive performance and brain functional connectivity across COMT and APOE genotype groups following transcranial photobiomodulation, as a single composite comparison outcome. Genetic profile (grouping variable): COMT Val158Met polymorphism and APOE genotype (ε2, ε3, ε4 alleles), determined by genotyping analysis from peripheral blood samples; unit: genotype category (COMT: Val/Val, Val/Met, Met/Met; APOE: ε2 carrier, ε3/ε3, ε4 carrier). Cognitive performance measure: Montreal Cognitive Assessment (MoCA) total score; measurement tool: standardized MoCA test; unit: change in total score from baseline (points; range 0-30). Brain connectivity measure: Default Mode Network (DMN) functional connectivity; measurement tool: resting-state fMRI-based functional connectivity analysis using Pearson correlation of BOLD time series; unit: change in connectivity strength from baseline.
Time frame: Baseline genetic assessment and post-intervention outcomes after completion of 8 sessions
Plan to share: No — De-identified individual participant data (IPD), including genetic, neuroimaging, and cognitive assessment data, will not be shared outside the primary research team due to ethical, legal, and institutional restrictions related to participant privacy and data protection.
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