About this trial

The goal of this clinical trial is to test whether transcranial photobiomodulation (tPBM), a non-invasive brain stimulation technique using near-infrared light, can improve brain blood flow regulation (neurovascular coupling) and cognitive function in people with mild cognitive impairment (MCI). The main questions it aims to answer are:

* Does tPBM enhance cognitive function and cerebral hemodynamic responses during memory and finger tapping tasks? * Does tPBM reduce oxidative stress, inflammation, and mitigate brain cell damage? * Is cognitive improvement linked to amyloid status, greater cerebral hemodynamic response, and lower levels of brain inflammation and oxidative stress? Researchers will compare an active tPBM treatment arm to a sham treatment arm to see if tPBM leads to measurable improvements in brain activity and cognitive function compared to no active stimulation.

Participants will:

* Receive a 20-minute-long active tPBM or sham stimulation session once per day, 6 times per week, for 12 weeks. * Complete questionnaires and an iPad-based cognitive testing protocol. * Complete memory and motor tasks while their brain activity is measured using non-invasive techniques: simultaneous functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG). Dynamic analysis of the vessels in the eye will also be performed based on eligibility. Transcranial Doppler (TCD) flowmetry is optionally performed. * Provide blood samples to test for biomarkers of inflammation, oxidative stress, and brain cell damage.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age: 55-95 years of age

Clinical Dementia Rating (CDR) equal to 0.5 and/or Montreal Cognitive Assessment (MoCA) <26 and ≥19

Adequate hearing and visual acuity to participate in the examinations

English speaker

Disqualifiers

Active CNS disease including multiple sclerosis, uncontrolled seizures, active brain cancer

Cerebrovascular accident other than TIA within 60 days prior to Visit 0

Diagnosis of amyloid angiopathy

Major psychiatric disease, including major depression not controlled on medications, alcohol or drug abuse

Trial design

Design model

Parallel

Treatments tested in this trial

Active Vielight Neuro RX-Duo device -Active transcranial photobiomodulation
Device
The active Vielight Neuro RX-Duo devices (© Vielight Inc.) will be used to transmit pulsed near-infrared (NIR) energy through the cranium. The device emits NIR photons at an 810-nm wavelength, generating \~250 mW/cm² of pulsed NIR power modulated at 10 and 40 Hz frequencies (Alpha and Gamma modes). The six NIR light sources are positioned along the midline over the frontal, parietal, and occipital cortices, bilaterally over the temporal cortices, and intranasally. Because of their portable design, Vielight Neuro RX-Duo instruments can be used in the laboratory, at the bedside, or in the participant's home. Active photobiomodulation sessions will last 20 minutes and will be administered in a laboratory, home, or office setting, depending on participant preference. TPBM will be delivered once per day, six times per week, for 12 weeks. Participants will complete an adverse-events questionnaire after each session.
Sham Vielight Neuro RX-Duo device -Sham transcranial photobiomodulation
Device
Sham Vielight Neuro RX-Duo devices (© Vielight Inc.) will be used. These devices are identical in appearance to the active devices; however, they do not emit near-infrared (NIR) light at an 810-nm wavelength. The six light sources are positioned along the midline over the frontal, parietal, and occipital cortices; bilaterally over the temporal cortices; and intranasally. Because of their portable design, Vielight Neuro RX-Duo instruments can be used in the laboratory, at the bedside, or in the participant's home. Sham photobiomodulation sessions will last 20 minutes and will be administered in a laboratory, home, or office setting, depending on participant preference. TPBM will be delivered once per day, six times per week, for 12 weeks. Participants will complete an adverse-events questionnaire after each session.

Treatment groups

40 Participants

are divided into 2 treatment groups

Group A: Active near-infrared light therapyActive comparator 1 intervention

Group B: Sham near-infrared light therapySham comparator 1 intervention

Trial outcomes

Primary outcomes

1

Change in cortical neurovascular coupling

Functional near infrared spectroscopy (fNIRS) and electroencephalography (EEG) will be performed during the cognitive n-back task. fNIRS approach generates data that represent a relative change in oxygenated and deoxygenated hemoglobin measured over the cortical brain tissues. EEG records electrical potential changes in the brain cortex. Neurovascular coupling will be evaluated as a change in oxy- and deoxy-hemoglobin between before and after treatment, normalized to change in EEG. The change in regression coefficient reflecting change in neurovascular coupling responses is a dimensionless measure.

Time frame

From baseline visit to the follow-up visit after completing a 12 week intervention protocol

Secondary outcomes

1

Change in fluid cognition composite score

NIH Toolbox will be used to assess fluid cognitive performance by calculating a composite score based on subscores from select tests targeting relevant domains, including attention, working memory, and executive function, as described in other pre-specified outcomes. Units of measure - score (from 0 to 200, the bigger the number, the better). Reported as a %change from baseline, before and after intervention.

Time frame