The goal of this clinical trial is to learn if photobiomodulation therapy (PBMT) can help treat mild cognitive impairment and mild Alzheimer's disease in adults aged 50 to 85 years. It will also learn about the safety of PBMT. The main questions it aims to answer are: Does PBMT improve cognitive function in adults with mild cognitive impairment or mild Alzheimer's disease? What medical problems do participants have when using PBMT? Researchers will compare an active PBMT device to a sham (look-alike) device that delivers no active light therapy to see if PBMT improves cognitive function. Participants will: Use a transcranial near-infrared light therapy device (or a matching sham device) once a day for 20 minutes, 5 days a week, for 6 months Visit the clinic for cognitive, mood, sleep, and daily-function assessments at the start of the study, at Month 3, and at Month 6 Have brain MRI scans at the start of the study, at Month 3, and at Month 6
Alzheimer's disease and its prodromal stage, mild cognitive impairment, are characterized by progressive neurodegeneration for which disease-modifying options remain limited. Photobiomodulation therapy (PBMT) delivers non-ionizing red and near-infrared light to neural tissue, where it is absorbed by cytochrome c oxidase in the mitochondrial respiratory chain. This is hypothesized to enhance ATP production, modulate reactive oxygen species and intracellular signaling, increase regional cerebral blood flow, and support neuroprotective and anti-inflammatory processes, providing the biological basis for evaluating PBMT as a non-invasive intervention in early Alzheimer's disease. This is a single-center, prospective, randomized, double-blind, sham-controlled trial conducted at the Department of Cognitive Disorders, Beijing Tiantan Hospital, Capital Medical University. Eligible participants are randomly allocated in a 1:1 ratio to the active PBMT arm or the sham-control arm using a computer-generated randomization sequence. To preserve double blinding, the active and sham devices are identical in appearance and operation; the sham device emits visible light at a wavelength without established photobiomodulatory effect, so that neither participants nor outcome assessors can distinguish between arms. Treatment is self-administered at home according to a fixed schedule over the 6-month intervention period, with adherence monitored through device usage records and scheduled study visits. Assessments are performed at baseline, Month 3, and Month 6 by trained raters blinded to group allocation. Beyond the clinical and neuropsychological battery, structural and functional MRI is used to examine treatment-associated changes in cortical and hippocampal volume, white matter integrity, and cerebral blood flow perfusion, supporting exploratory analysis of the candidate mechanisms above. Safety is monitored throughout via adverse-event reporting, device-related event tracking, and review of skin and nasal tolerability. Efficacy analyses compare between- and within-group change from baseline across the cognitive, neuropsychiatric, sleep, daily-function, and caregiver-burden domains, with imaging and tolerability data used to characterize the safety profile and explore possible mechanisms of action of PBMT in AD-derived MCI and mild AD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
20
transcranial photobiomodulation
transcranial photobiomodulation
Department of Cognitive Disorders, Beijing Tiantan Hospital, Capital Medical University
Beijing, China
RECRUITINGMini-Mental State Examination
The Mini-Mental State Examination (MMSE) assesses orientation, registration, attention and calculation, recall, and language using 11 items. Total scores range from 0 to 30; lower scores indicate worse cognitive function and higher scores indicate better cognitive function.
Time frame: Baseline, Month 3, Month 6
Montreal Cognitive Assessment
The Montreal Cognitive Assessment (MoCA) assesses visuospatial and executive function, naming, attention, language, abstraction, delayed recall, and orientation. Total scores range from 0 to 30; higher scores indicate better cognitive function and lower scores indicate worse cognitive function.
Time frame: Baseline, Month 3, Month 6
Alzheimer's Disease Assessment Scale-Cognitive Subscale
The Alzheimer's Disease Assessment Scale-Cognitive Subscale, 11-item version (ADAS-Cog-11), assesses cognitive domains including memory, language, orientation, and praxis. The total score ranges from 0 to 70, with 0 indicating the least cognitive impairment and 70 indicating the most severe cognitive impairment. Higher scores indicate worse cognitive function. A decrease in score indicates improvement, whereas an increase indicates worsening.
Time frame: Baseline, Month 3, Month 6
Clinical Dementia Rating
The Clinical Dementia Rating (CDR) assesses cognition and daily functioning. The CDR Sum of Boxes (CDR-SB) ranges from 0 to 18; higher scores indicate greater impairment. The global CDR score ranges from 0 to 3: 0 = normal, 0.5 = questionable, 1 = mild, 2 = moderate, and 3 = severe; higher scores indicate worse outcomes.
Time frame: Baseline, Month 3, Month 6
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) compares differences in cortical/hippocampal atrophy, white matter degeneration, and cerebral blood flow perfusion before and after treatment.
Time frame: Baseline, Month 3, Month 6
Hamilton Depression Rating Scale
The 17-item Hamilton Depression Rating Scale (HAMD-17) is a clinician-rated assessment of depression severity covering mood, anxiety, somatic symptoms, cognition, sleep, and related symptoms. Total scores range from 0 to 52; higher scores indicate more severe depression and a worse outcome.
Time frame: Baseline, Month 3, Month 6
Hamilton Anxiety Rating Scale
The Hamilton Anxiety Rating Scale (HAMA) is a 14-item, clinician-rated assessment of psychic and somatic anxiety. Total scores range from 0 to 56; higher scores indicate greater anxiety severity and a worse outcome.
Time frame: Baseline, Month 3, Month 6
Neuropsychiatric Inventory
The Neuropsychiatric Inventory (NPI) assesses behavioral and psychological symptoms of dementia across 12 domains. It measures symptom frequency, severity, and caregiver distress. The total score ranges from 0 to 144, with higher scores indicating more severe neuropsychiatric symptoms.
Time frame: Baseline, Month 3, Month 6
Pittsburgh Sleep Quality Index
The Pittsburgh Sleep Quality Index (PSQI) is a 19-item, self-rated assessment of sleep quality over the previous month across seven components. Total scores range from 0 to 21; higher scores indicate poorer sleep quality and a worse outcome.
Time frame: Baseline, Month 3, Month 6
Activities of Daily Living Scale
The 20-item Activities of Daily Living Scale (ADL-20) assesses basic and instrumental activities of daily living. Total scores range from 20 to 80; higher scores indicate greater dependence and worse functional ability, while lower scores indicate greater independence.
Time frame: Baseline, Month 3, Month 6
Caregiver Burden Inventory
The Caregiver Burden Inventory (CBI) assesses time-dependence, developmental, physical, social, and emotional burden. Total scores range from 0 to 96; higher scores indicate greater caregiver burden and a worse outcome.
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Time frame: Baseline, Month 3, Month 6