The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.

ADCS-ADL assesses the competence of patients with AD in basic and instrumental activities of daily living (ADLs). It can be completed by a caregiver in questionnaire format, or administered by a clinician/researcher as a structured interview with a caregiver. ADCS-ADL scores range from 0-53, with higher scores indicating greater independence. The changes score was determined by calculating the ratio of the week 16 ADCS-ADL score over the baseline ADCS-ADL score. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in ADCS-ADL compared to baseline.

Although Aβ42 is present in plasma, it is unclear whether it originates from peripheral sources or from the brain. Because Aβ can be transported bidirectionally across the blood-brain barrier, it has been hypothesized that there may be an equilibrium between CSF and plasma pools of Aβ. Decreased levels of Aβ42 in CSF occurs in conjunction with cognitive decline. However, patients with mutations in chromosome 21 that cause early-onset familial AD and patients with trisomy 21 have increased levels of plasma Aβ42 before the onset of the symptoms of dementia. Therefore, it is possible that plasma Aβ42 levels increase with cognitive decline. The change score was determined by calculating the ratio of plasma Aβ42 at week 16 over the ADAS-cog score at baseline.

Aβ42 is a biomarker of AD pathology. CSF levels of Aβ42 decrease in conjunction with the cognitive decline. The change score was determined by calculating the ratio of CSF Aβ42 at week 16 over the ADAS-cog score at baseline. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF levels of Aβ42 compared to baseline.

Tau, the microtubule-associated protein, forms insoluble filaments that accumulate as neurofibrillary tangles in Alzheimer's disease (AD). Research suggests that plasma tau levels increased with AD severity. The change score was determined by calculating the ratio of the week 16 plasma tau over the baseline plasma tau levels. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in plasma tau compared to baseline.

Tau forms insoluble filaments that accumulate as neurofibrillary tangles in AD. Increased levels of tau in CSF is a key characteristic of AD and is considered to result from neurodegeneration. The change score was determined by calculating the ratio of week 16 CSF tau over baseline CSF tau. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF tau compared to baseline.

Neurofilament light chain (NfL) is a marker of axonal degeneration and is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. The change score was determined by calculating the ratio of week 16 plasma levels of NfL over the baseline levels of plasma NfL. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in plasma levels of NfL compared to baseline.

Neurofilament light chain (NfL) is a marker of axonal degeneration and is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. There is a strong relationship with cerebrospinal fluid (CSF) NfL, suggesting that these biomarker modalities reflect the same pathological process. The change score was determined by calculating the ratio of week CSF NfL over baseline CSF NfL. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF NfL compared to baseline.

This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks.

Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.

Total of all reporting groups

The Mini-Mental State Exam (MMSE) is a widely used test of cognitive function. It is an 11-question measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The MMSE ranges from 0 to 30. Higher scores are better.

The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia. It is one of the most widely used cognitive scales in clinical trials and is considered to be the "gold standard" for assessing antidementia treatments. Scores (errors) on single scale range from 0 to 70. Higher scores are indicative of greater cognitive impairment.

The Neuropsychiatric Inventory (NPI) measures the presence and severity of 12 neuropsychiatric symptoms. Symptoms are rated in terms of frequency (1=rarely, <1x/week; 2=sometimes, ~1x/week; 3=often, several times/week; and 4=very often, >1x/day) and severity (1=mild; 2=moderate; 3=severe). The composite symptom domain score (frequencyXseverity) ranges from 0 (no behavioral symptoms) to 144 points. Caregiver distress is rated for each positive neuropsychiatric symptom domain (0=no distress; 1=minimal distress; 2=mild distress; 3=moderate distress; 4=severe distress; and 5=very severe distress).

The ADCS-ADL assesses the competence of patients with dementia in basic and instrumental activities of daily living (ADLs). It can be completed by a caregiver in questionnaire format, or administered by a clinician/researcher as a structured interview. The ADCS-ADL is a 23 item scale that includes 6 basic activities of daily living items (e.g., grooming/dressing) and 17 instrumental activities of daily living items (e.g., cooking/managing finance) that provide a total score from 0-78, with a lower score indicating greater severity.

The Color Trails Test (CTT) is a neuropsychological test that assesses frontal and executive functioning, while minimizing the cultural and language barriers inherent in similar measures such as the traditional Trail Making Test. For test 1, the participant uses a pencil to rapidly connect circles numbered 1 through 25 in sequence.

The Color Trails Test (CTT) is a neuropsychological test that assesses frontal and executive functioning, while minimizing the cultural and language barriers inherent in similar measures such as the traditional Trail Making Test. For test 2, the participant rapidly connects numbered circles in sequence, alternating between two different colors.

The index is a ratio of the time it takes to complete the Color Trails Test (CTT) 2 over the time it takes to complete the CTT 1. The index provides a method for partialling out the effects of undivided attention and simple perceptual tracking on the alternating demands of CTT-2. Higher index scores indicate greater interference, less cognitive flexibility.

Aβ40 is a 40 amino acid proteolytic product from the amyloid precursor protein (APP) that has gained attention as a biomarker correlating with Alzheimer disease (AD) onset, mild cognitive impairment, vascular dementia, and other cognitive disorders.

Aβ42 is the 42 amino acid form of amyloid-β that plays a key role in the pathogenesis of Alzheimer's disease (AD) and is considered a core biomarker for the diagnosis of AD.

Decreased ratio of Aβ 42/40 is a strong marker of Alzheimer's disease and can be detected early in the disease progression, even before clinical dementia occurs.

Tau is a microtubule-associated protein that forms insoluble filaments that accumulate as neurofibrillary tangles in Alzheimer's disease (AD).

Tau phosphorylated at threonine 181 (p-tau181) is a highly specific biomarker for Alzheimer's disease pathology. Concentrations of P-tau181 might be increased in Alzheimer's disease (AD).

Neurofilament light chain (NfL) is a neuronal cytoplasmic protein highly expressed in large myelinated axons. Its levels increase in cerebrospinal fluid (CSF) and blood proportionally to the degree of axonal damage in a variety of neurological disorders, including Alzheimer's disease.

Glial fibrillary acidic protein (GFAP) is a monomeric intermediate filament protein found in the astroglial cytoskeleton. This protein is not routinely secreted in blood or CSF and is only released after cell death or injury.

This arm will receive active photobiomodulation (PBM), delivered with the Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks.

Vielight Neuro Gamma: The Vielight Neuro Gamma is headset that delivers transcranial (through the scalp and skull) and intranasal (through the nose) near infrared (NIR) light. The device is engineered for increased efficacy and easy domestic use for comprehensive brain photobiomodulation (PBM). The NIR lights are pulsed at a 40 Hz rate, which correlates with electroencephalogram (EEG) gamma brain wave entrainment.

This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks.

Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.

CTT is a non-verbal test of visual attention, graphomotor sequencing, and effortful executive processing abilities (i.e., sustained attention and set shifting). A higher index score indicates less cognitive flexibility, a lower ability to shift attention.

One Active PBM patient did not return for post-treatment assessment due to pandemic-related lock-down. Two Sham PBM patients did not return for post-treatment assessment due to worsening of symptoms that necessitated placement in memory care facility. One Sham PBM patient was excluded due to unblinding.

NPI is a well-validated, reliable, multi-item instrument to assess psychopathology (e.g., behavioral symptoms) in AD based on a questionnaire completed by the participants' study partners. Higher scores indicate more symptoms and/or more severe symptoms.

The changes score was determined by calculating the ratio of the week 16 NPI score over the baseline NPI score. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in NPI compared to baseline.

One Active PBM patient did not return for post-treatment assessment due to pandemic-related lock-down. Two Sham PBM patients did not return for post-treatment assessment due to worsening of symptoms that necessitated placement in memory care facility. One Sham PBM patient was excluded due to unblinding.

ADCS-ADL assesses the competence of patients with AD in basic and instrumental activities of daily living (ADLs). It can be completed by a caregiver in questionnaire format, or administered by a clinician/researcher as a structured interview with a caregiver. ADCS-ADL scores range from 0-53, with higher scores indicating greater independence. The changes score was determined by calculating the ratio of the week 16 ADCS-ADL score over the baseline ADCS-ADL score. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in ADCS-ADL compared to baseline.

One Active PBM patient did not return for post-treatment assessment due to pandemic-related lock-down. Two Sham PBM patients did not return for post-treatment assessment due to worsening of symptoms that necessitated placement in memory care facility. One Sham PBM patient was excluded due to unblinding.

Although Aβ42 is present in plasma, it is unclear whether it originates from peripheral sources or from the brain. Because Aβ can be transported bidirectionally across the blood-brain barrier, it has been hypothesized that there may be an equilibrium between CSF and plasma pools of Aβ. Decreased levels of Aβ42 in CSF occurs in conjunction with cognitive decline. However, patients with mutations in chromosome 21 that cause early-onset familial AD and patients with trisomy 21 have increased levels of plasma Aβ42 before the onset of the symptoms of dementia. Therefore, it is possible that plasma Aβ42 levels increase with cognitive decline. The change score was determined by calculating the ratio of plasma Aβ42 at week 16 over the ADAS-cog score at baseline.

One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; another REAL PBM patient's post-treatment sample was contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Aβ42 is a biomarker of AD pathology. CSF levels of Aβ42 decrease in conjunction with the cognitive decline. The change score was determined by calculating the ratio of CSF Aβ42 at week 16 over the ADAS-cog score at baseline. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF levels of Aβ42 compared to baseline.

One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; two REAL PBM patient's post-treatment samples were contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Tau, the microtubule-associated protein, forms insoluble filaments that accumulate as neurofibrillary tangles in Alzheimer's disease (AD). Research suggests that plasma tau levels increased with AD severity. The change score was determined by calculating the ratio of the week 16 plasma tau over the baseline plasma tau levels. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in plasma tau compared to baseline.

One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; another REAL PBM patient's post-treatment sample was contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Tau forms insoluble filaments that accumulate as neurofibrillary tangles in AD. Increased levels of tau in CSF is a key characteristic of AD and is considered to result from neurodegeneration. The change score was determined by calculating the ratio of week 16 CSF tau over baseline CSF tau. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF tau compared to baseline.

One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; two REAL PBM patient's post-treatment samples were contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Neurofilament light chain (NfL) is a marker of axonal degeneration and is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. The change score was determined by calculating the ratio of week 16 plasma levels of NfL over the baseline levels of plasma NfL. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in plasma levels of NfL compared to baseline.

One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; another REAL PBM patient's post-treatment sample was contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

Neurofilament light chain (NfL) is a marker of axonal degeneration and is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. There is a strong relationship with cerebrospinal fluid (CSF) NfL, suggesting that these biomarker modalities reflect the same pathological process. The change score was determined by calculating the ratio of week CSF NfL over baseline CSF NfL. Thus, a change score of 1 signifies no change compared to baseline and change scores < 1 or > 1 reflect a decrease or an increase in CSF NfL compared to baseline.

One Active REAL PBM patient did not return for post-treatment assessment due to pandemic-related lock-down; two REAL PBM patient's post-treatment samples were contaminated. One SHAM patient was excluded for unblinding, two SHAM patients were institutionalized during the study; two other SHAM patients had failed lumbar punctures.

This arm will not receive active photobiomodulation (PBM). Instead, they will use a sham Vielight Neuro Gamma device, once every other day (e.g., Mon, Wed, Fri) for 20 minutes for 16 weeks.

Sham Vielight Neuro Gamma: The Sham Vielight Neuro Gamma headset is identical to the active Vielight Neuro Gamma headset and intranasal light emitting diode (LED) except it has a power output of 0.