Healthy Participants, Mild Cognitive Impairment
Conditions
Brief summary
This is a mechanism-driven translational project to test the efficacy of transcranial low-level light/laser therapy (LLLT), for enhancing cognitive function in middle-aged and older adults and participants with Mild Cognitive Impairment.
Detailed description
The goal of this project is to test the efficacy of LLLT to enhance neurocognitive function in middle-aged adults and examine the modulating influences of carotid atherosclerosis. The specific aims will be accomplished in a randomized controlled trial (RCT) by examining cognitive test performance and blood oxygen level-dependent (BOLD) response to a working memory task in middle-aged and older adults and participants with Mild Cognitive Impairment pre- and post- six-week long intervention of LLLT or placebo. In addition, the investigators will examine if carotid artery intima-media thickness (IMT) moderates the therapeutic effects of LLLT.
Interventions
DEVICELLLT
The treatment will consist of applying light of a specific wavelength (1064 nm) using a laser diode supplied by Cell Gen Therapeutics, LLC (CG-5000 laser, HD Laser Center, Dallas, TX, USA).
DEVICEPlacebo
The treatment will consist of applying light of a specific wavelength (1064 nm) using a laser diode supplied by Cell Gen Therapeutics, LLC (CG-5000 laser, HD Laser Center, Dallas, TX, USA). However, the placebo group will receive approximately 1/12th of the cumulative energy density as the treatment group.
Sponsors
University of Texas at Austin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Men and postmenopausal women, aged 45 and older * Participants with Mild Cognitive Impairment
Exclusion criteria
* neurological disease (e.g., large vessel stroke, seizure disorder, Parkinson's disease, Alzheimer's disease, clinically significant traumatic brain injury with loss of consciousness \> 30 minutes, multiple sclerosis, or brain infection/meningitis * baseline IQ \< 85 placing them below the average range of intellectual functioning * major psychiatric illness (e.g., schizophrenia, bipolar disorder) or substance abuse (diagnosed abuse and/or previous hospitalization for substance abuse) * severe cardiovascular disease (e.g., pacemaker), chronic obstructive pulmonary disease, liver or kidney disease, inflammatory illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Psychomotor Vigilance Task (PVT) | Time 1 represents PVT performance (reaction time in msec) at baseline, Time 2 represents PVT performance (reaction time in msec) six weeks later. | The psychomotor vigilance task (PVT) is a sustained-attention, reaction-timed task that measures the consistency with which subjects respond to a visual stimulus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | T1 represents score at baseline; T2 represents follow-up score, 6 weeks later | The outcome represents a score on a scale - brain activation in response to a working memory task (t-statistic). The range is approximately -15 to +15. Positive scores reflect greater engagement of working memory brain regions and better performance. |
| Working Memory (2 Back Task) | T1 represents 2back % Correct at baseline; T2 represents 2back % Correct 6 weeks later | 2Back task performance (%Correct) |
Countries
United States
Participant flow
Recruitment details
641 participants were screened, 155 passed initial phone screening, 91 were enrolled and randomized.
Participants by arm
| Arm | Count |
|---|---|
| LLLT Six weekly sessions of LLLT. The treatment will consist of applying light of a specific wavelength (1064 nm) using a laser diode supplied by Cell Gen Therapeutics, LLC (CG-5000 laser, HD Laser Center, Dallas, TX, USA). Each laser stimulation session will consist of total 8 min, with eight 1 min/cycle treatments alternating between two locations on the right forehead.
LLLT: The treatment will consist of applying light of a specific wavelength (1064 nm) using a laser diode supplied by Cell Gen Therapeutics, LLC (CG-5000 laser, HD Laser Center, Dallas, TX, USA). | 44 |
| Placebo The control group will undergo the same procedure as the treatment group, but will receive brief (5-s) stimulation to the intended site on the forehead, followed by 55 s of no stimulation, for each 1-min cycle. Thus the control group will receive approximately 1/12th of the cumulative energy density as the treatment group. This is sufficient to provide a brief sensation of slight heat (as active placebo) at the onset of each one-minute cycle, using a fraction of the energy received by the experimental group.
Placebo: The treatment will consist of applying light of a specific wavelength (1064 nm) using a laser diode supplied by Cell Gen Therapeutics, LLC (CG-5000 laser, HD Laser Center, Dallas, TX, USA). However, the placebo group will receive approximately 1/12th of the cumulative energy density as the treatment group. | 47 |
| Total | 91 |
Baseline characteristics
| Characteristic | LLLT | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.1 years STANDARD_DEVIATION 8.4 | 64.4 years STANDARD_DEVIATION 9.5 | 64.7 years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 33 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 9 Participants | 14 Participants |
| Psychomotor Vigilance Task (PVT) | 338.2 msec STANDARD_DEVIATION 96.8 | 342.8 msec STANDARD_DEVIATION 53.94 | 340.5 msec STANDARD_DEVIATION 77.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 9 Participants | 14 Participants |
| Race (NIH/OMB) White | 37 Participants | 36 Participants | 73 Participants |
| Sex: Female, Male Female | 27 Participants | 28 Participants | 55 Participants |
| Sex: Female, Male Male | 17 Participants | 19 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 47 |
| other Total, other adverse events | 0 / 44 | 2 / 47 |
| serious Total, serious adverse events | 0 / 44 | 0 / 47 |
Outcome results
Primary
Psychomotor Vigilance Task (PVT)
The psychomotor vigilance task (PVT) is a sustained-attention, reaction-timed task that measures the consistency with which subjects respond to a visual stimulus.
Time frame: Time 1 represents PVT performance (reaction time in msec) at baseline, Time 2 represents PVT performance (reaction time in msec) six weeks later.
Population: Cognitively unimpaired (CU) participants were analyzed separately from the Mild Cognitive Impairment (MCI) participants. One participant was missing data on T1 and 2 participants were missing data on T2 due to equipment failure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LLLT | Psychomotor Vigilance Task (PVT) | Time 1 CU | 341.89 msec | Standard Deviation 47.8 |
| LLLT | Psychomotor Vigilance Task (PVT) | Time 2 CU | 331.11 msec | Standard Deviation 62.85 |
| LLLT | Psychomotor Vigilance Task (PVT) | Time 1 MCI | 329.76 msec | Standard Deviation 165.87 |
| LLLT | Psychomotor Vigilance Task (PVT) | Time 2 MCI | 333.94 msec | Standard Deviation 139.73 |
| Placebo | Psychomotor Vigilance Task (PVT) | Time 2 MCI | 321.19 msec | Standard Deviation 62.4 |
| Placebo | Psychomotor Vigilance Task (PVT) | Time 1 CU | 344.09 msec | Standard Deviation 58.03 |
| Placebo | Psychomotor Vigilance Task (PVT) | Time 1 MCI | 339.81 msec | Standard Deviation 45.53 |
| Placebo | Psychomotor Vigilance Task (PVT) | Time 2 CU | 330.75 msec | Standard Deviation 45.97 |
Comparison: The contrast of interest was the Time x Treatment Group interaction. CU group.p-value: 0.79ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. MCI group.p-value: 0.87ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. CU group. 3 outliers removed, whose scores were outside 1.5 times the interquartile range.p-value: 0.16ANOVA
Secondary
Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task
The outcome represents a score on a scale - brain activation in response to a working memory task (t-statistic). The range is approximately -15 to +15. Positive scores reflect greater engagement of working memory brain regions and better performance.
Time frame: T1 represents score at baseline; T2 represents follow-up score, 6 weeks later
Population: No data were collected on the secondary outcome variables from participants with Mild Cognitive Impairment (MCI) per study design as this task is too difficult for people with cognitive impairment. Two participants were missing T1 data due to equipment failure; 2 participants were missing T2 due to equipment failure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Left middle frontal gyrus 1. | 2.47 score on a scale | Standard Deviation 2.59 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Left middle frontal gyrus 1. | 2.51 score on a scale | Standard Deviation 2.4 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Left medial frontal/superior frontal gyrus. | 2.90 score on a scale | Standard Deviation 2.22 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Left medial frontal/superior frontal gyrus. | 3.06 score on a scale | Standard Deviation 2.17 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Right superior parietal lobule. | 2.50 score on a scale | Standard Deviation 2.47 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Right superior parietal lobule. | 2.39 score on a scale | Standard Deviation 2.96 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Left inferior parietal lobule. | 2.87 score on a scale | Standard Deviation 2.39 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Left inferior parietal lobule. | 3.09 score on a scale | Standard Deviation 2.71 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Left middle frontal gyrus 2. | 1.80 score on a scale | Standard Deviation 2.11 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Left middle frontal gyrus 2. | 1.84 score on a scale | Standard Deviation 1.72 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Right superior frontal gyrus. | 2.26 score on a scale | Standard Deviation 2.36 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Right superior frontal gyrus. | 1.93 score on a scale | Standard Deviation 2.15 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Right middle frontal gyrus. | 3.09 score on a scale | Standard Deviation 2.9 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Right middle frontal gyrus. | 3.31 score on a scale | Standard Deviation 2.8 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Right inferior frontal gyrus. | 0.72 score on a scale | Standard Deviation 2 |
| LLLT | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Right inferior frontal gyrus. | 1.14 score on a scale | Standard Deviation 2.13 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Right inferior frontal gyrus. | 1.27 score on a scale | Standard Deviation 2.47 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Left middle frontal gyrus 1. | 3.00 score on a scale | Standard Deviation 1.54 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Left middle frontal gyrus 2. | 2.02 score on a scale | Standard Deviation 1.6 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Left middle frontal gyrus 1. | 3.39 score on a scale | Standard Deviation 2.15 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Right middle frontal gyrus. | 3.51 score on a scale | Standard Deviation 2.04 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Left medial frontal/superior frontal gyrus. | 2.67 score on a scale | Standard Deviation 1.36 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Left middle frontal gyrus 2. | 2.14 score on a scale | Standard Deviation 2.12 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Left medial frontal/superior frontal gyrus. | 2.89 score on a scale | Standard Deviation 2.29 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Right inferior frontal gyrus. | 1.19 score on a scale | Standard Deviation 2.13 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Right superior parietal lobule. | 2.81 score on a scale | Standard Deviation 1.72 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Right superior frontal gyrus. | 2.50 score on a scale | Standard Deviation 1.59 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Right superior parietal lobule. | 2.86 score on a scale | Standard Deviation 2.57 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Right middle frontal gyrus. | 3.89 score on a scale | Standard Deviation 2.86 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T1 Left inferior parietal lobule. | 3.46 score on a scale | Standard Deviation 1.71 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Right superior frontal gyrus. | 2.85 score on a scale | Standard Deviation 2.38 |
| Placebo | Brain Blood Oxygen Level Dependent Response to Working Memory (2Back) Task | CU T2 Left inferior parietal lobule. | 3.36 score on a scale | Standard Deviation 2.35 |
Comparison: The contrast of interest was the Time x Treatment Group interaction. Left middle frontal gyrus 1.p-value: 0.22ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. Left medial frontal/superior frontal gyrus.p-value: 0.69ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. Right superior parietal lobule.p-value: 0.25ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. Left inferior parietal lobule.p-value: 0.86ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. Left middle frontal gyrus 2.p-value: 0.28ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. Right superior frontal gyrus.p-value: 0.12ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. Right middle frontal gyrus.p-value: 0.26ANOVA
Comparison: The contract of interest was the Time x Treatment Group interaction. Right inferior frontal gyrus.p-value: 0.83ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy). Left middle frontal gyrus 1.p-value: 0.55ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy). Left medial frontal/superior frontal gyrus.p-value: 0.76ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy). Right superior parietal lobule.p-value: 0.38ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy). Left inferior parietal lobule.p-value: 0.93ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy). Left middle frontal gyrus 2.p-value: 0.41ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy). Right superior frontal gyrus.p-value: 0.06ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy). Right middle frontal gyrus.p-value: 0.18ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy). Right inferior frontal gyrus.p-value: 0.84ANOVA
Secondary
Working Memory (2 Back Task)
2Back task performance (%Correct)
Time frame: T1 represents 2back % Correct at baseline; T2 represents 2back % Correct 6 weeks later
Population: No data were collected on the secondary outcome variables from participants with Mild Cognitive Impairment (MCI) per study design as this task is generally too difficult for patients with cognitive impairment. Data were missing on 7 participants at T1 and 9 participants on T2 due to equipment failure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LLLT | Working Memory (2 Back Task) | CU %Correct T2 | 77.17 % correct responses of total responses | Standard Deviation 14.97 |
| LLLT | Working Memory (2 Back Task) | CU %Correct T1 | 73.93 % correct responses of total responses | Standard Deviation 14.57 |
| Placebo | Working Memory (2 Back Task) | CU %Correct T1 | 73.54 % correct responses of total responses | Standard Deviation 13.48 |
| Placebo | Working Memory (2 Back Task) | CU %Correct T2 | 79.59 % correct responses of total responses | Standard Deviation 13.01 |
Comparison: The contrast of interest was the Time x Treatment Group interaction.p-value: 0.53ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy).p-value: 0.74ANOVA
Secondary
Working Memory (2 Back Task)
2Back task performance (Reaction Time in msec)
Time frame: T1 represents 2back Reaction Time (RT) in msec at baseline; T2 represents Reaction Time (RT) in msec 6 weeks later
Population: No data were collected on the secondary outcome variables from participants with Mild Cognitive Impairment (MCI) per study design as this task is generally too difficult for people with cognitive impairment. Data were missing on 10 participants at T1 and 13 participants on T2 due to equipment failure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LLLT | Working Memory (2 Back Task) | CU RT T1 | 1289.19 msec | Standard Deviation 225.72 |
| LLLT | Working Memory (2 Back Task) | CU RT T2 | 1202.89 msec | Standard Deviation 261.49 |
| Placebo | Working Memory (2 Back Task) | CU RT T1 | 1173.98 msec | Standard Deviation 268.44 |
| Placebo | Working Memory (2 Back Task) | CU RT T2 | 1035.05 msec | Standard Deviation 271.38 |
Comparison: The contrast of interest was the Time x Treatment Group interaction.p-value: 0.72ANOVA
Comparison: The contrast of interest was the Time x Treatment Group interaction. In this sub-group analysis, we performed a sub-population analysis (N=36), including only participants who performed the 2Back task to criterion (\>50% accuracy).p-value: 0.97ANOVA