Aging
Conditions
Keywords
Cognitive Aging, Neuromodulation, Low Level Light Therapy, Near Infrared Light, Neurostimulation
Brief summary
Changes in mood and cognition are common in older adulthood. Some studies have suggested that transcranial application of near-infrared (NIR) light may have enhancing effects on cognitive and mood status in young adults and individuals with traumatic brain injury. This effect has not been examined in older adults. This study will involve a randomized sham-controlled trial to learn whether NIR stimulation improves cognition and mood in older adults, relative to sham treated controls. Aim 4 of this study (Parkinson Specific) is registered separately under NCT06688357
Detailed description
There is a dearth of clinically meaningful treatment options at this point in time for individuals who are at increased risk for transitioning to dementia, particularly those with the amnestic variant of mild cognitive impairment (aMCI). While waiting for causative cures and preventive approaches, investigators are faced with the task of identifying modifying therapies that might alter the course or slow down the transition from normal cognition to MCI to dementia. The proposed study hopes to contribute to this mission by testing the viability of a different type of intervention, one involving transcranial delivery of near-infrared (NIR) wavelengths (808-904nm). Near-infrared stimulation is safe, non-invasive and appears to improve mitochondrial function by promoting increased production of intracellular adenosine triphosphate (ATP) and possibly improved blood flow. Perhaps most compelling are recent findings of reduced beta-amyloid and neurofibrillary tangles in transgenic Alzheimer's mouse models after exposure to real vs sham transcranial NIR stimulation. Preliminary human involving traumatic brain injury (TBI), stroke, and young adult populations have also been promising in terms of positive effects of NIR on cognition. The overall goal of the present study is to learn whether this unconventional NIR stimulation approach has potential for improving cognition in older adults. To do so, investigators will conduct a randomized sham controlled pilot trial. The intervention will involve six sessions, over a 2-week period in which real or sham stimulation is transcranially applied using a delivery system that has been FDA-approved as a nonsignificant risk since 2003. Researchers hope to learn whether NIR stimulation, relative to sham, has positive effects on cognition and mood in older adults.
Interventions
DEVICEMedX 1116 Rehab Console
This intervention makes use of transcranially applied near infrared light using light emitting diodes. Near infrared light will be applied to the scalp for a period of 1 hour at each session. A total of six session will be held.
DEVICESham MedX 1116 Rehab Console
This intervention makes use of sham transcranially applied near infrared light using light emitting diodes. Light emitting diodes (but not near-infrared light) will be applied to the scalp for a period of 1 hour at each session. A total of six session will be held.
Sponsors
Ed and Ethel Moore Alzheimer's Disease Research Program
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
randomized, sham controlled
Eligibility
Sex/Gender
ALL
Age
62 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 62 years or above * Able to provide informed consent and perform cognitive and mood measures on a computer * Willingness to be randomized to Sham or Real intervention * Can devote 2 weeks to the intervention, and additional time for pre and post testing * 8th grade education and ability to read on 8th grade level based on scores on the Wechsler Test of Adult Reading (WTAR) or the Wide Range Achievement Test-IV (WRAT-IV); or a reading test at 14 pt. text * On stable doses of major medications; Since some older adults with memory complaints may be prescribed acetylcholinererase inhibitors or related medications by their primary care physicians (i.e., donepezil, rivastigmine, galantaominhe, memantime, or other potential memory-enhancing agent(s), we will not exclude them as long as they have been on stable medications for at least two months and plan to continue this medication during study participation. * Willingness to allow a study partner (spouse, family member, friend) to answer questions about their cognitive, mood, and other behaviors
Exclusion criteria
* Sensory loss (vision, hearing) or motor deficits that would preclude participation in the experimental cognitive tasks or neuropsychological assessment * Unstable and uncontrolled medical conditions (metabolic encephalopathy, HIV, moderate to severe kidney or liver disease) * Previous major strokes or other known significant brain abnormalities or diseases affecting cognition (i.e., multiple sclerosis, seizure disorder, brain surgery, moderate TBI, etc.). No history of brain surgery. Exceptions are a diagnosis of Parkinson's disease for the PD subgroup. * Evidence of potential dementia (e.g., scores \< 24 on the Mini Mental State Exam (MMSE), or \< 20 on the Montreal Cognitive Assessement (MoCA), or less than 5th percentile on the Dementia Rating Scale-2 (DRS-2) * Current or past history of major psychiatric disturbance including schizophrenia, or active psychosis, bipolar disorder, current major depressive episode, current alcohol or substance abuse or history thereof within the past six months. This will be assessed using the Mental Health Screen v.3 (Carroll & McGinley), a modification of the Structured Clinical Interview for DSM-IV psychiatric disorders. We are not excluding individuals who are taking antidepressants or anti-anxiety medications, however, use of antidepressants and anxiolytics will be recorded and data will be analyzed in post-hoc analyses * Use of antipsychotics, sedatives, or other medications with significant anticholinergic properties (due to potential influence on memory) * Use of photo-sensitive medications such as steroids or retin-A within 15 days of the study intervention * Diagnosis of cancer * Previous participation in a cognitive training study within the last 3 months or current involvement in another study at VITAL or ReVITALIZE, or another study involving cognitive training or intervention at the time of participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NIH Examiner Battery, Executive Composite Changes From Baseline to Post-testing | Change in baseline to approximately week 3 | Computer-based battery of executive functioning tests which yields a total or composite score to represent global executive functioning. Executive composite scores can range from -3.0 to 3.0, with higher scores corresponding to better executive functioning, and negative scores indicating impairment. A change score will be calculated by subtracting the baseline scores from the post-test scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite Learning-Retention Score From ARENA Task | Change in baseline to approximately week 3 | ARENA is a task of spatial memory and navigation that is a human analogue to the Morris water maze used in animal studies. Participants learn to navigate to a hidden target location relying on spatial cues in a simulated environment over a series of 8 learning trials and a final retention trial. The final ARENA outcome is an Overall Composite z-score combining learning and retention metrics as follows: \[-Learning z-score + Retention z-score\]/2. The learning z-score is based on two metrics (path length to target, time to reach target) that are converted to z-scores and averaged over the 8 learning trials. The retention z-score is based on percent time spent in the target quadrant during the retention trial. The Learning and Retention z-scores are combined to create a single final Arena Composite outcome. Higher composite scores reflect better memory performance. A change score is calculated by subtracting the Baseline Composite score from the post-test Composite Score |
| NIH Toolbox Emotion Psychological Wellbeing Scale Changes From Baseline to Post-testing | Change in baseline to approximately week 3 (Post - Baseline) | The Psychological Wellbeing Scale from the NIH Toolbox Emotion module Wellbeing Scale results in T-scores (mean=50, SD=10) for categories such as positive affect, life satisfaction, and meaning and purpose. Scores below 40 indicate low levels of wellbeing and scores above 60 indicating high levels of wellbeing. Change scores will be calculated by subtracting the baseline scores from the post-test scores. |
| NIH Toolbox Emotion Negative Affect Scale Changes From Baseline to Post-testing | Change from baseline to approximately week 3 (Post Intervention - Baseline) | The Negative Affect Scale from the NIH Toolbox Emotion module results in T-scores (mean=50, SD=10) for categories such as anger, sadness, and apathy. Scores below 40 indicate low levels of negative affect and scores above 60 indicate high levels of negative affect. Change scores will be calculated by subtracting the baseline scores from the post-test scores. |
Countries
United States
Participant flow
Recruitment details
The older adult cohort was recruited from the community via advertisements. Recruitment began in 2015 and ended in 2018. This protocol also includes participants with Parkinson disease reported in NCT-TBD.
Pre-assignment details
Three participants dropped out prior to beginning the sham intervention due study demands and family health issues.
Participants by arm
| Arm | Count |
|---|---|
| Older Adult Group NIR Transcranial Near Infrared Stimulation for cognitively normal participants who will attend a total of 6 treatment sessions over a two week period. During each session, stimulation via light emitting diode clusters will occur for a total of 60 minutes. Four light emitting diode (LED) clusters will be applied in 3 distinct configurations. There will be 20 minutes of stimulation at each of these 3 configurations. Each configuration will target 4 sites, for a total of 12 sites over the course of the 60 minute session. The power density used will be 500 milliwatts (mW) with a cumulative fluence (energy density) of 312 Joules/cm2 (26 J/cm2 applied at 12 sites). It is estimated that approximately 6 Joules/cm2 will reach the cortex with each daily treatment.
MedX 1116 Rehab Console: This intervention makes use of transcranially applied near infrared light using light emitting diodes. Near infrared light will be applied to the scalp for a period of 1 hour at each session. A total of six session will be held. | 8 |
| Older Adult Group - Sham Cognitively Normal Participants in the sham control group will undergo identical procedures as the intervention group - screening, baseline testing, and LED cluster placement procedures. However, during the near infrared (NIR) session, the MedX console will not be turned on and no active stimulation will be applied.
Sham MedX 1116 Rehab Console: This intervention makes use of sham transcranially applied near infrared light using light emitting diodes. Light emitting diodes (but not near-infrared light) will be applied to the scalp for a period of 1 hour at each session. A total of six session will be held. | 5 |
| Total | 13 |
Baseline characteristics
| Characteristic | Total | Older Adult Group - Sham | Older Adult Group NIR |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 5 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 74.9 years STANDARD_DEVIATION 5.9 | 74.4 years STANDARD_DEVIATION 4.6 | 75.2 years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| MoCA | 28.2 units on a scale STANDARD_DEVIATION 1.1 | 28.3 units on a scale STANDARD_DEVIATION 1 | 28.1 units on a scale STANDARD_DEVIATION 1.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 5 |
| other Total, other adverse events | 0 / 8 | 0 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 5 |
Outcome results
Primary
NIH Examiner Battery, Executive Composite Changes From Baseline to Post-testing
Computer-based battery of executive functioning tests which yields a total or composite score to represent global executive functioning. Executive composite scores can range from -3.0 to 3.0, with higher scores corresponding to better executive functioning, and negative scores indicating impairment. A change score will be calculated by subtracting the baseline scores from the post-test scores.
Time frame: Change in baseline to approximately week 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Older Adult Group NIR | NIH Examiner Battery, Executive Composite Changes From Baseline to Post-testing | 0.33 z-score | Standard Deviation 0.5 |
| Older Adult Group - Sham | NIH Examiner Battery, Executive Composite Changes From Baseline to Post-testing | 0.22 z-score | Standard Deviation 0.1 |
Comparison: An independent sample t-test was used to examine difference in Pre-post intervention change scores for the Active and Sham groups;. Cohen's d was calculated to determine effect size.p-value: 0.575t-test, 2 sided
Secondary
Composite Learning-Retention Score From ARENA Task
ARENA is a task of spatial memory and navigation that is a human analogue to the Morris water maze used in animal studies. Participants learn to navigate to a hidden target location relying on spatial cues in a simulated environment over a series of 8 learning trials and a final retention trial. The final ARENA outcome is an Overall Composite z-score combining learning and retention metrics as follows: \[-Learning z-score + Retention z-score\]/2. The learning z-score is based on two metrics (path length to target, time to reach target) that are converted to z-scores and averaged over the 8 learning trials. The retention z-score is based on percent time spent in the target quadrant during the retention trial. The Learning and Retention z-scores are combined to create a single final Arena Composite outcome. Higher composite scores reflect better memory performance. A change score is calculated by subtracting the Baseline Composite score from the post-test Composite Score
Time frame: Change in baseline to approximately week 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Older Adult Group NIR | Composite Learning-Retention Score From ARENA Task | 0.17 z-score | Standard Error 0.6 |
| Older Adult Group - Sham | Composite Learning-Retention Score From ARENA Task | -.41 z-score | Standard Error 0.5 |
Comparison: independent t-test, cohen's d effect sizep-value: 0.16t-test, 2 sided
Secondary
NIH Toolbox Emotion Negative Affect Scale Changes From Baseline to Post-testing
The Negative Affect Scale from the NIH Toolbox Emotion module results in T-scores (mean=50, SD=10) for categories such as anger, sadness, and apathy. Scores below 40 indicate low levels of negative affect and scores above 60 indicate high levels of negative affect. Change scores will be calculated by subtracting the baseline scores from the post-test scores.
Time frame: Change from baseline to approximately week 3 (Post Intervention - Baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Older Adult Group NIR | NIH Toolbox Emotion Negative Affect Scale Changes From Baseline to Post-testing | -1.92 T-score | Standard Deviation 3.6 |
| Older Adult Group - Sham | NIH Toolbox Emotion Negative Affect Scale Changes From Baseline to Post-testing | 2.11 T-score | Standard Deviation 4.5 |
Comparison: independent sample t-test, Cohen's d effect sizep-value: 0.099t-test, 2 sided
Secondary
NIH Toolbox Emotion Psychological Wellbeing Scale Changes From Baseline to Post-testing
The Psychological Wellbeing Scale from the NIH Toolbox Emotion module Wellbeing Scale results in T-scores (mean=50, SD=10) for categories such as positive affect, life satisfaction, and meaning and purpose. Scores below 40 indicate low levels of wellbeing and scores above 60 indicating high levels of wellbeing. Change scores will be calculated by subtracting the baseline scores from the post-test scores.
Time frame: Change in baseline to approximately week 3 (Post - Baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Older Adult Group NIR | NIH Toolbox Emotion Psychological Wellbeing Scale Changes From Baseline to Post-testing | -0.04 T-score | Standard Deviation 7.8 |
| Older Adult Group - Sham | NIH Toolbox Emotion Psychological Wellbeing Scale Changes From Baseline to Post-testing | -3.50 T-score | Standard Deviation 5.3 |
Comparison: independent t-test, Cohen's d effect sizep-value: 0.424t-test, 2 sided