Aging
Conditions
Keywords
Slow gait, Executive function, Transcranial direct current stimulation
Brief summary
The objective of this study is to determine whether augmentation of prefrontal brain excitability using noninvasive transcranial direct current stimulation (tDCS) lessens the severity of the symptom triad associated with cerebral microvascular disease (CMD); that is, slow gait, cognitive dysfunction and depressive symptoms. Investigators will complete this objective by conducting a pilot, double-blinded randomized controlled trial of a 10-day intervention of real versus sham tDCS in 40 subjects.
Detailed description
Biological aging, especially when coupled with cardiovascular risk factors, leads to chronic endothelial dysfunction within cerebral micro-vessels that impairs the brain's ability to meet the metabolic demands placed upon it by everyday life. This chronic mismatch between blood supply and metabolic demand often leads to cerebral microvascular disease (CMD), or the accumulation of ischemic damage within a network of frontal and subcortical regions. CMD is recognized as white matter hyperintensities on MRI scans and manifests clinically as mobility impairment, executive dysfunction and depressed affect. As 11-17% of elderly individuals present with this constellation of symptoms, and each of these symptoms is independently linked to increased morbidity and mortality, CMD is a critical yet understudied healthcare issue with rapidly-growing personal and economic costs. There is currently no cure for CMD and trials aimed at pharmacological improvement of nonselective systemic vasodilation report no therapeutic value (Sorrond & Lipsitz, 2011). Our team, however, has demonstrated that the severity of clinical symptoms suffered by those with CMD is critically dependent upon the brain's remaining capacity to activate the appropriate cortical networks when metabolic demand is increased by the performance of various cognitive-motor tasks (Purkayastha et al., 2014; Sorond et al., 2010; Sorond et al., 2011). Therefore, investigators predict that improvement in the capacity to activate the appropriate cortical networks in response to increased metabolic demand would ameliorate the symptoms and improve the quality of life of patients with CMD. Transcranial direct current stimulation (tDCS) enables noninvasive, selective and sustained modulation of cortical activation. tDCS works by sending low-level currents between two or more scalp electrodes, which alters brain polarity and thus, perfusion and cortical excitability. One 20-minute session of tDCS targeting the left prefrontal cortex acutely increases cortical activation during both cognitive and motor task performance in healthy adults. Investigators have demonstrated that this same stimulation improves mobility and cognitive performance in community-dwelling older adults. Moreover, repeated tDCS sessions over a one month period reduce symptoms of depression and may improve executive function in healthy individuals. This preliminary evidence suggests that tDCS may be an effective intervention for CMD; however, the impact of tDCS on this disease has not been investigated. The study investigators ultimately aim to investigate the therapeutic efficacy of tDCS in patients with CMD by conducting a double-blind, proof-of-principle, sham-controlled trail along with extensive functional and neurophysiological assessments. In order to finalize the design and plan the implementation of this definitive trial, investigators currently aim to: 1. Conduct a pilot study to establish the feasibility of deployment of tDCS in large populations of individuals with CMD, and to obtain preliminary evidence for a causal effect of the intervention on mobility, executive function and depressive symptoms in this population. 2. Within the pilot study, investigate the effects of the tDCS intervention on cortical activation in response to cognitive-motor tasks. This study will provide first-of-its-kind, proof-of-principle evidence on whether tDCS provides meaningful symptomatic relief to patients with CMD. Moreover, it will inform a more definitive, larger-scale randomized controlled trial (RCT) by providing information on recruitment and retention, compliance, estimates of effect size, and the neurophysiological underpinnings of expected functional improvements. If successful, knowledge gained is also expected to spur the investigation of tDCS as treatment for many other diseases-from dementia to diabetes-that negatively impact the brain's capacity to activate appropriate cortical networks.
Interventions
OTHERReal tDCS
Transcranial direct current stimulation (tDCS) enables noninvasive, selective and sustained modulation of cortical activation. tDCS works by sending low-level currents between two or more scalp electrodes, which alters brain polarity and thus, perfusion and cortical excitability.
OTHERSham tDCS
For sham tDCS, current will only be applied for the first 60 seconds of each 20 minute session. This is a reliable sham control as sensations arising from tDCS diminish considerably after the first minute of stimulation.
Sponsors
Beth Israel Deaconess Medical Center
The Falk Medical Research Trust, Bank of America, N.A. Trustee
Hebrew SeniorLife
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Slow gait, defined by an over-ground preferred walking speed of less than or equal to 1.0 m/s. * Executive dysfunction, defined by a Trail Making Test B z-score of greater than one standard deviation below age- and gender-based norms.
Exclusion criteria
* Non-ambulatory * Clinical history or brain imaging evidence of a previous stroke * Parkinson's Disease * Normal pressure hydrocephalus * Other neurodegenerative condition * Severe depression * Lower-extremity arthritis or pain causing slow gait * Inability or unwillingness to understand or participate in the study protocol * Contraindications to MRI or tDCS, including (but not limited to) personal or family history of epilepsy, use of neuro-active drugs, claustrophobia or risk of metal objects in the body.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Post Intervention on Dual Task Cost to Standing Postural Sway Speed | baseline, immediately after intervention and 2 weeks post intervention | Postural sway speed - assessed by measuring standing postural sway (ie., center-of pressure fluctuations) during six, 30-second trials of standing with eyes open (single task) or performing a cognitive task (dual task standing) on a stationary force platform (Kistler, Amherst, NY). Dual task cost is defined as the percent change of sway speed from single task standing to dual task standing. The outcome was obtained by averaging the dual task costs of the six trials. |
| Percent Change From Baseline to Post Intervention on Mobility | baseline, immediately after intervention and 2 weeks post intervention | Mobility and turning will be assessed by the timed up-and-go test (TUG) (Podsiadlo & Richardson, 1991). The participant will be seated in an armed chair. On the word go, the subject will stand up using the arm rests if needed, walk (with assistive device if needed) around a cone placed three meters in front of the chair, return and sit down as quickly as possible. Time to complete the TUG test will be used as the outcome measure. |
| Percent Change From Baseline to Post Intervention on Global Cognition Impairment | Baseline, immediately after intervention and 2 weeks post intervention | The Montreal Cognitive Assessment (MoCA) score is used as the outcome measure of Global Cognition Impairment. MoCA score ranges from 0 to 30. Lower MoCA score represents poorer cognitive function (i.e., more severe Global Cognition Impairment). |
| Percent Change From Baseline to Post Intervention on Dual Task Cost to Walking Speed in 24-meter Walking Test | baseline, immediately after intervention and 2 weeks post intervention | Six 24-meter walking trials at a preferred speed are completed and each three of them are in normal or dual task condition. The GaitRite pressure mat (Havertown, PA) will be used to record bilateral foot placements and measure the walking speed. Dual task cost to walking speed is defined as the percent change of walking speed from normal walking to dual task walking. The outcome was calculated by averaging the dual task costs of the six trials. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Post Intervention on Geriatric Depression Scale (GDS) Score | baseline, immediately after intervention and 2 weeks post intervention | GDS total Score. The GDS total score ranges from 0 to 15. Higher GDS score represents more severe depression. |
| Percent Change From Baseline to Post Intervention on Trial Making Test (TMT) | baseline, immediately after intervention and 2 weeks post intervention | Time to complete Trail Making Test part B minus time to complete TMT part A. Slower time to complete TMT-B as compared to TMT-A represents poorer executive function. |
| Percent Change From Baseline to Post Intervention on Dual-task Cost to Standing Sway Area | baseline, immediately after intervention and 2 weeks post intervention | Postural sway speed - assessed by measuring standing postural sway (ie., center-of pressure fluctuations) during six, 30-second trials of standing with eyes open (single task) or performing a cognitive task (dual task standing) on a stationary force platform (Kistler, Amherst, NY). Dual task cost is defined as the percent change of sway area from single task standing to dual task standing. The outcome was calculated by averaging the dual task costs of the six trials. |
| Percent Change From Baseline to Post Intervention on Dual Task Cost to Stride Time in 24-meter Walking Test | baseline, immediately after intervention and 2 weeks post intervention | Six 24-meter walking trials at a preferred speed are completed and each three of them are in normal or dual task condition. The GaitRite pressure mat (Havertown, PA) will be used to record bilateral foot placements and measure the walking speed. Dual task cost to stride time is defined as the percent change of stride time from normal walking to dual task walking.The outcome was calculated by averaging the dual task costs of the six trials. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Real tDCS The real tDCS intervention will consist of 10 daily 20-minute sessions of transcranial direct current stimulation (tDCS) at a target current intensity of 1.5 mA.
Real tDCS: Transcranial direct current stimulation (tDCS) enables noninvasive, selective and sustained modulation of cortical activation. tDCS works by sending low-level currents between two or more scalp electrodes, which alters brain polarity and thus, perfusion and cortical excitability. | 9 |
| Sham tDCS The sham tDCS intervention will consist of 10 daily 20-minute sessions of transcranial direct current stimulation, except current will only be applied for the first 60 seconds of each session.
Sham tDCS: For sham tDCS, current will only be applied for the first 60 seconds of each 20 minute session. This is a reliable sham control as sensations arising from tDCS diminish considerably after the first minute of stimulation. | 10 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Real tDCS | Sham tDCS | Total |
|---|---|---|---|
| Age, Continuous | 83.10 years STANDARD_DEVIATION 10.36 | 78.12 years STANDARD_DEVIATION 10.79 | 80.46 years STANDARD_DEVIATION 10.57 |
| Body Mass Index (BMI) | 29.17 kg/m^2 STANDARD_DEVIATION 4.44 | 31.46 kg/m^2 STANDARD_DEVIATION 5.75 | 30.38 kg/m^2 STANDARD_DEVIATION 5.15 |
| Difference between the time to complete Trail Make Test Section B section and Section A | 148.62 seconds STANDARD_DEVIATION 81.64 | 143.57 seconds STANDARD_DEVIATION 71.96 | 145.94 seconds STANDARD_DEVIATION 74.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 8 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Gait Speed | 0.73 m/s STANDARD_DEVIATION 0.17 | 0.73 m/s STANDARD_DEVIATION 0.14 | 0.73 m/s STANDARD_DEVIATION 0.15 |
| Geriatric Depression Scale Score | 3.00 units on a scale STANDARD_DEVIATION 3.02 | 4.00 units on a scale STANDARD_DEVIATION 2.55 | 3.06 units on a scale STANDARD_DEVIATION 2.21 |
| 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 | 1 Participants | 2 Participants | 3 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 7 Participants | 15 Participants |
| Region of Enrollment United States | 9 participants | 10 participants | 19 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 9 |
| other Total, other adverse events | 1 / 8 | 1 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 9 |
Outcome results
Primary
Percent Change From Baseline to Post Intervention on Dual Task Cost to Standing Postural Sway Speed
Postural sway speed - assessed by measuring standing postural sway (ie., center-of pressure fluctuations) during six, 30-second trials of standing with eyes open (single task) or performing a cognitive task (dual task standing) on a stationary force platform (Kistler, Amherst, NY). Dual task cost is defined as the percent change of sway speed from single task standing to dual task standing. The outcome was obtained by averaging the dual task costs of the six trials.
Time frame: baseline, immediately after intervention and 2 weeks post intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Standing Postural Sway Speed | Percent Change (Baseline to Immediate Follow Up) | -23.1 percentage change | Standard Deviation 24.5 |
| Real tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Standing Postural Sway Speed | Percent Change (Baseline to 2-Week Follow up) | -11.5 percentage change | Standard Deviation 20.2 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Standing Postural Sway Speed | Percent Change (Baseline to Immediate Follow Up) | 16.5 percentage change | Standard Deviation 27.5 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Standing Postural Sway Speed | Percent Change (Baseline to 2-Week Follow up) | 15.3 percentage change | Standard Deviation 30.6 |
p-value: 0.004ANOVA
Primary
Percent Change From Baseline to Post Intervention on Dual Task Cost to Walking Speed in 24-meter Walking Test
Six 24-meter walking trials at a preferred speed are completed and each three of them are in normal or dual task condition. The GaitRite pressure mat (Havertown, PA) will be used to record bilateral foot placements and measure the walking speed. Dual task cost to walking speed is defined as the percent change of walking speed from normal walking to dual task walking. The outcome was calculated by averaging the dual task costs of the six trials.
Time frame: baseline, immediately after intervention and 2 weeks post intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Walking Speed in 24-meter Walking Test | Percent Change (Baseline to 2-Week Follow up) | 6.1 percent change | Standard Deviation 8.4 |
| Real tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Walking Speed in 24-meter Walking Test | Percent Change (Baseline to Immediate Follow Up) | 14.9 percent change | Standard Deviation 17.3 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Walking Speed in 24-meter Walking Test | Percent Change (Baseline to Immediate Follow Up) | 3.9 percent change | Standard Deviation 14.5 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Walking Speed in 24-meter Walking Test | Percent Change (Baseline to 2-Week Follow up) | 3.9 percent change | Standard Deviation 14.5 |
p-value: 0.37ANOVA
Primary
Percent Change From Baseline to Post Intervention on Global Cognition Impairment
The Montreal Cognitive Assessment (MoCA) score is used as the outcome measure of Global Cognition Impairment. MoCA score ranges from 0 to 30. Lower MoCA score represents poorer cognitive function (i.e., more severe Global Cognition Impairment).
Time frame: Baseline, immediately after intervention and 2 weeks post intervention
Population: 19 participants were enrolled in the study and completed baseline assessments. One participant withdrew from the follow-up session due to illness deemed unrelated to participation. 18 participants completed all the study sessions.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS | Percent Change From Baseline to Post Intervention on Global Cognition Impairment | Percent Change (Baseline to Immediate Follow Up) | 7.9 percent change | Standard Deviation 16.9 |
| Real tDCS | Percent Change From Baseline to Post Intervention on Global Cognition Impairment | Percent Change (Baseline to 2-Week Follow up) | 12.6 percent change | Standard Deviation 14.5 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Global Cognition Impairment | Percent Change (Baseline to Immediate Follow Up) | 0.1 percent change | Standard Deviation 8.2 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Global Cognition Impairment | Percent Change (Baseline to 2-Week Follow up) | -0.4 percent change | Standard Deviation 7.8 |
p-value: 0.03ANOVA
Primary
Percent Change From Baseline to Post Intervention on Mobility
Mobility and turning will be assessed by the timed up-and-go test (TUG) (Podsiadlo & Richardson, 1991). The participant will be seated in an armed chair. On the word go, the subject will stand up using the arm rests if needed, walk (with assistive device if needed) around a cone placed three meters in front of the chair, return and sit down as quickly as possible. Time to complete the TUG test will be used as the outcome measure.
Time frame: baseline, immediately after intervention and 2 weeks post intervention
Population: 19 participants were enrolled in the study and completed baseline assessments. One participant withdrew from the follow-up session due to illness deemed unrelated to participation. 18 participants completed all the study sessions.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS | Percent Change From Baseline to Post Intervention on Mobility | Percent Change (Baseline to Immediate Follow Up) | -3.0 percent change of TUG time | Standard Deviation 17.1 |
| Real tDCS | Percent Change From Baseline to Post Intervention on Mobility | Percent Change (Baseline to 2-Week Follow up) | -6.1 percent change of TUG time | Standard Deviation 17.6 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Mobility | Percent Change (Baseline to Immediate Follow Up) | 10.4 percent change of TUG time | Standard Deviation 37.2 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Mobility | Percent Change (Baseline to 2-Week Follow up) | 3.4 percent change of TUG time | Standard Deviation 24.1 |
p-value: 0.24ANOVA
Secondary
Percent Change From Baseline to Post Intervention on Dual-task Cost to Standing Sway Area
Postural sway speed - assessed by measuring standing postural sway (ie., center-of pressure fluctuations) during six, 30-second trials of standing with eyes open (single task) or performing a cognitive task (dual task standing) on a stationary force platform (Kistler, Amherst, NY). Dual task cost is defined as the percent change of sway area from single task standing to dual task standing. The outcome was calculated by averaging the dual task costs of the six trials.
Time frame: baseline, immediately after intervention and 2 weeks post intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS | Percent Change From Baseline to Post Intervention on Dual-task Cost to Standing Sway Area | Percent Change (Baseline to Immediate Follow Up) | -32.9 percentage change | Standard Deviation 43.6 |
| Real tDCS | Percent Change From Baseline to Post Intervention on Dual-task Cost to Standing Sway Area | Percent Change (Baseline to 2-Week Follow up) | -34.4 percentage change | Standard Deviation 24.3 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Dual-task Cost to Standing Sway Area | Percent Change (Baseline to Immediate Follow Up) | 51.1 percentage change | Standard Deviation 54.2 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Dual-task Cost to Standing Sway Area | Percent Change (Baseline to 2-Week Follow up) | 211.8 percentage change | Standard Deviation 153.2 |
p-value: 0.0007ANOVA
Secondary
Percent Change From Baseline to Post Intervention on Dual Task Cost to Stride Time in 24-meter Walking Test
Six 24-meter walking trials at a preferred speed are completed and each three of them are in normal or dual task condition. The GaitRite pressure mat (Havertown, PA) will be used to record bilateral foot placements and measure the walking speed. Dual task cost to stride time is defined as the percent change of stride time from normal walking to dual task walking.The outcome was calculated by averaging the dual task costs of the six trials.
Time frame: baseline, immediately after intervention and 2 weeks post intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Stride Time in 24-meter Walking Test | Percent Change (Baseline to Immediate Follow Up) | -25.7 percent change | Standard Deviation 38.4 |
| Real tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Stride Time in 24-meter Walking Test | Percent Change (Baseline to 2-Week Follow up) | -16.3 percent change | Standard Deviation 37.1 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Stride Time in 24-meter Walking Test | Percent Change (Baseline to Immediate Follow Up) | 83.8 percent change | Standard Deviation 175.5 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Dual Task Cost to Stride Time in 24-meter Walking Test | Percent Change (Baseline to 2-Week Follow up) | 57.0 percent change | Standard Deviation 136.9 |
p-value: 0.04ANOVA
Secondary
Percent Change From Baseline to Post Intervention on Geriatric Depression Scale (GDS) Score
GDS total Score. The GDS total score ranges from 0 to 15. Higher GDS score represents more severe depression.
Time frame: baseline, immediately after intervention and 2 weeks post intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS | Percent Change From Baseline to Post Intervention on Geriatric Depression Scale (GDS) Score | Percent Change (Baseline to Immediate Follow Up) | 10.5 percent change | Standard Deviation 54.4 |
| Real tDCS | Percent Change From Baseline to Post Intervention on Geriatric Depression Scale (GDS) Score | Percent Change (Baseline to 2-Week Follow up) | 27.3 percent change | Standard Deviation 92.5 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Geriatric Depression Scale (GDS) Score | Percent Change (Baseline to Immediate Follow Up) | -12.9 percent change | Standard Deviation 72.6 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Geriatric Depression Scale (GDS) Score | Percent Change (Baseline to 2-Week Follow up) | -2.4 percent change | Standard Deviation 76.2 |
p-value: 0.37ANOVA
Secondary
Percent Change From Baseline to Post Intervention on Trial Making Test (TMT)
Time to complete Trail Making Test part B minus time to complete TMT part A. Slower time to complete TMT-B as compared to TMT-A represents poorer executive function.
Time frame: baseline, immediately after intervention and 2 weeks post intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Real tDCS | Percent Change From Baseline to Post Intervention on Trial Making Test (TMT) | Percent Change (Baseline to 2-Week Follow up) | -38.1 percent change | Standard Deviation 34.8 |
| Real tDCS | Percent Change From Baseline to Post Intervention on Trial Making Test (TMT) | Percent Change (Baseline to Immediate Follow Up) | -65.8 percent change | Standard Deviation 25.2 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Trial Making Test (TMT) | Percent Change (Baseline to Immediate Follow Up) | -17.1 percent change | Standard Deviation 49.5 |
| Sham tDCS | Percent Change From Baseline to Post Intervention on Trial Making Test (TMT) | Percent Change (Baseline to 2-Week Follow up) | -17.2 percent change | Standard Deviation 58.9 |
p-value: 0.54ANOVA