Dementia Alzheimers, Military Activity, Traumatic Brain Injury
Conditions
Keywords
veteran
Brief summary
Patients with a history of traumatic brain injury (TBI) are at elevated risk for Alzheimer's disease and related dementias (ADRD). Improvements in TBI treatment may mitigate this risk. Complex motor activities, which combine physical and cognitive demands, have been shown to have well established neurocognitive benefits. This study seeks to address the need for novel TBI interventions optimized for adults with history of TBI by determining the effectiveness of an immersive computer game designed to integrating complex cognitive-motor interventions.
Detailed description
Patients with a history of traumatic brain injury (TBI) are at elevated risk for Alzheimer's disease and related dementias (ADRD). Improvements in TBI treatment may mitigate this risk. The treatment of TBI, especially for those with chronic neuropsychiatric sequelae, is moving toward multi-modal approaches that include non-pharmacological interventions such as exercise and cognitive enrichment. Complex motor activities, which combine physical and cognitive demands, have been shown to have well established neurocognitive benefits. However, there are a lack of cognitive enhancing interventions that utilize these complex motor activities. Many adults with history of TBI face significant barriers to engaging in physical activity which limit the adults' ability to participate in many neurocognitive interventions. This study seeks to address the need for novel TBI interventions optimized for adults with history of TBI by determining the effectiveness of an immersive computer game designed to integrating complex cognitive-motor interventions. During this proposed 12-month study involving patients with history of TBI (n=66) the investigators will examine cognition, independent function, mood and ADRD related brain biomarkers after 12 weeks of a randomized intervention, as well as 9 months post-intervention to assess for durability of any benefits. The investigators hypothesize that complex motor activities will improve cognitive health in adults with a history of TBI and that promising results would have implications for early intervention for those at risk for Mild Cognitive Impairment and ADRD.
Interventions
DEVICEMindPod Dolphin
The immersive video game being tested in this study is called Bandit the Dolphin, developed by neurologist Dr. John Krakauer, and engineers in the Brain, Learning, Animation, and Movement Lab at Johns Hopkins. Bandit the Dolphin provides an oceanic environment in which the individual's arm movements control a simulated dolphin. The neuromotor effects of this game have been designed to be used in the clinical setting to rehabilitate arm and hand function following stroke. The game has further been modified to a Microsoft Kinect-based system and piloted for play in non-laboratory settings among community-dwelling adults. The game offers a unique combination of skilled arm movements plus varying levels of cognitive challenge. In this way, the individual's arms are challenged the same way the legs would be when walking in a complex, outdoor environment. Importantly, the participant plays while standing, thus engaging the whole body in this novel multi-sensorial experience.
BEHAVIORAL10 Keys to Healthy Aging
The 10 Keys™ to Healthy Aging Program in an evidence-based program that originated from the University of Pittsburgh Center for Aging and Population Health. This educates and empowers older adults to reach personal goals and help others to so in the community as well. It is designed to teach older adults how to reduce the risk of disease over the aging process by promoting healthy lifestyle changes with the most recent established scientific guidelines. The 10 Keys program also aims to empower individuals to be health ambassadors in the individual's own families and communities, teaching individuals to 'Share the Wealth on Health'. Participants will work towards personal health goal(s) adapted to the participant's lifestyle and abilities.
Sponsors
United States Department of Defense
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* English speaking * 40 years of age and older * History of at least one remote TBI (\>3 years ago) of mild and moderate severity as diagnosed by Veteran's Affairs / Department of Defense (VA/DoD) criteria. * Ability to perform most independent activities of daily living without physical assistance (e.g., no canes or walkers because person needs both hands to participate); Chedoke Arm and Hand Activity Inventory - mean score \>5, indicating modified or complete independence in hand and arm functioning. * Ability to dedicate 3 hours per week for about 12 weeks-approximately 20 to 26 hours of total time-to the intervention study. * Ability to give informed consent and understand the tasks involved
Exclusion criteria
* Presence of cognitive impairment based on a Mini-Mental State Exam (MMSE) score ≤ 24. * Presence of diseases associated with gross motor abnormalities that restrict ambulation (e.g., stroke with paresis, multiple sclerosis, amyotrophic lateral sclerosis, cerebellar or spinal cord disorders, peripheral nerve disorders, severe rheumatic or osteoarthritic disorders, limb amputation) * Untreated major mental illness that may preclude successful completion of the study (e.g., major depressive disorder, anxiety disorders, etc.) * History of physical or neurological condition that interferes with study procedures or assessment of motor function (e.g., epilepsy, severe arthritis, severe neuropathy, Parkinson's disease). * Current diagnosis of color blindness. * Social or personal circumstances that interfere with ability to complete 12-14 weeks of training sessions and follow-up evaluation. * Inability to sit in a chair or stand and perform upper limb exercises for one hour at a time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brain Magnetic Resonance Imaging (MRI) Amygdala Volume (mm3) | Baseline, 12 weeks | Brain volumetrics will be calculated using a Philips 3 Tesla (T) head-only scanner using established methods. Amygdala volumes were automatically segmented using Freesurfer and were summed across both hemispheres to calculate total volume. Change in total amygdala volume from baseline to 12 weeks was used as the primary measure. |
| Change in Physical Mobility Outcome as Assessed by the Short Physical Performance Battery | Baseline, 12 weeks | The Short Physical Performance Battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. We measured the change in SPPB score from baseline to 12-week post-intervention follow-up assessments. Total score of 0 to 12, with a higher score indicating better physical function. |
| Change in Brain Magnetic Resonance Imaging (MRI) Hippocampal Volume (mm3) | Baseline, 12 weeks | Brain volumetrics will be calculated using a Philips 3 Tesla (T) head-only scanner using established methods. Hippocampal volumes were automatically segmented using Freesurfer and was summed across both hemispheres to calculate total volume. Change in total hippocampal volume from baseline to 12 weeks was used as the primary measure. |
| Change in Executive Functioning as Assessed by the Trail Making Test | Baseline, 12 weeks | The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two timed parts (Part A and B) in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. Our primary measure was the difference in time (seconds) taking to complete Part B subtracted by Part A, which is an indicator of task-switching. |
| Change in Executive Functioning as Assessed by the Stroop Test | Baseline, 12 weeks | The Stroop Test is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. Our primary measure was the Stroop Effect (i.e., reaction time (milliseconds) for incongruent trials subtracted by reaction time for congruent trials). |
| Change in Processing Speed Score as Assessed by the Pattern Comparison Test | Baseline, 12 weeks | This test measures speed of processing by asking participants to discern whether two side-by-side pictures are the same or not. The processing speed score was the total number of trials completed correctly within the specified time limit. |
| Change in Verbal Learning as Assessed by the Rey Auditory Verbal Learning Test (RAVLT) | Baseline, 12 weeks | The investigators will assess for change in verbal learning using the RAVLT. The RAVLT is a neuropsychological assessment designed to evaluate verbal memory in patients, 16 years of age and older. The RAVLT can be used to evaluate the nature and severity of memory dysfunction and to track changes in memory function over time. The test is designed as a list-learning paradigm in which the patient hears a list of 15 nouns and is asked to recall as many words from the list as possible. Our primary measure was the number of words correctly recalled after a long delay (20 minutes), an indicator of long-term verbal memory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Depressive Symptoms as Assessed by the Patient Health Questionnaire - 9 (PHQ-9) | Baseline, 12 weeks | The PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The PHQ-9 incorporates Diagnostic and Statistical Manual-IV depression diagnostic criteria with other leading major depressive symptoms into a brief self-report tool. Depression Severity: 0-4 none, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe (total score range of 0-27). Higher score worse/more severe symptoms. |
| Change in Time (Minutes) Spent Outside Home as Assessed by the Apple Watch GPS | Baseline, 12 weeks | The investigators will assess time spent outside the home from an Apple Watch GPS. Time spent out of home is measured by summing total duration spent in latitude/longitude coordinates that fall outside of a 120 meter radial buffer around the participant's home address. |
Countries
United States
Participant flow
Recruitment details
Recruitment sources included Johns Hopkins Alzheimer's Disease Research Center (ADRC), Bayview Community Psychiatry Program (CPP), Johns Hopkins Community Physicians (JHCP), JHCP Clinic Champion: advertises study in JHCP, Clinical Connection, ClinicalTrials.gov, ResearchMatch.org, MyChart, and newsletters/flyers.
Participants by arm
| Arm | Count |
|---|---|
| MindPod Dolphin Arm Bandit the Dolphin provides an oceanic environment in which the individual's arm movements control a simulated dolphin. The neuromotor effects of this game have been designed to be used in the clinical setting to rehabilitate arm and hand function following stroke. | 14 |
| 10 Keys to Healthy Aging The 10 Keys™ to Healthy Aging Program is designed to teach older adults how to reduce the risk of disease over the aging process by promoting healthy lifestyle changes with the most recent established scientific guidelines. | 9 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 3 |
Baseline characteristics
| Characteristic | 10 Keys to Healthy Aging | Total | MindPod Dolphin Arm |
|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 13.3 | 59.3 years STANDARD_DEVIATION 10.6 | 60.4 years STANDARD_DEVIATION 8.9 |
| 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 | 3 Participants | 9 Participants | 6 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 | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 13 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 9 |
| other Total, other adverse events | 0 / 14 | 0 / 9 |
| serious Total, serious adverse events | 0 / 14 | 0 / 9 |
Outcome results
Primary
Change in Brain Magnetic Resonance Imaging (MRI) Amygdala Volume (mm3)
Brain volumetrics will be calculated using a Philips 3 Tesla (T) head-only scanner using established methods. Amygdala volumes were automatically segmented using Freesurfer and were summed across both hemispheres to calculate total volume. Change in total amygdala volume from baseline to 12 weeks was used as the primary measure.
Time frame: Baseline, 12 weeks
Population: Nine participants who had both baseline and 12 week MRI data were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MindPod Dolphin Arm | Change in Brain Magnetic Resonance Imaging (MRI) Amygdala Volume (mm3) | 67.1 mm3 | Standard Error 181.1 |
| 10 Keys to Healthy Aging | Change in Brain Magnetic Resonance Imaging (MRI) Amygdala Volume (mm3) | -63.7 mm3 | Standard Error 148.8 |
Comparison: We conducted t-tests of differences in volumetric change comparing intervention to control arms.p-value: 0.5995% CI: [-259.7, 248.6]t-test, 2 sided
Primary
Change in Brain Magnetic Resonance Imaging (MRI) Hippocampal Volume (mm3)
Brain volumetrics will be calculated using a Philips 3 Tesla (T) head-only scanner using established methods. Hippocampal volumes were automatically segmented using Freesurfer and was summed across both hemispheres to calculate total volume. Change in total hippocampal volume from baseline to 12 weeks was used as the primary measure.
Time frame: Baseline, 12 weeks
Population: Nine participants who had both baseline and 12 week MRI data were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MindPod Dolphin Arm | Change in Brain Magnetic Resonance Imaging (MRI) Hippocampal Volume (mm3) | -109.7 mm^3 | Standard Error 63.1 |
| 10 Keys to Healthy Aging | Change in Brain Magnetic Resonance Imaging (MRI) Hippocampal Volume (mm3) | -10.3 mm^3 | Standard Error 192.2 |
Comparison: We conducted t-tests of differences in volumetric change comparing intervention to control arms.p-value: 0.60595% CI: [-334.3, 533]t-test, 2 sided
Primary
Change in Executive Functioning as Assessed by the Stroop Test
The Stroop Test is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. Our primary measure was the Stroop Effect (i.e., reaction time (milliseconds) for incongruent trials subtracted by reaction time for congruent trials).
Time frame: Baseline, 12 weeks
Population: One participant was excluded due to missing data at both baseline and 12 week visits.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MindPod Dolphin Arm | Change in Executive Functioning as Assessed by the Stroop Test | -49.5 change in milliseconds |
| 10 Keys to Healthy Aging | Change in Executive Functioning as Assessed by the Stroop Test | 31.8 change in milliseconds |
Comparison: Mixed effects models were fit including fixed effects for intervention arm, visit (baseline, 12 week) and intervention by visit interaction; and random intercepts and slopes for each participant.p-value: 0.05795% CI: [-165.2, 2.5]Mixed Models Analysis
Primary
Change in Executive Functioning as Assessed by the Trail Making Test
The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two timed parts (Part A and B) in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. Our primary measure was the difference in time (seconds) taking to complete Part B subtracted by Part A, which is an indicator of task-switching.
Time frame: Baseline, 12 weeks
Population: One participant was excluded due to missing data at both baseline and 12 week visits.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MindPod Dolphin Arm | Change in Executive Functioning as Assessed by the Trail Making Test | -9.2 change in seconds |
| 10 Keys to Healthy Aging | Change in Executive Functioning as Assessed by the Trail Making Test | 24.7 change in seconds |
Comparison: Mixed effects models were fit including fixed effects for intervention arm, visit (baseline, 12 week) and intervention by visit interaction; and random intercepts and slopes for each participant.p-value: 0.32395% CI: [-100.9, 33.2]Mixed Models Analysis
Primary
Change in Physical Mobility Outcome as Assessed by the Short Physical Performance Battery
The Short Physical Performance Battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. We measured the change in SPPB score from baseline to 12-week post-intervention follow-up assessments. Total score of 0 to 12, with a higher score indicating better physical function.
Time frame: Baseline, 12 weeks
Population: There were 10 intervention participants and 6 control group participants that had data collected at both baseline and post-intervention 12-week follow-up assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MindPod Dolphin Arm | Change in Physical Mobility Outcome as Assessed by the Short Physical Performance Battery | 0.67 score on a scale | Standard Deviation 1.03 |
| 10 Keys to Healthy Aging | Change in Physical Mobility Outcome as Assessed by the Short Physical Performance Battery | -0.60 score on a scale | Standard Deviation 1.83 |
p-value: 0.14795% CI: [-0.5, 3.03]t-test, 2 sided
Primary
Change in Processing Speed Score as Assessed by the Pattern Comparison Test
This test measures speed of processing by asking participants to discern whether two side-by-side pictures are the same or not. The processing speed score was the total number of trials completed correctly within the specified time limit.
Time frame: Baseline, 12 weeks
Population: One participant was excluded due to missing data at both baseline and 12 week visits.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MindPod Dolphin Arm | Change in Processing Speed Score as Assessed by the Pattern Comparison Test | 2.0 trials |
| 10 Keys to Healthy Aging | Change in Processing Speed Score as Assessed by the Pattern Comparison Test | -1.0 trials |
Comparison: Mixed effects models were fit including fixed effects for intervention arm, visit (baseline, 12 week) and intervention by visit interaction; and random intercepts and slopes for each participant.p-value: 0.04795% CI: [0.03, 6.08]Mixed Models Analysis
Primary
Change in Verbal Learning as Assessed by the Rey Auditory Verbal Learning Test (RAVLT)
The investigators will assess for change in verbal learning using the RAVLT. The RAVLT is a neuropsychological assessment designed to evaluate verbal memory in patients, 16 years of age and older. The RAVLT can be used to evaluate the nature and severity of memory dysfunction and to track changes in memory function over time. The test is designed as a list-learning paradigm in which the patient hears a list of 15 nouns and is asked to recall as many words from the list as possible. Our primary measure was the number of words correctly recalled after a long delay (20 minutes), an indicator of long-term verbal memory.
Time frame: Baseline, 12 weeks
Population: One participant was excluded due to missing data at both baseline and 12 week visits.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MindPod Dolphin Arm | Change in Verbal Learning as Assessed by the Rey Auditory Verbal Learning Test (RAVLT) | 1.5 words |
| 10 Keys to Healthy Aging | Change in Verbal Learning as Assessed by the Rey Auditory Verbal Learning Test (RAVLT) | 0.9 words |
Comparison: Mixed effects models were fit including fixed effects for intervention arm, visit (baseline, 12 week) and intervention by visit interaction; and random intercepts and slopes for each participant.p-value: 0.56595% CI: [-1.4, 2.6]Mixed Models Analysis
Secondary
Change in Depressive Symptoms as Assessed by the Patient Health Questionnaire - 9 (PHQ-9)
The PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The PHQ-9 incorporates Diagnostic and Statistical Manual-IV depression diagnostic criteria with other leading major depressive symptoms into a brief self-report tool. Depression Severity: 0-4 none, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe (total score range of 0-27). Higher score worse/more severe symptoms.
Time frame: Baseline, 12 weeks
Population: There were 10 intervention and 4 control group participants with available data for PHQ-9 at both baseline and 12-week post-intervention assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MindPod Dolphin Arm | Change in Depressive Symptoms as Assessed by the Patient Health Questionnaire - 9 (PHQ-9) | 0.10 score on a scale | Standard Deviation 4.72 |
| 10 Keys to Healthy Aging | Change in Depressive Symptoms as Assessed by the Patient Health Questionnaire - 9 (PHQ-9) | -1 score on a scale | Standard Deviation 6.68 |
p-value: 0.73195% CI: [-7.91, 5.71]t-test, 2 sided
Secondary
Change in Time (Minutes) Spent Outside Home as Assessed by the Apple Watch GPS
The investigators will assess time spent outside the home from an Apple Watch GPS. Time spent out of home is measured by summing total duration spent in latitude/longitude coordinates that fall outside of a 120 meter radial buffer around the participant's home address.
Time frame: Baseline, 12 weeks
Population: There were 10 intervention group participants and 6 control group participants that had data collected for time spent outside of home at both baseline and 12-week post-intervention assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MindPod Dolphin Arm | Change in Time (Minutes) Spent Outside Home as Assessed by the Apple Watch GPS | 59.99 minutes | Standard Deviation 172.65 |
| 10 Keys to Healthy Aging | Change in Time (Minutes) Spent Outside Home as Assessed by the Apple Watch GPS | 35.27 minutes | Standard Deviation 60.09 |
p-value: 0.74395% CI: [-183.11, 133.68]t-test, 2 sided