Amnestic Mild Cognitive Impairment
Conditions
Brief summary
The mSIM study involves developing and conducting feasibility testing of a web-based application that will deliver mobile-based simultaneous exercise and memory skills training program (mSIM) for amnesic Mild Cognitive Impairment (aMCI) patients. The randomized control trial (RCT) will evaluate the efficacy of mSIM on memory performance and everyday functioning using 2 study arms (Group 1 activity monitoring control (via Fitbit) (CON) vs Group 2 mSIM intervention plus activity monitoring via Fitbit). mSIM treatment response will be evaluated using neuropsychological and functional evaluation. Concentration levels of peripheral biomarkers Brain-derived neurotrophic factor (BDNF) and norepinephrine (NE) also be assessed.
Detailed description
The purpose of the study is to create a web-based cognitive compensatory, and predominately memory skills, training course that is delivered on a mobile device and compatible with use on a stationary bicycle and test its efficacy on memory and functional ability. Participants will be recruited from (1) the Pacific Brain Health Center in Santa Monica, which is a high-volume memory-care and dementia outpatient clinic within a large physician medical group affiliated with Providence Saint John's Health Center, (2) advertisement to participants in the local community, and (3) establishment of a website landing page that permits interested individuals to contact the trial coordinator. Up to five participants will be course beta testers. They will receive a truncated version of the course and will provide detailed feedback. 30 participants will be randomized into one of two groups. Group 1 (control arm) will have their physical activity levels continuously monitored (via Fitbit). Participants will receive the Experimental Research Subject's Bill of Rights prior to signing the informed consent form (ICF), authorization of use and disclosure of protected health information (PHI), and authorization of medical record release for the subject's treating physician, will be obtained from each participant prior to enrolling in the study. A copy of all signed ICF's will be given to the participants, and the investigator will retain the original. Group 2 (active arm) will receive the mSIM intervention plus activity monitoring (via Fitbit). Group 2 will first undergo 2-6 week of an exercise ramp-up (2x/week) until they can sustain 40 minutes at 50% heart rate reserve (HRR). The intensity for mSIM training will be 40-60% HRR. After the ramp-up phase the mSIM participants will begin the 12-week intervention, comprised of 2 60-minute sessions/week. mSIM treatment response will be evaluated using neuropsychological and functional evaluation. Assessments will occur at baseline, mid-trial (3-4 months) and post-trial (5-6 months). Concentration levels of peripheral biomarkers BDNF and NE at baseline and post-trial (5-6 months) will also be assessed.
Interventions
BEHAVIORALmSIM intervention plus activity monitoring
Participants will receive the full mSIM intervention and be monitored (via Fitbit)
BEHAVIORALActivity monitoring
Participants will have activity monitored (via Fitbit)
Sponsors
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Jennifer Bramen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study will include two arms: Arm 1: activity monitoring only control (CON), Arm 2: active intervention with mSIM program (mSIM) plus activity monitoring (via Fitbit), to evaluate the efficacy of the mSIM intervention on memory performance and everyday functioning. The 'Activity monitoring only' arm will serve as the control group. Study objectives include measuring treatment related changes in memory performance and everyday functioning along with putative biomarkers of the behavioral changes.
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must be age 50 to 80 at time of informed consent. * Subjects must confirm an aMCI diagnosis either by providing records from a clinical assessment within 6 months of enrollment in this study or through a brief memory assessment by study staff at screening. * Subjects must be proficient in spoken and written English for consenting as well as for study participation since the intervention in this study is currently only available in English. * Subjects with medical conditions must be stable for these conditions. Stable control on medication is acceptable. * Subjects, with or without assistance, must be able to use a computer and web interface. If assistance is needed, it must be readily available to them. * Subjects are required to have internet with Wi-Fi at the location of their mSIM training. * Subject must have normal visual acuity (or corrected to normal) and normal color vision as indicated by self-report. * Subject must have adequate hearing acuity as indicated by self-report. * Subject must have adequate motor capacity to use a mobile phone/iPad/computer as indicated by self-report. * Subjects must be able to provide medical clearance to participate in an unsupervised, moderate intensity exercise program from a physician.
Exclusion criteria
* Subjects must not have an existing diagnosis of a neurodegenerative disorder (e.g., Alzheimer's Disease, Lewy Body Dementia, Frontal-Temporal Dementia). * Subjects must not have a prior diagnosis that might impact cognition and movement abilities including: significant cardiovascular disease, significant respiratory disease, illness or injury, substance abuse, schizophrenia, bipolar disorder, or other neurological diseases. * Subjects must not have a previous Mini Mental State Exam (MMSE) score below 19. * Subjects must not have a previous Clinical Dementia Rating (CDR) global score of ≥2. * Subjects must not have a Montreal Cognitive Assessment (MoCA)43 score of below 18 previously or during their screening evaluation. * Subjects must not demonstrate a progression of aMCI to dementia at screening based on the best judgement of a study Clinical Neuropsychologist. * Subjects must not currently participate in a high level of physical activity prior to study start as assessed by the International Physical Activity Questionnaire (IPAQ) at screening. * Subjects must not endorse that they are unable to participate in moderate intensity aerobic activities, such as fast walking or passing/kicking a ball to a partner at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Memory Function Composite Score | Baseline, approximately 3 months and approximately 6 months | Global Z-Score including results from RAVLT (Rey's Auditory Verbal Learning Test), Wechsler Memory Scale Fourth Edition (WMS-IV) Logical Memory and Visual Reproduction tests. The global z score was constructed by: First z-transforming all raw test scores (RAVLT, Logical Memory (LM) I Total, LM II Total, Visual Reproduction (VR) I and VR II) Averaging over RAVLT Z, LM Z, and VR Z to obtain a global Z 0=sample mean; higher scores indicate better outcomes. |
| Functional Abilities | Baseline, approximately 3 months and approximately 6 months | Assessed using the Multifactorial Memory Questionnaire (MMQ) Satisfaction Sub-scale (0-72 points). Higher scores indicate better outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resting Brain-derived Neurotrophic Factor (BDNF) | Baseline and approximately 6 months | Resting level of serum-derived BDNF |
| Resting Norepinephrine (NE) | Baseline and approximately 6 months | Resting level of plasma-derived norepinephrine (NE) |
Countries
United States
Participant flow
Pre-assignment details
Of the 22 participants that were consented, 1 failed screening due to MoCa score and 2 were lost to follow up. Participants were then screened prior to randomization, which included exercise clearance and full neurocognitive assessment. Of the 19 that were screened, 12 were randomized because 6 failed to meet criteria due to neurocognitive assessment, and 1 was unable to obtain clearance to participate in an exercise intervention.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (No Treatment) Group 1: Participants will have continuous activity monitoring (via Fitbit) | 4 |
| Group 2 (Experimental) Group 2: Participants will receive the mSIM treatment and have their activity monitored continuously (via Fitbit) | 8 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Group 1 (No Treatment) | Group 2 (Experimental) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 7 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Continuous | 76.3 years STANDARD_DEVIATION 6.4 | 69.7 years STANDARD_DEVIATION 4.5 | 71.7 years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 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 | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 8 |
| other Total, other adverse events | 3 / 4 | 2 / 8 |
| serious Total, serious adverse events | 0 / 4 | 0 / 8 |
Outcome results
Primary
Functional Abilities
Assessed using the Multifactorial Memory Questionnaire (MMQ) Satisfaction Sub-scale (0-72 points). Higher scores indicate better outcomes.
Time frame: Baseline, approximately 3 months and approximately 6 months
Population: Of the 8 participants that were randomized into the intervention, only 7 participated in baseline assessments. Of the 7 with baseline data, only 2 completed follow up assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (No Treatment) | Functional Abilities | Baseline | 24.67 scores on a scale | Standard Deviation 13.01 |
| Group 1 (No Treatment) | Functional Abilities | 3 Months | 26.33 scores on a scale | Standard Deviation 14.19 |
| Group 1 (No Treatment) | Functional Abilities | 6 Months | 32.67 scores on a scale | Standard Deviation 16.77 |
| Group 2 (Experimental) | Functional Abilities | Baseline | 26.86 scores on a scale | Standard Deviation 15.65 |
| Group 2 (Experimental) | Functional Abilities | 3 Months | 19.00 scores on a scale | Standard Deviation 11.31 |
| Group 2 (Experimental) | Functional Abilities | 6 Months | 21.00 scores on a scale | Standard Deviation 5.66 |
Primary
Memory Function Composite Score
Global Z-Score including results from RAVLT (Rey's Auditory Verbal Learning Test), Wechsler Memory Scale Fourth Edition (WMS-IV) Logical Memory and Visual Reproduction tests. The global z score was constructed by: First z-transforming all raw test scores (RAVLT, Logical Memory (LM) I Total, LM II Total, Visual Reproduction (VR) I and VR II) Averaging over RAVLT Z, LM Z, and VR Z to obtain a global Z 0=sample mean; higher scores indicate better outcomes.
Time frame: Baseline, approximately 3 months and approximately 6 months
Population: Of the 8 participants that were randomized into the intervention, only 7 participated in baseline assessments. Of the 7 with baseline data, only 2 completed follow up assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 (No Treatment) | Memory Function Composite Score | Baseline | 0.5 Z-score | Standard Deviation 0.84 |
| Group 1 (No Treatment) | Memory Function Composite Score | 3 Months | 0.87 Z-score | Standard Deviation 0.49 |
| Group 1 (No Treatment) | Memory Function Composite Score | 6 Months | 0.66 Z-score | Standard Deviation 1.63 |
| Group 2 (Experimental) | Memory Function Composite Score | Baseline | -0.21 Z-score | Standard Deviation 1.8 |
| Group 2 (Experimental) | Memory Function Composite Score | 3 Months | -1.30 Z-score | Standard Deviation 4.19 |
| Group 2 (Experimental) | Memory Function Composite Score | 6 Months | -0.98 Z-score | Standard Deviation 4.33 |
Secondary
Resting Brain-derived Neurotrophic Factor (BDNF)
Resting level of serum-derived BDNF
Time frame: Baseline and approximately 6 months
Secondary
Resting Norepinephrine (NE)
Resting level of plasma-derived norepinephrine (NE)
Time frame: Baseline and approximately 6 months