Cognitive Remediation to Improve Mobility in Sedentary Seniors (CREM)

Cognitive Intervention to Improve Simple and Complex Walking

The investigators propose to conduct a single-blind randomized clinical trial to test the efficacy of a computerized cognitive remediation intervention program on improving locomotion in sedentary seniors, a group at an especially high risk for disability. The hypothesis is that executive functions will respond to the cognitive remediation program and in turn enhance locomotion.

Study Overview

• Status: Completed
• Conditions: Motor Activity; Mobility Limitation; Difficulty Walking; Cognitive Ability General
• Intervention / Treatment: Other: Cognitive Remediation; Other: Active Control

Detailed Description

Emerging evidence indicates that Executive Functions play an important role in maintaining locomotion in aging and preventing mobility disabilities. However, use of cognitive training programs to improve executive functions as a strategy to increase mobility has not been explored. Exciting results from the preliminary study support the efficacy and feasibility of the cognitive remediation approach to improve locomotion in older adults.

The premise of this clinical trial is that disability among seniors is a potentially preventable chronic condition rather than an irreversible consequence of aging and disease. The investigators proposed novel approach to locomotion has the potential to shift treatment paradigms in the field of disability by introducing cognitive approaches to mobility that can be applied to prevention and rehabilitation in diverse settings. Through this 'proof of concept' secondary prevention trial the investigators will fill an important gap in knowledge for practicing evidence-based medicine and developing effective interventions for a major health outcome affecting a substantial proportion of the U.S. aging population.

• Study Type: Interventional
• Enrollment (Actual): 383
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adults aged 70 and older, residing in the community.
2. Plan to be in area for next year.
3. Able to speak English at a level sufficient to undergo our cognitive assessment battery.
4. Ambulatory. Subjects are classified as 'non-ambulatory' if they are unable to leave the confines of their home and attend a clinic visit.
5. Gait velocity ≤1 m/s.
6. Short Physical Performance Battery score ≤9.

Exclusion Criteria:

1. Presence of dementia identified by any one of the following: Telephone based Memory Impairment Screen score (T-MIS) of <5, Alzheimer's Disease 8 (AD8) ≥ 2. Or dementia diagnosed by baseline cognitive assessment.
2. Serious chronic or acute illness such as cancer (late stage, metastatic, or on active treatment), chronic pulmonary disease on ventilator or continuous oxygen therapy or active liver disease.
3. Mobility limitations solely due to musculoskeletal limitation or pain (e.g., severe osteoarthritis) that prevent subjects from completing mobility tests. Presence of arthritis will not be used to exclude subjects if they can complete the mobility tasks.
4. Any medical condition or chronic medication use (e.g., neuroleptics) that will compromise safety or affect cognitive functioning or terminal illness with life expectancy less than 12 months.
5. Presence of progressive, degenerative neurologic disease (e.g., Parkinson's disease or ALS).
6. Hospitalized in the past 6 months for severe illness or surgery that specifically affects mobility (e.g. hip or knee replacement) and that prevent subjects from completing mobility tests or plans for surgery affecting mobility in the next 6 months.
7. Severe auditory or visual loss.
8. Active psychoses or psychiatric symptoms (such as agitation) noted during the clinic visit that will prevent completion of study protocols.
9. Living in nursing home.
10. Participation in other intervention trial or observational studies. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive Remediation; An individualized computerized cognitive remediation program.	Other: Cognitive Remediation; This computerized program has successfully been used by seniors in different settings. It trains a number of cognitive processes including attention and Executive Function.The Cognitive Remediation (CREM) training is constructed based on the program's built in baseline cognitive evaluation.
Active Comparator: Active control; Individualized computer based exposure and interactive health education classes.	Other: Active Control; Computer, multimedia and group based health education programs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Walking Speed During Single and Dual-task Conditions.	Between group difference in change per arm of gait speed (centimeters/second) measured during normal pace walking and walking while talking conditions using an instrumented walkway (GAITRite® electronic walkway system).	Baseline and 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Short Physical Performance Battery (SPPB).	Between group difference in change per arm in mobility measured using the SPPB. The SPPB is comprised of balance, chair rise, and gait speed tests. A score is assigned in each of these three areas (0-4), and summed to obtain an overall summary score (0-12, higher better).	Baseline and 2 months
Stride Length.	Between group difference in change per arm in stride length (cm) collected during normal walking and walking while talking conditions on an instrumented walkway.	Baseline and 2 months
Gait Variability.	Between group difference in change per arm in gait stride length variability, measured in standard deviation units, collected during normal walking and walking while talking on an instrumented walkway. Gait variability is defined as differences in length from one stride to the next.	Baseline and 2 months
Number of Participants With Substantial Gait Speed Change.	Substantial gait speed improvement is defined as change of ≥1 standard deviation units from baseline performance in gait speed measured during normal walking and walking while talking conditions.	Baseline and 2 Months
Flanker Task.	Between group difference in change per arm on the Flanker task, a measure of speed of processing, attention and inhibitory control. Scoring is based on reaction time in milliseconds (ms) and calculated as the difference in reaction time that it takes a person, on average, to respond to an incongruent minus congruent stimulus. Lower values reflect better outcome.	Baseline and 2 Months
Digit Symbol Substitution Test.	Between group difference in change per arm on the Digit Symbol Substitution Test (a subtest of the Wechsler Adult Intelligence Scale - Revised), a measure of attention, transcription and speed of processing. Scoring is based on the total number of correct responses generated during a 90-sec time interval. Scores range from 0-133 with higher scores indicating better performance.	Baseline and 2 Months
Trail Making Test Form A.	Between group difference in change per arm on Trail Making Test form A, a timed measure of attention. Scoring is based on the time required to complete the task and on accuracy. Scores range from 0-300 seconds with longer time indicating worse performance. Scores were log transformed prior to analysis.	Baseline and 2 Months
Trail Making Test Form B.	Between group difference in change per arm on Trail Making Test form B, a timed measure of attention, set shifting and processing speed. Scoring is based on the time required to complete the task and on accuracy. Scores range from 0-300 seconds with longer time indicating worse performance. Scores were log transformed prior to analysis.	Baseline and 2 Months
Controlled Oral Word Association Test.	Between group difference in change per arm on the Controlled Oral Word Association Test, a verbal fluency test that measures word generation performance under specified timed phonemic and semantic conditions. Performance measured by the total number of correct words as well as the number of errors. Scores range from 25-41 seconds with higher scores indicating better performance.	Baseline and 2 Months
Repeatable Battery for the Assessment of Neuropsychological Status.	Between group difference in change on the Repeatable Battery for the Assessment of Neuropsychological Status, a relatively brief battery that assesses overall level of cognitive function This battery consists of 10 neurocognitive tests measuring memory (immediate and delayed), attention, language, visuospatial abilities and executive functions. Performance is converted to standardized scores derived from a normative sample.	Baseline and 2 Months
Neuroplasticity.	Changes in prefrontal activation measure using functional near infra-red spectroscopy.	Baseline and 2 Months
Durability	Between group difference in change per arm in gait speed during normal pace and walking while talking conditions measured at six months.	Baseline and 6 months
Stair Climbing Time.	Between group difference in change per arm in mobility and balance assessed during stair climbing, which provides a valid assessment tool for predicting disability. Scores are measured as time in seconds to climb 3 stairs with longer time indicating worse performance. Scores were log transformed prior to analysis.	Baseline and 2 Months
Disability Scale.	Between group difference in change per arm in mobility assessed by activities of daily living tasks on the Activities of Daily Living-Prevention Instrument. Scores range from 0-45 and higher scores indicate poorer function.	Baseline and 2 Months
Variability in Gait Domains	Between group difference in change per arm in gait domains (summary measures reported as standard deviation units) derived from factor analysis of quantitative gait variables collected on an instrumented walkway during normal walking and walking while talking. Based on previous findings of gait patterns, pace, rhythm and variation factors are defined (using z-scores based on mean and standard deviation at baseline). Higher values are indicative of better performance for pace and rhythm factors and indicative of worse performance for variation factors.	Baseline and 2 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Geriatric Depression Scale (GDS).	Between group difference in change per arm in depressive symptoms assessed using the 30 item GDS, scores range from 0 (not depressed) to 30 (depressed).	Baseline and 2 months
Rosenberg Self-Esteem Scale.	Between group difference in change per arm in self-esteem assessed using a ten-item Likert-type scale (higher scores are better).	Baseline and 2 months
Falls Efficacy Scale.	Between group difference in change per arm in self-efficacy scores (range 0-100). Higher scores indicate less confidence.	Baseline and 2 months
12-Item Short Form Health Survey (SF-12).	Between group difference in change per arm in perceptions of health and quality of life in domains that include social, physical, emotional and mental functions. The SF-12 has 12 items; two component scores capturing perceptions of mental and physical function can be derived. The Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) scores are calculated using 12 questions with a range of 0-100 (zero indicating the poorest level of health measured and 100 indicating the highest).	Baseline and 2 months
Falls.	Presence and number of falls over 12 months from baseline.	Baseline and 12 Months
Number of Participants With Progression in Cognitive Impairment From Normal Cognitive Function at Baseline to Mild Cognitive Impairment (MCI)	Progression in cognitive impairment from normal cognitive function at baseline to MCI.	Baseline and 2 Months
Number of Participants With Progression in Cognitive Impairment From Normal Cognitive Function at Baseline to Dementia	Progression in cognitive impairment from baseline normal cognitive function to dementia.	Baseline and 2 Months
Number of Participants With Progression in Cognitive Impairment From Normal Cognitive Function at Baseline to Motoric Cognitive Risk Syndrome (MCR)	Progression in cognitive impairment from baseline normal cognitive function to MCR.	Baseline and 2 Months
Number of Participants With Progression in Cognitive Impairment From Normal Cognitive Function at Baseline to Cognitively Impaired	Progression in cognitive impairment from baseline normal cognitive function to cognitive impairment defined as presence of incident MCI, dementia, or MCR.	Baseline and 2 Months

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Joe Verghese, MD, Albert Einstein College of Medicine; Principal Investigator: Roee Holtzer, PhD, Albert Einstein College of Medicine

Publications and helpful links

General Publications

• Verghese J, Mahoney J, Ambrose AF, Wang C, Holtzer R. Effect of cognitive remediation on gait in sedentary seniors. J Gerontol A Biol Sci Med Sci. 2010 Dec;65(12):1338-43. doi: 10.1093/gerona/glq127. Epub 2010 Jul 19.
• Verghese J, Mahoney JR, Ayers E, Ambrose A, Wang C, Holtzer R. Computerised cognitive remediation to enhance mobility in older adults: a single-blind, single-centre, randomised trial. Lancet Healthy Longev. 2021 Sep;2(9):e571-e579. doi: 10.1016/s2666-7568(21)00173-2. Epub 2021 Sep 2.
• Verghese J, Ayers E, Mahoney JR, Ambrose A, Wang C, Holtzer R. Cognitive remediation to enhance mobility in older adults: the CREM study. Neurodegener Dis Manag. 2016 Dec;6(6):457-466. doi: 10.2217/nmt-2016-0034. Epub 2016 Nov 4.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: August 17, 2015
• First Submitted That Met QC Criteria: October 1, 2015
• First Posted (Estimated): October 2, 2015

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mobility Limitation
• Other Study ID Numbers: 2015-4752; R01AG050448-01 (U.S. NIH Grant/Contract)