Cognitive Function
Conditions
Brief summary
The purpose of this pilot study is to develop and conduct well-designed trial to assess whether a multi-factorial intervention involving physical activity and cognitive training reduces the risk of significant cognitive decline in older individuals.
Detailed description
Evidence from small or uncontrolled studies indicates that physical exercise and cognitive training have considerable promise as prevention strategies, to the extent that they are often recommended; however, their efficacy has not been established by an adequately powered randomized clinical trial. This pilot study will provide the experience and data to assess whether physical activity and cognitive training separately improve cognitive function over 6 months. It will also determine whether a combination intervention holds promise beyond individual interventions without compromising adherence, and will provide information necessary to design a well-organized and efficient full scale, multi-center randomized clinical trial. The Physical Activity Training (PAT) will consist of center-based and home-based sessions to include aerobic, strength, flexibility, and balance training. The actual time spent exercising will vary from person to person and will also vary depending on what stage of the study they are in. The Cognitive Training (CT) intervention was developed to improve consciously-controlled memory processing or recollection of episodic memory information and produces changes in performance that transfer to executive function, such as working memory, planning and memory monitoring, as well as long term item memory and cognitive processing speed. The Healthy Aging Education (HAE) control will combine health education-based lectures with light stretching and toning. HAE will include an experiential component, in which participants will learn how to take charge of their health and seek out appropriate medical services and information. Topics such as medications, foot care, traveling and nutrition will be covered.
Interventions
BEHAVIORALPhysical Activity Training
Two 1-hour center and two 15- to 45-minute home-based training sessions per week to include aerobic, strength, flexibility, and balance training for 6 months. The ultimate goal is to accumulate 150 minutes of walking per week between center and home-based sessions.
BEHAVIORALCognitive Training
Two 1-hour sessions per week for the first two months and then one 1-hour session per week for months 3-6.
BEHAVIORALHealthy Aging Education
One 1-hour lecture each week for 3 months, then monthly.
Sponsors
National Institute on Aging (NIA)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Data collection related to study outcomes was performed by staff who were masked to intervention assignment.
Intervention model description
Participants were randomly assigned, with equal probability to one of four conditions: an educational control condition, moderate-intensity physical activity training, repetition lag cognitive training, or both physical activity and repetitive lag training.
Eligibility
Sex/Gender
ALL
Age
70 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 70 to 85 years * Summary score between 88 (80 for less than 8 years of education) and 95 on the Modified Mini-Mental Exam * Sedentary lifestyle, i.e., not actively participating in a formal exercise program within the past 3 months (defined as 30 minutes or more of formal exercise at least once a week; brisk walks will be considered formal exercise, leisurely walks will not) * Fluency in standard American English (to limit staffing and translation costs in this pilot) * Willingness to be randomized to any of the four intervention conditions
Exclusion criteria
* Failure to provide the name of a personal physician * Living in a nursing home; persons living in assisted or independent housing will not be excluded * Unable to communicate because of severe hearing loss or speech disorder * Severe visual impairment, which would preclude completion of the assessments and/or intervention * Neurologic disease, e.g. Alzheimer's (or other types of dementia), stroke that required hospitalization, Parkinson's, multiple sclerosis, amyotrophic lateral sclerosis, or prior diagnosis of mild cognitive impairment (MCI) * Abnormal functioning based on the modified Telephone Interview for Cognitive Status (less than 30) * Positive screen for MCI or dementia * Scores greater than or equal to 1.5 standard deviations below normal on memory and non-memory domain tests (speed of processing, and verbal fluency) * Severe rheumatologic or orthopedic diseases, e.g., awaiting joint replacement, active inflammatory disease * Terminal illness with life expectancy less than 8 months, as determined by a physician * Severe pulmonary disease, e.g., on home oxygen or chronic steroids * Severe cardiac disease, including New York Health Association Class III or IV congestive heart failure, clinically significant aortic stenosis, history of cardiac arrest which required resuscitation, use of a cardiac defibrillator, or uncontrolled angina * Other significant co-morbid disease that would impair ability to participate in the exercise-based intervention, e.g. renal failure on hemodialysis, severe or acute psychiatric disorder (e.g. bipolar disorder or major depression, schizophrenia), excessive alcohol use (more than 14 drinks per wk); persons with managed depression (on stable dosage for at least 3 months) will not be excluded * Baseline Geriatric Depression Scale score greater than 6 * Other significant factors that may affect the ability for cognitive training, including a history of head trauma resulting in a loss of consciousness, current use of benzodiazepines, hypnotic or anticholinergic agents, and current use of cognitive enhancing prescription or investigational medications (e.g., donepezil, selegiline, tacrine) * Member of household is already enrolled * Lives distant from the study site or is planning to move out of the area in next 3 years or leave the area for more than 3 months during the next year * History of participation in a cognitive program in the last 2 years (includes research studies involving memory training) * Myocardial infarction, coronary artery bypass graft, or valve replacement within past 6 months * Serious conduction disorder (e.g., 3rd degree heart block), uncontrolled arrhythmia * Pulmonary embolism or deep venous thrombosis within past 6 months * Stroke, hip fracture, hip or knee replacement, or spinal surgery within past 4 months * Receiving physical therapy for gait, balance, or other lower extremity training * Severe hypertension, e.g., systolic blood pressure over 160 mmHg, diastolic blood pressure over 110 mmHg * Other temporary intervening events, such as sick spouse, bereavement, or recent move * Participation in another intervention trial; participation in an observational study may be permitted * Inability to commit to intervention schedule requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Cognitive Function in Z-scores (i.e. Which Converts Raw Data to Standard Deviation (SD) Units: [Score-mean]/SD]). This Composite is Formed by Averaging the Z-scores From Individual Tests. | Changes from baseline at 4 months in z-scores. | 6 measures of executive functioning: Self-Ordered Pointing task (24): working memory 1- and 2-Back tests (25-26): working memory Eriksen flanker (27): response inhibition Task Switching (28): attentional flexibility Trail Making (29): executive function z-score=(raw score-mean)/standard deviation 4 measures of episodic memory Hopkins Verbal Learning Test (30) Wechsler Memory Scale-III (31) A composite of 10 scores: dividing each's difference from the baseline mean by the baseline SD, averaging the 6 executive function and 4 episodic memory z-transformed measures, and norming to have SD 1. 24\. Petrides. Neuropsych 1982;20:249-62. 25. Dobbs. Psychol Aging 1989;4:500-3. 26. Jonides. J Cog Neurosci 1997;9:462-75. 27. Ericksen. Br J Sports Med 2009;43:22-4. 28. Kramer. Acta Psychologica 1999;101:339-78. 29. Reitan. Per Motor Skills 1958;8:271-6. 30. Brandt. Clin Neuropsych 1991;5:125-42. 31. Wechsler D.1997. Psychological Corporation, Harcourt, Inc: San Antonio. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Executive Function: Z-score Formed by Averaging the Individual Z-scores From the Five Tests Listed Below. | Baseline to 4 months | Composite of 5 tasks: Self-Ordered Pointing Task of planning, working memory, and monitoring. Subjects view 16 abstract shapes and choose a shape so that each is selected by the 16th trial and none is chosen more than once. (Eriksen, Percept Psychophysiology 1974;16:143-49). N-Back Test of working memory. Subjects see individual letters and indicate whether the letter is the same as the nth back letter, with n equal to 1 and 2. (Dobbs, Psychol Aging 1989;4:500-3.) Eriksen flanker task of response incompatibility. Subjects see an arrow facing either right or left and indicate the direction.The target displays can be neutral congruent, or incongruent. (Eriksen, Percept Psychophys 1974;16:143-49.) Trail Making Test-Part B of alternating attention. Subjects connect 25 labeled circles and are scored by completion time. The lower the scores the better the performance. See details in the primary outcome. Raw scores for each test were converted to z-scores. |
| Composite Episodic Memory | Change a 4 months | Composite of 4 components. The Hopkins Verbal Learning Test (HVLT) of verbal learning. Subjects hear 12 words and repeat as many as possible. This is repeated twice for a total of 3 trials. 20 mins later the subject is asked to recall as many words as possible. Subjects also do a recognition trial with 24 words. Scores for immediate and delayed recall, and recognition are calculated.(Brandt J. Clin Neuropsych 1991;5:125-42). The Logical Memory (LM) test The LM test has 2 parts. In Part 1, subjects hear a story and recall as many pieces as possible immediately and after a 30 minute delay. Subjects receive a story unit score for accuracy of re-telling story details and a thematic score for recalling story themes. The higher the scores the better the performance. ( Wechsler D. The Wechsler Memory Scale-3rd Edition (WHM-III). Psycholog Corp, Harcourt, Inc.) Individual scores are converted to z-scores and averaged to form the composite. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Physical Activity Training The Physical Activity Training ((PAT) intervention consisted of center-based and home-based sessions comprised of aerobic, strength, flexibility, and balance training with a targeted duration of 150 minutes/week. It included two center and two home-based training sessions per week for four months. Its primary focus was walking with the explicit intent of improving cardiovascular fitness. Other forms of endurance activity (e.g., stationary cycling) were used when regular walking was contraindicated for medical or behavioral reasons. Center-based physical activity sessions were supplemented with additional tailored home-based walking sessions at 1-2 per week during the first month.
Physical Activity Training (PAT): Two 1-hour center and two 15- to 45-minute home-based training sessions per week to include aerobic, strength, flexibility, and balance training for 6 months. The ultimate goal is to accumulate 150 minutes of walking per week between center and home-based sessions. | 18 |
| Cognitive Training The Cognitive Training (CT) intervention was developed to improve consciously-controlled memory processing or recollection of episodic memory information. Sessions were center-based, conducted via computer, carried out with small groups, and monitored by skilled trainers. Training consisted of four consecutive 10-12 min sessions per day, administered two times per week for two months, which then tapered to one time per week for two additional months. For each session, participants studied a list of 30 words, followed by a recognition test consisting of the 30 studied words and 30 new words with each new word repeated once, and asked to respond yes to study words and no to the new items both times they occurred.
Cognitive Training (CT): Two 1-hour sessions per week for the first two months and then one 1-hour session per week for months 3-6. | 18 |
| Combined Intervention The Combined Intervention (PACT) was designed so that participants received both cognitive and physical activity training on the same day. To avoid the potential impact of physical fatigue on cognitive training, the cognitive treatment was delivered prior to the physical activity treatment. It included both the PA and CT interventions.
Physical Activity Training (PAT): Two 1-hour center and two 15- to 45-minute home-based training sessions per week to include aerobic, strength, flexibility, and balance training for 6 months. The ultimate goal is to accumulate 150 minutes of walking per week between center and home-based sessions.
Cognitive Training (CT): Two 1-hour sessions per week for the first two months and then one 1-hour session per week for months 3-6. | 19 |
| Healthy Aging The Healthy Aging Education control intervention consisted of weekly lectures based on health education and was based on a program developed by the Lifestyle Interventions and Independence for Elders pilot trial \[Rejeski, 2005; LIFE, 2006\]. Topics such as medications, foot care, traveling and nutrition were covered. The purpose of the intervention was to provide contact time with participants.
Healthy Aging Education (HAE): One 1-hour lecture each week for 3 months, then monthly. | 18 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Physical Activity Training | Total | Healthy Aging | Combined Intervention | Cognitive Training |
|---|---|---|---|---|---|
| 400 meter walk time | 360 Seconds STANDARD_DEVIATION 48 | 342 Seconds STANDARD_DEVIATION 55 | 331 Seconds STANDARD_DEVIATION 66 | 347 Seconds STANDARD_DEVIATION 56 | 331 Seconds STANDARD_DEVIATION 50 |
| Age, Continuous | 77.5 years STANDARD_DEVIATION 4.8 | 76.4 years STANDARD_DEVIATION 4.7 | 75.4 years STANDARD_DEVIATION 4.8 | 76.9 years STANDARD_DEVIATION 4 | 76.0 years STANDARD_DEVIATION 5.2 |
| Modified MiniMental State Exam Score | 94.6 Units on a scale STANDARD_DEVIATION 3.9 | 94.8 Units on a scale STANDARD_DEVIATION 3.5 | 94.3 Units on a scale STANDARD_DEVIATION 2.4 | 94.6 Units on a scale STANDARD_DEVIATION 4.3 | 95.6 Units on a scale STANDARD_DEVIATION 3.4 |
| Race/Ethnicity, Customized African-American | 1 Participants | 7 Participants | 1 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants | 66 Participants | 17 Participants | 15 Participants | 17 Participants |
| Region of Enrollment United States | 18 Participants | 73 Participants | 18 Participants | 19 Participants | 18 Participants |
| Sex: Female, Male Female | 10 Participants | 37 Participants | 7 Participants | 12 Participants | 8 Participants |
| Sex: Female, Male Male | 8 Participants | 36 Participants | 11 Participants | 7 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 19 | 0 / 18 |
| other Total, other adverse events | 8 / 18 | 5 / 18 | 6 / 19 | 1 / 18 |
| serious Total, serious adverse events | 0 / 18 | 1 / 18 | 0 / 19 | 0 / 18 |
Outcome results
Primary
Composite Cognitive Function in Z-scores (i.e. Which Converts Raw Data to Standard Deviation (SD) Units: [Score-mean]/SD]). This Composite is Formed by Averaging the Z-scores From Individual Tests.
6 measures of executive functioning: Self-Ordered Pointing task (24): working memory 1- and 2-Back tests (25-26): working memory Eriksen flanker (27): response inhibition Task Switching (28): attentional flexibility Trail Making (29): executive function z-score=(raw score-mean)/standard deviation 4 measures of episodic memory Hopkins Verbal Learning Test (30) Wechsler Memory Scale-III (31) A composite of 10 scores: dividing each's difference from the baseline mean by the baseline SD, averaging the 6 executive function and 4 episodic memory z-transformed measures, and norming to have SD 1. 24\. Petrides. Neuropsych 1982;20:249-62. 25. Dobbs. Psychol Aging 1989;4:500-3. 26. Jonides. J Cog Neurosci 1997;9:462-75. 27. Ericksen. Br J Sports Med 2009;43:22-4. 28. Kramer. Acta Psychologica 1999;101:339-78. 29. Reitan. Per Motor Skills 1958;8:271-6. 30. Brandt. Clin Neuropsych 1991;5:125-42. 31. Wechsler D.1997. Psychological Corporation, Harcourt, Inc: San Antonio.
Time frame: Changes from baseline at 4 months in z-scores.
Population: Participants assessed at four months post-randomization. Note that this does not include all who were randomized due to dropout.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Training | Composite Cognitive Function in Z-scores (i.e. Which Converts Raw Data to Standard Deviation (SD) Units: [Score-mean]/SD]). This Composite is Formed by Averaging the Z-scores From Individual Tests. | 0.71 z-scores (e.g.Standard Deviation Units) | Standard Error 0.18 |
| Cognitive Training | Composite Cognitive Function in Z-scores (i.e. Which Converts Raw Data to Standard Deviation (SD) Units: [Score-mean]/SD]). This Composite is Formed by Averaging the Z-scores From Individual Tests. | 0.62 z-scores (e.g.Standard Deviation Units) | Standard Error 0.18 |
| Combined Intervention | Composite Cognitive Function in Z-scores (i.e. Which Converts Raw Data to Standard Deviation (SD) Units: [Score-mean]/SD]). This Composite is Formed by Averaging the Z-scores From Individual Tests. | 0.71 z-scores (e.g.Standard Deviation Units) | Standard Error 0.17 |
| Healthy Aging | Composite Cognitive Function in Z-scores (i.e. Which Converts Raw Data to Standard Deviation (SD) Units: [Score-mean]/SD]). This Composite is Formed by Averaging the Z-scores From Individual Tests. | 0.65 z-scores (e.g.Standard Deviation Units) | Standard Error 0.18 |
Comparison: Marginal comparisons of physical activity training vs no physical activity trainingp-value: 0.66ANOVA
Comparison: Marginal comparisons of physical activity training versus no physical activity trainingp-value: 0.55ANOVA
Comparison: Marginal comparisons of cognitive training versus no cognitive trainingp-value: 0.95ANOVA
Comparison: Marginal comparisons of cognitive training versus no cognitive trainingp-value: 0.48ANOVA
Secondary
Change in Executive Function: Z-score Formed by Averaging the Individual Z-scores From the Five Tests Listed Below.
Composite of 5 tasks: Self-Ordered Pointing Task of planning, working memory, and monitoring. Subjects view 16 abstract shapes and choose a shape so that each is selected by the 16th trial and none is chosen more than once. (Eriksen, Percept Psychophysiology 1974;16:143-49). N-Back Test of working memory. Subjects see individual letters and indicate whether the letter is the same as the nth back letter, with n equal to 1 and 2. (Dobbs, Psychol Aging 1989;4:500-3.) Eriksen flanker task of response incompatibility. Subjects see an arrow facing either right or left and indicate the direction.The target displays can be neutral congruent, or incongruent. (Eriksen, Percept Psychophys 1974;16:143-49.) Trail Making Test-Part B of alternating attention. Subjects connect 25 labeled circles and are scored by completion time. The lower the scores the better the performance. See details in the primary outcome. Raw scores for each test were converted to z-scores.
Time frame: Baseline to 4 months
Population: Participants assessed at 4 months -- note some dropouts occurred
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Training | Change in Executive Function: Z-score Formed by Averaging the Individual Z-scores From the Five Tests Listed Below. | 0.32 z-scores (e.g. SD units) | Standard Error 0.19 |
| Cognitive Training | Change in Executive Function: Z-score Formed by Averaging the Individual Z-scores From the Five Tests Listed Below. | 0.58 z-scores (e.g. SD units) | Standard Error 0.19 |
| Combined Intervention | Change in Executive Function: Z-score Formed by Averaging the Individual Z-scores From the Five Tests Listed Below. | 0.60 z-scores (e.g. SD units) | Standard Error 0.18 |
| Healthy Aging | Change in Executive Function: Z-score Formed by Averaging the Individual Z-scores From the Five Tests Listed Below. | 0.58 z-scores (e.g. SD units) | Standard Error 0.19 |
Secondary
Composite Episodic Memory
Composite of 4 components. The Hopkins Verbal Learning Test (HVLT) of verbal learning. Subjects hear 12 words and repeat as many as possible. This is repeated twice for a total of 3 trials. 20 mins later the subject is asked to recall as many words as possible. Subjects also do a recognition trial with 24 words. Scores for immediate and delayed recall, and recognition are calculated.(Brandt J. Clin Neuropsych 1991;5:125-42). The Logical Memory (LM) test The LM test has 2 parts. In Part 1, subjects hear a story and recall as many pieces as possible immediately and after a 30 minute delay. Subjects receive a story unit score for accuracy of re-telling story details and a thematic score for recalling story themes. The higher the scores the better the performance. ( Wechsler D. The Wechsler Memory Scale-3rd Edition (WHM-III). Psycholog Corp, Harcourt, Inc.) Individual scores are converted to z-scores and averaged to form the composite.
Time frame: Change a 4 months
Population: Participants assessed at 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Physical Activity Training | Composite Episodic Memory | 0.84 z-scores (e.g. SD units) | Standard Error 0.21 |
| Cognitive Training | Composite Episodic Memory | 0.42 z-scores (e.g. SD units) | Standard Error 0.21 |
| Combined Intervention | Composite Episodic Memory | 0.56 z-scores (e.g. SD units) | Standard Error 0.2 |
| Healthy Aging | Composite Episodic Memory | 0.47 z-scores (e.g. SD units) | Standard Error 0.21 |
Comparison: Marginal comparisons of physical activity training versus no physical activity training.p-value: 0.23ANOVA
Comparison: Marginal comparisons of cognitive training versus no cognitive trainingp-value: 0.42ANOVA