mental exercise: ongoing intervention trials george w. rebok, ph.d. symposium: cognitive activity...
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Mental Exercise: Ongoing Intervention Trials
George W. Rebok, Ph.D.
Symposium: Cognitive Activity from Bedside-to-Bench: Findings from the NIA R13 Conference Grant
American Geriatrics Society
Chicago, IL
May 6, 2006
Cognitive Training “in the News”
• Brain training takes aging Japan by storm
• By George Nishiyama Mon Apr 10, 10:58 AM ET
• TOKYO (Reuters) - Tamako Kondo says 10 minutes of exercise every morning keeps her fit. But the 80-year-old doesn't hit the treadmill or take aerobics classes. Instead, she sits at a desk, pencil in hand, and tackles simple arithmetic and other quizzes, part of a "brain training" program that has taken Japan by storm.
• Bookshops now have separate sections for workbooks with the exercises and video game versions are selling like hot cakes among the growing ranks of older Japanese who hope the drills will reinvigorate their gray matter.
• "I want to delay becoming senile as much as possible," said Kondo, who lives in a Tokyo home for the elderly.
“Use it or Lose it?”“It’s a fortunate person whose brainIs trained early, again and again,And who continues to use itTo be sure not to lose it,So the brain, in old age, may not wane.”
(Rosenzweig MR, Bennett EL. Behavioral Brain Research 1996;78:57-65)
“Despite the frequent assertions of the mental exercise hypothesis, its intuitive plausibility, and an understandably strong desire to believe that it is true….., there is currently little scientific evidence that differential engagement in mentally stimulating activities alters the rate of mental aging.”
(Salthouse TA. Mental exercise and mental aging: Evaluating the validity of the “Use it or lose it” hypothesis. Perspectives on Psychological Science 2006; 1:68-87.)
Growing Interest in Promoting Public Cognitive Health
• Staying Sharp project (AARP)• Maintain Your Brain (Alzheimer’s Association)
• Keep Your Brain Young (McKhann & Albert, 2002)• The New Brain (Restak, 2004)• Age-Proof Your Mind (Tan, 2005)
Outline of Talk• To present evidence on the effectiveness of ongoing
intervention trials in improving and maintaining cognitive functioning of older adults
• To explore the question of the extent to which skills acquired during cognitive training transfer to similar tasks having a more real-world component
• To discuss challenges and what steps might be taken to develop the next generation of training studies
A Taxonomy of Behavioral and Non-Behavioral Intervention Strategies (adapted from Baltes)
Goal Level Target Type Mode SettingEnrich
Prevent
Remediate
Compensate
Individual
Small group
(e.g., n =3-5)
Large group
(e.g., n > 5)
Neighborhood
Community
Cognitive ability (e.g., memory, attention, executive function)
Cognitive complaints
Efficacy beliefs
Functional skills
Cognitive training-practice
Cognitive rehabilitation
Pharmaco-therapy
Life-style modification (e.g., exercise, health habits, diet, stress reduction)
Cognitive engagement
Biomedical
Single component
Multiple component (e.g., cognitive training + pharmaco-therapy;
Cognitive training + exercise therapy)
Laboratory
Clinic
Hospital
Home
School
Workplace
Community center
Internet
Multiple settings (e.g., Clinic + Internet; clinic + home)
Training on Basic Abilities: Background• Programmatic Research on Basic Abilities: 1970’-
1980’s– Early childhood education programs - plasticity
• Does range of cognitive plasticity vary across life span?
– Adult cognitive longitudinal studies: Variability in rate of cognitive decline
• Early Basic Ability Training in Old Age: 1970-1990– Focus on abilities showing “early” decline in 60’s (abstract
reasoning, perceptual speed, working memory)– Ability-specific (single ability) training - focus on
strategies associated with ability– Significant training effect compared to no-treatment or
social contact control group (retest gain)• Training gain: 0.50-0.75 Sd
Training on Basic Abilities: Background (2)• Some evidence for temporal durability of training effects
(up to 7 yrs for reasoning; 3.5 yrs for memory; 18 months for speed)
• “New Questions” for Training Research:– Long-term clinical outcomes of interventions– “Transfer” to measures of functioning, everyday tasks
• Concerns re Generation 1 Training Research:– Representativeness of samples - regional, convenience samples;
lack of diversity in samples– Clinical Trial Design - Intent to treat design - attrition– Replicability of findings– Clinically meaningful outcomes– ACTIVE
ACTIVE - Generation 2 of Cognitive Training Studies
RFA initiated by NIA and NINR
ACTIVE - Advanced Cognitive Training for Independent and Vital Elderly Randomized Controlled Clinical Trial Common multi-site intervention protocol with “proven interventions” Include intent-to-treat analyses
Primary Aim of ACTIVE To test the efficacy of three cognitive interventions to improve or
maintain the cognitively demanding activities of daily living. Important Shift in Major Outcome of Cognitive Training Research
Primary outcome is cognitively demanding activities, NOT Basic Cognitive Abilities. Outcome of ACTIVE trial specified by RFA
• Thus, the pre-specified ACTIVE design necessarily had to use basic intervention strategies which are known to be challenging for achieving real-world transfer
ACTIVE Steering Committee
• University of Alabama- Birmingham
Karlene Ball, Ph.D.• Hebrew Rehabilitation Center
for Aged, BostonJohn Morris, Ph.D.
• Indiana UniversityFrederick Unverzagt, Ph.D.
• Johns Hopkins UniversityGeorge Rebok, Ph.D.
• Pennsylvania State UniversitySherry Willis, Ph.D.
• University of Florida / Wayne State University
Michael Marsiske, Ph.D.
• New England Research Institutes, Coordinating Center
Sharon Tennstedt, Ph.D.
• National Institute on Aging
Jeffrey Elias, Ph.D.
• National Institute of Nursing Research
Kathy Mann-Koepke, Ph.D.
Participant Characteristics
Conceptual Model
Training CognitiveAbilities
Daily Function
ProximalOutcomes
PrimaryOutcomes
Reasoning Speed
No
Contact Memory
Refused Ineligible Screen for Eligibility
Eligible and Consenting
Baseline Measurements
Randomize to Training
Post - Test (PT)
Booster Booster
Yes No Yes
No Yes No
Booster
-
Figure 1. Study Design
Booster Booster Booster
1-Yr Test (A1)
2-Yr Test (A2)
3-Yr Test (A3)
5-Yr Test (A5)
Net Effect of ACTIVE Training on Proximal Outcome Composites
Memory Training
Reasoning Training
Speed Training
Memory Composite (+), PT 0.2566*** -0.0197 -0.0449 ", A1 0.2085*** 0.0178 -0.0499 ", A2 0.1751*** 0.0431 -0.0324 ", A3 0.2207*** -0.0103 0.0062
Reasoning Composite (+), PT -0.0019 0.4797*** 0.0014 ", A1 -0.0039 0.3998*** -0.0296 ", A2 -0.0228 0.2568*** -0.0402 ", A3 0.0132 0.3812*** -0.0370
Speed Composite (+), PT -0.0089 -0.0262 -1.4541*** ", A1 -0.0201 -0.0032 -1.2000*** ", A2 -0.0503 -0.0192 -0.8616*** ", A3 0.0456 0.0053 -0.9538***
Net effect size defined as [Training Mean - Control Mean at indicated time] - [Training mean - Control mean at baseline] divided by intra-subject standard deviation of the composite. (+) indicates direction of positive response.
*** p < 0.0001 testing for net effect significantly different from zero.
Net Effect of ACTIVE Booster Training on Cognitive Abilities
Memory Booster
Reasoning Booster
Speed Booster
Memory Composite (+), A1 0.0473 -0.0391 -0.0001 ", A2 0.0588 -0.0139 0.0413 ", A3 0.1631*** 0.0027 0.0374
Reasoning Composite (+), A1 -0.0041 0.302*** 0.1256*** ", A2 -0.04 0.151*** -0.0358 ", A3 -0.072 0.3756*** 0.0902*
Speed Composite (-), A1 -0.0352 -0.0412 -0.907*** ", A2 -0.0218 -0.066 -0.3398*** ", A3 0.0569 -0.0193 -0.9946***
Net effect size defined as [Boosted mean - Unboosted training mean at indicated time] - [Boosted mean - Unboosted training mean at baseline] divided by intra-subject standard deviation of the composite. (+) indicates direction of positive response. * p < 0.05 testing for net effect significantly different from zero. *** p < 0.0001 testing for net effect significantly different from zero.
ACTIVE Findings:Effects on Everyday Task & Functioning
• No Transfer from Basic Ability Training to Everyday Functioning for any of the 3 Treatment groups - Report through A3– Decline in Functioning occurs later than decline in
basic abilities– Positive selected control group - delay in onset of
functional decline
• Findings of A5 to be reported - manuscript under review
Normal Memory vs Memory Impaired:Impact on Training on Memory,
Reasoning, and Speed
Interven Time
Memory Reasoning Speed
Memory
PT .300*** -.009 -0.050
A1 .254*** .033 -0.061
A2 .214*** .052 -0.057
Reason
PT .001 .477*** 0.025
A1 .013 .416*** -0.026
A2 -.003 .262*** -0.021
Speed
PT .004 -.017 -1.488***
A1 .004 .009 -1.238***
A2 -.024 -.013 -0.886***
Inteven Time
Memory Reasoning Speed
Memory
PT -.012 -.117 0.105
A1 -.175 -.163 0.107
A2 -.100 -.015 0.400*
Reason
PT -.048 .573*** -0.277
A1 -.230 .208 -0.155
A2 -.331 .276* -0.434*
Speed
PT -.108 -.111 -1.420***
A1 -.163 -.097 -1.100***
A2 -.298 .079 -0.755***
Next-Generation Training Platforms
• Technology-based: video training, computerized training, internet-based
• Experiential/engagement: global, non-ability specific interventions
•Trainer-less Training: collaborative, interactive but little feedback provided
•Combinatorial Training: little work done on combined training (exercise and cognition, pharmacotherapy and cognition, etc.)
Experiential/Engagement
• “Engagement” hypothesis (e.g., Schooler & Mulatu, 2001; Verghese et al., 2003) – Age-related declines in cognitive functioning may to some extent be mitigated by a lifestyle marked by social and intellectual engagement
• Broad-based effects• Evidence is correlational
Experience Corps model• Volunteers 60 and older• Serve in public elementary schools: K-3• Meaningful roles; important needs• High intensity: >15 hours per wk• Reimbursement for expenses: $150/mo• Sustained dose: full school year• Critical mass, teams• Health behaviors: physical, social, and cognitive activity• Leadership and learning opportunities • Infrastructure to support program• Program evaluation• Diversity
– Freedman M, Fried LP; Experience Corps monograph, 1997
What We’ve Learned So Far• Can recruit and retain a large group of elderly
volunteers
• Volunteers accept the need for randomization
• Program perceived as widely attractive to older adults, well-accepted by participants, including principals, teachers, and children
• Results show initial positive benefit in selected areas of function among older adults:– physical: improved chair stand – cognitive: improved executive functioning
Characteristic Participants Controls
Age, mean years 68 (r: 62-78) 68 (r: 63-75)
Female, n (%) 8 (100) 9 (100)
African American, n (%) 8 (100) 9 (100)
Education, mean years 12 12
Widowed, n (%) 5 1
MMSE, mean 24.5 25.6
EC Functional Brain MRI (fMRI)Pilot Study (Drs. Carlson, Kramer, &
Colcombe): Demographics of Intervention (N=8) & Controls
(N=9)
Preliminary Conclusions
• fMRI trial is feasible
• Change in patterns of activation are evident• Behavioral RT and fMRI data correspond in showing
improved ability to selectively attend during the most demanding condition
o Increased activity in attentional control regions suggests more successful filtering/inhibiting of conflicting information
o Corresponding reduction in dACC suggests better filtering of conflicting information
• Consistent with patterns observed in a 6-month physical activity intervention (Colcombe et al., PNAS 2003)
Some Challenges• What is the acceptable transfer mechanism? - Not much
consensus on the critical domains, e.g., ACTIVE• What is the time course of expected transfer? - May not
see immediate transfer to everyday outcomes. Are we building a “reserve” of maintained cognitive ability, which may be drawn upon in the future to attenuate the rate of decline?
• Do we need training at all? - Practice may be as effective as formal training; transfer effects may be narrower
• “Bottom-up” or “Top-down” interventions – Train at the level of complex activities or basic abilities
• Single-component or multi-component interventions• Mechanisms for the delivery of interventions – computer,
internet, video, peers/couples• Learning lessons from neurorehabilitation, education, and
physical exercise research about compliance, dosing, cross-training, coaching/monitoring, etc.
To Be Determined:
• What are the best methods for specific training outcomes?
• How can current cognitive theory inform cognitive training, and vice versa?
• How should we define successful training?• Who are the best candidates for successful
training?• Does cognitive training in later adulthood develop
cognitive reserve or serve a protective function?• How do we make training appealing, accessible,
and cost-effective?
Some Caveats• Training gains are of lower magnitude than many elderly,
patients, and caregivers expect and progress may not be steady; problem of raising “false hope” and “blaming the victim” for cognitive declines
• Training effects tend to be highly task-specific and show limited generalizability; effects are reasonably durable but maintenance doesn’t automatically occur.
• Training may not prevent cognitive decline, BUT it can boost performance and may delay normative cognitive decline.
• A few sessions of cognitive training may not be sufficient to alter the life course with respect to decline, BUT it may compress the point of disability into a smaller window at the end of life.
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