1

Computerized Cognitive Training Within Community Settings for Cognitively

Intact Older Adults

Karen J. Miller, Ph.D. & Gary Small, M.D.UCLA

Disclosure

Data presented on the Dakim BrainFitnessprogram in this presentation is from aprivately funded grant and study that wassponsored by Dakim, Inc.

Karen Miller, Ph.D.kmiller@mednet.ucla.edu310-267-2663

Memory System Theories

• Primary & secondary memory (James 1890)

• Procedural & declarative memory (Cohen & Squire, 1980)

• Explicit & implicit memory (Schacter et al., 1993)

• Episodic & semantic memory (Tulving, 1972, 1983)

• Working memory (Baddeley and Hitch, 1974)

• Sensory (iconic and echoic), short-term, and long-term memory (Atkinson and Shiffrin, 1968)

• Immediate, recent, and remote memory (Kirshner, 1986; Sttub and Black, 1993)

2

Learning:Creating a New Memory

1. Encoding – registration2. Rehearsal and Consolidation – repetition

and transfer3. Storage – retention4. Recall or Retrieval (free vs. cued)5. Recognition and False Positives

Nondeclarative vs. Declarative Memory

• Nondeclarative Memory - do not involve conscious recollections – but action/performance based tasks– often the focus of rehab interventions

• Declarative Memory – conscious recollections– Semantic memory (facts)– Episodic memory (single events)– Declines in both for MCI and AD– Target of memory training programs

Forms of Memory• Sensory Memory• Primary Memory• Secondary Memory• Tertiary Memory

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Memory Changes and Aging

• Sensory, Primary and Tertiary Memory– Show no or mild age effects

• Secondary Memory – RECALL most strongly affected by age

– Age-related effects relatively small

– 10% decline per decade beginning in midlife

– RECOGNITON remains stable during lifespan

Cognitive Changes Associated with Aging

• MetaMemory – self perceptions• Memory complaints (e.g., names, recent events)• Slowed learning• Delayed retrieval• Word-finding difficulties

Factors Affecting Memory

• Attention and distraction• Negative expectations• Stress and anxiety• Depression and loss• Fatigue and illness

• Nutrition• Alcohol• Medication• Inactivity• Lack of organization

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Cognitive Interventions

• Cognitive Stimulation - group discussions• Cognitive Rehabilitation – individualized

intervention programs – often TBI• Cognitive Training – improve specific

cognitive functions

Cognitive Training Approaches: Focusing on Memory Training

• Errorless Learning – errors are minimized while trying to learn new information

• Spaced Retrieval – expanded rehearsal – learning over increasingly longer periods

• Mnemonics – enhancing meaningfulness– Categorizing– Visual Imagery – Method of Loci– Face Name Association

Cognitive / Memory Training

• Direct Instruction within a classroom or one-on-one approach

• Computerized Cognitive Training, some of which is more cognitive stimulation based vs. a focus on improving specific cognitive functions

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ACTIVE Study:Willis et al, 2006; JAMA

• 5 year follow-up indicated that:– Reasoning training resulted in less functional

decline in IADL– Cognitive training resulted in improved

cognitive abilities for specific abilities trained: memory, reasoning, speed of processing

– 3 intervention groups vs. no-contact control group

Posit ScienceMahncke et al., 2006; PNAS

• Increasingly difficult tasks of stimulus recognition, discrimination, sequencing, memory

• Those with mild cognitive changes associated with age showed increase on all computer tasks, with improved attention for 3-month follow-up

• Intervention compared to active and no-contact control groups

IMPACT StudySmith, et al, 2009; JAGS

• Builds upon the initial Posit Science article• Multisite, randomized controlled double-

blind trail with 2 treatment groups: computerized cognitive training vs. cognitive stimulation program (active control)

• 40 hours of training – 1 hr sessions, 5 days, 8 weeks

• Improved auditory memory/attention + word list total recall and delayed recall + digits backward and LNS.

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UCLA’s Approach:The Past Decadde

• Research Study on Memory Training • Community Memory Training

Program, The Memory Bible• Memory Fitness Program for Erickson,

The Memory Prescription• Brain Boot Camp at UCLA• Dakim BrainFitness

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Domains & LevelsDOMAINS: • Short-Term Memory:• Critical Thinking:• Visuospatial:• Long-Term Memory:• Calculation:• Language:Approximately 300-400 events/games for each domain

5 levels for participants to begin at – events designed for increased difficulty for each level

Pilot Data: Study #1

• N of 22, Dakim intervention, active control watched videos

• 5 times a week, 30 minutes, 2 months• X age = 74, X ed = 14• Dakim group improved on working memory• Higher level playing Dakim subjects

improved on measures of visual and verbal memory

Pilot Data: Study #2

• Reviewed the content of Dakim, focus was initially on working memory and attention tasks vs. short-term and long-term memory tasks

• Added new events: learn a list of words, short story recall, visualize and associate – verbal pairs, recall face/names

• N of 8, 2 weeks, 5 sessions per week; no control group; X age was 80+

• Improved processing speed and verbal memory (measured by verbal pairs). On average recalled 5 word pairs vs. 3 at baseline for 30 minute delay

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“Clinical Trial” for Dakim:2 & 6 month Follow-up Study

• Screening (ACMI, MCI included), AD excluded• Pre-Testing – 2 hour NP battery • Randomized into Intervention / Control (wait list)• 5 sessions a week, 8 weeks = 40 sessions• 2 month testing• Enrolled everyone in Dakim’s BrainFitness• 6 month post-testing

Preliminary Analyses• Preliminary Analysis of subjects revealed better delayed

recall for list learning from the Hopkins Verbal Learning Test –revised

• ANOVA (N=41) for the Brain Fitness group compared to the control group (F (1,39) = 4.62, p=.04). HVLT-R: recall of 12 words after a 20-minute delay (3 learning trials). Dakim intervention group improved by recalling 8.3 words as compared to their initial recall of 7.6 words during baseline testing; control group declined, recalling on average 5.3 words during the post-testing as compared to the initial recall of 6.8 words. Alternative Formats were used and counterbalanced.

Present Analyses

• Final Analysis of 100 subjects on the 2 month data available at AAGP session

• 6 month data collection is presently underway, preliminary results for this will also be available at AAGP

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Memory Training• Dakim and most Memory Training Programs use the

following basics and advance techniques

• Basics - make information meaningful, relevant:– Pay attention– Associate– Use imagery

• Advanced Techniques: – Visualize and Associate– Story Method– Face Name Association

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1

Maintaining Brain Fitness and Avoiding Cognitive Decline:

What is the Evidence?

Chair: William E. Reichman, MD

Faculty: Mary Sano, PhDKaren Miller, PhDGary Small, MD

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The Brain Fitness Movement:Hope or Hype?

William E. Reichman, MD

President and Chief Executive OfficerBaycrest

Professor of PsychiatryUniversity of Toronto

3

An Increasing Focus onBrain Fitness vs. Brain Failure

Brain functioning can be strengthened throughout lifespan (neurogenesis and neuroplasticity)Risk factors for brain failure can be potentially mitigatedPathological changes of neurodegenerative diseases (AD, PD) might precede onset of clinical signs and symptoms by several years Brain imaging, cognitive stress tests, biomarkers may predict incident Alzheimer’s

Wojtowicz JM. In: Cognitive Neurorehabilitation. 2nd Ed. DT Stuss et al. eds., 2008. Cambridge University Press; Tierney MC et al. Neurology 2005 Jun 14;64(11):1853-9; Saxton J. et al. Neurology 2004 Dec 28;63(12):2341-7.

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Brain Fitness: The Opportunity

Impact Points:

Early DiagnosisTreatment and Rehabilitation

New preventions, interventions and maintenance programs can transform brain health.

PreventionStatus Quo

Low

High

Cog

nitiv

e St

atus

Age

30 40 50 60 70 80 90

Prevention

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Schematic Representation of theReserve Hypothesis

RESERVE

Pathogenesis Brain changesClinical

(cognitive)outcome

Brain reserve Cognitivereserve

Treatment/intervention

targets

Successful Cognitive and Emotional Aging, edited by Colin A. Depp, Ph.D., Dilip V. Jeste, M.D.; Chapter 9 Cognitive and Brain Reserve, Adam M. Brickman, Ph.D., Karen L. Liedlecki, Ph.D., Yaakov Stern, Ph.D., APA Press, 2010

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Schematic Representation of Passive and Active Models of Reserve

RESERVE

PassiveModels

ActiveModels

Brain reserve/Brain reserve

capacityCognitive reserve

Neural reserve Neural compensation

Increased efficiencyand capacity

Recruitment of brain areasnot typically used

• Cranial capacity• Neural density• Synaptic connectivity

Successful Cognitive and Emotional Aging, edited by Colin A. Depp, Ph.D., Dilip V. Jeste, M.D.; Chapter 9 Cognitive and Brain Reserve, Adam M. Brickman, Ph.D., Karen L. Liedlecki, Ph.D., Yaakov Stern, Ph.D., APA Press, 2010

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Brain Fitness Approaches

Techniques to assess and monitor cognitive performanceCognitive exercisesNutritional choicesLifestyle decisionsPhysical exerciseNeuroprotective agentsNeuroenhancing drugs

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The Goal of Brain Fitness

Optimize pre-clinical and clinical diagnostics

Maximize cognitive abilities− Attention and concentration− Executive functions

• Planning, organizing, mental flexibilityand information processing speed

− Memory

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Brain Fitness: Cognitive Exercisesand Neurorehabilitation

Pencil and paperpuzzles, games,brain teasers

Web-based applications, computer gamingMemory training exercises, programsMemory support software applications (PDA-based)

FROM THIS …. TO THIS ….

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Immediate and Delayed Effects of Cognitive Interventions in Healthy Elderly: A Review of

Current Literature and Future Directions

The existing literature is limited by a lack of consensus on what constitutes the most effective type of cognitive training, insufficient follow-up times, a lack of matched active controls, and few outcome measures showing changes in daily functioning, global cognitive skills, or progression to early AD

Papp KV, Walsh SJ, Snyder PJ Alzheimers Dement. 2009 Jan;5(1):50-60

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1212

5

1313

14

Promising marketplace…

Range of Projections for 2015

15

0

1000

2000

3000

4000

5000

2005E 2007E 2008E 2015P

4 billion

1 billion265225100

US$

(M)

Source: SharpBrains analysis

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Sustained Growth Thanks to Consumers and Healthcare/LTC Channels

Brain Fitness Market by Segment

16

0

50

100

150

200

250

300

2005E 2007E 2008E

Corp., Mil., Sports

K12 Education

Healthcare

Consumer

CAGR: 38%

Source: SharpBrains analysis

Rev

enue

in U

S$ (M

)

Snapshot of Customer Segments

Source: SharpBrains analysis17

Enhance professional task-related performance, such as decision making in sports performance. Establish cognitive baselines to better detect potential brain damage.

ACE, CogniFit, Cogstate2520

Corporate –Fortune 1000 Companies, Military & Sports Teams

Help to address cognitive problems such as dyslexia or strong reacting difficulties.

Earobics, Scientific Learning

6560K12 School Systems

Assess and train cognitive skills to identify/help alleviate cognitive symptoms, and to potentially improve driver safety.

BRC, CDR, Cogmed, Dakim, NovaVision, Posit Science

8065Healthcare & Insurance Providers

Provide a vehicle for mental stimulation, potentially enhancing/ maintaining cognitive abilities important for healthy aging.

CogniFit, Lumos Labs, Nintendo, Posit Science

9580Consumer

Value Proposition of Brain Fitness Programs

Selected Companies

Size US$ (M) (2008E)

Size US$ (M)

(2007E)

Customer Segment

The Research-Market Momentum Matrix

Source: SharpBrains analysis 18

DakimNintendoVivity Labs

Advanced Brain Technologies (ABT)Brain Center AmericaCNS Vital SignsCogStateLearning Enhancement Corporation (LEC)Vigorous Mind

LEADERSHIGH POTENTIALS

CROSSWORDS 2.0WAIT & SEE

Brain ResourceCognitive Drug Research (CDR)Lumos LabsPosit Science

Applied Cognitive Engineering (ACE)CogmedCogniFitHoughton MifflinNovaVisionScientific Brain Training (SBT)Scientific LearningTransAnalytics

MARKET MOMENTUM

RES

EAR

CH

MO

MEN

TUM

Lower Higher

Low

erH

ighe

r

7

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Cognition and Aging Commercial Opportunities

The cost of treating cognitive impairment is increasing by $45 billion per year worldwide, fueling the rapid growth of the global brain fitness market.

The global brain fitness market,which includes tools for cognitiveassessment, rehabilitation ofcognitive impairment, andsolutions to delay the onset ofdementia, is expected to reach$4 billion by 2010.

Baycrest creates Centre for Brain Fitness with $10-million investment from Ontario GovernmentApr 7, 2008 – 16:05 EST__________________________________________________________________________________________

TORONTO, April 7 /CNW/ - As Ontario braces for a doubling of its senior population over the next 20 years, it is turning to Baycrest to develop and commercialize a range of innovative products aimed at improving the brain health of aging adults.

Today the Ontario Government took a large step in this direction by announcing it is investing $10 million dollars to create the Centre for Brain Fitness at Baycrest.

“There are few things as frightening as the prospect of declining brain fitness as we age and the loss of our mental faculties,” said Dr. Tony Melman, Chair of Baycrest Board. “Baycrest’s strengths make it well positioned to develop innovative, market-driven research products that will transform the way we age.”

Baycrest will partner with the Toronto-based MaRS Venture Group to develop and market scientifically-proven products for the clinic, workplace and home environments.

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21

8

22

An Opportunity Seized

Creation of for-profit spin-out company

Cogniciti Inc.Partnership between Baycrest and MaRS with support from Ontario Government and private donors

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Gary Small, M.D.AAGP Symposium

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Can We Teach An Old Brain New Can We Teach An Old Brain New Technology Tricks?Technology Tricks?

Can We Teach An Old Brain New Can We Teach An Old Brain New Technology Tricks?Technology Tricks?

Gary Small MDGary Small MDGary Small, MDGary Small, MD

Director, UCLA Center on AgingDirector, UCLA Center on AgingSemel Institute for Neuroscience & Human Behavior Semel Institute for Neuroscience & Human Behavior

David Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLADivision of Geriatric PsychiatryDivision of Geriatric Psychiatry

DisclosuresDisclosuresDisclosuresDisclosuresSources of supportSources of support

NIA Program Project/R01 Grants, Alzheimer’s NIA Program Project/R01 Grants, Alzheimer’s Disease Research Center; Dept. of Energy; Disease Research Center; Dept. of Energy; Foundations (Ahmanson, Foundations (Ahmanson, ArchstoneArchstone, Brewster, Dana, , Brewster, Dana, HillblomHillblom); Endowments (); Endowments (ElgartElgart, Stark, , Stark, ParlowParlow--Solomon, Solomon, PlottPlott))

Consulting/SpeakingConsulting/SpeakingDakimDakim, Eisai, Forest, Mattel, , Eisai, Forest, Mattel, MedivationMedivation, Myriad, , Myriad, Novartis, OrthoNovartis, Ortho--McNeil, Pfizer, Radica Games, McNeil, Pfizer, Radica Games, Siemens, Starwood HotelsSiemens, Starwood Hotels

PatentsPatentsCoCo--inventor of FDDNPinventor of FDDNP--PET (Previously licensed to PET (Previously licensed to Siemens by UCLA)Siemens by UCLA)

Malleable Young BrainsMalleable Young BrainsMalleable Young BrainsMalleable Young BrainsUpsideUpside –– llearning is fastearning is fast

LanguagesLanguagesMusical instrumentsMusical instruments

DownsideDownside –– still a lot to still a lot to learnlearn

Frontal lobeFrontal lobeAmygdalaAmygdala

By adolescence, 60% of By adolescence, 60% of synapses are trimmed synapses are trimmed away or “pruned”away or “pruned”

Courtesy of A. Toga, P. ThompsonCourtesy of A. Toga, P. Thompson

Study of 197 students, age range 17 to 23 yrsStudy of 197 students, age range 17 to 23 yrs

Participants played video games and then watched Participants played video games and then watched a series of calm facial expressions morpha series of calm facial expressions morph

Participants were asked to rapidly identify the Participants were asked to rapidly identify the

How Does Technology Affect FaceHow Does Technology Affect Face--toto--Face Social Skills?Face Social Skills?How Does Technology Affect FaceHow Does Technology Affect Face--toto--Face Social Skills?Face Social Skills?

emotion during the morphemotion during the morph

KirshKirsh SJ, Mounts JRW. SJ, Mounts JRW. Aggressive Behavior Aggressive Behavior 2007;33:3532007;33:353--358.358.

Computer use associated with ADHD in elementary Computer use associated with ADHD in elementary school childrenschool children

> 1 hr video games per day> 1 hr video games per dayIncreases symptoms of ADHDIncreases symptoms of ADHD

Technology and Attention DeficitTechnology and Attention DeficitTechnology and Attention DeficitTechnology and Attention Deficit

Lowers overall GPALowers overall GPA

BUT BUT cause and effect relationship cause and effect relationship notnot certaincertain

Chan & Chan & RabinowitzRabinowitz. . Ann Gen Psychiatry Ann Gen Psychiatry 2006;5:16; 2006;5:16; YooYoo et al. et al. Psychiatry Psychiatry ClinClinNeurosciNeurosci 2004;58:4872004;58:487--94.94.

DIGITAL IMMIGRANTS: Who Are We?DIGITAL IMMIGRANTS: Who Are We?DIGITAL IMMIGRANTS: Who Are We?DIGITAL IMMIGRANTS: Who Are We?

We come to technology as adultsWe come to technology as adults

Our older brains may be slower to learn new Our older brains may be slower to learn new technologiestechnologies

More reluctant to embrace new technologiesMore reluctant to embrace new technologiesMore reluctant to embrace new technologies More reluctant to embrace new technologies and spend less time with theand spend less time with the

Our brains are gradually decliningOur brains are gradually decliningReaction timeReaction timeMemory abilityMemory abilitySensorimotorSensorimotor functionfunction

Gary Small, M.D.AAGP Symposium

2

Effect of Technology on the Brain: Effect of Technology on the Brain: Computer Use According to AgeComputer Use According to AgeEffect of Technology on the Brain: Effect of Technology on the Brain: Computer Use According to AgeComputer Use According to Age

60708090

% of people

0102030405060

18-29 30-39 40-49 50-64 65-74 75+

p pusing computers

Your Brain on Google: Patterns of Cerebral Your Brain on Google: Patterns of Cerebral Activation During Internet SearchingActivation During Internet SearchingYour Brain on Google: Patterns of Cerebral Your Brain on Google: Patterns of Cerebral Activation During Internet SearchingActivation During Internet Searching

InvestigatorsInvestigators: : Gary Small, Teena Moody, Prabha Siddarth, Susan Gary Small, Teena Moody, Prabha Siddarth, Susan BookheimerBookheimer

FundingFunding: : ParvinParvin FoundationFoundation

Published this month inPublished this month in: : American Journal of Geriatric Psychiatry American Journal of Geriatric Psychiatry 2009;17:1162009;17:116--126126

Subject GroupsSubject GroupsSubject GroupsSubject GroupsNet Naïve

(N=12)

Net Savvy

(N=12)

Average age (yrs) 65 62

Education (yrs) 18 17

% Female 92% 75%

Frequency of computer use* 1.9 ± 0.9 4.5 ± 1.2

Frequency of Internet use* 1.2 ± 0.4 4.5 ± 1.2

Self-rating of Internet expertise* 1.2 ± 0.1 3.6 ± 0.5

*P < .001*P < .001

Functional MRIFunctional MRIFunctional MRIFunctional MRI

Your Brain on GoogleYour Brain on GoogleYour Brain on GoogleYour Brain on Google

Net NaiveNet Naive

TextText InternetInternet

Net SavvyNet Savvy

Major FindingsMajor FindingsMajor FindingsMajor Findings

Net Net SavvysSavvys –– Internet vs. reading taskInternet vs. reading taskmore than twomore than two--fold greater extent of activation fold greater extent of activation than Net Naïvesthan Net Naïvesmuch greater activity in brain regions much greater activity in brain regions controlling complex reasoning/decisioncontrolling complex reasoning/decision--makingmaking

Mentally stimulating computer activities, like Mentally stimulating computer activities, like Web searching, engage complex neural Web searching, engage complex neural circuitscircuits

Gary Small, M.D.AAGP Symposium

3

Your Brain on Google Study Part 2Your Brain on Google Study Part 2Your Brain on Google Study Part 2Your Brain on Google Study Part 2

ComputerComputer--SavvySavvy

BaselineBaseline Practice 7 Days Practice 7 Days FollowFollow--UpUp

ComputerComputer--NaiveNaive

Moody et al. Neural activity patterns in older adults following Internet training. Moody et al. Neural activity patterns in older adults following Internet training. Society for Neurosciences. 2009Society for Neurosciences. 2009..

Brain Circuit Activation After Seven Brain Circuit Activation After Seven Hours of Internet SearchingHours of Internet SearchingBrain Circuit Activation After Seven Brain Circuit Activation After Seven Hours of Internet SearchingHours of Internet Searching

Moody et al. Neural activity patterns in older adults following Internet training. Moody et al. Neural activity patterns in older adults following Internet training. Society for Neurosciences. 2009Society for Neurosciences. 2009..

Computer Brain Training Alters Computer Brain Training Alters Neural CircuitryNeural CircuitryComputer Brain Training Alters Computer Brain Training Alters Neural CircuitryNeural Circuitry

Internet searching activates frontal circuits Internet searching activates frontal circuits (Small et al, 2008)(Small et al, 2008)

Video gaming increases and decreases activityVideo gaming increases and decreases activityFrontal circuitsFrontal circuitsAmygdalaAmygdala

Brain responses depend on Brain responses depend on contentcontent and and noveltynovelty of tasksof tasks

MathiakMathiak & Weber. & Weber. Hum Brain Hum Brain MappMapp. 2006;27:948. 2006;27:948--56; Matsuda & 56; Matsuda & HirakiHiraki.. .. NeuroImageNeuroImage. . 2006;29:7072006;29:707--11. 11.

tion

tion

Cognitive Cognitive efficiency with efficiency with task repetitiontask repetition

Neural Network Responses to Mental Neural Network Responses to Mental ChallengeChallengeNeural Network Responses to Mental Neural Network Responses to Mental ChallengeChallenge

Task strategy Task strategy engagementengagement

TimeTime

Bra

in A

ctiv

atB

rain

Act

ivat

Unfamiliar Unfamiliar tasktask

Cerebral Metabolic Effects of 14Cerebral Metabolic Effects of 14--Day Day Healthy Lifestyle Healthy Lifestyle Change in Cerebral GlucoseChange in Cerebral Glucose

Cerebral Metabolic Effects of 14Cerebral Metabolic Effects of 14--Day Day Healthy Lifestyle Healthy Lifestyle Change in Cerebral GlucoseChange in Cerebral Glucose

5% decline in left dorsolateral prefrontal cortex (5% decline in left dorsolateral prefrontal cortex (PP<0.0005)<0.0005)Small et al. Small et al. Am J Geriatr Psychiatry. Am J Geriatr Psychiatry. 2006;14:5382006;14:538--45; 45; Small G, Vorgan G. Small G, Vorgan G. The Longevity Bible.The Longevity Bible. Hyperion. New York. 2006.Hyperion. New York. 2006.

ConclusionsConclusionsConclusionsConclusions

Technology is not only changing our lives, it’s Technology is not only changing our lives, it’s changing our changing our BRAINSBRAINS

The new generation gap is a The new generation gap is a brain gap brain gap between digital natives and digital immigrantsbetween digital natives and digital immigrantsbetween digital natives and digital immigrantsbetween digital natives and digital immigrants

We We cancan find balance in our lives and bridge find balance in our lives and bridge the brain gap the brain gap

by improving technology and social skillsby improving technology and social skillsknowing when to use themknowing when to use them