Cognitive Behavioral Cognitive Behavioral

Management of Management of

ChemotherapyChemotherapy--Related Related

Cognitive DysfunctionCognitive Dysfunction

Robert J. Ferguson, Ph.D.Robert J. Ferguson, Ph.D.

Eastern Maine Medical CenterEastern Maine Medical CenterUniversity of Maine Dept. of Psychology, University of Maine Dept. of Psychology,

Dartmouth Medical SchoolDartmouth Medical School

Janet Bayleran, PhDJanet Bayleran, PhD

Theresa White, CCRPTheresa White, CCRP

Sandra Sigmon, PhDSandra Sigmon, PhD

Sharon LaBrie, MSSharon LaBrie, MS

Merrill Garrett, MDMerrill Garrett, MD

Thomas Openshaw, MDThomas Openshaw, MD

Christine Fink, PhDChristine Fink, PhD

Shawn Ell, PhDShawn Ell, PhD

Tim Ahles, PhDTim Ahles, PhD

Paul Jacobsen, PhDPaul Jacobsen, PhD

Brenna McDonald, PsyD, Brenna McDonald, PsyD,

MBAMBA

••QuestionsQuestions

–– How to manage the problem?How to manage the problem?

––What are the proposed treatment What are the proposed treatment approaches?approaches?

••Behavioral/Cognitive BehavioralBehavioral/Cognitive Behavioral

••Rehabilitation Rehabilitation

••Pharmacological Pharmacological

Rehabilitation: Parallel Worlds?Rehabilitation: Parallel Worlds?

•• Compensatory Compensatory

Strategies:Strategies:–– Learning adaptive strategies Learning adaptive strategies

with retained cognitive skills with retained cognitive skills

and functional reand functional re--organization organization

of the brainof the brain

–– Enhance performance on Enhance performance on

everyday tasks that require everyday tasks that require

remembering (Rohling, et al., remembering (Rohling, et al.,

2010; Wilson, 2005)2010; Wilson, 2005)

•• Cognitive Cognitive Retraining:Retraining:–– Directly retrain cognitive Directly retrain cognitive

processes to promote processes to promote repair of damaged repair of damaged circuitry or development circuitry or development

of new circuitry with of new circuitry with repetitive practicerepetitive practice

(Rohling, et al., 2010; (Rohling, et al., 2010; Roberston & Murre, Roberston & Murre, 1999)1999)

Pine Street Foundation, Pine Street Foundation, Becoming Your Own Advocate NewsletterBecoming Your Own Advocate Newsletter, 2005., 2005.

Adjusted ZAdjusted Z--transformed domain scores for transformed domain scores for

chemotherapy vs. local therapy groups.chemotherapy vs. local therapy groups.

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

VerbalAbility

VerbalLearning

VerbalMemory*

VisualMemory

Psycho-motor*

Motor Attention/Correct

Attention/RT

BlockDesign

Neuropsychological Domain

Local Therapy

Chemotherapy

Normal neuropsych testingNormal neuropsych testing

scores? scores?

What Impairment?!What Impairment?!

www.huricanevoices.orgwww.huricanevoices.org

Employment function Employment function TannockTannock & Vardy, 2007& Vardy, 2007

www.huricanevoices.orgwww.huricanevoices.org

Home function Home function TannockTannock & Vardy, 2007& Vardy, 2007

Diathesis Stress ModelDiathesis Stress ModelNon-cancer Twin-Twin B

Chemotherapy-treated Twin-Twin A

3-back>0-back2-back>0-back1-back>0-back

Memory and Attention Memory and Attention Adaptation Training Adaptation Training

(MAAT):(MAAT):A Brief Behavioral Skills Program A Brief Behavioral Skills Program

for Cancer Survivors with for Cancer Survivors with Attention and Memory Problems Attention and Memory Problems Associated with ChemotherapyAssociated with Chemotherapy

Robert J. Ferguson, Ph.D.*Robert J. Ferguson, Ph.D.*Behavioral Medicine Section Behavioral Medicine Section Dartmouth Medical SchoolDartmouth Medical SchoolRUNNING HEAD: Memory and Attention TrainingRUNNING HEAD: Memory and Attention Training**This is not a published document. Please do not reproduce or diThis is not a published document. Please do not reproduce or distribute stribute without permission of the author.without permission of the author.

CognitiveCognitive--Behavioral Approach to Behavioral Approach to

Management of Cognitive Management of Cognitive

ProblemsProblems

•• Education and Education and ““memory failure memory failure

reattributionreattribution””

•• SelfSelf--awareness trainingawareness training

•• SelfSelf--regulation and stress managementregulation and stress management

•• Cognitive Compensatory strategiesCognitive Compensatory strategies

Brief CognitiveBrief Cognitive--Behavioral Treatment ScheduleBehavioral Treatment Schedule

VISIT CONTENT 1

• TREATMENT OVERVIEW & PROVISION OF BOOKLET • EDUCATION ON MEMORY AND ATTENTION AND EFFECTS OF

CHEMOTHERAPY • SELF-MONITORING INSTRUCTION • RELAXATION TRAINING • HOMEWORK

PHONE CONTACT 1

• REVIEW HOMEWORK, PROBLEM SOLVE

2

• HOMEWORK REVIEW • COMPENSATORY STRATEGY(IES) SELECTION, INSTRUCTION,

AND REHEARSAL • HOMEWORK

PHONE CONTACT 2

• REVIEW HOMEWORK, PROBLEM SOLVE

3

• HOMEWORK REVIEW • COMPENSATORY STRATEGY SELECTION, INSTRUCTION,

AND REHEARSAL • ACTIVITY PACING AND SCHEDULING • HOMEWORK • OVERVIEW

PHONE CONTACT 3

• REVIEW HOMEWORK, PROBLEM SOLVE

4

• HOMEWORK REVIEW • COMPENSATORY STRATEGY REVIEW • ACTIVITY PACING AND SCHEDULING REVIEW • PLAN FOR RELAPSE PREVENTION • WRAP-UP

MedicationsMedications

•• dexmethylphenidate (ddexmethylphenidate (d--MPH; Focalin)MPH; Focalin)–– N = 152 doubleN = 152 double--blind placebo controlblind placebo control

–– 27.7 mg/day, patients with various cancers (non27.7 mg/day, patients with various cancers (non--CNS; CNS; n = 77 dn = 77 d--MPH; 7 placebo) > 2 months postMPH; 7 placebo) > 2 months post--chemochemo

–– 8 weeks d8 weeks d--MPH or placeboMPH or placebo

–– Improvements in fatigue (FACITImprovements in fatigue (FACIT--Fatigue) Fatigue)

–– and memory (High Sensitivity Cog. Screen)and memory (High Sensitivity Cog. Screen)

–– 40.8% headaches; 27.6% nausea40.8% headaches; 27.6% nausea

(Lower, et al., 2005)(Lower, et al., 2005)

MedicationsMedications

•• modafinil (Provigil)modafinil (Provigil)–– N = 68 Breast cancer survivors doubleN = 68 Breast cancer survivors double--blind placebo blind placebo controlcontrol

–– 22.8 months after chemotherapy22.8 months after chemotherapy

–– Improvements in speed of memory, continuity of Improvements in speed of memory, continuity of attention, and quality of episodic secondary memory attention, and quality of episodic secondary memory on computerized neurocognitive measure vs. placebo on computerized neurocognitive measure vs. placebo

–– (Cognitive Drug Research computerized assessment)(Cognitive Drug Research computerized assessment)

(Kohli, et al., 2007)(Kohli, et al., 2007)

““Levels of EvidenceLevels of Evidence”” and CBT and CBT

DevelopmentDevelopment

1.1. OneOne--group pilot studygroup pilot study

2.2. Waitlist Control Waitlist Control RCTRCT (absolute efficacy)(absolute efficacy)

-- (No longer recommended, Herbert, 2003)(No longer recommended, Herbert, 2003)

3.3. RCT with active control conditionRCT with active control condition

4.4. Component AnalysisComponent Analysis

CognitiveCognitive--Behavioral Treatment of ChemotherapyBehavioral Treatment of Chemotherapy--

Related Attention and Memory Problems Among Related Attention and Memory Problems Among

Breast Cancer Survivors: A Pilot StudyBreast Cancer Survivors: A Pilot StudyPI: Ferguson, R. J. CoPI: Ferguson, R. J. Co-- PI: PI: Ahles, T.A. Ahles, T.A.

NCI: 1 R03 CA090151NCI: 1 R03 CA090151--02; Lance Armstrong Foundation02; Lance Armstrong Foundation

•• One group pilot design (feasibility, satisfaction)One group pilot design (feasibility, satisfaction)

•• Baseline, postBaseline, post--treatment, 2treatment, 2--month followmonth follow--upup

•• N = 29, Stage I, II BCA, no CNS tx, intrathecal tx, or N = 29, Stage I, II BCA, no CNS tx, intrathecal tx, or psychiatric, substance abuse, neurologic psychiatric, substance abuse, neurologic

•• Mean Age = 56 (7.81), mean IQ, est: 112.82, 15 yrs eduMean Age = 56 (7.81), mean IQ, est: 112.82, 15 yrs edu

•• YearsYears--post chemotherapy: 8.2 (4.4)post chemotherapy: 8.2 (4.4)

•• OUTCOMES:OUTCOMES:–– Improved Multiple Abilities SelfImproved Multiple Abilities Self--report Questionnaire (MASQ)report Questionnaire (MASQ)

–– Improved CVLTImproved CVLT--II Total Score (54, 55, 61, 59)II Total Score (54, 55, 61, 59)

–– Digit Symbol, Stroop, TrailDigit Symbol, Stroop, Trail--making improvementsmaking improvements

–– High Satisfaction 7.14 (1.09) 0High Satisfaction 7.14 (1.09) 0--8 rating8 rating

““Behavioral Management of Cognitive Behavioral Management of Cognitive Impairment Associated with Impairment Associated with ChemotherapyChemotherapy””

Lance Armstrong FoundationLance Armstrong FoundationR. Ferguson, PIR. Ferguson, PI

INCLUSIONINCLUSION

•• diagnosis of stage I and II breast cancer; diagnosis of stage I and II breast cancer;

•• at least 18 months postat least 18 months post--treatment currently disease free (not treatment currently disease free (not excluding individuals on hormonal therapies such as selective excluding individuals on hormonal therapies such as selective estrogen receptor modulators); estrogen receptor modulators);

•• treatment involved standard dose adjuvant chemotherapy; treatment involved standard dose adjuvant chemotherapy;

•• complaint of memory and attention following chemotherapy; complaint of memory and attention following chemotherapy;

•• able to speak read English;able to speak read English;

•• at least 18 years of age at diagnosis and able to provide informat least 18 years of age at diagnosis and able to provide informed ed written consent. written consent.

EXCLUSIONEXCLUSION

•• history of CNS disease; history of CNS disease;

•• history of CNS radiation, intrathecal therapy or CNShistory of CNS radiation, intrathecal therapy or CNS--involved involved surgery; surgery;

•• neuroneuro--behavioral risk factors such as traumatic brain injury, history behavioral risk factors such as traumatic brain injury, history of neurological disorder, learning disability or substance addicof neurological disorder, learning disability or substance addiction; tion;

•• current psychiatric disorder. current psychiatric disorder.

Outcome MeasuresOutcome Measures•• Multiple Abilities SelfMultiple Abilities Self--Report Questionnaire (MASQ)Report Questionnaire (MASQ)(Seidenberg, Haltiner, Taylor, Hermann, & Wyler, 1994)(Seidenberg, Haltiner, Taylor, Hermann, & Wyler, 1994)

–– 48 items, 5 pt Likert scale, almost always/never48 items, 5 pt Likert scale, almost always/never

–– Language, visualLanguage, visual--perceptual, visual memory, attention, verbal perceptual, visual memory, attention, verbal memorymemory

•• Quality of LifeQuality of Life--Cancer Survivor Scale (QOLCancer Survivor Scale (QOL--CS)CS)(Ferrell, Dow, & Grant, 1995)(Ferrell, Dow, & Grant, 1995)

–– 41 items, physical, psychological, social, spiritual scales41 items, physical, psychological, social, spiritual scales

–– 00--10 Likert scale10 Likert scale

•• CESCES--DD--StateState--Trait AnxietyTrait Anxiety

Outcome MeasuresOutcome Measures

SatisfactionSatisfaction

•• General (0 = not at all satisfied; 8 = completely General (0 = not at all satisfied; 8 = completely

satisfied)satisfied)

•• Improving Improving or helping to or helping to compensate forcompensate for

problems of memory and attention (0 = not at all problems of memory and attention (0 = not at all

helpful; 8 = completely helpful)helpful; 8 = completely helpful)

Outcome MeasuresOutcome MeasuresNeuropsychological Neuropsychological

Verbal DomainVerbal Domain

CVLTCVLT--2 Total Score2 Total Score

Processing SpeedProcessing Speed

Trail Making NumberTrail Making Number--Letter SwitchingLetter Switching

Stroop ColorStroop Color--Word Word

Stroop ColorStroop Color--Word SwitchingWord Switching

Digit SymbolDigit Symbol

SatisfactionSatisfaction

•• Mean General Satisfaction ratingMean General Satisfaction rating

–– 7.0 (7.0 (SD SD = 1.05; 0 = not at all satisfied; 8 = completely = 1.05; 0 = not at all satisfied; 8 = completely

satisfied)satisfied)

–– compensatingcompensating for daily memory failures for daily memory failures

((MM = 6.7; = 6.7; SDSD = 1.54)= 1.54)

–– improvingimproving memory (memory (MM = 5.2; = 5.2; SDSD = 1.59) = 1.59)

( 0 = not at all helpful; 8 = completely helpful) ( 0 = not at all helpful; 8 = completely helpful)

5 Top5 Top--rated strategies included:rated strategies included:0 = Not at all helpful; 4 = Completely helpful0 = Not at all helpful; 4 = Completely helpful

1.1. applied relaxation methods (selfapplied relaxation methods (self--regulation, regulation,

arousal reduction) arousal reduction) 3.63.6

2.2. using a schedule or day planner/organizerusing a schedule or day planner/organizer

3.3. verbal rehearsal methodsverbal rehearsal methods

4.4. activity pacing and scheduling activity pacing and scheduling

5.5. selfself--instructional traininginstructional training 3.03.0

ConclusionsConclusions

and Limitationsand Limitations

•• It appears that MAAT (CBT) may be effective It appears that MAAT (CBT) may be effective

to help improve to help improve coping and selfcoping and self--managementmanagement

of chemotherapy cognitive changeof chemotherapy cognitive change

•• Some evidence of verbal recall improvementSome evidence of verbal recall improvement

•• Participants are satisfiedParticipants are satisfied

•• Effect sizes are comparable, if not larger, than Effect sizes are comparable, if not larger, than

many cognitive rehabilitation interventions many cognitive rehabilitation interventions

(fair comparison?)(fair comparison?)

ConclusionsConclusions

and Limitationsand Limitations

•• The study was small, underpowered and The study was small, underpowered and

required linear interpolationrequired linear interpolation

•• No active treatment controlNo active treatment control

•• One clinician completed all treatment (RF)One clinician completed all treatment (RF)

•• More precise outcome measures: More precise outcome measures:

–– Improved measures of QOL impact: FACTImproved measures of QOL impact: FACT--Cog; Cog;

MIAMIA--AnxietyAnxiety

–– neuropsychological measures, secondaryneuropsychological measures, secondary

–– Memory selfMemory self--efficacy?efficacy?

Treatment Summary

Brief

Educational,

group format,

practice,

mastery

experience

More

research

needed

May not

improve

verbal

memory NP

performance

Visual-motor

speed (brief

visuospatial

memory test)

Daily

cognitive

complaints

Memory Self-

efficacy

Older adults

Mean age 82

11 cancer

survivors,

8 women;

3men

84 years

12Group CBT, face

to face

Eight 90-minute

visits

Compensatory

4 components:

1. Stress inoc.

2. Health Prmtn

3. Self-efficacy

4. Strategy trng

CBMEM

Cognitive

Behavioral

Model of

Everyday

Memory

(McDougall, et

al., 2011)

Pros & ConsTargeted

Outcomes

PopulationHours of

Contact

Type/FormatIntervention

Name

Treatment Summary

Longer but

Home-based

Does not

require visits

Does improve

auditory

processing

speed, likely

verbal-

auditory NP

performance

May not fully

generalize to

real world

application (?)

Adverse

events,

headache,

pain (34 of

487-7%)

RBANS

auditory

memory,

Processing

speed

.87

Overall

memory .30

Word list

delayed recall

.20

Older adults

Mean Age

75.3 (6.45)

40 Self-

administered,

Computer-based

40, 1-hour

sessions (5d/wk;

8wks),

Training (85%

adjusted

performance)

4 of 6 exercises

per session

Auditory

processing

speed training

(Cognitive

Stimulation)

Brain Fitness

Program, Posit

Science

(IMPACT

study)

Exp. Tx (ET)

Active Cont.

(AC)—

educational

DVD w/

quizzes

No Contact

cont. (NCC)

Pros & ConsTargeted

Outcomes

PopulationHours of

Contact

Type/FormatIntervention

Name

Future DirectionsFuture Directions

•• Increase MAAT Increase MAAT ““dosingdosing”” 8 visits8 visits

•• An active treatment RCT is needed with larger numbers and An active treatment RCT is needed with larger numbers and multiple cliniciansmultiple clinicians–– MAAT vs. Supportive Psychotherapy (Borkovec) or POSITMAAT vs. Supportive Psychotherapy (Borkovec) or POSIT--Science Science

•• FACTFACT--Cog (QOL impact), MIACog (QOL impact), MIA--A as the principal outcomesA as the principal outcomes–– This will also aid inclusion criteria This will also aid inclusion criteria

•• MAAT MAAT –– electronic? on line, Ielectronic? on line, I--phone based, Video conferencephone based, Video conference

•• Applied to Applied to –––– Other cancer treatments that contribute to cognitive impairmentOther cancer treatments that contribute to cognitive impairment

–– CNS diseaseCNS disease--related cognitive impairmentrelated cognitive impairment

–– MTBIMTBI

When in doubt, more cowbellWhen in doubt, more cowbell