Does Cognitive Stimulation Boost Effects of Neuropharmacology in Alzheimers

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Does Cognitive Stimulation Boost Effects of
Neuropharmacology in Alzheimers?
Sandra Bond Chapman, PhD Audette Rackley,MS
Executive Director, Center for BrainHealth
Cognitive-Communication Specialist Professor,
Behavioral and Brain Science UTD Center for
BrainHealth Dee Wyly Distinguished Chair in Brain
Health 214.905.3007 This research was
supported by a grant from Pfizer, Inc. and Eisai,
Inc.
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Objectives

• Discuss approaches to mitigate loss of function
  in AD
• Report findings of a randomized study in early
  stage AD
• Explanation of findings and extension of work
• Present implications for clinical practice

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3 Approaches to Treatment in AD

• Brain dysfunction Neurotransmitter deficit with
  Acetylcholinesterase inhibitors
• Direct cognitive intervention to improve or
  maintain function
• Caregiver training to reduce burden

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1. Acetylcholinersterase Inhibitor Aricept

• Well tolerated and easy to administer
• Higher mean level of performance in cognitive and
  global function over placebo
• Extended long-term potentiation decay times in
  hippocampus and neocortex in animal studies
• (Rogers et al., 1998 Barnes et al., 2000)

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One serious contender contributing to loss of
cognitive function in AD

• Loss of basal forebrain cholinergic neurons in
  early stages of AD
• Associated with decrease of choline-acetyltransfer
  ase
• Cholinergic dysfunction plays an important role
  in memory loss in Alzheimers
• Goal is to increase the acetycholine at synapse

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2. Direct Cognitive Intervention

• Improved cognitive functioning
• Active Cognitive Stimulation
• (Quayhagen et al., 1995)
• Enhanced communication
• Memory Wallets
• (Bourgeois and Mason, 1996)
• Long term maintenance of cognitive abilities
• Exercise Stimulation
• (Arkin 2001)
• Improved retention of names of common objects,
  face-name and object-location associations
• Spaced-Retrieval Interventions
• (Camp et al., , 1990, 1993, 1996)

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3. Caregiver Training

• Increased use of facilitation strategies
• Improved communication satisfaction
• Increased knowledge
• Altered caregiver attitudes
• (Ripich, 1994 Ripich et al, 1995)

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Expanding on Previous Studies

• Small sample size (n lt10)
• Few control groups
• Not randomly assigned to conditions
• Patients poorly characterized
• Responses are time limited and task specific

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Defining Effective Treatment in a Progressive
Brain Disease

• Prevent premature loss of abilities
• Delay the progression of the disease
• Decrease cost to patient and family
• Decrease cost to society
• Improve quality of life for patient and care
  partner
• Reveal a positive functional impact

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A Randomized StudyEffects of
Cognitive-Communication Stimulation for
Alzheimers Disease Patients Treated with
DonepezilSandra Chapman, Myron Weiner, Audette
Rackley, Linda Hynan, Jennifer ZientzJournal
of Speech. Language, and Hearing Research,47,
1149-1163
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Question Does cognitive-communication
intervention plus Aricept/ Donepezil impact
outcomes?

• We hypothesized that Donepezil paired with
  cognitive-communication stimulation would show
  benefit in 5 domains
• Relevance of verbalization
• Performance of functional abilities
• Emotional symptoms of irritability and apathy
• Quality of life
• Overall global function

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Study Parameters

• Random assignment
• Intervention Group
• (Aricept cognitive intervention)
• Non-Intervention Group
• (Aricept only)
• Evaluation administration
• Baseline (pre-test)
• 4 months (post test)
• 8 and 12 months (follow-up tests)

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Subject Characteristics

• Complete workup to indicate a diagnosis of
  probable Alzheimers disease
• Taking Aricept for at least 3 months
• MMSE of 14 or above
• Involvement of family caregiver
• Agreement to participate 1 year

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Subject Characteristics

• Acknowledgement of memory loss
• Diagnosis conveyed to patient
• Ability to converse
• Ability to read enough to follow written handouts
• Ability to sit for a period of 1 hour without
  problematic agitation
• English speaking
• Exclusion Criteria no head trauma, other
  neurologic disease, or psychiatric disease

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Group Characteristics
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Patient Measures
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Intervention Program

• Group Composition
• Six individuals with AD
• Project Coordinator (SLP)
• 3 masters level students
• Intervention (8 weekly sessions for 1 1/2 hours)
  
• Relevant verbal content
• Functional activities
• Quality of life

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Program Content
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Analyses

• I. All continuous variables were analyzed using
  ANCOVA
• Baseline variable was used as the covariate
• Between group factor was the group intervention
  vs. non-intervention
• Repeated measurements were the measures at 4, 8
  and 12 months
• II. Change scores (12-month measurements minus
  baseline) for continuous variables were
  calculated
• One-sample t tests were conducted to determine if
  the change for each group was significantly
  different from zero

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Relevant Verbal Content

• No significant difference for group, time, and
  interaction of group and time.
• However, average change from baseline showed
• a nonsig change in Intervention group
• A sig decline in Donepezil-only

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Functional Abilities

• No sig difference for group, time, and
  interaction
• Both showed decline from baseline, but Donepezil
  plus stimulation declined less

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Quality of Life IrritabilityNote A decrease
in NPI score signifies a positive change or
decrease in symptomatology

• A significant interaction of group by time for
  rating severity of behavior in individual

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Overall Global Function
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Interpreting Findings

• The most important findings from this study were
  positive outcomes when Donepezil paired with
  cognitive-communication stimulation
• Relevant discourse
• Functional abilities
• Emotional Well-being
• Global Function

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Does Cognitive Stimulation Boost Effects of
Neuropharmacology in Alzheimers?

• The intervention group showed slower rate of
  decline over time in discourse, functional
  abilities and psychiatric behaviors
• These effects were found with relatively
  short-term intervention 8 sessions/12 hours.
• The intervention showed effects that extended
  beyond the treatment and beyond the specific
  program

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Generalized BenefitsInterprete with Caution

• The intervention showed effects that
• Extended beyond the treatment and
• Generalized to areas outside the specific tasks
  of intervention, e.g.,
• Emotional symptoms irritability, apathy
• Functional Abilities
• Caution Effects were modest and did not improve
  memory function

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What is mechanism of cholinesterase inhibitor to
promote brain health?

• In other studies, treatment with Cholinesterase
  Inhibitor revealed
• Slower rate of decline in cerebral glucose
  metabolism on PET
• Increased cerebral glucose metabolism in right
  frontal region
• Positive correlation between changes in glucose
  metabolism and patients with higher doses
• Cholinesterase Inhibitors increases cerebral
  metabolism and is assoc. with cognitive benefits
  in mild AD over 12 month period
• Stefanova et al, Jr. of Neural Transmission, 2006

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What is mechanism of cholinesterase inhibitors
to promote brain health?

• Cognitive effects of treatment thought to be
  mediated by improvement in neuronal transmission
• Increase cortical metabolic response to
  activation

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How Could Cognitive Stimulation Boost Effects of
Neuropharmacology in Alzheimers?

• Drug increases brain metabolism that could
  provide environment to enhance plasticity even in
  progressive brain disease.
• Cognitive stimulation may be necessary to provide
  the necessary activation to maintain more intact
  and supporting brain networks.

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Clinical Implications of Study

• Intervention consisted of
• Meaningful conversation as opposed to drills
• Focus on preserved abilities rather than
  weaknesses
• Weekly homework assignments to promote carryover
  and increase involvement.

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Early Reframing of functionality may have Later
Benefits

• Unexpectedly, no differences were present at 4
  months (end of active stimulation)
• However, benefits were measured at 8 months after
  the active stimulation program ended.
• The intervention showed effects that extended
  beyond the treatment and beyond the specific
  program

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Factors that might enhance outcome

• Increase the dose (frequency of treatment) and
  evaluate response
• Add more Individualized treatment
• More integrated caregiver-patient training
• Intervene earlier
• Ecological validation of training transfer

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Limitations

• Participants were not blinded to group
  assignments
• Study may have attracted a select group of
  participants who had high hopes of benefit
• Not possible to always blind test administrators
  to group assignments.

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Using Functional Brain Imagingto study changes
in AD

• Reveal how brain is working when thinking in AD
• Indicate appropriate level of stimulation to
  engage brain
• Measure response to treatments

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• Evidence suggests Cognitive Stimulation could
  boost effects of neuropharmacology in
  Alzheimers.
• Dr. Sandra Bond Chapman
• Executive Director, Center for BrainHealth
• 2200 Mockingbird
• Dallas, Texas 75235
• 214.905.3007
• Centerforbrainhealth.org