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Food for thought: Psychological approaches to cognitive decline in schizophrenia. Til Wykes Institute of Psychiatry King’s College London. June 2011. What happened in the last century?. UK reduced the number of inpatient beds 140,000 in 1950s to 40,000 in 1994 Long stay hospitals closed

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food for thought psychological approaches to cognitive decline in schizophrenia

Food for thought: Psychological approaches to cognitive decline in schizophrenia

Til Wykes

Institute of Psychiatry

King’s College London

June 2011

what happened in the last century
What happened in the last century?
  • UK reduced the number of inpatient beds
    • 140,000 in 1950s to 40,000 in 1994
  • Long stay hospitals closed
    • To reduce institutionalism
  • Increased care opportunities in the community
    • To increase assimilation
  • Rehabilitation options
    • To improve work outcomes and daily living skills
where did that leave people with a diagnosis of schizophrenia
Where did that leave people with a diagnosis of schizophrenia?
  • Still a high cost of acute care beds in UK
    • £652m : 5.4% all UK NHS costs
  • No improvements in social outcomes (Mason et al, 1996)
  • Poor employment record
  • High re-admission rates, particularly following a first episode
in the usa for serious mental illness
In the USA for Serious mental illness
  • $193.2 billion in lost earnings
  • $100.1 billion in Health care
  • $24.3 in disability benefits
  • Grand total --- $317.6 billion

Kessler et al, AJP 2008

slide5
Aims
  • Do people with a diagnosis of schizophrenia experience cognitive problems?
  • Are these cognitive problems important for recovery?
  • How might we treat them?
slide6

Between episodes

“My concentration is very poor. I jump from one thing to another. If I am talking to someone they only need to cross their legs or scratch their head and I am distracted and forget what I was saying.”

McGhie and Chapman, 1961

slide7

During an episode

“Where did all this start and could it possibly have started the possibility operates some of the time having the same decision as you and possibility that I must now reflect or wash out any doubts that’s bothering me ……”

From Wykes and Leff, 1982

slide8
“I was looking at A or B for some subjects now I’m looking at C or D if I’m lucky.”

“Memory loss is the new thing that’s bothering me.”

“I have low concentration”

“I’m coming to terms with the fact that I have got a learning difficulty.”

Michael, Aged 16 years

Inside my head - Channel 4, June 2002

First episode

do cognitive problems predate the onset of disorder
Do cognitive problems predate the onset of disorder?
  • Jones et al (1998, 2000)
    • UK Birth cohort
    • Cognitive abnormalities in children pre-schizophrenia
  • Lewis et al (1998, 1999)
    • Conscripts in Denmark
    • Lower IQ in conscripts pre-schizophrenia
  • Cannon M. et al (2001)
    • New Zealand birth cohort
    • Cognitive difficulties at all stages pre-schizophrenia
slide10

Learning from service users

“I want to be able to do things that other people do, like have a boyfriend and a job …”

Vocational Functioning

“I want to have friends”

Social functioning

“I want to be able to cook and eat when I want”

Life skills

“I want to live in my own place not a hostel”

Dependence on services

slide11
Work

From Bell et al (2001)

Cognitive variables (in yellow)

Memory, Attention, Flexibility, Learning

What did symptoms add?

Nothing

social functioning
Social functioning
  • What effect do positive symptoms add?
  • NOTHING
life skills
Life Skills

Velligan et al 1999

Positive

symptoms

Life

skills

Cognition

Negative

symptoms

life skills1
Life Skills

Velligan et al 1999

Positive

symptoms

Life

skills

Cognition

42%

Negative

symptoms

dependence on care the netherne series
Dependence on careThe Netherne Series

Wykes, Katz, Hemsley, Dunn & Sturt, 1990 -1994

Thinking flexibility

Positive

symptoms

Dependence on

psychiatric services

60%

Negative

symptoms

Length of illness

Previous skills

average weekly costs for service users in sl m nhs trust
Average weekly costs for service users in SL&M NHS Trust

Wykes, Reeder, Williams, Corner, Rice and Everitt, 2003

slide17

Thinking, symptoms and outcomes

Occupational Functioning

Cognition

Social

Functioning

Positive and/or

negative symptoms

Life Skills

Dependence on

psychiatric care

slide18

Thinking, symptoms and outcomes

Occupational Functioning

Cognition

Social

Functioning

Positive and/or

negative symptoms

Life Skills

Dependence on

psychiatric care

Perlick et al, 2008

community activities
Community activities

Bowie et al 2006

what do we know about cognition in schizophrenia
What do we know about cognition in schizophrenia?
  • Definition of schizophrenia
    • Cognition is important (Kraepelin and Bleuler)
    • DSMV considering cognition as a diagnostic adjunct
  • Cognitive disturbances present
    • before onset
    • during episodes
    • between episodes of acute symptoms
summary cognitive difficulties experienced by people with schizophrenia
Summary: Cognitive difficulties experienced by people with schizophrenia
  • Speed
  • Memory
  • Attention
  • Reasoning
  • Tact/Social cognition
  • Synthesis

© Keshavan

about cognitive difficulties in schizophrenia
About cognitive difficulties in schizophrenia
  • Start early – before onset
  • Persist even when symptoms are absent
  • Interfere with functioning outcomes
  • Not related to medication (although it can make them worse)
pharmacological treatments for cognition
Pharmacological Treatments for Cognition

1

0.9

(L)

)

0.8

d

0.7

0.6

(M)

0.5

Effect Size (Cohen's

0.4

0.3

(S)

0.2

0.1

0

Antipsychotics

(Keefe

d-Cycloserine

Glycine

Galantamine

PracticeEffect

(Buchanan et

(Buchanan et

(Buchanan et

(Goldberg et

et al., 2007)

al., 2007)

al., 2007)

al., 2008)

al., 2007)

© Keshavan

the basis of clinical decisions isaacs and fitzgerald bmj 1999
The basis of clinical decisionsIsaacs and Fitzgerald BMJ 1999
  • Eminence
    • seniority of the protagonist with a touching faith in clinical experience
  • Vehemence
    • Volume substitutes for evidence
  • Eloquence
    • Good dress sense and verbal skill
  • Confidence
    • Only applicable to surgeons
  • Evidence
    • Randomised controlled trials, meta-analyses
what does this mean for treatments
What does this mean for treatments?
  • Methodologically rigorous evaluation to assess success
  • Evidence of how to match therapy to patients
  • Treatments are feasible and acceptable
  • Avoiding:
    • Presumptions such as statistical significance is the same as clinical significance
  • Preventing treatment failure
slide27

‘Scientific evidence has shown

that regular brain training, as

offered by the CD, can help defer

the onset of age-related brain decline’

“prevent brain ageing, .. improve memory".

26th Feb 2009

Nintendo brain-trainer 'no better than pencil and paper'

Brain training? Think again, says study

Experts say they are no better than a crossword

'Brain training' claims dismissed

slide28
Few reports in the peer reviewed literature

Experimental data was not collected on the specific training product

When there was a study

No independent data

Studies often had no control group

Improvements in performance on the task only (practice)

When there was a comparison group

No differences between the product and comparison groups

Comparison group was better

Why?

26th Feb 2009

brain training tested
Brain training tested
  • 11,000+ participants (normal people?) randomly assigned to:
  • 2 Expt groups
    • Playing specially designed games for reasoning and problem solving
    • Wide range of games similar to commercial software
  • Control group
    • Surfed the web to answer obscure questions but no games
  • at least 10 mins per day 3 times per week for 6 weeks
  • Looked at generalisation to other tasks
  • RESULTS
  • No evidence that brain training worked
  • Despite improvements on trained tasks there was no improvement in the generalisation tasks – more than the control

Owen et al, Nature May 2010

slide31

Can we change cognition?

  • Cognitive rehabilitation for schizophrenia: Is it possible? Is it necessary?
          • Bellack, 1992
  • Cognitive Remediation in schizophrenia: Proceed … with caution!
  • Hogarty and Flesher, 1992
why was there therapeutic pessimism
Why was there therapeutic pessimism?
  • Cognitive difficulties are
    • part of the diagnosis genesis (Kraepelin and Bleuler)
    • apparent before onset (Cannon et al, 2001)
    • Cross-sectional studies and longitudinal studies show few changes over time except in some elderly patients
  • But stability does not mean immutability
what is cognitive remediation therapy crt
What is Cognitive Remediation Therapy (CRT) ..
  • Is a therapy
  • Designed to improve cognitive processes
  • Such as: attention, memory, executive, social cognition and metacognition
  • Involves training

Cognitive Remediation Experts Workshop (CREW) Florence April 2010

what has been developed
What has been developed?
  • Cognitive rehabilitation programmes:
    • Neurocognitive Enhancement Therapy (NET)
    • Computer Assisted Cognitive Remediation (CACR)
    • Brain Fitness
    • NEAR
    • REHACOM
    • COGREHAB
    • Cognitive enhancement Therapy (CET)
    • IPT
    • Cognitive Remediation Therapy - CIRCuiTS
training usually involves
Training usually involves ….

Errorless learning

Trying not to allow errors

Keeps reinforcement high and learning accurate

Verbal monitoring

Overtly then covertly

Scaffolding

So that tasks are always a manageable challenge

what do people think they are changing
What do people think they are changing?
  • The brain
    • Neuroplasticity (a bit vague but somehow to increased the potency of some connections)
  • Cognition
    • Specifically to increase the use of sustained attention, cognitive flexibility
  • Metacognition
    • Increase the use of metacognitive knowledge or regulation (knowing what you know and how to use this information)
does it work meta analysis of crt studies
Does it work?Meta-analysis of CRT studies
  • Studies had a random allocation procedure
  • CRT vs any control
  • Contact with all major contributors
  • 40 treatments in 39 trials in 109 reports

Til Wykes, Vyv Huddy, Caroline Cellard, Susan McGurk, Pal Czobar (2011)

slide41

Issue date: March 2009

Schizophrenia

Core interventions in the treatment and management of schizophrenia in adults in primary and secondary care

This is an update of NICE clinical guideline 1

NICE clinical guideline 82

Developed by the National Collaborating Centre for Mental Health

www.nice.org.uk

ctam total score 100
CTAM – total score 100
  • Sample
  • Allocation
  • Assessment
  • Control
  • Analysis
  • Treatment Description

Thornley & Adams, 1998

Moher et al, 1998, 1995

Marshall et al, 2000

Schultz et al,

Chalmers et al 1981

Jadad et al, 1996

Juni et al, 1999, 2001

Kazdin and Bass, 1989

Sterne et al, 2002

Added

Therapy description

manual

treatment fidelity

Wykes et al, 2008; Tarrier and Wykes 2004

clinical trials rating ctam 40 studies
Clinical Trials rating (CTAM*)40 studies
  • CRT mean score 57 (35-87)
  • CBTp mean score 61 (27-100)
    • Not different from each other

*Tarrier and Wykes, 2004; Wykes et al, 2008

effect of methodology on cbtp outcome1
Effect of methodology on CBTp outcome

*

Better method

* Only target (positive) symptoms show significant effect

Wykes et al 2008

effect of method on crt outcome1
Effect of method on CRT outcome

*

*

Better method

Wykes et al 2011

do crt effects last
Do CRT effects last?

Wykes et al 2011

do crt effects last1
Do CRT effects last?

Durable change

Wykes et al 2011

are changes large enough
Are changes large enough?

Changes from poor to normal performance

MEMORY

(within one standard deviation

of the normal digit span score)

Numbers of people with poor memory

Baseline N: CRT 21,Control 18,

Post-treatment N: CRT 12 Control 16

Fisher exact test p=0.037,

Number needed to treat = 3.1

Wykes, Reeder, Landau, et al 2007

slide53

Tangible effects - Reducing failurePeople who have already failed in supported employment

McGurk et al, 2007

are any crt differences important
Are any CRT differences important?

Group vs individual

Paper and pencil vs Computer

Therapist present vs absent

Integrated into services or stand alone

Embedded in skills training vs not

Type of training employed:

drill and practice

practice + strategic learning (use of metacognition)

metacognition
Metacognition
  • Metacognition: ‘thinking about thinking’
    • Metacognitive skills: the ability to reflect upon one’s own thinking
    • Metacognitive knowledge: knowledge about

(i) one’s own cognitive abilities

(ii) the sorts of cognitive abilities needed for a particular task

(iii) knowledge about thinking in general

slide56

CRT aimed at meta-cognitive skills should…

  • KNOWLEDGE ABOUT THINKING
  • Awareness of strengths and weaknesses
  • Database of strategies

Thrive in Job

REGULATION

3. When and where to apply strategies

evidence for a role of meta cognition and social functioning
Evidence for a role of meta-cognition and social functioning

Metacognition measures

Using WCST

Around 0.5 or more ***

Cognition

WCST Categories and perseverative errors

Social Functioning

GAF, Life Skills

Particularly social contacts and total scores

Stratta et al, 2009

do the differences really matter
Do the differences really matter?

Strategic approach only produced a significant functional effect

DP=0.34 (95% CI -0.11, 0.78); SC+=0.47 (95% CI 0.22, 0.73)

Adjunctive psychiatric rehabilitation increases functional gains

Rehab=0.59 (95% CI 0.30, 0.88); CRT only=0.28(95% CI -0.02, 0.58)

SC+

Rehab

DP+

Rehab

Effect sizes when rehab provided

does anything predict crt response
Does anything predict CRT response?
  • Age
    • Older people do not improve as much (Wykes et al 2010; McGurk et al, 2009; Kontis et al, 2011)
  • Stable symptoms
  • Cognitive reserve
    • grey matter density related to increased effect (Eack et al, 2010)
    • Also premorbid IQ affects outcome (Kontis et al, submitted)
we need to know more
We need to know more
  • How does CRT improve functioning?
  • How much improvement is important?
  • Which improvements are important?
does cognitive improvement drive functioning improvement
Does cognitive improvement drive functioning improvement?
  • People receiving cognitive remediation and supported work (paid or voluntary)
  • Measured
    • Cognition
    • Work quality
a process model
A process model

Cognitive Flexibility

Memory

Planning

WORK

quality

CRT

Til Wykes, Clare Reeder, Vyv Huddy, Christopher Rice, Rumina Taylor, Helen Wood, Natalia Ghirasim, Dimitrios Kontis and Sabine Landau

so what next
So what next?
  • A therapy based on metacognition and strategy use
  • Which service users value
  • Which is more feasible?
computerised therapy
Computerised therapy

CIRCuiTS

Computerised Interactive

Remediation of Cognition –

Training for Schizophrenia

Wykes, Reeder, Bjorkland, 2010

improving metacognition
Improving metacognition
  • Strategy-use integral to task completion
  • Before beginning a task
    • Rate expected difficulty
    • Rate expected time to complete task
  • On completing the task
    • Score given
    • Rate usefulness of strategies
    • Rate actual difficulty of the task
    • Actual time taken shown
an exercise
An exercise
  • Ecologically valid – map on to real-life activities
  • Mainly reliant upon multiple executive functions
  • Fall under functioning categories:
    • Work
    • Social situations
    • Cooking and shopping
    • Travelling
what now
What now?
  • Can health services afford them?
  • Our paper and pencil therapy costs about £580 per person
  • Graduate psychologists, clinical psychology supervision
adjusted costs post treatment
Adjusted costsPost-treatment

Costs in £s

Baseline adjusted mean costs

Advantage for CRT - £1086 in health care & £1284 in societal costs, adjusted for baseline costs and PANSS scores: 95% CI skewed but ns

Wykes, Patel, Knapp et al, 2007; Patel et al, 2009

learning from service users wykes et al 2007 study
Learning from service usersWykes et al 2007 study

“When you improved in therapy then you felt good about yourself but when you didn’t improve you felt much worse”

  • If memory improves at post-treatment then
    • self esteem improved(mean change 1.5 points)
  • But when no memory improvement
    • self esteem got worse(mean change -3.5 points).

Rose et al 2008

summary
Summary
  • Cognitive difficulties interfere with recovery
  • Cognitive remediation therapy
    • improves cognition and functioning
    • but not symptoms after therapy has ceased
  • CRT plus rehab gives the best result
thanks to a little help from my friends
Thanks to a little help from my friends
  • Clare Reeder
  • Kathy Greenwood
  • Vyv Huddy
  • Sabine Landau
  • Rumina Taylor

In particular for the CIRCuiTS trial

happy birthday
Happy Birthday

23rd June

Bethan