- Cambridge Cognition

Report
Assessing Cognition
10th September 2014, v1.0 draft
Aims of this resource
This presentation provides an overview of the assessment of cognition, and has been
designed for post-graduates and PhD students.
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Page 2
Summary of contents
• Discussion of different reasons for assessing cognition – perspective of society/groups
and of individuals, with examples:
• Understanding relationships between cortico-subcortical circuitry,
neuromodulators, and behaviour
• Study gene by environment interactions
• Identify and treat cognitive problems across a multitude of disorders
• Occupational uses: impact of sleep deprivation in military personal;
enhancing cognition in sleep-deprived doctors
• Individual level: early detection of dementia
• Consideration of what would make an ‘ideal’ set of cognitive tests
• Pros and cons of different methods of cognitive assessment (clinician rated versus
self-report; pen & paper versus computerized)
• Introduction to the CANTAB method of cognitive assessment, exemplified with the
CANTAB ADHD battery
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Why assess cognition?
Cognitive assessment refers to the objective measurement of distinct cognitive
abilities, such as working memory, inhibition, cognitive flexibility, and executive planning
Cognitive functioning is critical for day-to-day life, governing our thoughts and
actions
Reasons for assessing cognition can be considered from different vantage points:
- Perspective of society (and of groups)
- Perspective of the individual
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Why assess cognition?
Perspective of society
Understand key aspects of human and animal behavior, and how this arises from distinct
circuits and neurotransmitters in the brain1
neuromodulators
1Arnsten
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et al., Bio Psych, 2011
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Why assess cognition?
Perspective of society
Understand how genetic and environmental factors can influence brain function across
the lifespan
Genetic factors
•
Gene variants
•
Gene expression
Assessing Cognition © Cambridge Cognition 2014. All rights reserved
Environmental factors
e.g.
•
Stress
•
Trauma
•
Inflammation
•
Diet and drug use
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Why assess cognition?
Perspective of society
Example: studies have identified negative effect of maternal smoking on subsequent
cognitive abilities in infancy / early childhood, which can be influenced by genes1
Genetic factor
GSTM1
polymorphism (codes
for enzyme involved
in breakdown of
tobacco by-products)
Environmental factor
Maternal smoking
Maternal smoking in women with a defective form of
GSTM1 gene polymorphism was associated with worse
cognition in children, when assessed four years after
birth.
1Morales
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et al., Int J Epidem, 2009
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Why assess cognition?
Perspective of society
Example: the Apolipoprotein E4 gene (APOE4) is involved in lipid metabolism and is
widely studied as a risk factor for cognitive decline in older age (including dementia)1
Genetic factor
Environmental factor
APOE4 gene
Cortisol level (stress axis)
Higher levels of cortisol were associated with worse
cognition in community dwelling older adults; however,
this relationship was particularly strong in individuals
with at least one APOE4 allele
1Lee
et al., Am J Psych, 2008
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Why assess cognition?
Perspective of society
Cognitive assessment is invaluable for understanding the role of brain dysfunction
across a multitude of disorders/syndromes
Examples of conditions in which cognitive impairment can occur:
Alzheimer's disease
Mild cognitive impairment
Depression
ADHD
Schizophrenia
Pain
Sleep disorders
Down's syndrome
Parkinson's disease
Diabetes
Traumatic brain injury
Substance abuse
Cancer
Huntington's disease
Epilepsy
Autism
Fragile X
Bipolar disorder
Multiple sclerosis
Impulse-control disorders
Allergic diseases
Genetic disorders
Cardiovascular disease
Eating disorders
Obesity
Respiratory disorders
Anxiety disorders/stress
Stroke
These impairments represent key treatment targets1
1e.g.
Assessing Cognition © Cambridge Cognition 2014. All rights reserved
Chamberlain et al., Bio Psych, 2011
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Why assess cognition?
Perspective of society
Cognitive assessment is widely used in occupational contexts
“Psychometric Testing” to screen potential employees
Use of “cognitive rehabilitation” and “cognitive (re)training”
e.g. in children with special educational needs, in people with Traumatic Brain
Injury (TBI)
Explore the impact of environmental factors on cognitive function, and safety, in
sensitive occupations (e.g. military, truck drivers, doctors)
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Why assess cognition?
Perspective of society
Example: impact of sleep deprivation on cognition in US Air Force Pilots1
more attentional
lapses
Sleep deprivation was associated
with a variety of cognitive deficits,
shown here in relation to
deterioration in sustained
attention
1pm 4pm
7pm
10pm
1am
4am
7am
10am
1pm
4pm
sleep
deprivation
begins
1Lopez
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2008
et al., J App Res Mem Cog,
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Why assess cognition?
Perspective of society
Cognitive assessment allows measurement of effects of interventions
This includes both unwanted effects:
psychomotor slowing, impaired attention, impaired ability to
undertake goal-directed planning (important: e.g. driving abilities)
and desired effects:
cognitive enhancement, remediation of cognitive deficits
These effects may be unexpected
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Why assess cognition?
Perspective of society
Example: synergistic effect of benzodiazepine and antipsychotic medication on reaction
time slowing1
Reaction Times
deterioration
equivalent to
BAC>0.1%
Combination of benzodiazepine
and antipsychotic medication had
a synergistic unwanted effect on
reaction times in volunteers
The combination was equivalent to
being over the drink-driving limit
in virtually all jurisdictions, in
terms of effects on cognition
equivalent to
BAC>0.05%
BAC = Blood alcohol concentration
1Internal
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Camcog data
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Why assess cognition?
Perspective of society
Example: effect of modafinil on cognition in sleep-deprived doctors1
Modafinil improved the ability of
sleep-deprived doctors to solve
difficult trials on an executive
planning task (p<0.05)
slower problem
solving
Placebo
Modafinil
1Sugden
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et al., Ann Surg, 2012
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Why assess cognition?
Individual level
Cognitive assessment also has many applications at the level of the individual person
An individual’s performance can be compared to normative data
Clinicians and researchers can quantify to what extent an individual’s cognition is
impaired (or better than expected), in which domains, and to what extent
Objective quantification of cognitive impairments can inform early
detection, diagnosis, and treatment
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Why assess cognition?
Individual level
Example: early detection of memory
problems requiring further investigation in
General Practice
Patient undertakes brief assessment using
medical device in GP surgery
One-page report generated for GP
Software indicates where further medical
investigations are needed; and reassures
where no problems were detected
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Characteristics of an ‘ideal’ set of cognitive tests
• Capture the spectrum of different cognitive functions and separate them
• Good psychometric properties
• Reliability (consistency, test-retest)
• Validity (face, content, discriminant)
• Sensitive: able to maximize detection of cognitive impairments in
disorders/syndromes; and effects of interventions
• Translational: can be directly related to neural circuitry and neurochemical systems
• Respected by scientific community
• Availability of a large normative database
Assessing Cognition © Cambridge Cognition 2014. All rights reserved
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Methods of cognitive assessment: pros and cons
Clinician-rated versus self-rated
Clinician-rated (or supervised) cognitive assessment refers to trained individuals
assessing cognition by asking questions/tasks of patients, or overseeing the testing
process
For example, Mini Mental State Examination (MMSE), widely used in clinical practice
as a broad composite measure of cognition, and to detect possible dementia1
Takes about 10 minutes to complete
e.g. “What year is it?”
“What is this?” [point to object]
“Please copy this figure”
Measures orientation, registration, short-term
memory, and language
Scores (maximum 30):
25-30 normal
21-24 mild impairment
10-20 moderate impairment
<10 severe impairment
1Folstein
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et al., J Psych Res, 1975
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Methods of cognitive assessment: pros and cons
Clinician-rated versus self-rated
Self-rated cognitive assessment refers to individuals doing tests themselves, typically
following written instructions, such as from their own homes or over the Internet
For example, the Self-Administered Geocognitive Examination (SAGE), designed
to detect signs of dementia1
e.g. “What is today’s date?”
“Name the following pictures”
“Copy this picture”
Takes about 15-20 minutes to complete
Four pages long
Measures various cognitive functions
Score (maximum 22)
<17 suggests cognitive impairment
1Scharre
Assessing Cognition © Cambridge Cognition 2014. All rights reserved
2010
et al., Alz Dis Assoc Dis,
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Methods of cognitive assessment: pros and cons
Clinician-rated versus self-rated
Clinician-rated (or supervised) assessment
- Greater objectivity
- Greater control over testing environment and test administration
- Less ‘statistical noise’ and superior data control
But,
- Requires training
- Potential inconvenience (supervisor and person being assessed together
at the same site)
Self-rated assessment
- Convenience (can be done from home)
- No need to train and employ testers
But,
- Limited control over testing environment and test administration
- Difficult to quantify or record various confounding factors
Assessing Cognition © Cambridge Cognition 2014. All rights reserved
Page 20
Methods of cognitive assessment: pros and cons
Pen/Paper versus Computerized assessment
Cognitive assessment initially relied on pen/paper tests, before the advent of computer
technology
Computerized assessment is now the gold standard, with potential
advantages:
- Objectively tease apart distinct cognitive abilities
- Automated data collection and processing; quality control
- Accuracy (such as in measurement of response latencies)
- Can be made less reliant on complex motor skill; special interface technology
- Translational: neuroimaging, animal models
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Computerized assessment: CANTAB
Comprehensively captures all important cognitive domains
Established validation including excellent psychometric properties
Proven sensitivity to drug and disease effects where cognition is a factor
Comprehensively validated by >30 years of global translational research, and >1300
peer-reviewed papers
Used in over 700 academic research institutions worldwide
Extensive normative and clinical data
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Validated touchscreen tests
Reaction Time
Verbal Recall
Emotion Recognition
Compulsivity
Spatial Working
Visual Information
Paired Associates
Memory
Processing
Learning
Measuring effects across cognitive domains
Psychomotor
speed
Attention
Memory
Executive
function
Social
cognition
Applied to research of disorders and syndromes
Drug Safety
Drug Efficacy
Alzheimer's
disease
Depression
ADHD
Schizophrenia
Abuse Liability
Parkinson's
disease
Pain
Sleep
Down’s
syndrome
Multiple sclerosis
Autism
Cancer
Cardiovascular
Huntington’s
Traumatic
Assessing
Cognition © Cambridge
Cognition 2014. All rights
reserved
disease
disease
brain
injury
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C AN TAB C og n it ive Tes t s an d Brain Reg ion s
Delayed Matching to
Sample
Reaction Time Task
Rapid Visual
Information Processing
Emotion
Recognition Test
Affective
Go/No-go
Spatial Working
Memory
Stockings of
Cambridge
Attention Switching
Task
Associates
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rights reserved
Stop Signal Task
Learning
Verbal Recall /
Recognition Memory
Pattern or SpatialPage 24
Recognition Memory
CANTAB
The high sensitivity, and established validation of Cantab enables research that is
lower cost and lower risk for your academic research
Cantab detects effects in smaller
sample sizes over shorter periods of time
(large effect sizes versus placebo for drug
manipulations, even in healthy volunteers)1
Cantab is sensitive to the discovery of
effects that other tests would miss2
1Turner
et al., Psychopharm, 2003; Deakin et al.,
Psychopharm, 2004; 2Greig et al., Curr Alz Res, 2005
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CANTAB
Enables you to pinpoint cognitive deficits in syndromes/disorders, and effects of drug
manipulations and interventions (high precision)1
The translational bridge from pre-clinical
research increases chance of success with
grant applications, and maximises the
scientific impact of your research2
Computerized, language-independent
delivery enables easy deployment, and
maximises signal-to-noise3
1Chamberlain
et al., Bio Psych, 2011; 2Robbins et al.,
Neurosci Biobehav Rev, 2013; 3e.g. Yurko-Mauro et al., 2010;
Shiina et al., 2010
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CANTAB
Tailored packages
Core Cognitive Battery
Research key aspects of cognitive performance using computerized tests that
have proven sensitivity to pharmacological manipulation
Dementia Battery
For measuring the severity of impairment in patients with prodromal
Alzheimer’s disease and those functioning within the dementia range
Schizophrenia Battery
Accurately research cognitive effects in schizophrenia and related syndromes
ADHD Battery
Reliably study the cognitive effects in conditions characterized by excessive
impulsivity and the inability to control behaviors
Depression Battery
For research into cognitive impairment associated with depression (including
treatment resistant depression) and related mood disorders during acute
mood episodes and periods of remission
Or create your own test combination
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Page 27
Example: CANTAB ADHD Battery
Fast, reliable and highly sensitive, the CANTAB ADHD Battery allows accurate quantification
of cognitive problems in ADHD, and effects of interventions
Attention /
reaction time
Executive
Function
Rapid Visual Information
Processing (RVP)
Spatial Working
Memory (SWM)
Assessing Cognition © Cambridge Cognition 2014. All rights reserved
Response
Control
Stop Signal Task
(SST)
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CANTAB ADHD Battery
Sensitive to cognitive impairments
Maximize scope for detecting cognitive benefits of intervention, and enrich samples, with
large baseline deficits in ADHD1
significant clinical
impairment
Sustained Attention (RVP)
greater
impairment
Executive Function (SWM)
CANTAB discriminates the
cognitive profile of ADHD
from other conditions
including2
Response Control (SST)
0
0.5
1
-Anxiety/Depression
-Personality Disorder
-Conduct Disorder
Impairment (Cohen’s D) in
ADHD v Controls
1From
Chamberlain et al., Bio Psych, 2011; and Gau & Huang, Psych Med, 2014; see also Fried et al., Journ Atten Disorders, 2012; 2Dowson et al.,
Acta Psych Scand, 2010; Lipszyc & Schachar, J Int Neuropsych Soc, 2010
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CANTAB ADHD Battery
Functionally relevant
CANTAB predicts day-to-day function in ADHD1,2. In path modelling, CANTAB SWM significantly
mediated the relationship between ADHD and social problems1
Executive
Dysfunction
1Tseng
p<0.01
p<0.01
ADHD
Social
Problems
Cognitive impairment in
ADHD contributes to
functional impairment across
multiple areas (including
academic, work, and social
domains)2
& Gau, J Child Psychol and Psych, 2013; 2Clark et al., J Child Psychol and Psych, 2002; Kofler et al., J Abnorm Child Psychol, 2011
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CANTAB ADHD Battery
Translational
Volume of damage (cm3)
CANTAB SST is sensitive to frontal lobe
damage, especially to the right inferior
frontal gyrus (correlation p<0.001)1
more cortex
damage
40
CANTAB SST detects the effects of ADHD
medications on brain function, even
following a single dose2
Enhanced brain
activation in the right
inferior frontal gyrus
following atomoxetine
treatment, detected
using CANTAB2
worse inhibitory
control
0
100
1Aron
Stop Signal Reaction Time
(SST)
450
CANTAB performance correlates with structural
and functional brain abnormalities in ADHD, such
as with disorganized white matter tracts3
et al., Nat Neurosci, 2003; see also Aron et al., Trends Cog Sci, 2014; 2Chamberlain et al., Bio Psych, 2009; 3Shang et al., Psych Med, 2013
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Page 31
CANTAB ADHD Battery
Sensitive to cognitive enhancing effects of interventions
* p < 0.05 significant linear
reduction in errors with increasing
methylphenidate dose
Errors (SWM)
55
50
45
40
better
working
memory
35
30
Placebo
Low
Medium
High
CASE STUDY:
CANTAB SST detected cognitive benefits of
atomoxetine (selective norepinephrine
reuptake inhibitor) following just a singledose in N=22 patients with ADHD2
Stop Signal Reaction Time
(SST)
CASE STUDY:
CANTAB SWM showed dose-dependent
improvement from single-dose
methylphenidate treatment in N=26 patients
with ADHD1
* p < 0.05
250
230
better inhibitory
control
210
190
170
150
Placebo
Atomoxetine
higher dose
1Bedard
et al., J Am Child Adolesc Psych, 2004
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2Chamberlain
et al., Bio Psych, 2007
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