Upload
jaylynn-kennison
View
216
Download
1
Tags:
Embed Size (px)
Citation preview
10th September 2014, v1.0 draft
Assessing Cognition
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 2
Aims of this resource
This presentation provides an overview of the assessment of cognition, and has been designed for post-graduates and PhD students.
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 3
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
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 4
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
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 5
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
1Arnsten et al., Bio Psych, 2011
neuromodulators
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 6
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
Environmental factorse.g.• Stress• Trauma• Inflammation• Diet and drug use
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 7
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 Environmental factor
Maternal smoking
1Morales et al., Int J Epidem, 2009
GSTM1 polymorphism (codes for enzyme involved in breakdown of tobacco by-products)
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.
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 8
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
Cortisol level (stress axis)
1Lee et al., Am J Psych, 2008
APOE4 gene
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
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 9
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:
These impairments represent key treatment targets1
Alzheimer's diseaseMild cognitive impairmentDepressionADHDSchizophreniaPainSleep disordersDown's syndrome
Parkinson's diseaseDiabetesTraumatic brain injurySubstance abuseCancerHuntington's diseaseEpilepsyAutismFragile XBipolar disorder
Multiple sclerosisImpulse-control disordersAllergic diseasesGenetic disordersCardiovascular diseaseEating disordersObesityRespiratory disordersAnxiety disorders/stressStroke
1e.g. Chamberlain et al., Bio Psych, 2011
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 10
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)
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 11
Why assess cognition? Perspective of society
1Lopez et al., J App Res Mem Cog, 2008
Example: impact of sleep deprivation on cognition in US Air Force Pilots1
Sleep deprivation was associated with a variety of cognitive deficits, shown here in relation to deterioration in sustained attention
more attentional lapses
sleep deprivation
begins
1pm 4pm 7pm 10pm 1am 4am 7am 10am 1pm 4pm
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 12
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
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 13
Why assess cognition? Perspective of society
Example: synergistic effect of benzodiazepine and antipsychotic medication on reaction time slowing1
1Internal Camcog data
deterioration
equivalent to BAC>0.05%
equivalent to BAC>0.1%
Reacti
on
Tim
es
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
BAC = Blood alcohol concentration
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 14
Why assess cognition? Perspective of society
1Sugden et al., Ann Surg, 2012
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)
Placebo Modafinil
slower problem solving
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 15
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
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 16
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
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 17
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 Page 18
Methods of cognitive assessment: pros and cons
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
e.g. “What year is it?”“What is this?” [point to object]“Please copy this figure”
Clinician-rated versus self-rated
1Folstein et al., J Psych Res, 1975
Takes about 10 minutes to complete
Measures orientation, registration, short-term memory, and language
Scores (maximum 30):
25-30 normal21-24 mild impairment10-20 moderate impairment<10 severe impairment
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 19
Methods of cognitive assessment: pros and cons
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”
Clinician-rated versus self-rated
1Scharre et al., Alz Dis Assoc Dis, 2010
Takes about 15-20 minutes to complete
Four pages long
Measures various cognitive functions
Score (maximum 22)
<17 suggests cognitive impairment
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 20
Methods of cognitive assessment: pros and cons
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
Clinician-rated versus self-rated
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 21
Methods of cognitive assessment: pros and cons
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
Pen/Paper versus Computerized assessment
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 22
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
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 23
Psychomotor speed
Attention MemorySocial
cognitionExecutive function
Reaction Time
Visual Information Processing
Paired Associates Learning
Spatial Working Memory
CompulsivityEmotion RecognitionVerbal Recall
Alzheimer's disease
Depression ADHD Schizophrenia Abuse Liability
Parkinson's disease
Pain SleepDown’s
syndromeMultiple sclerosis
Cardiovascular disease
Huntington’s disease
Traumatic brain injury
Autism Cancer
Validated touchscreen tests
Measuring effects across cognitive domains
Applied to research of disorders and syndromes Drug Safety Drug Efficacy
Assessing Cognition © Cambridge Cognition 2014. All rights reserved Page 24
Stop Signal Task
Verbal Recall / Recognition Memory
Reaction Time Task
Delayed Matching to Sample
Paired Associates Learning
Spatial Working Memory
Stockings of Cambridge
Attention Switching Task
Pattern or Spatial Recognition Memory
Affective Go/No-go
Emotion Recognition Test
Rapid Visual Information Processing
CANTAB Cognitive Tests and Brain Regions
Page 25Assessing Cognition © Cambridge Cognition 2014. All rights reserved
CANTAB
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
The high sensitivity, and established validation of Cantab enables research that
is lower cost and lower risk for your academic research
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
Page 26Assessing Cognition © Cambridge Cognition 2014. All rights reserved
CANTAB
The translational bridge from pre-clinical
research increases chance of success with
grant applications, and maximises the
scientific impact of your research2
Enables you to pinpoint cognitive deficits in syndromes/disorders, and effects of drug
manipulations and interventions (high precision)1
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
Page 27Assessing Cognition © Cambridge Cognition 2014. All rights reserved
CANTAB
Core Cognitive BatteryResearch key aspects of cognitive performance using computerized tests that have proven sensitivity to pharmacological manipulation Dementia BatteryFor measuring the severity of impairment in patients with prodromal Alzheimer’s disease and those functioning within the dementia range Schizophrenia BatteryAccurately research cognitive effects in schizophrenia and related syndromes ADHD BatteryReliably study the cognitive effects in conditions characterized by excessive impulsivity and the inability to control behaviors Depression BatteryFor 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
Tailored packages
Page 28Assessing Cognition © Cambridge Cognition 2014. All rights reserved
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
Rapid Visual Information Processing (RVP)
Spatial Working Memory (SWM)
Executive Function
Response Control
Stop Signal Task (SST)
Page 29Assessing Cognition © Cambridge Cognition 2014. All rights reserved
CANTAB ADHD Battery
Response Control (SST)
Executive Function (SWM)
Sustained Attention (RVP)
0 0.5 1Impairment (Cohen’s D) in
ADHD v Controls1From 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
greater impairment
Maximize scope for detecting cognitive benefits of intervention, and enrich samples, with large baseline deficits in ADHD1
significant clinicalimpairment
CANTAB discriminates the cognitive profile of ADHD from other conditions including2
-Anxiety/Depression -Personality Disorder -Conduct Disorder
Sensitive to cognitive impairments
Page 30Assessing Cognition © Cambridge Cognition 2014. All rights reserved
CANTAB ADHD Battery
1Tseng & Gau, J Child Psychol and Psych, 2013; 2Clark et al., J Child Psychol and Psych, 2002; Kofler et al., J Abnorm Child Psychol, 2011
CANTAB predicts day-to-day function in ADHD1,2. In path modelling, CANTAB SWM significantly mediated the relationship between ADHD and social problems1
Cognitive impairment in ADHD contributes to functional impairment across multiple areas (including academic, work, and social domains)2
ADHD
Executive Dysfunction
Social Problems
p<0.01 p<0.01
Functionally relevant
Page 31Assessing Cognition © Cambridge Cognition 2014. All rights reserved
CANTAB ADHD Battery
1Aron 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
CANTAB SST detects the effects of ADHD medications on brain function, even following a single dose2
CANTAB SST is sensitive to frontal lobe damage, especially to the right inferior frontal gyrus (correlation p<0.001)1
40
0
100 450
Volu
me o
f d
am
ag
e (
cm
3)
Stop Signal Reaction Time (SST)
worse inhibitory control
more cortex damage Enhanced brain
activation in the right inferior frontal gyrus following atomoxetine treatment, detected using CANTAB2
CANTAB performance correlates with structural and functional brain abnormalities in ADHD, such as with disorganized white matter tracts3
Translational
Page 32Assessing Cognition © Cambridge Cognition 2014. All rights reserved
CANTAB ADHD Battery
Placebo Atomoxetine150
170
190
210
230
250
CASE STUDY: CANTAB SWM showed dose-dependent improvement from single-dose methylphenidate treatment in N=26 patients with ADHD1
1Bedard et al., J Am Child Adolesc Psych, 2004 2Chamberlain et al., Bio Psych, 2007
better inhibitory control
CASE STUDY: CANTAB SST detected cognitive benefits of atomoxetine (selective norepinephrine reuptake inhibitor) following just a single-dose in N=22 patients with ADHD2
Sto
p S
ign
al R
eac
tio
n T
ime
(SS
T)
* p < 0.05
Placebo Low Medium High30
35
40
45
50
55
Err
ors
(S
WM
)
better working memory
higher dose
* p < 0.05 significant linear reduction in errors with increasing
methylphenidate dose
Sensitive to cognitive enhancing effects of interventions
Page 33Clinical Trials © Cambridge Cognition 2014. All rights reserved
Cambridge Cognition LtdTunbridge CourtBottishamCambridge, CB25 9TU UK
Call +44 1223 810700
Email [email protected]
Get further information www.cantab.com/research
Download resources www.cantab.com/ignition
Search the research library www.cantab.com/biblography