assessing cognition

10th September 2014, v1.0 draft

Assessing Cognition

Assessing Cognition © Cambridge Cognition 2014. All rights reserved

Aims of this resource

This presentation provides an overview of the assessment of cognition, and has been designed for post-graduates and PhD students.


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


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


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



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



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.



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



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



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)



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



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



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



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


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


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


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


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



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”


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



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




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


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


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


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


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


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


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


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)


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


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


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


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

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assessing cognition

Documents

assessment of cognition

different aspects of

cognitive flexibility

cognitive problems

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different functions

different reasons

distinct circuits