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Cambridge%20Neuropsychological%20Test%20Automated%20Battery%20(CANTAB)
Availability
Please visit this website for more information about the instrument: Cambridge Automated Neuropsychological Test Battery
 
The Cambridge Automated Neuropsychological Test Battery (CANTAB) is owned by Cambridge Cognition which licenses the product for use in pharmaceutical clinical trials, academic research and healthcare organizations.
Classification
Supplemental: Myalgic encephalomyelitis/Chronic fatigue syndrome (ME/CFS) and Parkinson's Disease (PD)
Short Description of Instrument
Creation: The Cambridge Automated Neuropsychological Test Battery (CANTAB) was created by Professor Trevor Robbins and Professor Barbara Sahakian at The University of Cambridge in the 1980's.
 
Purpose: The impetus for creating the CANTAB was to adapt paradigms that had been successful in the study of animal models, into versions suitable for humans, and to deconstruct complex human tests such as the Wisconsin Card Sort Test to isolate specific cognitive domains. Computerized administration was employed to achieve improved consistency in test administration, and to make possible more accurate collection of a broader range of endpoints in each test.
 
The development of CANTAB tests created a translational bridge between animal and human research, enabling better integration of basic and clinical research. The cognitive deficits in Parkinson's disease were one of the first targets of this strategy (Morris et al., 1988, Sahakian et al., 1988).
 
The need to record behavior of often elderly subjects with motor impairments (as is typical in Parkinson's disease), and the preference for cross-species comparison influenced the design of the battery. Most tests involve large, abstract visual stimuli and touch input is employed as the most applicable interface for delivering the tasks.
 
Various tests of the CANTAB battery have been used in PD and to lesser extent PDD.
 
Overview: CANTAB contains a total of 25 cognitive tasks, each loading onto specific cognitive domains across memory, attention, executive function, social cognition, psychomotor and processing speed. Individual tests can be grouped together to create a battery relevant for research. In 2021 Cambridge Cognition lists 23 tests and groups them into 4 areas: memory, executive, attention and psychomotor speed, and social and emotional cognition. Cambridge Cognition has created recommended batteries based on experience within different therapeutic areas, including Parkinson's Disease. Where appropriate, adaptive testing procedures have been used to manage test burden and enable objective data to be collected from subjects with a wide range of abilities.
 
Test instructions are administered using standardized voiceovers and interactive tutorials, which are available in numerous languages, helping to facilitate global research collaborations and clinical trials. The touch-screen interface permits accurate capture of reaction time and error scores for each task, as well as automatic calculation of derived variables.
 
Cited from CANTAB website: "The tests use non-verbal visual stimuli for use on broad populations across all languages and cultures. Parallel modes and automatic stimuli randomization prevent practice effects to ensure participants can be re-tested over different time periods. Dynamic tasks variants adjust to the participants' performance level, ending tasks when they reach their limit to prevent any unnecessary testing and maintain user engagement. Adaptive modes allow investigators to change the difficulty of the tests dependent on their age and ability, adapting for healthy volunteers, impaired patients and children, avoiding the possibility of floor or ceiling effects."
 
Depending upon how many of the tasks are administered, the time to complete this test could range from 20 minutes to over an hour.
Comments/Special Instructions
Since the instructions and training for these tests are built into the software, and data capture is automatic, the battery may be administered by a wide range of professional personnel after a brief introductory training session. No prior experience of neuropsychological testing is required.
 
Parkinson's Disease-specific: Currently six CANTAB tasks form the recommended battery for research into Parkinson's disease. These are the Motor Screening Task (MOT, motor screening), the Reaction Time Task (RTI, psychomotor speed), the Paired Associate Learning Task (PAL, visual episodic memory), the Pattern Recognition Memory Task (PRM, visual recognition memory), the Spatial Working Memory task (SWM, working memory) and the One Touch Stockings of Cambridge (OTS, planning). The intra-extradimensional set shifting (IED) task (similar to the Wisconsin) has also been used in PD.
 
ME/CFS-specific: The CANTAB could be used in functional neuroimaging if separate tasks were taken out of the battery. This tool has been used in studies of ME/CFS, but specific norms are not available.
Scoring and Psychometric Properties
Scoring: This scale is scored by computer algorithm. The data captured by the CANTAB software is automatically transferred to the CANTAB Connect cloud in a secure manner which meets regulatory requirements for clinical trials and patient integrity. Outcome measures for each of the cognitive tests are computed automatically, eliminating human error from the scoring and data entry procedure. Data tables are available in real time and can be exported from the Connect platform directly into conventional statistical packages for further analysis by the user.
 
The key variables for each of the tests in the recommended Parkinson's Disease battery are as follows:
 
MOT: MOT Mean Latency
The mean latency for a participant to correctly respond to the stimulus on screen during assessed trials, measured in milliseconds.
 
RTI: RTI Median Five-Choice reaction time
The median duration it takes for a participant to release the response button after the presentation of a target stimulus. Calculated across correct, assessed trials in which the stimulus could appear in any one of five locations. Measured in milliseconds.
 
RTI: RTI Median Five-Choice movement time
The median time taken for a participant to release the response button and select the target stimulus after it flashed yellow on screen. Calculated across correct, assessed trials in which the stimulus could appear in any one of five locations. Measured in milliseconds.
 
PAL: PAL total errors adjusted
The number of errors committed by the subject plus an adjustment for the estimated number of errors they would have made on any stages that were not reached. A measure of episodic (object in place) memory.
 
PRM: PRM Percent Correct Immediate
The number of correct patterns selected by the participant in the immediate forced- choice condition, expressed as a percentage.
 
PRM: PRM Percent Correct Delayed
The number of correct patterns selected by the participant in the delayed forced- choice condition, expressed as a percentage.
 
SWM: SWM between errors
A measure of spatial working memory calculated as the number of times that the subject revisited a box in which a token had previously been found in that problem.
 
SWM: SWM strategy
The number of distinct boxes used by the subject to begin a new search for a token, within the same problem, as a measure of use of a consistent search strategy.
 
OTS: OTS Problems Solved on First Choice:
The total number of assessed trials where the participant chose the correct answer on their first attempt.
 
OTS: OTS Median Latency to First Choice:
The median latency, measured from the appearance of the "balls" until the first box choice was made by the participant. Calculated across assessed trials where the participant's first response was correct.
 
Since cognitive performance can be influenced by numerous demographic factors, including age, gender and educational achievement, Cambridge Cognition does not recommend using standard performance cut-off scores to define clinically significant deficits in these tests. For group comparisons, the use of Cohen's d is recommended (>0.3, mild, >0.5 moderate and >0.8 severe) and for individual subjects a Reliable Change Index (RCI) should be calculated.
 
Psychometric Properties: Normative data are generally unavailable. However, some statistically derived normative data have been published for a subset of tests from an epidemiologic study of persons in mid- to late life (Abbott et al., 2019): PAL, RTI, SWM.
 
Psychometric data pertaining to reliability, sensitivity to change, validity etc. appear to be proprietary.
 
Cutoff scores are not available.
Rationale/Justification
Parkinson's Disease-specific:
Cambridge Cognition has experience in over 160 clinical trials, of which 43% have been in neurodegenerative disorders such as Parkinson's Disease, Alzheimer's Disease and Huntington's Disease. Moreover, out of the 1800 peer reviewed papers using CANTAB, 121 publications have been in Parkinson's disease research, highlighting the breadth of application of this test battery has in this therapeutic area.
 
The following paragraphs will outline the justification for each test based on published research.
 
MOT
  • Primarily used for screening motor skills and ensuring accurate touch screen responding

 
RTI (psychomotor and processing speed):
  • Patients with mild PD show significant deficits in simple and choice reaction time and movement time. L-dopa administration markedly improves movement time and reaction time. Noradrenergic manipulations (Clonidine) and cholinergic manipulations (e.g., Tacrine) significantly affect performance on the choice reaction time (attentional) component of the task (Riekkinen et al., 1998).

 
PAL (episodic memory):
  • The Paired Associates Learning task is a visuospatial measure of episodic memory with performance dependent on the functional integrity of the medial temporal lobe, particularly the hippocampus and parahippocampal regions (De Rover et al., 2011; Owen, Sahakian, Semple, Polkey & Robbins, 1995).

  • Evidence shows that memory is the most common cognitive domain affected in Parkinson's Disease with 15% of participant's performance 1.5 Standard deviations from normative values measured using PAL (Yarnell et al., 2014).

  • Cognitive impairment in memory within PD populations correlated with levels of CSF A?42 and A?40 in patients, suggesting the use of CANTAB measures as useful behavioral biomarkers (Yarnell et al., 2014).

 
PRM (recognition memory):
  • The Pattern Recognition Memory task (PRM) is a measure of visual working memory requiring intact medial temporal lobe function for successful performance and shows impairments among PD populations (Sahakian et al., 1988). PD populations exhibit global deficits in recognition  but differences within sub-types, such as spatial recognition vs. pattern recognition depending on the type of Parkinson's disease shown (TrÖster, 2011).

  • Pattern recognition deficits are symptomatic of Parkinson's disease dementia, with temporal lobe deficits appearing with the presence of Lewy body disposition (Williams-Gray et al., 2009). The inclusion of CANTAB PRM serves as a useful tool for differentiating those patients who maintain a trajectory of predominantly frontal lobe dysfunction, compared to those showing additional disease progression in the temporal lobes.

  • Williams-Gray et al. (2009) demonstrated that differences in PRM performance indicates the beginning of a segregation between demented and non-demented patients in terms of cognitive impairments among PD populations. 10% of PD patients' progress into a demented state, aligning with data that 9% of participants with global cognitive deficits showed specific impairments on PRM, and these individuals were most symptomatic of a demented trajectory (Foltynie et al., 2004). 

 
SWM (working memory and executive function):
  • Performance on the SWM task has been shown to be impaired by damage to the prefrontal cortex, especially dorsolateral prefrontal cortex (Manes et al., 2002; Owen et al., 1990; Owen et al., 1996b). Neuroimaging studies have revealed that SWM performance activates dorsolateral and mid ventrolateral prefrontal cortex (Owen et al., 1996a).

  • Numerous studies have suggested that SWM performance is sensitive to dopamine manipulation. For example, SWM is impaired by acute tyrosine depletion (Harmer et al., 2001), and improved by D2 agonist administration. Dorsolateral prefrontal cortex activation during SWM performance is dependent on dopamine modulation (Mehta et al., 2000).

  • SWM performance is impaired in Parkinson's disease (Owen et al., 1993; Owen et al., 1992, Owen et al., 1997). L-dopa withdrawal impairs SWM task performance in patients with Parkinson's disease (Lange et al., 1992). Neuroimaging evidence suggests that the beneficial effect of L-dopa is mediated by improved efficiency in the dorsolateral prefrontal cortex (Cools et al., 2002). 

 
SOC/OTS (executive function, planning):
  • SOC performance is impaired in patients with Parkinson's disease (Lange et al., 1992; Morris et al., 1988; Owen et al., 1992). These deficits are measurable using this CANTAB test, even in patients screened as normal using conventional pencil and paper measures.

  • SOC is sensitive to dopamine manipulation in Parkinson's disease. Deficits in planning accuracy are remediated by L-Dopa in patients with Parkinson's disease (Lange et al., 1992; Owen et al., 1997). L-Dopa also improves speed of thinking on SOC in these patients (Lange et al., 1992). Neuroimaging evidence suggests that this improvement is mediated by improved efficiency in the dorsolateral prefrontal cortex (Cools et al., 2002). Furthermore, in healthy volunteers, caudate D2 receptor availability predicts performance on SOC (Reeves et al., 2005).

  • Like SOC, OTS is impaired in Parkinson's Disease (Rochester et al., 2014), and was one component of the executive function score used in the recent ICICLE-PD study of mild cognitive impairment in Parkinson's disease (Mak et al., 2015, Lawson et al., 2016). In a study of atomoxetine in Parkinson's disease, drug plasma concentration predicted superior problem solving in the OTS (Kehagia, et al., 2014). 

 
PAL, SWM, and SOC correlate with instrumental activities of daily living as assessed with the Performance Assessment of Self-care Skills (PASS) (Foster and Doty, 2021)
 
IED task is sensitive in differentiating between PD patients with and without freezing of gait (Stefanova et al., 2014).
 
IED is sensitive to the effects of bilateral pallidotomy (Scott et al., 2002)
 
Strengths: Used in many studies and widely validated. Computerized administration and scoring require minimal training. May be especially useful in clinical trials.
 
Weaknesses: CANTAB is not a test but a collection of tests and there is variability in the tests chosen by various studies. There is no single score that across tests that is diagnostically useful. Limited information on test-retest reliability or interrater reliability in PD. Correlations with traditional neuropsychological tests may only be modest and become inconsistent when age and education effects on test performance are controlled for (Smith et al., 2013).
 
ME/CFS-specific: A limitation for use in ME/CFS could be that this test is administered via computer, if subjects have difficulty multitasking or viewing the computer screen due to photosensitivity.
References
Key References:
Morris RG, Downes JJ, Sahakian BJ, Evenden JL, Heald A, Robbins TW. Planning and spatial working memory in Parkinson's disease. J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):757-66.
 
Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R, Philpot M, Robbins TW. A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. Brain. 1988 Jun;111 ( Pt 3):695-718.
 
Parkinson's Disease-Specific References:
Abbott RA, Skirrow C, Jokisch M, Timmers M, Streffer J, van Nueten L, Krams M, Winkler A, Pundt N, Nathan PJ, Rock P, Cormack FK, Weimar C. Normative data from linear and nonlinear quantile regression in CANTAB: Cognition in mid-to-late life in an epidemiological sample. Alzheimers Dement (Amst). 2018 Nov 12;11:36-44.
 
Cools R, Stefanova E, Barker RA, Robbins TW, Owen AM. Dopaminergic modulation of high-level cognition in Parkinson's disease: the role of the prefrontal cortex revealed by PET. Brain. 2002 Mar;125(Pt 3):584-94.
 
de Rover M, Pironti VA, McCabe JA, Acosta-Cabronero J, Arana FS, Morein-Zamir S, Hodges JR, Robbins TW, Fletcher PC, Nestor PJ, Sahakian BJ. Hippocampal dysfunction in patients with mild cognitive impairment: a functional neuroimaging study of a visuospatial paired associates learning task. Neuropsychologia. 2011 Jun;49(7):2060-70.
 
Foltynie T, Brayne CE, Robbins TW, Barker RA. The cognitive ability of an incident cohort of Parkinson's patients in the UK. The CamPaIGN study. Brain. 2004 Mar;127(Pt 3):550-60.
 
Foster ER, Doty T. Cognitive Correlates of Instrumental Activities of Daily Living Performance in Parkinson Disease Without Dementia. Arch Rehabil Res Clin Transl. 2021 Jul 3;3(3):100138.
 
Harmer CJ, McTavish SF, Clark L, Goodwin GM, Cowen PJ. Tyrosine depletion attenuates dopamine function in healthy volunteers. Psychopharmacology (Berl). 2001 Feb;154(1):105-11.
 
Kehagia AA, Housden CR, Regenthal R, Barker RA, Müller U, Rowe J, Sahakian BJ, Robbins TW. Targeting impulsivity in Parkinson's disease using atomoxetine. Brain. 2014 Jul;137(Pt 7):1986-97.
 
Lange KW, Robbins TW, Marsden CD, James M, Owen AM, Paul GM. L-dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction. Psychopharmacology (Berl). 1992;107(2-3):394-404.
 
Lawson RA, Yarnall AJ, Duncan GW, Breen DP, Khoo TK, Williams-Gray CH, Barker RA, Collerton D, Taylor JP, Burn DJ; ICICLE-PD study group. Cognitive decline and quality of life in incident Parkinson's disease: The role of attention. Parkinsonism Relat Disord. 2016 Jun;27:47-53.
 
Mak E, Su L, Williams GB, Firbank MJ, Lawson RA, Yarnall AJ, Duncan GW, Owen AM, Khoo TK, Brooks DJ, Rowe JB, Barker RA, Burn DJ, O'Brien JT. Baseline and longitudinal grey matter changes in newly diagnosed Parkinson's disease: ICICLE-PD study. Brain. 2015 Oct;138(Pt 10):2974-86.
 
Manes F, Sahakian B, Clark L, Rogers R, Antoun N, Aitken M, Robbins T. Decision-making processes following damage to the prefrontal cortex. Brain. 2002 Mar;125(Pt 3):624-39.
 
Mehta MA, Owen AM, Sahakian BJ, Mavaddat N, Pickard JD, Robbins TW. Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain. J Neurosci. 2000 Mar 15;20(6):RC65.
 
Owen AM, Beksinska M, James M, Leigh PN, Summers BA, Marsden CD, Quinn NP, Sahakian BJ, Robbins TW. Visuospatial memory deficits at different stages of Parkinson's disease. Neuropsychologia. 1993 Jul;31(7):627-44.
 
Owen AM, Doyon J, Petrides M, Evans AC. Planning and spatial working memory: a positron emission tomography study in humans. Eur J Neurosci. 1996 Feb;8(2):353-64.
 
Owen AM, Iddon JL, Hodges JR, Summers BA, Robbins TW. Spatial and non-spatial working memory at different stages of Parkinson's disease. Neuropsychologia. 1997 Apr;35(4):519-32.
 
Owen AM, James M, Leigh PN, Summers BA, Marsden CD, Quinn NP, Lange KW, Robbins TW. Fronto-striatal cognitive deficits at different stages of Parkinson's disease. Brain. 1992 Dec;115 (Pt 6):1727-51.
 
Owen AM, Morris RG, Sahakian BJ, Polkey CE, Robbins TW. Double dissociations of memory and executive functions in working memory tasks following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Brain. 1996 Oct;119 ( Pt 5):1597-615.
 
Owen AM, Sahakian BJ, Semple J, Polkey CE, Robbins TW. Visuo-spatial short-term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia. 1995 Jan;33(1):1-24.
 
Reeves SJ, Grasby PM, Howard RJ, Bantick RA, Asselin MC, Mehta MA. A positron emission tomography (PET) investigation of the role of striatal dopamine (D2) receptor availability in spatial cognition. Neuroimage. 2005 Oct 15;28(1):216-26.
 
Riekkinen M, Kejonen K, J?k?l? P, Soininen H, Riekkinen P Jr. Reduction of noradrenaline impairs attention and dopamine depletion slows responses in Parkinson's disease. Eur J Neurosci. 1998 Apr;10(4):1429-35.
 
Rochester L, Galna B, Lord S, Burn D. The nature of dual-task interference during gait in incident Parkinson's disease. Neuroscience. 2014 Apr 18;265:83-94.
 
Scott RB, Harrison J, Boulton C, Wilson J, Gregory R, Parkin S, Bain PG, Joint C, Stein J, Aziz TZ. Global attentional-executive sequelae following surgical lesions to globus pallidus interna. Brain. 2002 Mar;125(Pt 3):562-74.
 
Smith PJ, Need AC, Cirulli ET, Chiba-Falek O, Attix DK. A comparison of the Cambridge Automated Neuropsychological Test Battery (CANTAB) with "traditional" neuropsychological testing instruments. J Clin Exp Neuropsychol. 2013;35(3):319-28.
 
Stefanova E, Jecmenica Lukic M, Ziropadja L, Markovic V, Stojkovic T, Tomic A, Draga?evic Mi?kovic N, Kostic V. Attentional set-shifting in Parkinson's disease patients with freezing of gait-acquisition and discrimination set learning deficits at the background? J Int Neuropsychol Soc. 2014 Oct;20(9):929-36.
 
TrÖster AI. A prÉcis of recent advances in the neuropsychology of mild cognitive impairment(s) in Parkinson's disease and a proposal of preliminary research criteria. J Int Neuropsychol Soc. 2011 May;17(3):393-406.
 
Williams-Gray CH, Evans JR, Goris A, Foltynie T, Ban M, Robbins TW, Brayne C, Kolachana BS, Weinberger DR, Sawcer SJ, Barker RA. The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort. Brain. 2009 Nov;132(Pt 11):2958-69.
 
Yarnall AJ, Breen DP, Duncan GW, Khoo TK, Coleman SY, Firbank MJ, Nombela C, Winder-Rhodes S, Evans JR, Rowe JB, Mollenhauer B, Kruse N, Hudson G, Chinnery PF, O'Brien JT, Robbins TW, Wesnes K, Brooks DJ, Barker RA, Burn DJ; ICICLE-PD Study Group. Characterizing mild cognitive impairment in incident Parkinson disease: the ICICLE-PD study. Neurology. 2014 Jan 28;82(4):308-16.
 
ME/CFS-Specific References:
Capuron L, Welberg L, Heim C, Wagner D, Solomon L, Papanicolaou DA, Craddock RC, Miller AH, Reeves WC. Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome. Neuropsychopharmacology. 2006 Aug;31(8):1777-84.
 
Joyce E, Blumenthal S, Wessely S. Memory, attention, and executive function in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1996 May;60(5):495-503.
 
Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER; International Chronic Fatigue Syndrome Study Group. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res. 2003 Dec 31;3(1):25.
 
Torgersen J, Flaatten H, Engelsen BA, Gramstad A. Clinical Validation of Cambridge Neuropsychological Test Automated Battery in a Norwegian Epilepsy Population. Journal of Behavioral and Brain Science. 2012 Feb;2(1):108-116.
 
Document last updated August 2022
Recommended Instrument for
ME/CFS and PD