18 December 2018

6 tests for assessing cognition in Parkinson’s disease

Cognitive dysfunction in Parkinson’s disease remains a significant, unmet therapeutic need for patients; as such it is vital that there is rigorous research into the topic. Here we will discuss six CANTAB tasks that can address this research gap.

Parkinson’s disease is a complex and progressive neurodegenerative disorder. Over 10 million people worldwide are estimated to be living with the condition, and prevalence is set to rise by a further fifth before 20251. In light of this rising pandemic, understanding and addressing the symptoms of the disease has never been more important – but what are the signs?

Although the exact manifestation of Parkinson’s disease varies between patients, the main motor symptoms consist of resting tremor, difficulty in initiating movements, muscular rigidity, and postural and gait problems2.

Secondary symptoms can include altered moods and behaviour, interrupted or irregular sleep and cognitive impairment from deteriorated memory, difficulty processing information and slower reaction times.

Indeed, the impact of Parkinson’s disease on cognitive function is severe, with 50% of patients eventually developing a dementia diagnosis3. Nevertheless, the search for effective and well-tolerated pharmacological interventions for disease progression and cognitive dysfunction in Parkinson’s disease is ongoing, representing a significant unmet need4, 5.

CANTAB has a battery of six cognitive tests that are specially designed for academic research and clinical trials of cognitive dysfunction in Parkinson’s disease. These tests capture a range of key domains typically impaired in patients, presenting objective targets for pharmacological manipulation.

Here we will discuss how the cognitive tests can be efficiently executed with patients for a reliable and systematic process of data retrieval.

Motor Screening Task

What does this task measure?

MOT is a 2-minute familiarisation task that trains participants on how to appropriately respond by touching the screen.

What does this task involve?
The task presents a series of flashing crosses at different locations on the screen and participants touch each of the presented crosses.

Why use this task?
Patients with Parkinson’s disease often exhibit motor-related deficits, including difficulties in initiating movements; therefore the MOT serves as a useful screening task to evaluate whether patients are able to complete the subsequent test battery. It recognises reactions and the accuracy; specifically, the task can identify those who are unable to make responses to the iPad-delivered tasks, and also helps to identify other factors that could impair performance, such as problems with vision and language comprehension.

Paired Associates Learning

What does this task measure?

PAL measures visual memory and new learning, and is a sensitive tool for accurate assessment of episodic memory.

What does this task involve?
Six boxes are presented on the screen, which open one by one in a randomized order to reveal patterns hidden inside. The patterns are then displayed in the middle of the screen, one at a time, and the subject must touch the box where the pattern was originally located. If the subject makes an error, the patterns are re-presented to remind the subject of their locations. The task becomes progressively more difficult, starting from a two pattern stage, to a four pattern, a six pattern and an eight pattern stage. If a participant continues to make errors on the fourth attempt at any stage, the task with automatically terminate due to the understanding that there is significant cognitive impairment and are unable to identify.

Why use this task?
PAL is an interactive tool to evaluate episodic memory, which is often impaired in the early stages of Parkinson’s disease5. Tasks such as this which hone in on the recall of patients helps establish the link between dementia and Parkinson’s; how the retrogression of the memory and messages decay within the substania nigra which leads to dementia within 50%+ of patients3.

Reaction Time

What does this task measure?

RTI provides assays of motor and mental response speeds, as well as measures of movement time, reaction time and response accuracy.

What does this task involve?

In this reaction time task the subject must hold down a virtual button at the bottom of the screen. A yellow spot will momentarily appear inside one of five yellow circles at the top of the screen. Subjects must respond to the spot as quickly as they can by letting go of the button and touching the circle where the yellow spot appeared and if missed or too slow, it becomes incorrect. This is repeated for 30 trials. Practice trials are initially available to familiarise subjects with the task. RTI provides 11 outcome measures, including reaction times, movement times, and error scores.

Why use this task?

Within Parkinson’s disease, the neurotransmitters slow and decay leading to slower processing of information, resulting in increase of reaction time. Through trials done using this task, when compared to other illnesses and problems caused such as Alzheimer’s, cognitive impairment and weakened working memory, Parkinson’s suffered the poorest reaction times17. This can come down to the issue that many suffer from a late diagnosis.

Which tasks will be most effective in my clinical trial?

Pattern Recognition Memory

What does this task measure?
PRM assesses visual pattern recognition memory in a 2-choice forced discrimination paradigm.

What does this task involve?

Participants are presented with a series of visual patterns, one at a time, in the centre of the screen. These patterns are designed as abstract patterns and shapes to avoid any association to recognisable, every-day stimuli. Once presented with the patterns, the participant is required to choose between a pattern they have already seen and a novel pattern. In this phase, the test patterns are presented in the reverse order to the original order of presentation. This is then repeated, with new patterns. The second recognition phase can be given either immediately or after a delay.

Why use this task?
A study found that Parkinson’s disease patients without dementia at baseline, performance on the CANTAB PRM task declined over 4 years and was associated with changes in EEG signals that may reflect potential markers of the disease7. The PRM task is therefore sensitive to changes in cognition, benefiting and reducing the possibility of oncoming dementia, even among those with Parkinson’s disease who do not have a formal diagnosis of dementia.

One Touch Stockings of Cambridge

What does this task measure?
OTS evaluates executive function, spatial planning and working memory based upon the Tower of Hanoi test.

What does this task involve?

The participant is shown two displays of coloured balls held in stockings suspended from a beam. There is a row of numbered boxes along the bottom of the screen. The participant is asked to solve problems by working out how they would move the balls in the bottom display in order to make them match the arrangements of the ball sin the top display. After some training and practice problems, the participant is asked to work out in their head how many moves the solutions to these problems require, and then touch the appropriate box at the bottom of the screen to indicate their response.

Why use this task?
Performance on the OTS task by Parkinson’s patients is associated with the COMT genotype in the early stages of the disease8. In this sense, the COMT gene is responsible for levels of hormones and communication of neurotransmitters. When the COMT gene is no longer fully functioning, dopamine levels may drop and serotonin may rise. Following this, communication between neurotransmitters can fail. This can lead to an inability to spatially plan as communication within the frontal lobe, responsible for planning, solving and organising, has failed.

Spatial Working Memory

What does this task measure?
SWM requires retention and manipulation of visuospatial information. This test has notable executive function demands, measures strategy use and cognitive processing as well as errors.

What does this task involve?

The test begins with three coloured boxes being shown on the screen. The aim of this test is that, by touching the boxes and using a process of elimination, the subject should find one ‘token’ in each of the boxes and use them to fill up an empty column on the right hand side of the screen. The colour and position of the boxes used are changed from trial to trial to discourage the use of stereotyped search strategies. Two practice trials with three boxes are available to familiarize subjects with the task. These are followed by a four box, six box and eight box stage. The key outcome measures for SWM include errors (revisiting boxes which have already been found to contain a token) and a measure of strategy.

Why use this task?
Patients with Parkinson’s disease often exhibit impairments in spatial working memory, Robbins et al proved the ability of CANTAB SWM to detect these impairments9. This task has also demonstrated sensitivity to changes associated with L-dopa administration10 ; with the addition of L-dopa, dopamine levels are reintroduced, resulting in higher drive and concentration levels.

What research has been done and the need to improve:

CANTAB Connect for Parkinson’s disease is a rapid, reliable, and highly sensitive system for academic research or clinical trials. The CANTAB battery has demonstrated potential advantages when compared to other neuropsychological tests, such as for detecting cognitive impairment in Parkinson’s disease7 and also avoiding floor and ceiling effects. It is highly sensitive to disease progression, can discriminate cognitive impairment due to comorbid depression, and detects untoward effects of medications on cognition11-14. It has also been shown to predict conversion to dementia in patients with Parkinson’s disease15. The use of CANTAB in research of Parkinson’s disease is clinically relevant: cognitive decline measured by the battery correlates with loss of day-to-day functioning in patients with Parkinson’s disease16.

Furthermore, CANTAB maximises scope for sample enrichment, and for demonstrating disease modifying capability of interventions.

There are currently over 125 peer-reviewed publications supporting the application of CANTAB in research of Parkinson’s disease. To find out more, search our bibliography.


1. Parkinson’s UK research Jan 2018 – causation and predictions for the diagnosis of Parkinson’s

2. Kalia LV, Lang AE. Parkinson’s disease. Lancet, 2015; Apr 17. pii: S0140-6736(14)61393-3.

3. Alzheimer’s Association ‘Parkinson’s disease dementia’. Focusing on the prevalence of Parkinson’s

4. Goldman JG & Weintraub D. Advances in the treatment of cognitive impairment in Parkinson’s disease. Movement Disorders, 2015; 30(11): 1471-1489.

5. Kalia, LV, Kalia, SK, & Lang, AE. Disease‐modifying strategies for Parkinson’s disease. Movement Disorders, 2015; 30(11): 1442-1450.

6. Elgh, E, Domellöf, M, Linder, J, Edström, M, Stenlund, H & Forsgren, L (2009), Cognitive function in early Parkinson’s disease: a population-based study. European Journal of Neurology, 16: 1278–1284.

7. Dubbelink, KTO., Stoffers, D, Deijen, JB, Twisk, JW, Stam, CJ, Hillebrand, A, & Berendse, HW (2013). Resting-state functional connectivity as a marker of disease progression in Parkinson’s disease: A longitudinal MEG study. NeuroImage: Clinical, 2, 612-619.

8. Williams-Gray, CH, Evans, JR, Goris, A, Foltynie, T, Ban, M, Robbins, TW, Brayne, C, Kolachana, BS, Weinberger, DR, Sawcer, SJ, & Barker, RA (2009). The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain, 132(11), 2958-2969.

9. Robbins, TW, James, M, Owen, AM, Lange, KW, Lees, AJ, Leigh, PN, Marsden, CD, Quinn, NP & Summers, BA (1993). Cognitive deficits in progressive supranuclear palsy, Parkinson’s disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction. Journal of Neurology, Neurosurgery and Psychiatry. 1994;57:79-88

10. Lange, KW, Robbins, TW, Marsden, CD, James, M, Owen, AM, & Paul, GM (1992). L-dopa withdrawal in Parkinson’s disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction. Psychopharmacology, 107(2-3), 394-404.

11. 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: A Journal of Neurology, 1992; 115: 1727-1751.

12. 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; 31(7): 627-644.

13. Schneider, JS, Sendek, S, & Yang, C. Relationship between Motor Symptoms, Cognition, and Demographic Characteristics in Treated Mild/Moderate Parkinson’s Disease, PLOS ONE, 2015; doi: 10.1371/journal.pone.0123231.

14. Stefanova, E., Potrebic, A., Ziropadja, L., Maric, J., Ribaric, I., & Kostic, V. S. (2006). Depression predicts the pattern of cognitive impairment in early Parkinson’s disease. Journal of the neurological sciences, 248(1), 131-137.

15. Dubbelink, KTEO, Hillebrand, A, Twisk, JWR, Deijen, JB, Stoffers, D, Schmand, BA, Stam, CJ, & Berendse, HW (2014). Predicting dementia in Parkinson disease by combining neurophysiologic and cognitive markers.Neurology, 82(3), 263-270.

16. Nathan et al, 2015: Characterisation of cognitive decline over 5 years in an incident Parkinson’s Disease Cohort: Results from the CamPaIGN Study- Poster presented at ADPD.

17. Yarn all 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;82(4):308-16.

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