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13 July 2021

COVID-19 Cognitive Assessment Battery

To understand the impact of COVID-19 on cognitive function, researchers must use sensitive and reliable cognitive assessments which target appropriate domains. In this article Operational Scientist, Iona Pickett, discusses the challenges of designing a cognitive testing battery for use in those recovering from COVID-19 and describes our recommended CANTAB battery for COVID-19 studies.

In our previous blog posts: ‘Cognition and COVID-19 – What we know’ and ‘Understanding the challenges of assessing cognitive function in patients recovering from COVID-19’, we discussed the neuropsychological effects of COVID-19, and the challenges which must be overcome to study the impact of COVID-19 on cognition. Understanding the causes and nature of COVID-19 -related cognitive impairment is an important step towards providing long-term care and support to those recovering from COVID-19. To achieve this, researchers need to use sensitive assessments which target relevant cognitive domains, and methods which can ensure research continuity during an ongoing pandemic. This article presents a recommended CANTAB battery which we believe will help researchers to complete meaningful research in this area by providing theory-driven cognitive test which are not reliant on face-to-face, in-clinic assessment

Designing a COVID-19 Battery

In our previous blog post, we discussed the challenges faced by researchers assessing cognition in COVID-19 survivors. These included:

  • Uncertainty in the cognitive domains affected by COVID-19.
  • The need to balance the breadth and depth of cognitive test batteries with efficiency to meet time and resource constraints.
  • The ability to measure and account for other factors commonly found in COVID-19 survivors, which may also impact cognition, including fatigue, depression and anxiety.
  • Potential future increases in pandemic-related restrictions, which may disrupt or prevent face-to-face assessment and research.

Taking these considerations into account, the Science team at Cambridge Cognition has compiled a CANTAB test battery which aims to target domains implicated in COVID-19-related cognitive impairment and is suitable for both in-clinic and web-based testing. The core recommended battery for studies assessing cognition in patients recovering from COVID-19 is presented below.

The CANTAB COVID-19 Battery

The tasks included in the CANTAB COVID-19 battery, summarised in the table below, have been selected to target the brain regions and cognitive processes which are currently thought to be most impaired in COVID-19 survivors. Depending on task variants used, this battery is estimated to take between 39 and 45 minutes to complete. All tasks are suitable and validated for in-clinic or web-based testing, however it should be noted that reaction time outcome measures are not recommended for use with web-based testing.

Task:

  • Spatial Working Memory (SWM)
  • Paired Associates Learning (PAL)
  •  Stockings if Cambridge (SOC) 
  • Delayed Matching to Sample (DMS)
  • Rapid Visual Information Processing (RVP)  

Target Domain:

  • Working memory and strategy
  • Visual episodic memory 
  • Planning and executive function 
  • Attention and short term visual memory 
  • Sustained attention 

SWM targets short term memory and visuospatial processing, two cognitive domains which are strongly suggested to be impaired in COVID-19 survivors [1-3]. This task is also associated with brain activity in the frontal lobe and thalamic regions, which are areas found to be altered in some cognitively-impaired patients recovering from COVID-19 [2,4].

PAL is a highly sensitive test of episodic memory which is associated with activity in the hippocampus [5]. There is strong evidence to suggest that the hippocampus plays an important role in cognitive impairment in COVID-19 survivors [6, 7], so PAL is thought to be a particularly sensitive task for characterising deficits within this brain region. PAL has also been used to reliably differentiate between mild and more severe cognitive impairment in Alzheimer’s populations [8, 9], which may make it suitable for assessing cognition in a heterogenous post-COVID population.

SOC is a test of executive function and is associated with activity in the frontal lobe [10]. Executive function is a cognitive domain which includes high level thinking and decision making processes such as mental flexibility, problem solving, and planning. Many patients recovering from COVID-19 report deficits in executive function [2, 11], and there is some evidence that these deficits are associated with damage to the frontal lobe [4].

DMS is a test which targets visuospatial processing, attention, and short term memory, all domains which are consistently shown to be impaired in COVID-19 survivors [2, 12, 13]. These cognitive processes do not work in isolation, so by including a test which combines them, as well as tests which target them separately (PAL, RVP, and SWM), we may get a more detailed picture of cognitive impairment in COVID-19 survivors.

Finally, RVP is a measure of sustained attention. Attentional problems are frequently reported by patients recovering from COVID-19 [1 6, 14]. This task is highly sensitive and has detected clinically meaningful impairments in many patient populations, including Alzheimer’s, depression, and schizophrenia [15-17].

Additional testing considerations

Depending on the aims of the study and the subject population of interest, some additional tests may also be appropriate.

The Emotional Bias Task (EBT) is a short test of social cognition which may be used as an indicator of changes in cognition related to depression or anxiety. Questionnaires such as the Patient Health Questionnaire -9 or General Anxiety Disorder -7, used to assess symptoms of depression and anxiety, may also be useful to identify the presence of psychiatric symptoms which may also contribute to cognitive impairment following COVID-19. Similarly, questionnaires assessing fatigue, such as the Modified Fatigue Impact Scale, may help researchers to characterise fatigue in COVID-19 survivors and understand its relationship to comorbid cognitive impairments. This may be particularly useful in studies of patients with so-called “Long Covid”, where fatigue is a key symptom and contributor to low quality of life [2, 4, 12, 18].

Some studies may be more suited to short, high-frequency cognitive assessments, such as our Digital Health tasks, than longer, traditional CANTAB tasks. These types of assessment reduce patient burden and improve the ability to detect change in performance over time [19]. Fatigue appears to be a key symptom of Long Covid and may also be a therapeutic area particularly well suited to high-frequency tests, as discussed in our eBook and blog post. The CANTAB Digital Health tasks are also sensitive measures of global cognition, which may support cognitive assessment where the specific domains of impairment are unclear.

Summary

To investigate cognitive impairment in those recovering from COVID-19, researchers must balance the breadth and depth of their cognitive test battery (maximising the ability to capture clinically meaningful impairment) with practical constraints, such as task duration and adaptability to changing COVID-19 restrictions. The recommended CANTAB COVID-19 Battery targets multiple domains implicated in post-COVID cognitive impairment and includes tasks which are sensitive to even mild cognitive impairment. The battery is suitable for both in-clinic and web-based testing, ensuring research continuity in uncertain times. It can also be tailored to specific study requirements through incorporation of additional CANTAB tasks, digital questionnaires or Digital Health tasks.

To see how our COVID battery is being used in upcoming COVID-19 research, take a look at the blog posts written by our CANTAB Research Grant Winners, Julius Rave, Pim Heckman, and Jamileth More.

References 

  1. Woo, Marcel S.; Malsy, Jakob; Pöttgen, Jana; Seddiq Zai, Susan; Ufer, Friederike; Hadjilaou, Alexandros et al. (2020). Frequent neurocognitive deficits after recovery from mild COVID-19. Brain communications 2 (2), fcaa205. DOI: 10.1093/braincomms/fcaa205.
  2. Raman, B., Cassar, M., Tunnicliffe, E.M., Filippine, N., et al. (2020). Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. medRxiv Preprint. doi: https://doi.org/10.1101/2020.10.15.20205054
  3.  Pinna, P., Grewal, P., Hall, J.P., Tavarez, T., Dafer, R.M., Garg, R., Osteraas, N.D., Pellack, D.R., Asthana, A., Fegan, K., Patel, V., Conners, J.J., John, S., Silva, I.D.. (2020). Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline. J Neurol Sci., 415:116969. doi: 10.1016/j.jns.2020.116969. Epub 2020 Jun 3.
  4. Helms, J., Kremer, S., Merdji, H., Schenck, M., Severac, F., Clere-Jehl, R., Studer, A., Radosavljevic, M., Kummerlen, C., Monnier, A., Boulay, C., Fafi-Kremer, S., Castelain, V., Ohana, M., Anheim, M., Schneider, F., Meziani, F. (2020). Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients. Crit Care., 24(1):491. doi: 10.1186/s13054-020-03200-1. 
  5. Barnett, J. H., Blackwell, A. D., Sahakian, B. J., & Robbins, T. W. (2016). The Paired Associates Learning (PAL) Test: 30 Years of CANTAB Translational Neuroscience from Laboratory to Bedside in Dementia Research. Current topics in behavioral neurosciences, 28, 449–474. https://doi.org/10.1007/7854_2015_5001
  6. Ritchie, K., Chan, D., & Watermeyer, T. (2020). The cognitive consequences of the COVID-19 epidemic: collateral damage?. Brain Communications, 2,2, fcaa069, https://doi.org/10.1093/braincomms/fcaa069
  7. Lu, Yiping; Li, Xuanxuan; Geng, Daoying; Mei, Nan; Wu, Pu-Yeh; Huang, Chu-Chung et al. (2020). Cerebral Micro-Structural Changes in COVID-19 Patients – An MRI-based 3-month Follow-up Study. EClinicalMedicine 25. DOI: 10.1016/j.eclinm.2020.100484
  8. Saunders, N. L., & Summers, M. J. (2011). Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment. Neuropsychology, 25(2), 237–248. https://doi.org/10.1037/a0021134
  9. Swainson R, Hodges JR, Galton CJ, Semple J, Michael A, Dunn BD, et al. (2001.) Early detection and differential diagnosis of Alzheimer’s disease and depression with neuropsychological tasks. Dement Geriatr Cogn Dis, 12: 265-80
  10. Robbins, T. W., James, M., Owen, A. M., Sahakian, B. J., Lawrence, A. D., McInnes, L., & Rabbitt, P. M. (1998). A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Cambridge Neuropsychological Test Automated Battery. Journal of the International Neuropsychological Society : JINS, 4(5), 474–490. https://doi.org/10.1017/s1355617798455073
  11. Whiteside DM, Oleynick V, Holker E, Waldron EJ, Porter J, Kasprzak M. (2021). Neurocognitive deficits in severe COVID-19 infection: Case series and proposed model. Clin Neuropsychol., 1-20. 2.
  12. Baker, H. A., Safavynia, S. A., & Evered, L. A. (2020). The ‘third wave’: impending cognitive and functional decline in COVID-19 survivors. British journal of anaesthesia., S0007-0912(20)30849-7. Advance online publication. https://doi.org/10.1016/j.bja.2020.09.045
  13. Zubair A.S., McAlpine L.S., Gardin T., Farhadian S., Kuruvilla D.E., Spudich S. (2020). Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurol., 77(8):1018–1027. doi:10.1001/jamaneurol.2020.2065
  14. Hosey, M.M., Needham, D.M. (2020). Survivorship after COVID-19 ICU stay. Nat Rev Dis Primers 6, 60. https://doi.org/10.1038/s41572-020-0201-1
  15. Haig, G. M., Bain, E. E., Robieson, W. Z., Baker, J. D., & Othman, A. A. (2016). A Randomized Trial to Assess the Efficacy and Safety of ABT-126, a Selective α7 Nicotinic Acetylcholine Receptor Agonist, in the Treatment of Cognitive Impairment in Schizophrenia. The American journal of psychiatry, 173(8), 827–835. https://doi.org/10.1176/appi.ajp.2015.15010093
  16. Cabeça, H., Rocha, L. C., Sabbá, A. F., Tomás, A. M., Bento-Torres, N., Anthony, D. C., & Diniz, C. (2018). The subtleties of cognitive decline in multiple sclerosis: an exploratory study using hierarchichal cluster analysis of CANTAB results. BMC neurology, 18(1), 140. https://doi.org/10.1186/s12883-018-1141-1
  17. Egerházi, A., Berecz, R., Bartók, E., & Degrell, I. (2007). Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer’s disease. Progress in neuro-psychopharmacology & biological psychiatry, 31(3), 746–751. https://doi.org/10.1016/j.pnpbp.2007.01.011
  18. Zhou, H., Lu, S., Chen, J., Wei, N., Wang, D., Lyu, H., Shi, C., & Hu, S. (2020). The landscape of cognitive function in recovered COVID-19 patients. Journal of psychiatric research, 129, 98–102.
  19. Hassenstab, J., Aschenbrenner, A.J., Balota, D.A., McDade, E., Lim, Y.Y., Fagan, A.M., Benzinger, T.L., Cruchaga, C., Goate, A.M., Morris, J.C., and Bateman, R.J. (2020), Remote cognitive assessment approaches in the Dominantly Inherited Alzheimer Network (DIAN). Alzheimer’s Dement., 16: e038144. https://doi.org/10.1002/alz.038144

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Operational Scientist, Cambridge Cognition

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