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Associations of visual paired associative learning task with global cognition and its potential usefulness as a screening tool for Alzheimer’s Dementia

Published online by Cambridge University Press:  18 December 2020

Eleanora B. Hicks
UCD School of Medicine, University College Dublin, Dublin, Ireland Adult Neurodevelopmental and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Canada
Naba Ahsan
Adult Neurodevelopmental and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Canada
Apoorva Bhandari
Adult Neurodevelopmental and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Canada
Zaid Ghazala
Faculty of Medicine, University of Toronto, Toronto, Canada
Wei Wang
Adult Neurodevelopmental and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Canada College of Public Health, University of South Florida, Tampa, FL, USA
Bruce G. Pollock
Adult Neurodevelopmental and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Canada Faculty of Medicine, University of Toronto, Toronto, Canada
Tarek K. Rajji
Adult Neurodevelopmental and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Canada Faculty of Medicine, University of Toronto, Toronto, Canada
Sanjeev Kumar*
Adult Neurodevelopmental and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Canada Faculty of Medicine, University of Toronto, Toronto, Canada
Correspondence should be addressed to: Sanjeev Kumar, 6324, 80 Workman Way, Toronto, ONM6J1H4, Canada. Phone: +416 535 8501 ext. 39384; Fax: +416 583 1296. Email:



Appropriate screening is integral to the early diagnosis and management of Alzheimer’s Dementia (AD). The Paired Associates Learning (PAL) task is a digital cognitive task that is free of cultural, language, and educational biases. This study examined the association between the PAL task performance and global cognition and the usefulness of the PAL task as a screening tool for AD.




Academic hospital.


Twenty-five participants with AD and 22 healthy comparators (HC) were included. The Cambridge Neuropsychological Test Automated Battery PAL task and the Montreal Cognitive Assessment (MoCA) were used to assess cognition. We assessed the relationship between the PAL task and MoCA performance using Pearson correlation and linear regression. We also examined the PAL task’s ability to distinguish between AD and HC participants using Receiver Operating Characteristic curve (ROC) analysis.


MoCA Total Score had a strong positive correlation with PAL Stages Completed score (r = 0.8, p < 0.001), and a strong negative correlation with PAL Total Errors (adjusted) score (r = −0.9, p < 0.001). Further, PAL Total Errors (adjusted) score predicted the MoCA Total Score (F (4, 46) = 37.2, p < 0.001). On ROC analysis, PAL Total Errors (adjusted) score cut-off of 54 errors had 92% sensitivity and 86% specificity to detect AD.


Performance on the PAL task is highly associated with global cognition. Further, the PAL task can differentiate patients with AD from HCs with high sensitivity and specificity. Thus, the PAL task may hold potential usage as an easy-to-administer screening tool for AD.

Original Research Article
© International Psychogeriatric Association 2020

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Wei Wang’s affiliations have been updated. An erratum detailing this change has also been published (doi:10.1017/S1041610221000545).

First Co-Authors.


APA (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington: American Psychiatric Association. Google Scholar
Baker, J. E. et al. (2019). Visual paired associate learning deficits associated with elevated beta-amyloid in cognitively normal older adults. Neuropsychology, 33, 964974. CrossRefGoogle ScholarPubMed
Barnett, J. H., Blackwell, A. D., Sahakian, B. J. and 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, 449474. CrossRefGoogle ScholarPubMed
Black, C. M. et al. (2019). Quantifying the diagnostic pathway for patients with cognitive impairment: real-world data from Australia. International Psychogeriatrics, 32, 110. Google ScholarPubMed
Blackwell, A. D., Sahakian, B. J., Vesey, R., Semple, J. M., Robbins, T. W. and Hodges, J. R. (2004). Detecting dementia: novel neuropsychological markers of preclinical Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders, 17, 4248. CrossRefGoogle ScholarPubMed
Borson, S. et al. (2013). Improving dementia care: the role of screening and detection of cognitive impairment. Alzheimer’s & Dementia, 9, 151159. CrossRefGoogle ScholarPubMed
Bosco, A. et al. (2017). Italians do it worse. Montreal Cognitive Assessment (MoCA) optimal cut-off scores for people with probable Alzheimer’s disease and with probable cognitive impairment. Aging Clinical and Experimental Research, 29, 11131120. CrossRefGoogle Scholar
Brown, E. E., Kumar, S., Rajji, T. K., Pollock, B. G. and Mulsant, B. H. (2020). Anticipating and mitigating the impact of the COVID-19 pandemic on Alzheimer’s disease and related dementias. The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry, 28, 712721. CrossRefGoogle ScholarPubMed
Cambridge Cognition (2020). Paired Associates Learning (PAL). Cambridge Cognition Ltd, viewed 7 July 2020. Google Scholar
Chandler, J. M. et al. (2008). P3-111: cognitive assessment: discrimination of impairment and detection of decline in Alzheimer’s disease and mild cognitive impairment. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 4, T551T552. CrossRefGoogle Scholar
Chetelat, G. et al. (2003). Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment. Brain, 126, 19551967. CrossRefGoogle ScholarPubMed
de Rover, M. et al. (2011). Hippocampal dysfunction in patients with mild cognitive impairment: a functional neuroimaging study of a visuospatial paired associates learning task. Neuropsychologia, 49, 20602070. CrossRefGoogle ScholarPubMed
Egerhazi, A., Berecz, R., Bartok, E. and Degrell, I. (2007). Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer’s disease. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31, 746751. CrossRefGoogle ScholarPubMed
First, M.B. (2015). Structured Clinical Interview for the DSM (SCID). In: R.L. Cautin and S.O. Lilienfeld (Eds.), The Encyclopedia of Clinical Psychology. John Wiley & Sons, Inc. Google Scholar
Folstein, M. F., Folstein, S. E. and McHugh, P. R. (1975). Mini-mental state – practical method for grading cognitive state of patients for clinician. Journal of Psychiatric Research, 12, 189198. CrossRefGoogle ScholarPubMed
Fowler, K. S., Saling, M. M., Conway, E. L., Semple, J. M. and Louis, W. J. (2002). Paired associate performance in the early detection of DAT. Journal of the International Neuropsychological Society, 8, 5871. CrossRefGoogle ScholarPubMed
Fronza, G. P. and Dissanayaka, N. N. (2020). Time is brain in dementia. International Psychogeriatrics, 32, 551553. CrossRefGoogle Scholar
Hyman, B. T., Van Hoesen, G. W., Damasio, A. R. and Barnes, C. L. (1984). Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation. Science, 225, 11681170. CrossRefGoogle ScholarPubMed
Ismail, Z., Rajji, T. K. and Shulman, K. I. (2010). Brief cognitive screening instruments: an update. International Journal of Geriatric Psychiatry: A Journal of the Psychiatry of Late Life and Allied Sciences, 25, 111120. CrossRefGoogle ScholarPubMed
Kaur, A., Edland, S. D. and Peavy, G. M. (2019). The MoCA Memory Index Score: an efficient alternative to paragraph recall for the detection of amnestic mild cognitive impairment. Alzheimer Disease & Associated Disorders, 32, 120124. CrossRefGoogle Scholar
Lin, J.S. et al. (2013). Screening for Cognitive Impairment in Older Adults: An Evidence Update for the U.S. Preventive Services Task Force [Internet]. Rockville, MD: Agency for Healthcare Research and Quality (US); 2013 Nov. Report No.: 14-05198-EF-1, viewed 7 July 2020. Google Scholar
McKhann, G. M. et al. (2011). The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 263269. CrossRefGoogle Scholar
Milian, M., Leiherr, A. M., Straten, G., Muller, S., Leyhe, T. and Eschweiler, G. W. (2012). The Mini-Cog versus the Mini-Mental State Examination and the Clock Drawing Test in daily clinical practice: screening value in a German Memory Clinic. International Psychogeriatrics, 24, 766774. CrossRefGoogle Scholar
Nasreddine, Z. S. et al. (2005). The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53, 695699. CrossRefGoogle ScholarPubMed
Nathan, P. J. et al. (2015). Characterization of cognitive function with the cantab in individuals with amnestic mild cognitive impairment in relation to hippocampal volume, amyloid, and tau status: preliminary baseline results from the PharmaCog/european-ADNI study. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 11, P564. CrossRefGoogle Scholar
Parker, M., Barlow, S., Hoe, J. and Aitken, L. (2020). Persistent barriers and facilitators to seeking help for a dementia diagnosis: a systematic review of 30 years of the perspectives of carers and people with dementia. International Psychogeriatrics, 32, 611634. Google Scholar
Parkinson, J. K., Murray, E. A. and Mishkin, M. (1988). A selective mnemonic role for the hippocampus in monkeys: memory for the location of objects. Journal of Neuroscience, 8, 41594167. CrossRefGoogle Scholar
Razani, J. et al. (2007). Predicting caregiver burden from daily functional abilities of patients with mild dementia. Journal of the American Geriatrics Society, 55, 14151420. CrossRefGoogle ScholarPubMed
Razani, J. et al. (2009). Predicting everyday functional abilities of dementia patients with the Mini-Mental State Examination. Journal of Geriatric Psychiatry & Neurology, 22, 6270. CrossRefGoogle ScholarPubMed
Roalf, D. R., Moberg, P. J., Xie, S. X., Wolk, D. A., Moelter, S. T. and Arnold, S. E. (2013). Comparative accuracies of two common screening instruments for classification of Alzheimer’s disease, mild cognitive impairment, and healthy aging. Alzheimer’s & Dementia, 9, 529537. CrossRefGoogle ScholarPubMed
Rosene, D. L. and Van Hoesen, G. W. (1987). The hippocampal formation of the primate brain. In: Jones, E. G. and Peters, A. (Eds.), Cerebral Cortex. Boston, MA: Springer. Google Scholar
Rossetti, H. C., Lacritz, L. H., Cullum, C. M. and Weiner, M. F. (2011). Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample. Neurology, 77, 12721275. CrossRefGoogle Scholar
Sakai, K. and Miyashita, Y. (1991). Neural organization for the long-term memory of paired associates. Nature, 14, 152155. CrossRefGoogle Scholar
Smith, M. L. and Milner, B. (1981). The role of the right hippocampus in the recall of spatial location. Neuropsychologia, 19, 781793. CrossRefGoogle ScholarPubMed
Smith, P. J., Need, A. C., Cirulli, E. T., Chiba-Falek, O. and Attix, D. K. (2013). A comparison of the Cambridge Automated Neuropsychological Test Battery (CANTAB) with “traditional” neuropsychological testing instruments. Journal of Clinical and Experimental Neuropsychology, 35, 319328. CrossRefGoogle ScholarPubMed
Spaan, P. E. J. (2015). Episodic and semantic memory impairments in (very) early Alzheimer’s disease: the diagnostic accuracy of paired-associate learning formats. Cogent Psychology, 3, 1125076. CrossRefGoogle Scholar
Swainson, R. et al. (2001). Early detection and differential diagnosis of Alzheimer’s disease and depression with neuropsychological tasks. Dementia and Geriatric Cognitive Disorders, 12, 265280. CrossRefGoogle ScholarPubMed
Trivedi, D. (2017). Cochrane Review Summary: Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations. Primary Health Care Research & Development, 18, 527528. CrossRefGoogle ScholarPubMed
Webster, P. (2020). Virtual health care in the era of COVID-19. The Lancet, 395, 11801181. CrossRefGoogle ScholarPubMed