Abstract
BackgroundCognitive impairment is common in patients with multiple sclerosis (MS). Accurate and repeatable measures of cognition have the potential to be used as markers of disease activity.MethodsWe developed a 5-min computerized test to measure cognitive dysfunction in patients with MS. The proposed test – named the Integrated Cognitive Assessment (ICA) – is self-administered and language-independent. Ninety-one MS patients and 83 healthy controls (HC) took part in Substudy 1, in which each participant took the ICA test and the Brief International Cognitive Assessment for MS (BICAMS). We assessed ICA’s test-retest reliability, its correlation with BICAMS, its sensitivity to discriminate patients with MS from the HC group, and its accuracy in detecting cognitive dysfunction. In Substudy 2, we recruited 48 MS patients, 38 of which had received an 8-week physical and cognitive rehabilitation programme and 10 MS patients who did not. We examined the association between the level of serum neurofilament light (NfL) in these patients and their ICA scores and Symbol Digit Modalities Test (SDMT) scores pre- and post-rehabilitation.ResultsThe ICA demonstrated excellent test-retest reliability (r = 0.94), with no learning bias, and showed a high level of convergent validity with BICAMS. The ICA was sensitive in discriminating the MS patients from the HC group, and demonstrated high accuracy (AUC = 95%) in discriminating cognitively normal from cognitively impaired participants. Additionally, we found a strong association (r = − 0.79) between ICA score and the level of NfL in MS patients before and after rehabilitation.ConclusionsThe ICA has the potential to be used as a digital marker of cognitive impairment and to monitor response to therapeutic interventions. In comparison to standard cognitive tools for MS, the ICA is shorter in duration, does not show a learning bias, and is independent of language.
Highlights
Cognitive impairment is common in patients with multiple sclerosis (MS)
A high level of convergent validity is demonstrated between Integrated Cognitive Assessment (ICA) and Brief International Cognitive Assessment for MS (BICAMS)
Within the BICAMS battery, Symbol Digit Modalities Test (SDMT) had the highest correlation with the ICA test for Scatterplots show ICA vs. BICAMS correlation separately for MS and healthy controls (HC); combining results from both groups (n = 174 total), we find a correlation of 0.82 with SDMT (p < 10− 15), 0.71 with California verbal learning test - 2nd edition (CVLT-II) (p < 10− 10), and 0.60 with Brief visual memory test – revised (BVMT-R) (p < 10− 8)
Summary
Cognitive impairment is common in patients with multiple sclerosis (MS). Accurate and repeatable measures of cognition have the potential to be used as markers of disease activity. Cognitive dysfunction is common in MS patients (40–70% of these patients are reported to have cognitive impairment [2]), and is associated with a higher risk of disease progression in the subsequent years [2]. Cognitive impairment can have significant negative impacts on several domains of daily living activities, such as social functioning, employment [3] and driving [4]. On the other hand, neuroimaging and fluid biomarkers of disease activity [11,12,13], while more accurate, are less suitable for frequent monitoring of disease progression and more difficult to integrate into routine clinical practice. We propose an AI-assisted digital biomarker of cognitive function, appropriate for monitoring disease activity
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