Background 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.
Methods We developed a 5-minute 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. 91 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.
Results The 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.
Conclusions The 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.

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Posted 22 Apr, 2020
On 15 Apr, 2020
On 14 Apr, 2020
On 13 Apr, 2020
On 13 Apr, 2020
On 07 Apr, 2020
Received 10 Feb, 2020
Invitations sent on 05 Feb, 2020
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On 03 Dec, 2019
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On 14 Oct, 2019
On 02 Oct, 2019
Received 25 Jul, 2019
On 10 Jul, 2019
Invitations sent on 09 Jul, 2019
On 24 Jun, 2019
On 24 Jun, 2019
On 24 Jun, 2019
Background 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.
Methods We developed a 5-minute 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. 91 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.
Results The 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.
Conclusions The 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.

Figure 1
Figure 2

Figure 3

Figure 4

Figure 5

Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
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