Significant Differences in Perception of Cognitive Impairment in Multiple Sclerosis


Clinician perceived cognitive performance was significantly predicted by multiple factors, including cognitive scores, physical disability, age, and depression.

Mark Gudesblatt, MD, neurologist, South Shore Neurologic Associates

Mark Gudesblatt, MD

Using a multi-domain, validated computerized test battery, results from a recently published study suggest that patients with multiple sclerosis (MS) and their clinicians significantly differ in their perceptions of the patient’s cognitive impairment (CI), and that the factors driving these perceptions vary.

Led by Mark Gudesblatt, MD, neurologist, South Shore Neurologic Associates, the study showed that objective cognitive scores and fatigue significantly predicted patients’ subjective cognitive complaints. In contrast, clinician perceived cognitive deficits were predicted by a combination of factors including the patient with MS’s objective cognitive scores, physical disability, age, and depression.

Gudesblatt et al concluded that, "Nonetheless, these factors influence both PwMS and clinicians in detecting the presence or absence of CI and should be considered as individual important aspects of managing the disease impact and monitoring for change but perception should not be relied upon solely and should be both validated and enhanced by incorporating an examiner independent quantitative multi-dimensional validated screening battery simply as part of routine care."

The trial included 202 patients with MS ranging 20 to 88 years old, with 83% having no disability/minimal signs of disability. Twenty-five (12%) had global CI as determined by the global cognitive score (GCS). In addition to the NeuroTrax computerized multi-domain cognitive testing battery, patients self-reported measures of disease impact, fatigue, and depression, using the Multiple Sclerosis Impact Scale (MSIS-29), Modified Fatigue Impact Scale (MFIS), and Beck Depression Inventory (BDI-II), respectively. MS-related neurological disability was assessed through the Expanded Disability Status Scale (EDSS), an objective, but examiner dependent, measure used by healthcare providers.

In terms of perception of cognitive deficits, 78% (n = 158) of patients with MS reported noticing some level cognitive difficulties whereas 21% of clinicians predicted some degree of cognitive difficulties. Between the 2 groups, perceived cognitive deficits ratings were significantly different on Wilcoxon signed-rank test. Notably, patients with MS endorsed a higher severity of perceived cognitive deficits (mean difference [MD], 2.00; n = 202) compared with their clinicians (MD, 1.00; n = 202).

Reported CI in at least 1 domain was found in at least half (50.5%) of MS cohort. Among patients who showed impairment, clinicians perceived 160 (90.4%) of the 177 as having no cognitive impairment. For patient perceived cognitive deficits, positive predictive value (PPVs) were low across all cognitive domains, but was highest for memory (24.7%). Negative predictive values (NPVs) were highest for attention (97.6%) and GCS (90.9%). In comparison, PPVs were highest for memory (42.9%) and executive functioning (40.4%) and NPVs were highest for GCS (91.9%) and executive functioning (90.6%).

Using Cohen’s kappa, investigators found very little agreement between patient perceived cognitive deficits and objective cognitive functioning across most of the cognitive domains, except for attention (k = –.028; P = .010). Notably, there was a moderate level of agreement between clinician perceived cognitive deficits and objective global CI (k = –.037; P <.001) as well as in most individual cognitive domains.

Patient-Reported Outcomes Improved Through Earlier Initiation of MS Treatment

Using a cohort of more than 2500 patients with MS on disease-modifying therapies, treatment initiation within the first 2 years of disease onset was more beneficial on patient-reported outcomes than 2-4 years postonset.

Patient perceived cognitive deficits were significantly and negatively associated with most cognitive scores, except visual-spatial (rs = –.121; P = .087) and verbal abilities (rs = –.116; P = .100). Clinician perceived cognitive deficits were significantly associated with lower global cognitive scores (rs = –.346; P <.001) as well as all individual cognitive domains. In terms of patient-reported outcomes (PROs), patient and clinician perceived cognitive deficits were positively correlated with EDSS, though this correlation was stronger among clinician perceived cognitive deficits (rs = .283; P <.001).

Age, GCS, and PROs were included in a model to evaluate variables as predictors of change in patient perceived cognitive deficits. Here, investigators observed that GCS (P = .012) and MFIS (P <.001) were significant predictors, as patients with MS who achieved a lower GCS (odds ratio [OR], .976; 95% CI, .957-.995) and reported higher levels of fatigue (OR, 1.038; 95% CI, 1.018-1.058) were more likely to indicate greater severity in their cognitive dysfunction. BDI-II was not a significant predictor of patient perceived cognitive deficits (P = .226).

The second model, which assessed clinician perceived cognitive deficits as an outcome, demonstrated that GCS (P <.001), EDSS (P = .011), age (P = .021), and BDI-II (P = .038) significantly predicted these deficits. Clinicians were more likely to report greater severity perceived cognitive dysfunction if patients with MS were older (OR, 1.045; 95% CI, 1.007-1.085), achieved a lower GCS (OR, .951; 95% CI, .929-.974), had higher levels of disability (OR, 1.292; 95% CI, 1.060-1.574) and reported higher levels of depression (OR, 1.037; 95% CI, 1.002-1.074).

1. Jackson DA, Nicholson R, Bergmann C, et al. Cognitive impairment in people with multiple sclerosis: perception vs performance–factors that drive perception of impairment differ for patients and clinicians. Mult Scler Relat Disord. January 2023;69:104410. doi:10.1016/j.msard.2022.104410

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