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Mechanisms of Suboptimal Cognitive Performance in MS Remain a Mystery Despite Frequency

Invalid and valid performers did not differ regarding demographic, patient-reported, and disease-related outcomes.

Using validity testing, neuropsychological assessments, neuroimaging, and questionnaires, a group of investigators concluded that suboptimal cognitive performance occurs frequently in patients with multiple sclerosis (MS) and should be considered in the interpretation of cognitive complaints. They also concluded that no satisfactory explanation for suboptimal performance was detected, warranting future research on its underlying mechanisms and why performance validity test (PVT) failure occurs in a substantial percentage of patients with MS with cognitive complaints.

Senior author Martin Klein, PhD, professor of psychology, Vrije Universiteit Amsterdam, and colleagues analyzed 99 patients with MS in an outpatient setting and classified each individual as valid or invalid based on PVTs. Performance validity was assessed with the Amsterdam Short-Term Memory (ASTM) test, a forced-choice verbal recognition test specifically designed to indicate whether patients perform their actual level of competence. In addition, patients were categorized based on neuropsychological test results as cognitively impaired or preserved.

Demographic characteristics including age, sex, work status, and level of education were collected. In total, 20% (n = 20) of the patients scored below the PVT cut-off. Despite this, neither invalid or valid performers differed on demographic, disease-related, and patient-reported outcomes.

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Klein and colleagues wrote, "Even though it remains difficult to grasp the underlying reasons of suboptimal performance, absence of PVTs may result in invalid interpretations of cognitive test results and consequently in less relevant patient education and counseling. Performance validity during neuropsychological assessments of MS patients thereby warrants attention in clinical and research settings.”

Regardless of performance validity, 63% of the sample was categorized as cognitively impaired. Compared to valid performers, invalid performers had lower overall cognitive functioning (P = .001), verbal memory (P <.001), and response inhibition (P = .004). Results also showed that 56% of valid performers were classified as cognitively impaired compared to 90% of invalid performers.

Data from the regression analysis indicated that lower PVT scores, which tended toward lower validity, were related to lower overall cognitive functioning (ß = 0.55; P <.01). PVT scores also explained 29% of the variance in overall cognitive functioning. Other outcomes such as lower processing speed (P = .002), verbal memory (P <.001), visuospatial memory (P <.001), and response inhibition (P <.001) all correlated with lower PVT scores. Additional correlations included higher Expanded Disability Status Scale scores (P = .021), male sex (P = .008), and a lower education (P = .008) were also observed. Patient-reported outcomes were among other variables not significantly related to PVT scores.

In total, 29% (18 of 62) of patients with cognitive impairment had invalid performance. Investigators found however, no differences regarding demographic, disease-related, patient-reported, or cognitive outcomes between valid and invalid performers. Only 5% (2 of 37) of cognitively preserved patients had invalid performance, but due to the low sample size statistical analysis wasn’t performed.

Subgroups such as cognitively preserved valid performers, cognitively impaired valid performers, and cognitively impaired invalid performers differed with regard to disease severity and sex (P <.05). Specifically, the cognitively impaired valid and invalid performers had a higher lesion load (P = .003 and P = .027, respectively), smaller whole-brain volume (P = .002 and P = .020, respectively), and higher disability level (P = .004 and P = .009, respectively), than the cognitively preserved valid performers. Additionally, these groups consisted of relatively more males than the cognitively preserved valid performers (P = .003 and P = .016, respectively).

Nauta IM, Bertens D, van Dam M, et al. Performance validity in outpatients with multiple sclerosis and cognitive complaints. Mult Scler J. Published July 2, 2021. doi: 10.1177/1352458211025780