Brief, Automated Cognitive Test May Offer Key Advantages in MS

The National Institutes of Health Toolbox Cognitive Battery (NIHTB-CB), a 30-minute, automated, iPad-based battery of psychological tests, offers some key advantages over gold standard cognitive assessments in patients with relapsing-remitting multiple sclerosis (RRMS), new research shows

“To our knowledge this is the first psychometric evaluation of the NIH Toolbox Cognition Battery in MS,” study investigator Heena R. Manglani, MA, a clinical psychology fellow at Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“[The findings] suggest that the NIH Toolbox Cognition Battery may be used as an alternative to other gold-standard measures which may cover limited domains or require manual scoring,” added Manglani, who is working toward her PhD in clinical psychology.

The study was presented at the Consortium of Multiple Sclerosis Centers (CMSC) 2021 annual meeting.

An Indicator of Disease Activity?

Cognitive deficits affecting a range of functions — including memory, attention and communication — are common in MS and affect 34% to 65% of patients with the disease, and the ability to detect and monitor such deficits has important implications.



Heena Manglani

Cognitive changes can provide a unique opportunity to identify acute disease activity in patients with MS that might be already occurring before physical manifestations become apparent, said Manglani. “If we can detect subtle changes in cognition that might foreshadow other symptoms of disease worsening, we can then allocate interventions that might stave off cognitive decline,” she explained.

While there is an array of well-established neuropsychological tests for the assessment of cognitive deficits, each has limitations, so a shorter, computerized, convenient, and reliable test could prove beneficial.

The NIHTB-CB has been validated in a large, nationally representative sample of individuals aged 8 to 85 and represents a potentially attractive option, yielding composite measures and scores corrected for age, gender, education, race, and ethnicity.

Comparative Testing

To compare the test with other leading cognition tools used in MS, the investigators recruited 87 patients with RRMS (79% female, mean age 47.3 years).

Participants were recruited to perform the full NIHTB-CB (about 30 minutes) and the full Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS), which takes about 90 minutes, as well as some subsets from the Wechsler Adult Intelligence Scale-IV (WAIS-IV) covering processing speed and working memory. All patients had an EDSS of 5.0 or below and, on average, had been living with MS for about a decade.

The results showed the normative scores for NIHTB-CB had significant concordance with the other measures in terms of processing speed (concordance correlation coefficient [CCC] range = 0.28 – 0.48), working memory (CCC range = 0.27 – 0.37), and epi­sodic memory (CCC range = 0.21 – 0.32). However, agreement was not shown for executive function (CCC range = 0.096 – 0.11).

Manglani noted executive function included various submeasures such as planning and inhibitory control. “Perhaps our gold standard measures tapped into a different facet of executive function than measured by the NIHTB,” she said.

The investigators found the proportion of participants classified as cognitively impaired was similar between the MACFIMS and the NIHTB tests.

Further assessment of fluid cognition on the NIHTB-CB — a composite of processing speed, working memory, episodic memory, and executive function that is automatically generated by the toolbox — showed the measure was negatively associated with disease severity, as measured by the EDSS (P = .006). However, the measure was not associated with a difference in depression (P = .39) or fatigue (P = .69).

Of note, a similar association with lower disease severity on the EDSS was not observed with MACFIMS.

“Interestingly, we found that only the NIHTB-CB fluid cognition was associated with disease severity, such that it was associated with nearly 11% of the variance in EDSS scores, and we were surprised that we didn’t see this with MACFIMS,” Manglani said.

Key Advantages

The NIHTB-CB was developed as part of the NIH Blueprint for Neuroscience Research initiative and commissioned by 16 NIH Institutes to provide brief, efficient assessment measures of cognitive function.

The battery has been validated in healthy individuals and tested in other populations with neurologic disorders including patients who have suffered stroke and traumatic brain injury.

Manglani noted that the NIHTB-CB had key advantages over other tests.

“First, it is a 30-minute iPad-based battery, which is shorter than most cognitive batteries available, and one of the few that is completely computerized. In addition, it automatically scores performance and yields a report with both composite scores and scores for each subtest,” she said.

In addition, said Manglani, “the NIH toolbox has a large validation sample of individuals between 8-85 years of age and provides normative scores that account for age, gender, education, and race/ethnicity, which allows individuals’ performances to be compared with their peers.”

The findings underscore that with further validation, the battery could have an important role in MS, she added.

“The NIH Toolbox needs to be tested in all subtypes of MS, with a full range of disease severity, and in MS clinics to gauge the clinical feasibility. Larger samples and repeated assessments are also needed to assess the test-retest reliability,” she said.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

Consortium of Multiple Sclerosis Centers (CMSC) 2021 Annual Meeting: Presented October 25, 2021.

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