Visual, verbal impairments seen in third of NMOSD patients in study

Cognitive impairment was independent of disease duration and antibody status

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by Andrea Lobo |

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More than a third of people with neuromyelitis optica spectrum disorder (NMOSD) show cognitive impairment, particularly in visual processing speed and verbal domains, according to a large study in Germany.

This cognitive impairment was independent of disease duration and remained constant over two years of follow-up. It also did not differ between patients positive for antibodies against AQP4 — the most common target of NMOSD-causing antibodies — and those negative for both anti-AQP4 and anti-MOG antibodies.

The detected visual-related cognitive deficits, along with the fact that vision problems are a hallmark of NMOSD, suggest that “neuropsychological measurements should be adapted to physical and visual disabilities” of this patient population, researchers wrote.

The study, “Cognition in patients with neuromyelitis optica spectrum disorders: A prospective multicentre study of 217 patients (CogniNMO-Study),” was published in Multiple Sclerosis Journal.

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NMOSD is a progressive disease, in which the immune system mistakenly attacks cells from the nervous system, primarily causing inflammation of the optic nerve — the nerve that sends and receives signals from the eye — and the spinal cord. This leads to problems with vision and movement control.

Although the causes of the disease are not fully understood, antibodies targeting the AQP4 protein, found at the surface of certain brain cells, are thought to play a major role in driving the disease. These antibodies are found in about 70% of NMOSD patients, while other antibodies, such as those targeting the MOG protein, can also be detected.

Anti-MOG antibodies can cause a disease called MOG antibody disease, or MOGAD, which has been considered a subtype of NMOSD.

Previous studies have reported that 29% to 67% of NMOSD patients have cognitive impairments, particularly in attention, information processing speed, and memory.

This cognitive impairment does not seem to be related to the presence of anti-AQP4 antibodies or with disease duration, since even patients at early stages might be affected.

However, most of these studies were small and none evaluated cognitive changes over time.

We propose to develop a standard change-sensitive test battery adapted to NMOSD patients for use in future longitudinal studies to examine cognitive performance independently of visual and motor disabilities.

Researchers investigate cognitive performance of 217 adults with NMOSD

To know more, a team led by researchers in Germany investigated the cognitive performance of 217 adults with NMOSD and known antibody status, who were recruited at 17 German Neuromyelitis Optica Study Group centers from September 2015 to April 2021.

The median age of the patients was 52 years (range of 39-60 years), and most were women. Most patients had been living with the disease for a mean of six years. They were either positive for anti-AQP4 antibodies (174 patients; 80.2%), or negative for both anti-AQP4 and anti-MOG antibodies (43; 19.8%). None had MOGAD.

At the start of the study (baseline), the researchers considered only the 157 patients who were younger than 60 years to ensure comparability with data from 241 German-speaking healthy adults, used as a reference population.

On average, the patients performed worse than the average population on the Symbol Digit Modalities Test (SDMT) test, which is used to examine visual processing speed by asking the person to match symbols and numbers.

No group differences were observed on the Paced Auditory Serial-Addition Task, which assesses auditory processing speed.

NMOSD patients also performed worse on the verbal fluency and visual processing speed tests of MuSIC, a short battery of tests used in German-speaking countries.

In turn, patients showed no impairment when they were asked to recall, immediately or with a delay, two lists of words presented to them orally, and even performed better than the reference population when immediately recalling the second list of words.

About 40% of all patients performed poorly in at least one cognitive test, while 19% of the 123 patients who completed two or more tests showed cognitive impairment in at least two tests.

MuSIC visual processing speed was the test in which the greatest proportion of patients performed poorly — 41% of the 76 patients who completed it.

“The result for MuSIC [verbal] fluency constituted the sole exception from the rule that visual processing was affected, while nonvisual processing speed was left intact in NMOSD patients,” the researchers wrote.

“It remains to be seen whether or not this finding reflects the fact that the MuSIC [verbal] fluency task … places heavy demands on cognitive flexibility,” they added.

A total of 15 patients (10%) had an attack within the last 30 days of cognitive assessment, but no significant differences in cognitive performance were detected between these patients and those without a recent attack.

Also, no differences were observed between patients with anti-AQP4 antibodies and those who were double negative. This may be due to “whole-brain involvement with resulting impairment in visual processing speed and [verbal] fluency” in both patient groups, the team wrote.

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Data show below-average visual processing speed in NMOSD patients

One-year follow-up data, ranging from 11 to 16 months, were available for 79 patients, while two-year follow-up data, ranging from 23 to 28 months, were available for 23 patients.

“There was no significant change in performance across all cognitive test scores at 1- and 2-year follow-up,” the researchers wrote.

Patients performed significantly better on the MuSIC visual processing speed test at both follow-up time points than at baseline.

“Our data suggest below-average visual processing speed (as evidenced by the SDMT and MuSIC … results), but intact auditory processing speed in NMOSD patients,” as well as “episodic memory for auditory verbal material,” the team wrote.

Moreover, cognitive performance was not linked to disease duration. Visually impaired patients performed worse in the SDMT test, but not in MuSIC visual processing speed test, relative to those without visual impairments.

This suggests that SDMT “might not be suitable to assess cognitive abilities in NMOSD patients,” the researchers wrote.

“We propose to develop a standard change-sensitive test battery adapted to NMOSD patients for use in future longitudinal studies to examine cognitive performance independently of visual and motor disabilities,” they concluded.