ARTICLE IN BRIEF
Investigators reported that patients with primary progressive multiple sclerosis (PPMS) and relapsing-remitting relapsing MS fared worse than healthy controls on cognitive testing; and PPMS patients performed more poorly overall than the matched healthy controls on 16 out of 23 neuropsychological tests, doing worse in almost all domains except visual episodic memory, and visuoconstruction.
Patients with primary progressive multiple sclerosis (PPMS) tend to experience more cognitive impairment than patients with relapsing-remitting MS (RRMS), according to a study that involved extensive neuropsychological testing of participants.
The study sheds new light in particular on the cognitive profile of PPMS, a disease that MS experts say has been hard to characterize.
“Although PPMS is mainly characterized clinically by spinal cord involvement, we observed that cognitive functions are frequently impaired,” Bruno Brochet, MD, a study coauthor told Neurology Today. “Cognitive impairment appears to be more frequent and severe and concerns a wider range of cognitive functions than in relapsing-remitting MS.”
The study, published online Mar. 20 ahead of the print edition of Neurology, was conducted at the University of Bordeaux in France, where Dr. Brochet is a professor of neurology.
“The PPMS patients presented with a wide range of cognitive deficits in information processing speed (IPS), attention, working memory, executive function, and verbal episodic memory, whereas the impairments in RRMS were limited to IPS and working memory,” when compared with healthy controls in the study, the researchers reported.
The study authors noted that there is little published research on the cognitive dysfunction that occurs with PPMS as compared with RRMS, and the findings have not all lined up. Some previous studies had methodological flaws because they did not have separate control groups that took into account differences in age, sex, and education levels that occur between the two types of MS, they pointed out.
To overcome that shortcoming, the researchers set up a cross-sectional study involving 41 PPMS patients, 60 RRMS patients, and 415 healthy controls. The controls were divided into 20 groups according to age, sex, and education level so there was a good match to each group of MS patients. All participants were at least 18 years old. PPMS patients had symptoms of MS for 14 years or less and the RRMS patients had symptoms less than 10 years. Those with psychiatric illnesses, except for stable depressive symptoms, were excluded from the study.
Nearly 88 percent of both the PPMS patients and the RRMS patients were taking disease-modifying drugs at the time of their examination. The average age was 52 for the PPMS patients and just over 37 for the RRMS, and the PPMS group has a greater proportion of women. Disability, as measured by the Expanded Disability Status Scale — 0 to 10, with larger numbers indicating more disability — was 3.5 for the PPMS patients and 1.5 for the RRMS.
All participants underwent a battery of neuropsychological tests that focused on seven cognitive domains: information processing speed, attention, working memory, verbal and visual episodic memory, visuoconstruction, and executive function. Participants were also evaluated for depression, as well as for anxiety and fatigue.
The study authors found that both groups of MS patients fared worse than healthy controls on cognitive testing. PPMS patients performed more poorly overall than the matched healthy controls on 16 out of 23 neuropsychological tests, doing worse in almost all domains except visual episodic memory and visuoconstruction.
“Although cognitive impairment in PPMS has previously been documented, it is noteworthy that the reported rates vary widely in previously studies (from 7% to 58%),” the researchers wrote. “In our study, 47.4% of patients with PPMS were impaired in at least two cognitive domains.”
RRMS patients had lower scores on five out of 23 tests compared with the healthy controls, lagging behind on tests related to information processing speed, attention, and working memory.
Would greater disability in the PPMS group, as measured by EDSS, explain the differences in cognition? Study authors noted that even after controlling for disability and age, cognitive differences emerged in the PPMS and RRMS patients. The PPMS group did worse than the RRMS group on tests that measure working memory and verbal episodic memory.
The researchers noted that the study had some shortcomings because it did not include MRIs of the participants, an element that would have helped researchers “understand the mechanism underlying the cognitive impairments of patients with these different types of MS.” The researchers could have utilized MRIs to determine if cognitive impairment correlated with brain changes seen on imaging.
“We have previously shown that cognitive impairment may be a marker of diffuse brain abnormalities in early RRMS patients,” they wrote. “The observed group difference in the present study could reflect the fact that PPMS patients have more widespread brain damage; specifically, pathological studies suggest that PPMS patients have diffuse pathology in normal appearing white matter and gray matter injury (both cortical and deep gray matter damage).”
Dr. Brochet said in an e-mail interview that the findings should be useful to clinicians who may be evaluating and counseling MS patients who report cognitive difficulties with work or other activities.
“These results should encourage neurologists to assess cognitive functions in patients with PPMS as part of the clinical workup,” Dr. Brochet said. “Since impairment in processing speed is the most frequent deficit observed in PPMS, focusing on information processing speed could be a good strategy to detect cognitive impairment in routine clinical evaluation. There are a number of interventions that have been evaluated that suggest that cognitive reserve can be improved through increasing physical activity, social interaction and challenging mental activities.”
Lauren Krupp, MD, professor of neurology at Stony Brook University Medical Center in New York, told Neurology Today that the new study was an important addition to the understanding of PPMS, which she said is fortunately getting increasing attention from the scientific community. She said that this MS patient population has been difficult to characterize, in part because the disease is less common than RRMS, and the onset is more subtle and gradual. Patients with PPMS are at great risk in delays in diagnosis and perhaps misdiagnosis.
“It's harder to make the diagnosis and we don't have treatments to offer,” she said of PPMS. Sorting out whether cognitive changes are due to the disease itself or in combination with the added effects of aging can also be tough.
“Primary progressive patients tend to be older and those people then are struggling not only from the effects of the disease, but also with decline that can come with aging,” she said.
Dr. Krupp said she was recently awarded a grant from the National MS Society to study whether “cognitive retraining” using computer programs to enhance cognition could be helpful for MS patients, including those with PPMS.
Ralph Benedict, PhD, professor of neurology and psychiatry at University at Buffalo, told Neurology Today that he was somewhat surprised by the findings that patients with PPMS have such a greater extent of cognitive impairment than those with RRMS. “Some studies have reported that, but not to this degree,” he said.
Dr. Benedict, who studies MS, said one of his research aims is to understand grey matter atrophy and how brain changes affect clinical outcomes. He is also interested in the development of good psychometric measures that could be universally used to study cognitive function in MS patients. He noted that different studies use different measures, making comparison of findings difficult.