Photo Credit: Katarzyna Bialasiewicz

Patients with MS performed worse on cognitive tests when they had anxiety and depression, therefore depression plus comorbid anxiety may predict cognitive dysfunction in MS.

Depression and anxiety are linked with worsened cognitive function in patients living with multiple sclerosis, according to findings recently published in the Journal of Neurology.

“Cognitive dysfunction and impairment is an often unrecognized but important issue for a lot of people with MS,” Dr. David E. Freedman, MD, a resident physician in psychiatry at the University of Toronto, Canada, told Physician’s Weekly. It occurs in about 40% to 90% of people, and cognitive dysfunction can contribute to social isolation, unemployment, and reduced quality of life. That is the impetus for the importance of identifying potential modifiable contributors, and two such contributors may be depression and anxiety.”

How Depression and Anxiety Influence Cognition in MS

Dr. Freedman explains that previous literature on the subject has been mixed. “Some studies show that these issues are connected to cognitive impairment and people with MS, and some that do not find evidence of an independent link,” Freedman says. “No study has been conducted with a large sample, using validated scales, to look at the combined influence of depression and anxiety.”

Freedman and colleagues performed a cross-sectional analysis of 831 patients with a confirmed multiple sclerosis diagnosis. All patients were treated and assessed over 11 years at a Toronto tertiary care neuropsychiatric clinic. The researchers collected data on patients and their characteristics, such as level of education, sex, age, whether they had relapsing-remitting or secondary or primary progressive disease, degree of physical disability as measured by the Expanded Disability Status Scale, and the presence of disease-modifying therapy. They also made records of depression and anxiety symptoms, using the Hospital Anxiety and Depression Scale (HADS) for both anxiety (HADS-A) and depression (HADS-D) to quantify symptoms.

Freedman and colleagues divided the patients into four different strata: (1) neither anxiety nor depression, defined as a HADS-A score of less than 11 and HADS-D also less than 11; (2) only anxiety (HADS-A score of 11 or more and HADS-D of less than 11); (3) only depression, defined as HADS-D of 11 or greater and HADS-A of less than 11; and (4) both anxiety and depression (HADS-A and HANDS-D of 11 or more). The researchers assessed patients’ cognitive functioning using the Minimal Assessment of Cognitive Function in MS scale.

The patients were an average of 43.2 years old. The mean disease duration was 9.9 years, and patients had a median score of 2 on the disability status scale. Nearly three-quarters of patients were women (72%), and most (80%) had relapsing-remitting disease. Two-thirds (66.2%) were receiving disease-modifying treatment.

One-quarter of patients had only anxiety without depression (25%), whereas 5% had depression but not anxiety, Freedman and colleagues reported. Clinically significant anxiety and depression occurred in 12.6% of participants. Nearly half of patients (44%) had global cognitive impairment.

Patients with comorbid anxiety and depression performed significantly worse on all Minimal Assessment of Cognitive Function in MS measures than those without anxiety or depression, except for in the Brief Visuospatial Memory Test-Revised (BVMT-R) domain, the researchers wrote (P<0.05). The same was true when they compared patients with both anxiety and depression to patients who only had anxiety (P<0.05), Freedman and colleagues wrote, “with trends toward significance for BVMT-R and PASAT [Paced Auditory Serial Addition Test] tests.”

“We found that depressive symptoms, especially with comorbid anxiety, were independently predictive of many domains of cognition in people with MS,” Freedman explains. “And this remained true even after accounting for several other confounding variables, like sex, years of education, disease, the level of disability, the disease, subtype, and age—all of these things we were able to control for—and it remained an independent link.”

However, this did not hold true for all patients. Patients who had depression without anxiety still scored better in many areas than those with both conditions, though those with only depression still performed worse than those with neither comorbidity, the researchers reported.

“There were no significant differences between participants with only anxiety and neither depression nor anxiety, or between those with only anxiety or only depression,” Freedman and colleagues wrote in their paper.

The relationship was not necessarily causative, Freedman went on. The results raise several questions about the exact nature of the relationship between depression, anxiety, and cognitive function in people with MS.

Future Work

“Although we have many studies that found depression to be associated with cognitive dysfunction, it’s unclear at this stage why this anxiety and depression is indicative of, or associated with, greater cognitive dysfunction,” he said. “Could there be something that particularly has an adverse impact when depression and anxiety show up together? Is it possible that the comorbid anxiety is a marker of greater severity of depression so that these are people with a more severe depression, which may be more linked to cognitive dysfunction? Is it possible that decreased cognitive function contributes to changes in depression and anxiety?”

Freedman said he hopes the study has laid the groundwork for future researchers, including the question of whether care for depression and anxiety might improve cognitive function in these patients.

“This would be a really important question for a lot of people with MS,” he said. “Our study can’t answer that question. But it sets up the foundation for studies that can.”