Anxiety, Depression Contribute to Multiple Sclerosis Impaired Cognition

Ruth Ann Marrie, MD, PhD

Anxiety and depression could both contribute to the impaired cognition of patients with multiple sclerosis (MS), according to a recent study that measured their effects across several domains and compared these in patients without immune-mediated inflammatory diseases (IMID) and in those with IMID other than MS.

Ruth Ann Marrie, MD, PhD, a professor in the Department of Internal Medicine, Section of Neurology, and Department of Community Health at the University of Manitoba, and colleagues cited estimates that cognitive impairment occurs in 40% to 70% of persons with MS. While previous studies have suggested that depression influences cognition in MS, they note that findings have been inconsistent, and that there has been little investigation of such effect from anxiety in MS and in other IMID without direct CNS involvement.

"We aimed to examine the association of anxiety and depression on cognitive function in MS, and to determine whether the effects of anxiety and depression on cognition in MS were similar to those observed in inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), and in individuals with anxiety and depressive disorders without an IMID," investigators wrote.

That said, they recognized the challenges of disentangling the role of anxiety symptoms on cognitive function in patients with major depression.

In an accompanying editorial, Anthony Feinstein, MD, PhD, of the Department of Psychiatry at Sunnybrook and Women's College Health Science Centre in Toronto, CA, and colleagues elaborated on the challenges in assessing multiple aspects of mentation, and commended the investigators for "an innovative approach that extends our understanding of the association between cognitive abnormalities and symptoms of depression and anxiety."

Marrie and colleagues enrolled participants into 4 groups by diagnosis: those with MS (n= 225), with inflammatory bowel disease (n= 247), with rheumatoid arthritis (n= 154) and those with either major depressive disorder, any anxiety disorder (excluding specific phobias not found to influence cognition) or the combination but without IMID (n= 308). At the time of enrollment 72.2% of the MS cohort was relapsing-remitting, 18.8% were secondary progressive, and 9.0% were primary progressive. Most participants were female, and the average age ranged from 43-59 years across the 4 groups.

The presence of major depressive disorder or anxiety disorder per medical record was confirmed with the Structured Clinical Interview for DSM-IV (SCID-IV). Severity of current depression and anxiety symptoms was assessed with the Hospital Anxiety and Depression Scale (HADS), which has been validated for use in MS, IBD, RA and the general population.

Three neuropsychological tests were selected to assess core domains of cognitive functioning. In addition, the Wechsler Test of Adult Reading (WTAR) was used to estimate premorbid cognitive functioning, which, the investigators point out, is considered relatively resistant to brain disease.

Marrie and colleagues found that all 4 groups exhibited higher rates of impairment in the domains of processing speed, verbal learning, and delayed recall memory, in comparison to general population norms. Across all 4 groups, higher levels of anxiety symptoms were associated with slower processing speed, lower verbal learning, and lower working memory performance. Higher levels of depression symptoms were associated with slower processing speed.

Feinstein and colleagues characterized some findings as surprising. "Anxiety was more common than depression, which does not fit with recent epidemiologic data from the same research group," they noted. "Furthermore, comorbid anxiety and depression was not more likely than either condition alone to predict cognitive deficits. Recent MS data suggest the opposite."

They added that, while depression is commonly considered to influence cognition in the task initiation and multitasking of everyday life, "it is a striking observation that anxiety rather than depression exerted not only a more profound effect on cognition, but also a more consistent one across diverse disorders."

Marrie and colleagues suggested that the distinctions between the effects of depression and anxiety may be less pertinent than recognition that both contribute to cognitive impairment, and that both are treatable.

"Since symptoms of anxiety and depression represent potentially modifiable factors that influence the cognitive function of persons with MS and other populations, our findings highlight the importance of recognizing and managing these symptoms to mitigate their effect on the functioning of persons with these chronic conditions," the investigators advised.

The study, "Comorbid Anxiety, Depression, and Cognition in MS and Other Immune-Mediated Disorders," was published in Neurology.