Depression, Anxiety May Affect Cognitive Outcomes in MS Differently Based on Age

Age is an important moderating factor in the relationship between anxiety or depression and cognitive outcomes in MS.

Age may be an important moderator between mental health symptoms and cognitive outcomes among patients with multiple sclerosis (MS), according to study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023, held in San Diego, California, from February 23 to 25.

Demyelination of neurons in MS has significant effects on neuropsychiatric sequelae. Recent studies have focused on the relationship between symptoms of depression and anxiety with cognition, but previous studies have not considered age as a potential moderator.

Researchers from the University of Toronto in Canada recruited patients (N=802) attending an MS neuropsychiatry appointment to evaluate how age may factor into the relationship between mental health and cognitive outcomes. Patients responded to multiple depression and anxiety questionnaires and underwent cognitive evaluations. Cognitive impairment was defined as >1.5 standard deviations below the normative mean.

The study population was stratified into younger (n=558) and older (n=244) cohorts mean age, 37.80 and 55.10 years, respectively.

Considering age is necessary when exploring the links between depression or anxiety and cognition in people with MS.

In general, the older cohort had more progressive illness, greater disability, obtained a lower level of education, had less anxiety, and a longer disease duration compared with the younger cohort (all P <.01).

Among younger patients, Hospital Anxiety and Depression Scale-depression (HADS-D) scores were negatively related with cognitive impairment (P =.02) and with California Verbal Learning Test Second Edition (CVLT-II) scores (P <.01), Controlled Oral Word Association Test (COWAT) scores (P =.02), Brief Visuospatial Memory Test-Revised (BVMT-R) scores (P =.02), and Paced Auditory Serial Addition Test (PASAT) scores (P <.05).

Among older patients, HADS-D scores were negatively related with COWAT scores (P =.01) and Delis-Kaplan Executive Function Test (D-KEFS) scores (P =.03).

Significant depression and anxiety interactions were observed among the younger cohort with CVLT-II scores (P <.01) and among the older cohort with cognitive impairment (P <.01) and SDMT (P =.01), D-KEFS (P =.01), CVLT-II (P =.02), BVMT (P =.02), and COWAT (P =.03) scores.

The limitations of this study included the small sample size and the cohort imbalances.

The researchers highlighted that “Considering age is necessary when exploring the links between depression or anxiety and cognition in people with MS.”

Overall, symptoms of depression had a larger impact on cognitive impairment among younger patients, whereas anxious distress in depression is more important among older patients.


Freeman DE, Oh J, Feinstein. The age-dependent relationships between depression, anxiety and cognition. Presented at: ACTRIMS Forum 2023; February 23-25; San Diego, CA. Poster 368.