Cognitive Decline, Brain Atrophy More Rapid for Men With MS

Susan Jeffrey

October 20, 2011

October 20, 2011 (Amsterdam, the Netherlands) — A new investigation finds that 6 years after diagnosis, brain volumes and, particularly, cognition were more severely affected in men with multiple sclerosis (MS) than in women with the disease.

White and grey matter atrophy was present in all patients, and deep grey matter structures were also affected, but again particularly in men, the researchers, with lead author Menno M. Schoonheim, a PhD candidate from the Neuroscience Campus Amsterdam, Department of Radiology, VU University Medical Center, Amsterdam, the Netherlands, report.

Thalamic atrophy was most related to cognitive dysfunction out of all the brain structures investigated, Mr. Schoonheim added, and this atrophy was present in both men and women. However, the cognitive effect of the atrophy was mostly seen in the men. Volume changes in the right thalamus best predicted cognition, the authors note, and results were "clearly different" between the sexes.

"This highlights again that gender is important, not only in predisposition but also in clinical progression and cognitive status," Mr. Schoonheim concluded. "However, longitudinal studies are needed to investigate the progression throughout the disease, because this is still a cross-sectional study."

Their results were presented during the Young Scientific Investigators session here at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).

Sex Differences

Grey and white matter atrophy is common in MS, as is cognitive dysfunction, the authors point out. MS is known for its sex effects, with women being more susceptible to the disease, but with men generally facing a worse prognosis.

However, few studies have looked at specific sex effects on atrophy, the authors note. In this study, the researchers investigated the relationship between atrophy and cognition in MS, "focusing on modification of this relationship by gender."

Structural 3T magnetic resonance imaging, including 3DT1 for brain volumes, and cognitive evaluations were performed in 50 healthy control patients (20 men) and 120 patients with relapsing-remitting MS (40 men), part of an early-inception cohort, 6 years postdiagnosis. Sex groups were comparable with regard to age, education level, disability, lesion volume, and disease duration.

Normalized grey matter, white matter, and whole-brain volumes, corrected for head size, were calculated using a method called SienaX, and all subcortical grey matter volumes were determined using FIRST, a method that analyzes brain regions including the thalamus, caudate nucleus, putamen, and others, and provides measures of both right and left structures.

For the subsequent investigation of the interaction between atrophy and cognition, the researchers used only the FIRST measures, Mr. Schoonheim noted, "because there is obviously quite an overlap between the 2."

Cognition was assessed in 8 domains, including executive functioning, verbal and visuospatial memory, attention, and psychomotor speed, to derive a composite Z-score.

Multivariate general linear modeling analyses were used to investigate group differences and group–sex interactions. Stepwise linear regression was used to predict global cognition in the patient group only, using all significant variables.

Most volumes were reduced in patients, with the exception of bilateral hippocampus and amygdala in men and normalized grey matter volume, whole-brain volumes, bilateral putamen, and amygdala, as well as right hippocampus, in women. Volume reductions were larger in men (Cohen's effect size: men, −0.90; women, −0.56).

All cognitive domains except visuospatial memory were affected in men; no cognitive domain was significantly affected in women (Cohen's effect size: men, −0.91; women, −0.38). A group–sex interaction was significant for left caudate volume, verbal memory, and average cognition.

In the MS group, cognition could best be predicted by education, right thalamic volume, and sex. For individual regions, right thalamic volume correlated strongly with averaged cognition (r = .37; P < .0001).

"The thalamus keeps popping up, so it's obviously very important in cognition, as well as gender," Mr. Schoonheim said. "Interestingly, the T2 lesion volume was the only significant predictor of executive function."

Cognition of male patients with MS was predicted by right thalamic volume (r = 0.60; P = .0001) and age. Cognition of female patients with MS was only predicted by education and did not correlate with right thalamic volume, "even though there was thalamic atrophy present. In the male patients, there was about the same amount of atrophy present, but the cognitive domains go down a lot more," Mr. Schoonheim noted, "so interestingly, gender affects this relationship."

Not Unexpected

Asked to comment on these findings, session comoderator Gilles Edan, MD, from the Department of Neurology, University Hôpital Pontchaillou, Centre Hospitalier Universitaire, Service de Neurologie, Rennes, France, said the results were not unexpected, but were nevertheless of interest.

"We know that there are some differences in the natural course of disease between male and female," Dr. Edan told Medscape Medical News. "I would say it was expected, but we have the capability of demonstrating this fact on [magnetic resonance imaging] grounds, so it's quite interesting."

Mr. Schoonheim is sponsored by the Dutch MS Research Foundation. The other authors have disclosed no relevant financial relationships.

5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS): Abstract 9. Presented October 19, 2011.

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