BMI Not Found to Affect Cognitive Function, Brain Volume in Patients With RRMS

Body mass index (BMI) was not identified as a factor influencing cognitive function or brain mass in patients with relapsing-remitting multiple sclerosis (RRMS), investigators of a recent analysis concluded.

Body mass index (BMI) was not found to affect cognitive function and brain volume in patients with relapsing-remitting multiple sclerosis (RRMS), according to a study published in the Journal of Central Nervous System Disease.

The phase 3, multicenter randomized controlled study contradicted the long-held belief that a high BMI, which is often used in health care as an indicator for obesity, is linked to cognitive dysfunction and brain volume loss. Previous research has indicated that obesity can serve as a good predictor of cognitive impairment in MS.

Although several studies have established a link between cognitive impairment and brain volume loss in MS, it’s unclear whether this association is triggered by modifiable risk factors, such as BMI, and/or nonmodifiable factors, such as genetics. Additionally, past cross-sectional studies have produced conflicting results on whether a high BMI is related to brain volume loss and cognitive dysfunction.

“The role of BMI in MS continues to be controversial; therefore, there is a critical need for gaining a better understanding of the effect of BMI on cognitive function and brain volume in this population,” noted the investigators.

The study, which served as a secondary data analysis of the CombiRX study, included information on 768 patients who completed 3 years of follow-up. Data on sequential brain MRI films and brain volume calculations, BMI, and cognitive function measurements were analyzed. The Paced Auditory Serial Addition Test (PASAT) was used to test memory, speed of information processing, concentration, and attention, with higher scores indicating better cognitive performance. The impact of BMI on brain volume and cognitive function was assessed using multivariate linear regression, multivariate logistic regression, and mixed model of interaction with time analyses.

The mean (SD) age at baseline of the patients was 38.2 (9.4) years, 73.0% were women, and 88.8% were Caucasian. The baseline mean BMI was 28.80 (6.7) kg/m2, and 32.7% of the cohort had a normal BMI (24.99 kg/m2 or less), 31.0% were considered overweight (BMI, 25.00-29.99 kg/m2), and 36.3% were classified as obese (BMI, 30 kg/m2 or greater).

The mean baseline PASAT score was 53.84 (8.36), and after 36 months it remained unchanged. The investigators observed no significant correlation between baseline BMI and PASAT score at 36 months (P > .05).

In fact, the cognitive function of patients with MS improved over the 3-year time period (P < .001). PASAT scores improved from baseline to month 12 and month 24 but were stable between months 24 and 36. The investigators said that patients missing the PASAT at month 36 had lower baseline PASAT scores.

The multivariable logistic regression and the mixed model analyses did not show an effect of BMI on cognitive function in patients with RRMS. Additionally, a multivariate linear regression model failed to demonstrate a connection between baseline BMI and brain volume. Compared with the normal BMI group, the overweight BMI group showed significantly higher brain volume (P = .022). The obese BMI group showed a higher but statistically insignificant white matter volume compared with the normal BMI group (P = .432).

However, the investigators noted, “Although these results were statistically significant, their clinical meaningfulness is questionable in view of the lack of consistency, the large sample size, and the resulting high power for statistical significance in the analyses.”

The investigators noted several study limitations, including the lack of an age- and sex-matched control group, the exclusion of patients with comorbidities, and the inclusion of only patients with a new diagnosis. In addition, the follow-up time to detect meaningful changes may have needed to be longer than 3 years. BMI is often considered an inaccurate measure of body fat content as it does not take into account muscle mass, bone density, overall body composition, and racial and sex differences, the authors noted.

“To address some of the issues raised, given the mixed nature of the results, future longitudinal prospective research studies should include a few anthropometric measurements and other cognitive tests assessing their associations and the impact of these measurements on the course of MS,” wrote the investigators.


Ben-Zacharia AB, Janal MN, Brody AA, Wolinsky J, Lublin F, Cutter G. The effect of body mass index on brain volume and cognitive function in relapsing–remitting multiple sclerosis: a CombiRx secondary analysis. J Cent Nerv Syst Dis. Published online November 6, 2021. doi:10.1177/11795735211042173