Higher BMI Linked to Lower Brain Volume in MS

November 07, 2018

BERLIN — Higher body mass index (BMI) is associated with lower subsequent brain volume in patients with multiple sclerosis (MS), a new study shows, but vitamin D status did not appear to meaningfully relate to subsequent brain volumes.

The research was presented at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018 by Ellen Mowry, MD, Johns Hopkins School of Medicine, Baltimore, Maryland.

Another study by the same group suggested a link between higher-quality diets and lesser disease severity. The study employed measures of disability, mobility, and cognitive function.

"These are exciting results, and they should encourage further studies to see if modifying BMI can reduce brain volume loss," Mowry said of the BMI findings.

The co-chair of the session at which the BMI study was reported, Maria Pia Amato, MD, University of Florence, Italy, told Medscape Medical News that BMI is one of the most studied risk factors for MS and that increased BMI has been shown in numerous studies to be linked to higher risk of developing MS.

"Now we see that it is also associated with more severe disease in terms of brain atrophy, so it appears to be more than just a risk factor; it is a prognostic marker as well," Amato said. "I think it is time that neurologists explain to patients the importance of lifestyle factors. These lifestyle factors are modifiable — we should be putting more emphasis on eating a healthy diet and reducing body mass index.

"Vitamin D appears to be more complicated — it might be more important in the early stage of the disease," she noted.

Mowry and colleagues' BMI study involved a large cohort of patients with MS or clinically isolated syndrome (CIS). Patients were evaluated as to whether BMI or vitamin D levels were associated with subsequent gray matter loss.

"We were interested particularly in gray matter loss, as that is what is associated most in patients with MS with long-term disability," Mowry explained.

The researchers examined data from the EPIC cohort, a 5-year study that began in 2004, mostly from the University of California, San Francisco, MS Center. This cohort included white individuals with all types of MS whose Expanded Disability Status Scale (EDSS) score was less than 8.

Patients gave a blood sample and underwent a clinical evaluation and a brain MRI examination annually. Brain volume measures, including normalized gray matter volume (nGMV), white matter volume (nWMV), and brain parenchymal volume (nBPV), were determined using SIENAX (a cross-sectional version of the Structural Image Evaluation Using Normalization of Atrophy measure).

For the current study, patients were included if they had relapsing remitting MS or CIS and had undergone at least one follow-up visit. Vitamin D levels were measured from stored samples at baseline; BMI was calculated from self-reported height and weight, measured at baseline and subsequently.

Results were adjusted for age, sex, ethnicity, smoking status, use of MS therapy, disease duration, EDSS score, baseline T2 lesion volume, and new T2 lesions.

At baseline, the average age of the patients was 42 years; 70% were women; and 12% were smokers. Mean BMI was 25, and the mean baseline 25 hydroxyvitamin D level was 28 ng/mL. Vitamin D supplements were being taken by 9% of those included in the study. The average duration of MS was 5 years; 64% of the patients had received MS treatment within the prior year; and the median EDSS score was 1.5.

Results showed that higher BMI was associated with lower brain parenchymal volume and gray matter volume.

Table 1. Association of Body Mass Index With Brain Volumes

Endpoint BMI (per 1 kg/m2 Greater) P Value
Gray matter volume (cc) -1.1 .001
Brain parenchymal volume (cc) -1.1 .039
White matter volume (cc) -0.7 .42


There was also a strong relationship of BMI with gray matter loss over time, as indicated in Table 2.

Table 2. Gray Matter Loss by Quintile of BMI

Endpoint BMI < 25 (n = 244) BMI 25 - 30 (n = 127) BMI 30 - 35 (n = 55) BMI 35 - 40 (n = 13) BMI > 40 (n = 8)
Change in normalized gray matter volume (cc) 0 -0.02 -6.9 -12.6 -29.2
P for trend = .018.


However, the vitamin D results were not significant, as indicated in Table 3.

Table 3. Association of Vitamin D Levels With Brain Volumes

Endpoint 25-hydroxyvitamin D (per 10 ng/mL Greater) P Value
Gray matter volume (cc) -0.9 .36
Brain parenchymal volume (cc) 0.6 .74
White matter volume (cc) -0.7 .73


"This study suggests that MS patients with higher BMIs are more likely to have faster atrophy of the brain in the MS," Mowry commented.

"But it is probably more complicated than BMI alone — like in heart disease, where you carry your weight is relevant," she added. "Fat muscle ratio is likely also important, but I think we have enough data now to start to look at these modifiable risk factors."

Mowry noted that previous studies have suggested an association of vitamin D levels with brain volume loss as well as fewer relapses and fewer new lesions on MRI.

"But these generally included earlier patients," she said. "There is also good data suggesting higher vitamin D is associated with lower risk of developing MS. Our current study included patients with a longer history of MS — so maybe vitamin D has more of an impact earlier on."

High-Quality Diet Linked to Better Outcomes

In a separate study also presented by Mowry, for MS patients who consumed a high-quality of diet (similar to the Mediterranean diet), disease was less severe, as determined through use of measures of disability, mobility, and cognitive function.

"This was a cross-sectional study, so we can't really infer for sure that there is a causal relationship. But the results are exciting when planning future studies. We need to follow patients over time and see if changes in diet can bring about changes in outcomes," Mowry said.

"We don't know that there is a specific diet that helps MS. We know that carrying excess weight is associated with higher risk of developing MS and obesity-related complications, and we have now seen that higher BMI is linked to more brain atrophy.

"Further, it's known that a Mediterranean-style diet can reduce obesity and its complications," she added, "so I would think it is pretty reasonable to recommend following such a diet."

The diet study included 277 patients with MS who completed the MS Performance Test, which asseses neurologic function, and a 153-item food frequency questionnaire.

For each individual, a Healthy Eating Index score was calculated on the basis of a composite measure of dietary quality. For this measure, the intake of fruits, vegetables, legumes, seafood/plant proteins, whole grains, mono/polyunsaturated fat, and other proteins was favorably weighted; and the intake of sodium, added sugars, and refined grains was unfavorably weighted. Scores ranged from 0 (poorest quality) to 100 (optimal quality).

The researchers examined whether the diet scores were associated with MS outcomes, including disability (determined using the Patient Determined Disease Steps scale) and objective neurologic outcomes (walking speed, manual dexterity, and processing speed). Adjustment was made for age, sex, disease subtype and duration, years of education, and BMI.

Results showed that patients in the highest quartile of dietary quality had significantly higher processing speeds, faster 25-foot walking speeds, and marginally faster manual dexterity speeds relative to individuals in the lowest quartile.

Table 4. Differences in MS Outcomes for Highest vs Lowest Quartile Dietary Scores

Endpoint Highest vs Lowest Quartile Diet Score P Value
Processed speed score (number correct) 3.87 .02
Walking speed (% faster) 14 .009
Manual dexterity (% Ffaster) 6 .08
Odds ratio of moderate vs mild disability 0.25 .03


Dr Mowry received free glatiramer acetate from Teva Neuroscience for the investigator-initiated vitamin D trial, of which she is the principal investigator (PI). She is also the PI of investigator-initiated studies funded by Biogen and Sanofi-Genzyme and is a site investigator of trials sponsored by Sun Pharma, and Biogen. In addition, she receives royalties from Up-to-Date.

34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2018. Abstracts 169 and P364, presented October 10 and 11, 2018.

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