From the Journals

Low vitamin B12 tied to worsening mobility, cognition in early Parkinson’s

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Several issues within study need to be addressed

The course of PD can be quite variable, and it is difficult for clinicians to predict what will happen to an individual person with PD, but identifying prognostic factors ought to help practitioners answer their patients’ questions and potentially improve the understanding of mechanisms underlying the disease pathogenesis.

If vitamin B12 is related to the progression of PD as suggested in the study by Christine et al., its replacement may slow the decline of the disease. But there are several issues that need to be addressed in the context of their findings.

First, what constitutes a low vitamin B12 level is not a simple issue. If the evaluation is limited to measurement of vitamin B12 concentration, the diagnosis of genuine deficiency is unreliable. Most experts agree that combined measurement of vitamin B12 with determination of homocysteine levels is necessary and while Christine et al. measured both levels, their statistical analysis and subsequent conclusions are exclusively based on the levels of the vitamin.

Moreover, 34 patients in the study were classified as having “borderline-low” vitamin B12 levels, and 14 had both borderline-low B12 level and high homocysteine concentration. This brings into question whether the researchers identified PD patients who actually had low B12 levels.

The design of the DATATOP trial could also introduce some bias into the findings. At the time of publication, the study was criticized for disregarding the symptomatic effect of selegiline and for a lack of objective definition of criteria for the trial’s primary endpoint – introduction of levodopa.

This could have led to the termination of individuals at different stages of the disease, introducing a potential bias in the sample of patients who remained in the study for enough time to undergo subsequent determination of B12 levels.

The findings in the current study are also in contrast to previous research, and the underlying mechanism of vitamin B12 in PD is also unclear.

Nevertheless, the results of the study by Dr. Christine and his colleagues are intriguing and further investigations to address this hypothesis are warranted.

Francisco Cardoso, MD, PhD, is with the movement disorders unit within the neurology service at the Federal University of Minas Gerais, Belo Horizonte, Brazil. His comments are derived from an editorial accompanying the study by Dr. Christine and colleagues (Movement Dis. 2018 Mar 6. doi: 10.1002/mds.27366). He had no relevant disclosures.


 

FROM MOVEMENT DISORDERS

People with early, untreated Parkinson’s disease (PD) who have low B12 levels appear to have greater worsening of mobility and cognitive decline over time, suggesting that it may be worthwhile to examine the correction of low levels as a means of slowing disease progression.

Investigators led by Chadwick W. Christine, MD, of the department of neurology at the University of California, San Francisco, sought to understand what contributes to considerable variation in the progression of PD by building on previous research that revealed low serum vitamin B12 levels are common in patients with moderately advanced PD and are associated with neuropathy and cognitive impairment.

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Because little is known about B12’s role in early disease, the investigators analyzed data from patients with early, untreated PD who participated in the DATATOP study, a double-blind, randomized trial designed to test whether treatment with selegiline and/or the antioxidant, alpha-tocopherol, slowed PD progression.

They measured serum methylmalonic acid, homocysteine, and holotranscobalamin in addition to B12 because of the limited sensitivity of serum B12 testing alone to detect B12 deficiency. At baseline, 13% of 680 patients had borderline-low B12 levels (less than 184 pmol/L [250 pg/mL]), and 5% had deficient B12 levels (less than 157 pmol/L or 212 pg/mL). Homocysteine was moderately elevated (greater than 15 mmol/L) in 7% of subjects, and 14% of patients with borderline-low B12 also had elevated homocysteine, the investigators reported in Movement Disorders.

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