Relationship of Vitamin B12 Status and Parkinson's Disease
Biosample and Tissue Resource, 2013
Objective/Rationale: † † † † † ††
Vitamin B12 deficiency can cause a number of neurological symptoms, including instability, neuropathy (which may cause numbness and tingling) and cognitive defects. Recent studies in Parkinsonís disease (PD) patients with neuropathy have shown that B12 deficiency is common. Also, we have recently observed that B12 levels decline over the course of PD. These observations have led us to hypothesize that concurrent B12 deficiency may contribute to overall decline in some patients.
Project Description: † † † † † ††
The DATATOP study was a large study of patients with early PD conducted more than 20 years ago. As part of this study, standardized measurements of cognitive function and mobility were obtained over the course of the two-year study.† Blood samples were also collected and stored. In our study, we will measure blood levels of vitamin B12 and other markers of B12 deficiency in the DATATOP subjects to determine how common B12 deficiency is in early PD and if there is a relationship between low B12 levels and early cognitive or mobility problems. Since a number of patients underwent blood testing nine or more months after study entry, we also will measure B12 levels at study completion to determine whether B12 levels decline.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
If this study shows that B12 deficiency is common in early PD, it may be appropriate for health care providers to routinely measure B12 levels in patients when they are first diagnosed. Also, if B12 levels decline more rapidly than expected, it may be appropriate to measure B12 levels every two to three years to exclude the development of B12 deficiency. Finally, if low B12 levels are associated with greater disability, treatment studies using B12 supplementation should be considered.
Anticipated Outcome: † † † † †
This study will determine how common vitamin B12 deficiency is in the DATATOP study and whether B12 levels decline at a faster rate than expected.† It will also examine whether low levels of B12 are associated with more rapid progression of motor or cognitive problems in PD.
The DATATOP study was a two-year study conducted between 1987 and 1990 and was designed to test whether deprenyl or alpha-tocopherol delayed the time until patients developed disability requiring levodopa treatment. Eight hundred patients were randomized to one of four treatment groups: [placebo, alpha-tocopherol (vitamin E), deprenyl (Selegiline), or deprenyl + alpha-tocopherol]. Patients were followed in this study up to two years or until developing disability requiring levodopa treatment. For our study, we measured serum vitamin B12 levels in 680 of 800 subjects obtained at the baseline visit and in follow-up samples collected nine to 24 months later from 456 who did not require earlier dopaminergic treatment. Low serum B12 and high methylmalonic acid levels are indicative of B12 deficiency.
Using stringent criteria (B12 < 212 pg/l and methylmalonic acid > 400 nM), only 2% of the cohort was B12 deficient at baseline but 5% had levels below the normal range (< 212 pg/l). For those with a second B12 measurement, there was an increase in the average B12 level, but this did not occur in all subjects. Further analysis showed that low B12 status at baseline correlated with a lower score in a single measure of cognitive function (selective reminding test) at baseline. In those patients who remained in the study longer than nine months, a more rapid progression of PD symptoms (as measured by the Unified Parkinson's Disease Rating Scale) occurred in those with lower B12 levels than in those with higher levels. Our data raise the possibility that prevention or early correction of low B12 status may slow the onset of disability in PD.
Distinguished Professor of Pathology and Laboratory Medicine at University of California, Davis
Location: Davis, California, United States
Location: San Francisco, California, United States