Objective:

To measure blood levels of vitamin B12 and homocysteine (tHcy) in contemporary clinical trial cohorts and to correlate with Parkinson’s disease (PD) progression.

Background:

Our analysis of baseline serum in the DATATOP study showed geometric mean levels of B12 of 369pg/ml and 9.5µM for tHcy.  We found associations of low B12 with greater worsening of ambulatory capacity and of elevated tHcy(>15µM) with greater declines in the MMSE. Since DATATOP was performed in the late 1980’s, before mandatory folic acid fortification in the US, dietary changes may have altered these levels

Design/Methods:

We obtained baseline blood samples from 3 clinical trials of early PD (SURE-PD, STEADY-PDIII, and SURE-PD3), which recruited between 2009-17, and measured B12 and tHcy. We then tested for associations of analyte levels with annualized changes in clinical rating scales

Results:

The geometric mean B12 levels for SURE-PD, STEADY-PDIII, and SURE-PD3 were 484, 524, and 618pg/ml and for tHcy were 7.4, 10.0 and 9.7µM, respectively. B12 deficiency(≤212pg/ml) was rare, ranging between 1.1-3.7%, while tHcy>15 µM was 5% in STEADY-PDIII and SURE-PD3. Supplement use containing B12 ranged from 41-61%, and those taking supplements had 100-200pg/ml higher levels.  Compared to those with tHcy≤15µM, subjects combined from STEADY-PDIII and SURE-PD3 with tHcy>15 µM had more rapid declines in MoCA scores (0.7 vs 0.2 points/year, p=0.02).  No association was found for low B12 levels and ambulatory capacity.

Conclusions:

Compared with DATATOP, in these recent trials, B12 levels were substantially higher, likely due to increased supplement intake, while tHcy levels were similar.  Like DATATOP, there was greater cognitive decline in those with tHcy>15µM.  While an association of low B12 with greater worsening of ambulatory capacity was not found in this study, the smaller number of subjects with low B12 levels reduced the power to replicate this finding. Further study of tHcy with PD cognitive impairment is warranted.