Homocysteine Concentration Correlates with Baseline Clinical Status and Predicts Outcomes in a Large, Early Parkinson's Disease Cohort (DATATOP)

Abstract

OBJECTIVETo determine the prevalence of elevated homocysteine (Hcy) concentration and its association with cognitive and motor function measurements in early untreated Parkinson's disease (PD).BACKGROUNDPrevious studies have identified a relationship of elevated circulating Hcy levels with the development of cognitive impairment in aging but this relationship has not been established in early PD. We sought to determine the prevalence of elevated Hcy status in a cohort with early untreated PD and whether it was associated with greater initial and subsequent morbidity.DESIGN/METHODSWe measured Hcy using 677 baseline samples from the DATATOP cohort of patients with early, untreated PD. Elevated Hcy status was defined as mildly elevated (>11 μM) and moderately elevated (>15 μM). Outcomes included motor assessments by Unified Parkinson's Disease Rating Scale (UPDRS scores) and cognitive assessments (Mini‐Mental Status test (MMSE) and Symbol Digits Modalities Test (SDMT)) at baseline and follow‐up, calculated as an annualized rate of change for those who participated for 6 months to 2 years. Baseline analyses were adjusted for sex, age, baseline B12 levels and treatment assignment. Change analyses were also adjusted for baseline value of the outcome.RESULTSThe geometric mean Hcy level was 9.5 μM and was mildly elevated in 26% (179/677) and moderately elevated in 7% (46/677) of subjects. Analysis of baseline features showed lower MMSE and SDMT scores in those with moderately elevated Hcy. Analysis of outcomes showed greater decline in MMSE scores in those with moderately elevated Hcy. No associations were observed between mildly elevated Hcy and the baseline or outcome UPDRS motor scores.CONCLUSIONSIn this cohort of early, untreated PD subjects, 1 in 4 had mildly elevated Hcy. Moderately elevated baseline Hcy levels correlated with lower baseline cognitive measures and greater rate of cognitive decline. Because B vitamin supplementation can lower Hcy levels, this data raises the possibility that prevention or early correction of mild to moderate hyperhomocyteinemia through vitamin supplementation may slow the onset of cognitive decline in PD.Support or Funding InformationMJFOX Foundation