Cerebrospinal Fluid α-Synuclein Predicts Cognitive Decline in Parkinson's Disease Progression in the DATATOP Cohort

The importance of identifying biomarkers for PD cannot be overstated. 

Very interesting to see how CSF alpha-syn was related to cognitive parameters but important additional findings were 1) the decrease in alpha-syn over 2 years of early disease progression, which may have important implications for study in the premotor phase. However, 2) failure to find a relationship with motor severity rating scales, a finding which the authors spend some time considering.

Am J Pathol. 2014 Feb 27. pii: S0002-9440(14)00012-1. doi: 10.1016/j.ajpath.2013.12.007. [Epub ahead of print]

Stewart T, Liu C, Ginghina C, Cain KC, Auinger P, Cholerton B, Shi M, Zhang J; the Parkinson Study Group DATATOP Investigators.

Abstract

Most patients with Parkinson's disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of -0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, -0.12 (P = 0.037); delayed recall, -0.05 (P = 0.002); New Dot Test, -0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation.