• Changqin Liu, Brenna Cholerton, Min Shi, Carmen Ginghina, Kevin C Cain, Peggy Auinger, Parkinson Study Group DATATOP Investigators, and Jing Zhang.
• Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Endocrinology and Diabetes, The First Affiliated Hospital, Xiamen University, Xiamen, China. Electronic address: liuchangqin@126.com.
• Parkinsonism Relat. Disord. 2015 Mar 1; 21 (3): 271-6.

IntroductionA substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches.MethodsSubjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype.ResultsNo association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype.ConclusionsThe current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD.Copyright © 2015 Elsevier Ltd. All rights reserved.

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