Changqin Liu1, Brenna Cholerton2, Min Shi3, Carmen Ginghina4, Kevin C Cain5, Peggy Auinger6, Jing Zhang7. 1. 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. 2. Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA; Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA. Electronic address: bchol@uw.edu. 3. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: mshi70@uw.edu. 4. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: ginghina@uw.edu. 5. Department of Biostatistics, University of Washington School of Public Health, Seattle, WA, USA. Electronic address: cain@uw.edu. 6. Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. Electronic address: peggy.auinger@chet.rochester.edu. 7. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: zhangj@uw.edu.
Abstract
INTRODUCTION: A 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. METHODS:Subjects 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. RESULTS: No 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. CONCLUSIONS: The 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.
RCT Entities:
INTRODUCTION: A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PDpatients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. METHODS: Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PDpatients. 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. RESULTS: No 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. CONCLUSIONS: The 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.
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