title: Cerebrospinal fluid α-synuclein predicts cognitive decline in Parkinson disease progression in the DATATOP cohort.
abstract: Most patients with Parkinson 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.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Tessandra
authors.initials: T
authors.lastname: Stewart
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington; Department of Endocrinology and Metabolism and Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Changqin
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ginghina
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Cain
authors.affiliation: Department of Neurology, the Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, New York.
authors.forename: Peggy
authors.initials: P
authors.lastname: Auinger
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington; Geriatric Research, Education, and Clinical Center, Veterans Affairs of Puget Sound Health Care System, Seattle, Washington.
authors.forename: Brenna
authors.initials: B
authors.lastname: Cholerton
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington. Electronic address: zhangj@uw.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000627:therapeutic use; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000209:etiology*; D015331:Cohort Studies; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000150:complications* / Q000188:drug therapy; D012642:Selegiline / Q000627:therapeutic use; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*; D024502:alpha-Tocopherol / Q000627:therapeutic use
chemical_list: D000978:Antiparkinson Agents; D051844:alpha-Synuclein; D012642:Selegiline; D024502:alpha-Tocopherol