Associations between Cerebrospinal Fluid Biomarkers and Cognition in Early Untreated Parkinson’s Disease

Article type: Research Article

Authors: Skogseth, Ragnhild E.^{a; b; *} | Bronnick, Kolbjorn^{c; d} | Pereira, Joana B.^e | Mollenhauer, Brit^f | Weintraub, Daniel^g | Fladby, Tormod^{h; i} | Aarsland, Dag^{j; k}

Affiliations: [a] Haraldsplass Deaconess Hospital, Kavli Research Center for Geriatrics and Dementia, Bergen, Norway | [b] Department of Clinical Medicine, University of Bergen, Norway | [c] TIPS -Regional Center for Clinical Research in Psychosis, Stavanger University Hospital, Norway | [d] Faculty of Social Sciences, University of Stavanger, Norway | [e] Department of Neurobiology, Care Sciences and Society, Karolinska Institute H1, Division of Clinical Geriatrics, Sweden | [f] Paracelsus-Elena-Klinik and Department of Neuropathology, University Medical Center Göttingen, Germany | [g] Department of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania; Philadelphia VA Medical Center, Philadelphia, PA, USA | [h] Department of Neurology, Akershus University Hospital, Lørenskog, Norway | [i] Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway | [j] Center forAlzheimer’s Disease Research, Department of Neurobiology, CareSciences and Society, Karolinska Institutet H1, Division of Neurogeriatrics, Sweden | [k] Center for Age-Related Medicine Department of Psychiatry, Stavanger University Hospital, Norway

Correspondence: [*] Correspondence to: Ragnhild Eide Skogseth, Haraldsplass Deaconess Hospital, Postboks 6165 Postterminal, N-5892 Bergen, Norway. Tel.: +47 99 29 81 71; Fax: +47 55 97 85 55; E-mails: [email protected], [email protected].

Abstract: Background:Mild cognitive impairment and dementia are common, clinically important features of Parkinson’s disease (PD). The underlying disease pathology is heterogeneous and not yet well characterized. Biomarkers for cognitive impairment in PD could aid in diagnostic and prognostic evaluation and in the development of new cognitive enhancing treatments. Objective:To examine the relationship between CSF markers and cognition in a large, multicenter, cohort study of early, untreated PD, and compare marker concentrations between PD patients with and without MCI and healthy, age-matched controls. Methods:414 early, untreated PD (34% with mild cognitive impairment) and 189 healthy, cognitively intact controls with baseline neuropsychological testing and CSF abeta42, t-tau, p-tau181 and α-synuclein results were included. Multiple linear regression models were constructed with a composite cognition factor, or memory-, or visuospatial- or executive-attention domains as dependent variables, and CSF markers, demographic characteristics and MDS-UPDRS III score as predictors. Results:Lower α-synuclein was associated with reduced performance on the executive-attention domain and the composite cognition factor in the whole PD-group. Abeta42 was significantly decreased in PD with mild cognitive impairment compared with controls after adjusting for covariates, while values in PD without MCI were identical to healthy controls. Conclusions:The association between reduced CSF α-synuclein concentrations and cognition suggests that α-synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson’s disease are associated with the risk of future cognitive decline and dementia.

Keywords: Parkinson disease, cerebrospinal fluid, Mild cognitive impairment, alpha-synuclein, amyloid beta-peptides, tau Proteins

DOI: 10.3233/JPD-150682

Journal: Journal of Parkinson's Disease, vol. 5, no. 4, pp. 783-792, 2015