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Multicenter Study
. 2015;5(4):783-92.
doi: 10.3233/JPD-150682.

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

Ragnhild E Skogseth  1   2 , Kolbjorn Bronnick  3   4 , Joana B Pereira  5 , Brit Mollenhauer  6 , Daniel Weintraub  7 , Tormod Fladby  8   9 , Dag Aarsland  10   11
Affiliations
Multicenter Study

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

Ragnhild E Skogseth et al. J Parkinsons Dis. 2015.

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

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Figures

Fig. 1
Fig. 1
CSF marker concentrations in PD with normal cognition, PD-MCI and healthy controls, including scatter plots. PD-MCI = PD with mild cognitive impairment, HC= healthy controls. Each dot in the scatter plots represents an individual patient.
See this image and copyright information in PMC

References

    1. Svenningsson P, Westman E, Ballard C, Aarsland D. Cognitive impairment in patients with Parkinson's disease: Diagnosis, biomarkers, and treatment. Lancet Neurol. 2012;11:697–707. - PubMed
    1. Kehagia AA, Barker RA, Robbins TW. Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease. Lancet Neurol. 2010;9:1200–1213. - PubMed
    1. Irwin DJ, White MT, Toledo JB, Xie SX, Robinson JL, Van Deerlin V, Lee VM, Leverenz JB, Montine TJ, Duda JE, Hurtig HI, Trojanowski JQ. Neuropathologic substrates of Parkinson disease dementia. Ann Neurol. 2012;72:587–598. - PMC - PubMed
    1. Kandiah N, Zainal NH, Narasimhalu K, Chander RJ, Ng A, Mak E, Au WL, Sitoh YY, Nadkarni N, Tan LC. Hippocampal volume and white matter disease in the prediction of dementia in Parkinson's disease. Parkinsonism Relat Disord. 2014;20:1203–1208. - PubMed
    1. Compta Y, Parkkinen L, Kempster P, Selikhova M, Lashley T, Holton JL, Lees AJ, Revesz T. The significance of alpha-synuclein, amyloid-beta and tau pathologies in Parkinson's disease progression and related dementia. Neurodegener Dis. 2014;13:154–156. - PMC - PubMed

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