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Dissociable contribution of plasma NfL and p-tau181 to cognitive impairment in Parkinson's disease

  • Javier Pagonabarraga
    Correspondence
    Corresponding author. Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, AddressMas Casanovas 90, 08041, Barcelona, Spain.
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Rocío Pérez-González
    Correspondence
    Corresponding author. Biomedical Research Institute Sant Pau (IIB-Sant Pau), Laboratory of Parkinson's disease and movement disorders (P2-009), Sant Quintí 77-79, 08041, Barcelona, Spain.
    Affiliations
    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Helena Bejr-kasem
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Juan Marín-Lahoz
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Andrea Horta-Barba
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain
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  • Saul Martinez-Horta
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Ignacio Aracil-Bolaños
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain
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  • Frederic Sampedro
    Affiliations
    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Antonia Campolongo
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Elisa Rivas
    Affiliations
    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Arnau Puig-Davi
    Affiliations
    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain
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  • I. Ruiz-Barrios
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain
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  • Jesús Pérez-Pérez
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain
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  • Berta Pascual-Sedano
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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  • Jaime Kulisevsky
    Affiliations
    Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Department of Medicine, Barcelona, Spain

    Sant Pau Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain

    Centro de Investigación en Red - Enfermedades Neurodegenerativas (CIBERNED), Spain
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      Abstract

      Background

      Cognitive dysfunction is a disabling complication in Parkinson's disease (PD). Accuracy of diagnosis of mild cognitive impairment in PD (PD-MCI) depends on the tests performed, which limits results generalization. Blood-based biomarkers could provide additional objective information for PD-MCI diagnosis and progression. Blood neurofilament light chain (NfL), a marker of neuronal injury, has shown good performance for PD disease stratification and progression. While NfL is not disease-specific, phosphorylated-tau at threonine-181 (p-tau181) in blood is a highly specific marker of concomitant brain amyloid-β and tau pathology.

      Methods

      We investigated the potential of plasma NfL and p-tau181 levels as markers of cognitive impairment in a prospective cohort of 109 PD patients with and without PD-MCI (age 68.1 ± 7 years, education 12.2 ± 5 years), and 40 comparable healthy controls. After a follow-up of 4 years, we evaluated their predictive value for progression to dementia.

      Results

      Although NfL and p-tau181 levels were significantly increased in PD compared with healthy controls, only NfL levels were significantly higher in PD-MCI compared with PD with normal cognition (PD-NC) at baseline. After a follow-up of 4 years, only NfL predicted progression to dementia (HR 1.23, 95% CI 1.02–1.53; p = 0.038). Significant correlations between fluid biomarkers and neuropsychological examination were only found with NfL levels.

      Conclusions

      Plasma NfL levels objectively differentiates PD-MCI from PD-NC patients, and may serve as a plasma biomarker for predicting progression to dementia in PD. Plasma levels of p-tau181 does not seem to help in differentiating PD-MCI or to predict future cognitive deterioration.

      Keywords

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