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

• Published in: Parkinsonism & related disorders Vol. 105; pp. 132 - 138
• Main Authors: Pagonabarraga, Javier, Pérez-González, Rocío, Bejr-kasem, Helena, Marín-Lahoz, Juan, Horta-Barba, Andrea, Martinez-Horta, Saul, Aracil-Bolaños, Ignacio, Sampedro, Frederic, Campolongo, Antonia, Rivas, Elisa, Puig-Davi, Arnau, Ruiz-Barrios, I., Pérez-Pérez, Jesús, Pascual-Sedano, Berta, Kulisevsky, Jaime
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2022
• Subjects: Aged; Alzheimer Disease - diagnosis; Biomarkers; Blood-based biomarkers; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - etiology; Humans; Middle Aged; Mild cognitive impairment; Parkinson Disease - complications; Parkinson's disease; Plasma NfL; Plasma p-tau181; Prospective Studies; tau Proteins; Threonine; Plasma NfL; Parkinson's disease; Blood-based biomarkers; Plasma p-tau181; Mild cognitive impairment
• ISSN: 1353-8020; 1873-5126; 1873-5126
• DOI: 10.1016/j.parkreldis.2022.05.020

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. 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. 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. 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.