Plasma Neurofilament Light and p-tau181 and Risk of Psychosis in Parkinson’s Disease

Article type: Research Article

Authors: Gibson, Lucy L.^{a; *} | Pollak, Thomas A.^b | Heslegrave, Amanda^{c; d} | Hye, Abdul^a | Batzu, Lucia^e | Rota, Silvia^e | Trivedi, Dhaval^e | Nicholson, Timothy R.^b | ffytche, Dominic^a | Zetterberg, Henrik^{c; d; f; g; h} | Chaudhuri, K. Ray^e | Aarsland, Dag^{a; i}

Affiliations: [a] Old Age Psychiatry Department, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK | [b] Neuropsychiatry Research and Education Group, Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK | [c] Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK | [d] UK Dementia Research Institute at UCL, London, UK | [e] Department of Basic and Clinical Neuroscience, Parkinson Foundation International Centre of Excellence, Kings College Hospital and Kings College London, London, UK | [f] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [g] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Salhgrenska Academy at the University of Gothenburg, Gothenburg, Sweden | [h] Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China | [i] Centre for Age-Related Disease, Stavanger University Hospital, Stavanger, Norway

Correspondence: [*] Correspondence to: Lucy L. Gibson, 6th floor, Old Age Psychiatry Department, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK. E-mail: lucy.1.gibson@kcl.ac.uk.

Abstract: Background:Neuropsychiatric symptoms are common and important to people with Parkinson’s disease (PD), but their etiology is poorly understood. Plasma neurofilament light (NfL) and p-tau181 are biomarkers of neuro-axonal degeneration and tau pathology respectively, which have yet to be explored in association with the affective and psychotic symptoms in PD. Objective:To investigate the relationship between plasma NfL and p-tau181 with the affective and psychotic symptoms in PD. Methods:We assessed the baseline concentration of plasma NfL and p-tau181 in a cohort of 108 patients with PD and 38 healthy controls. A subgroup of patients (n = 63) were assessed annually with clinical measures for up to 7 years. Psychotic symptoms were assessed using the Non-Motor Symptom Scale and affective symptoms were measured in the Hospital Anxiety and Depression Scale. Results:Baseline plasma NfL was a significant predictor of psychotic symptoms longitudinally across the study adjusted for age, Hoehn and Yahr stage, duration of follow up, duration of disease, baseline levodopa and dopamine agonist medication, and baseline cognition: (OR 8.15 [95% CI 1.40–47.4], p = 0.020). There was no association between NfL concentration and the cumulative prevalence of affective symptoms. Plasma p-tau181 concentration was not associated with psychotic or affective symptoms. Conclusion:These findings suggest psychotic symptoms are associated with greater neurodegeneration in PD. Further studies are needed to explore NfL as a potential biomarker for psychosis in PD.

Keywords: Neurofilament light, p-tau, psychosis, neuropsychiatric symptoms, biomarker, Parkinson’s disease

DOI: 10.3233/JPD-223182

Journal: Journal of Parkinson's Disease, vol. 12, no. 5, pp. 1527-1538, 2022