Brain Amyloid Contribution to Cognitive Dysfunction in Early-Stage Parkinson’s Disease: The PPMI Dataset

Article type: Research Article

Authors: Fiorenzato, Eleonora^{a; 1} | Biundo, Roberta^{a; 1; *} | Cecchin, Diego^{b; c} | Frigo, Anna Chiara^d | Kim, Jinhee^{e; f} | Weis, Luca^a | Strafella, Antonio P.^{e; f; g} | Antonini, Angelo^h

Affiliations: [a] Fondazione Ospedale San Camillo IRCCS, Venezia, Italia | [b] Nuclear Medicine Unit, Department of Medicine - DIMED, University Hospital of Padua, Padua, Italy | [c] Padova Neuroscience Center, University of Padua, Padua, Italy | [d] Biostatistics, Epidemiology and Public Health Unit, Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padua, Padua, Italy | [e] Division of Brain, Imaging and Behaviour-Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Toronto, ON, Canada | [f] Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada | [g] Morton and Gloria Shulman Movement Disorder Unit and E.J. Safra Parkinson Disease Program, Neurology Division, Department of Medicine, Toronto Western Hospital, UHN, University of Toronto, Toronto, ON, Canada | [h] Department of Neurosciences, University of Padua, Padua, Italy

Correspondence: [*] Correspondence to: Roberta Biundo, Roberta Biundo, San Camillo Hospital IRCCS, Via Alberoni 70, 30126 Venice, Italy. Tel.: +39 041 2207537; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:The pathological processes underlying cognitive impairment in Parkinson’s disease (PD) are heterogeneous and the contribution of cerebral amyloid deposits is poorly defined, particularly in the early stages of the disease. Objective:To investigate regional [18F]florbetaben binding to amyloid-β (Aβ) and its contribution to cognitive dysfunction in early stage PD. Methods:A multicenter cohort of 48 PD patients from the Parkinson’s Progression Marker Initiative (PPMI) underwent [18F]florbetaben positron emission tomography (PET) scanning. Clinical features, including demographic characteristics, motor severity, cerebrospinal fluid (CSF), and cognitive testing were systematically assessed according to the PPMI study protocol. For the purpose of this study, we analyzed various neuropsychological tests assessing all cognitive functions. Results:There were 10/48 (21%) amyloid positive PD patients (PDAβ+). Increased [18F]florbetaben uptake in widespread cortical and subcortical regions was associated with poorer performance on global cognition, as assessed by Montreal Cognitive Assessment (MoCA), and impaired performance on Symbol Digit Modality test (SDMT). Further, we found that PDAβ+ patients had higher CSF total-tau/Aβ1 - 42 (p = 0.001) and phosphorylated-tau/Aβ1 - 42 in (p = 0.002) compared to amyloid-negative PD. Conclusion:These findings suggest that multiple disease processes are associated with PD cognitive impairment and amyloid deposits may be observed already in early stages. However, prevalence of amyloid positivity is in the range of literature age-matched control population. Increased cortical and subcortical amyloid is associated with poor performance in attentive-executive domains while cognitive deficits at MoCA and SDMT may identify amyloid-related dysfunction in early PD.

Keywords: Amyloid, cerebrospinal fluid, cognition, cognitive dysfunction, dementia, neuropsychology, Parkinson’s disease, positron emission tomography, synuclein

DOI: 10.3233/JAD-180390

Journal: Journal of Alzheimer's Disease, vol. 66, no. 1, pp. 229-237, 2018