Cross-Sectional and Longitudinal Cognitive Correlates of FDDNP PET and CSF Amyloid-β and Tau in Parkinson’s Disease¹

Article type: Research Article

Authors: Buongiorno, Mariateresa^{a; 2} | Antonelli, Francesca^{a; 2} | Compta, Yaroslau^{a; 2} | Fernandez, Yolanda^b | Pavia, Javier^{c; d} | Lomeña, Francisco^{c; e} | Ríos, José^f | Ramírez, Isabel^g | García, José Ramón^h | Soler, Marina^h | Cámara, Ana^a | Fernández, Manel^a | Basora, Misericòrdiaⁱ | Salazar, Fàtimaⁱ | Sanchez-Etayo, Gerardⁱ | Valldeoriola, Francesc^a | Barrio, Jorge Raúl^j | Marti, Maria Jose^{a; *}

Affiliations: [a] Parkinson’s Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic, Spain Instituto de Investigaciones Biomédicas August Pi i Sunyer IDIBAPS, Barcelona, Catalonia, Spain CIBER | [b] CIME, Esplugues de Llobregat, Catalonia, Spain | [c] Nuclear Medicine Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain | [d] Biomedical Research Networking Centre on Bioengineering, Biomaterials and. Nanomedicine (CIBER-BBN), Barcelona, Catalonia, Spain | [e] Biomedical Research Networking Centre for Mental Health (CIBERSAM), Barcelona, Catalonia, Spain | [f] Medical Statistics Core Facility, IDIBAPS, (Hospital Clinic), Barcelona, Spain. Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona. Catalonia, Spain | [g] BARNATRON Esplugues de Llobregat, Catalonia, Spain | [h] CETIR Nuclear Medicine Esplugues de Llobregat, Catalonia, Spain | [i] Anaesthesiology Service, Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain | [j] Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California, USA

Correspondence: [*] Correspondence to: Maria Jose Martí, Parkinson’s Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic, Universitat de Barcelona, Villarroel, 170 08036-Barcelona, Spain. Tel.: +34 93 227 5750; Fax: +34 93 227 5783; E-mail: [email protected].

Note: [1] This study is registered by EudraCT N 2009-012611-18 and Clinical.Trials.Gov NCT02243982.

Note: [2] These authors equally contributed to this work.

Abstract: Tau and amyloid-β (Aβ) aggregates have been suggested to play a role in the development of dementia in Parkinson’s disease (PD). Positron emission tomography (PET) with [18F]FDDNP and the determination of cerebrospinal fluid (CSF) levels of these proteins constitute a means to visualize in vivo Aβ and tau brain accumulation. Information about longitudinal changes of these CSF and PET biomarkers in PD with regard to progression to dementia is lacking. We assessed the cross-sectional and longitudinal associations of CSF and PET biomarkers of tau and Aβ with PD-related cognitive dysfunction in 6 healthy-controls (HC), 16 patients with PD without dementia (PDND), and 8 PD with dementia (PDD). All subjects underwent comprehensive neuropsychological testing, [18F]FDDNP PET, and CSF Aβ-tau determination. After 18 months, the PDND group was re-assessed clinically and by neuropsychological, PET, and CSF determinations. Cross-sectionally, PDD had higher [18F]FDDNP binding in lateral temporal regions and lower levels of CSF Aβ levels compared to PDND, with a congruent correlation between the [18F]FDDNP binding and CSF Aβ levels. Longitudinally, higher baseline lateral temporal [18F]FDDNP binding was associated to longitudinal worsening in cognitive performances and progression to dementia among subjects classified as PDND at baseline, who additionally disclosed at follow-up an increase in lateral-temporal FDDNP binding, as well as a reduction in CSF Aβ and an increase in CSF tau levels. These results confirm the relevance of these CSF and PET biomarkers to PDD, being specifically the first to show [18F]FDDNP PET as a dementia risk biomarker in PD, along with longitudinal CSF and PET changes over time.

Keywords: CSF Aβ, dementia, [¹⁸F]FDDNP PET, Parkinson’s disease

DOI: 10.3233/JAD-160698

Journal: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 1261-1272, 2017