Cross-Sectional and Longitudinal Cognitive Correlates of FDDNP PET and CSF Amyloid-β and Tau in Parkinson's Disease1.
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.
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.
Mariateresa
M
Buongiorno
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.
Francesca
F
Antonelli
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.
Yaroslau
Y
Compta
CIME, Esplugues de Llobregat, Catalonia, Spain.
Yolanda
Y
Fernandez
Nuclear Medicine Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain.|Biomedical Research Networking Centre on Bioengineering, Biomaterials and. Nanomedicine (CIBER-BBN), Barcelona, Catalonia, Spain.
Javier
J
Pavia
Nuclear Medicine Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain.|Biomedical Research Networking Centre for Mental Health (CIBERSAM), Barcelona, Catalonia, Spain.
Francisco
F
Lomeña
Medical Statistics Core Facility, IDIBAPS, (Hospital Clinic), Barcelona, Spain. Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona. Catalonia, Spain.
José
J
Ríos
BARNATRON Esplugues de Llobregat, Catalonia, Spain.
Isabel
I
Ramírez
CETIR Nuclear Medicine Esplugues de Llobregat, Catalonia, Spain.
José Ramón
JR
García
CETIR Nuclear Medicine Esplugues de Llobregat, Catalonia, Spain.
Marina
M
Soler
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.
Ana
A
Cámara
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.
Manel
M
Fernández
Anaesthesiology Service, Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain.
Misericòrdia
M
Basora
Anaesthesiology Service, Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain.
Fàtima
F
Salazar
Anaesthesiology Service, Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain.
Gerard
G
Sanchez-Etayo
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.
Francesc
F
Valldeoriola
Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California, USA.
Jorge Raúl
JR
Barrio
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.
Maria Jose
MJ
Marti
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009570:Nitriles / Q000493:pharmacokinetics*; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000150:complications / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography; D016875:tau Proteins / Q000134:cerebrospinal fluid*
C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D016229:Amyloid beta-Peptides; D009570:Nitriles; D016875:tau Proteins
CSF Aβ; Parkinson’s disease; [18F]FDDNP PET; dementia