title: Cross-sectional and longitudinal associations of motor fluctuations and non-motor predominance with cerebrospinal τ and Aβ as well as dementia-risk in Parkinson's disease.
abstract: Experimental, neuropathological and cerebrospinal fluid (CSF) studies support τ and amyloid-β (Aβ) relevance in Parkinson's disease (PD) related dementia. Lesser motor fluctuations (MFs) and non-motor features have also been related to PD-dementia. Yet, little is known about the association of MFs and non-motor symptoms with CSF τ and Aβ in PD. We hypothesized that lesser MFs and non-motor predominance are related to these CSF markers and dementia-risk in PD. We studied 58 PD patients (dementia at baseline, n=21; dementia at 18-months, n=35) in whom CSF Aβ and τ had been determined with ELISA techniques. MFs and a number of non-motor symptoms (apathy, anxiety, irritability, depression, visual hallucinations, spatial disorientation, memory complaints) over disease course were dichotomized as absent-mild vs. moderate-severe by retrospective clinical chart review blind to CSF findings. Non-motor predominance was defined as ≥3 non-motor symptoms (after the cohort-median of non-motor symptoms per patient) with ≥2 being moderate-severe and ≥1 having been present from onset, with all these being more disabling overall than motor features. Cross-sectionally, CSF biomarkers were non-parametrically compared according to dichotomized MFs and non-motor predominance. Longitudinally, dementia was the outcome (dependent variable), CSF markers, MFs and non-motor predominance were the predictors (independent variables), and potential modifiers as age, sex, and memory complaints were the covariates in binary regression models. Absent-mild MFs were associated with higher CSF τ markers and shorter time-to-dementia, while non-motor predominance and decreasing CSF Aβ independently increased longitudinal dementia-risk. In summary, absent-mild MFs, non-motor predominance and CSF τ and Aβ might define endophenotypes related to the timing or risk of dementia in PD.
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Catalonia, Spain; Parkinson's Disease and Movement Disorders Unit, Neurology Service, Segeberger Kliniken, Bad Segeberg, Germany.
authors.forename: Raluca
authors.initials: R
authors.lastname: Modreanu
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Catalonia, Spain; Neurology Unit, Hospital Universitario San Ignacio, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Sonia Catalina
authors.initials: SC
authors.lastname: Cerquera
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Martí
authors.affiliation: Statistics and Methodologic Support Unit, Unitat d'Avaluació, Suport i Prevenció (UASP), Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Ríos
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Sánchez-Gómez
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cámara
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Fernández
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, IDIBAPS, CIBERNED, University of Barcelona, Barcelona, Catalonia, Spain. Electronic address: ycompta@clinic.cat.
authors.forename: Yaroslau
authors.initials: Y
authors.lastname: Compta
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003430:Cross-Sectional Studies; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000453:epidemiology / Q000209:etiology; D058068:Endophenotypes; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000453:epidemiology / Q000523:psychology*; D012044:Regression Analysis; D012306:Risk; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins
keywords: CSF Aβ; CSF τ; Endophenotypes; Motor fluctuations; Non-motor symptoms; Parkinson's disease-dementia