title: Grey matter volume correlates of cerebrospinal markers of Alzheimer-pathology in Parkinson's disease and related dementia.
abstract: Regional brain grey matter volume (GMV) reductions and abnormal cerebrospinal fluid (CSF) levels of τ and Aβ, extensively studied as biomarkers of Alzheimer's disease (AD), have also been reported in Parkinson's disease (PD) and related dementia (PDD). However, the relationship between these CSF and MRI biomarkers in PD and PDD remains unexplored. We studied these associations in 33 PD patients (18 with no dementia [PDND]; 15 fulfilling PDD criteria) and 12 neurologically unimpaired controls, with neuropsychological assessment, CSF ELISA studies, and voxel-based morphometry (VBM) analysis of high-field brain MRI. Neuropsychological assessment showed a gradation in cognitive performance from controls to PDND (significantly worse on visuospatial performance) and then to PDD (more impaired on memory, naming, fluency and visuospatial functions). No CSF-VBM correlations were found in controls or PDND patients. In contrast, in the analysis of both the PDD subgroup and the entire PD (PDND + PDD) sample, we found significant negative CSF-GMV correlations for τ and phospho-τ and significant positive CSF-GMV correlations for Aβ in mostly frontal and temporal structures. The correlations in the entire PD sample fitted with a linear model and were thus unlikely to have been driven solely by the PDD subgroup. Additionally, an association between both the CSF markers and the CSF-associated GMV reductions with several neuropsychological functions was found. We interpret that CSF markers of AD pathology are associated with VBM-measures of brain atrophy in PD-related dementia and within the PD cognitive continuum, and deserve further attention as putative biomarkers of cognitive impairment and dementia in PD.
authors.affiliation: Parkinson's Disease & Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències/IDIBAPS, Centro de Investigación en Red de Enfermedades Neurodegenerativas, Hospital Clínic, Barcelona, Catalonia, Spain.
authors.forename: Yaroslau
authors.initials: Y
authors.lastname: Compta
authors.forename: Naroa
authors.initials: N
authors.lastname: Ibarretxe-Bilbao
authors.forename: Joana B
authors.initials: JB
authors.lastname: Pereira
authors.forename: Carme
authors.initials: C
authors.lastname: Junqué
authors.forename: Núria
authors.initials: N
authors.lastname: Bargalló
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.forename: Francesc
authors.initials: F
authors.lastname: Valldeoriola
authors.forename: Esteban
authors.initials: E
authors.lastname: Muñoz
authors.forename: Ana
authors.initials: A
authors.lastname: Camara
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Buongiorno
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Martí
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D009929:Organ Size; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins