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Published VersionCC BY V4.0, Open Access
Journal article
Path analysis of biomarkers for cognitive decline in early Parkinson's disease
PLoS One, Vol.17(5), pp.1-30
2022
PMCID: PMC9106174
PMID: 35560326
Appears in Thompson Institute Research Collection
Abstract
Clinical and biochemical diversity of Parkinson's disease (PD) and numerous demographic, clinical, and pathological measures influencing cognitive function and its decline in PD create problems with the determination of effects of individual measures on cognition in PD. This is particularly the case where these measures significantly interrelate with each other producing intricate networks of direct and indirect effects on cognition. Here, we use generalized structural equation modelling (GSEM) to identify and characterize significant paths for direct and indirect effects of 14 baseline measures on global cognition in PD at baseline and at 4 years later. We consider 269 drug-naïve participants from the Parkinson's Progression Marker Initiative database, diagnosed with idiopathic PD and observed for at least 4 years after baseline. Two GSEM networks are derived, highlighting the possibility of at least two different molecular pathways or two different PD sub-types, with either CSF p-tau181 or amyloid beta (1-42) being the primary protein variables potentially driving progression of cognitive decline. The models provide insights into the interrelations between the 14 baseline variables, and determined their total effects on cognition in early PD. High CSF amyloid concentrations (> 500 pg/ml) are associated with nearly full protection against cognitive decline in early PD in the whole range of baseline age between 40 and 80 years, and irrespectively of whether p-tau181 or amyloid beta (1-42) are considered as the primary protein variables. The total effect of depression on cognition is shown to be strongly amplified by PD, but not at the time of diagnosis or at prodromal stages. CSF p-tau181 protein could not be a reliable indicator of cognitive decline because of its significantly heterogeneous effects on cognition. The outcomes will enable better understanding of the roles of the clinical and pathological measures and their mutual effects on cognition in early PD.
Details
- Title
- Path analysis of biomarkers for cognitive decline in early Parkinson's disease
- Authors
- Dmitri K Gramotnev (Corresponding Author) - Research and Data Analysis Centre (Brisbane) - RDCGalina Gramotnev (Author) - Research and Data Analysis Centre (Brisbane) - RDCAlexandra Gramotnev (Author) - University of the Sunshine Coast, Queensland, Thompson InstituteMathew J Summers (Author) - University of the Sunshine Coast, Queensland, School of Health and Behavioural Sciences - Legacy
- Publication details
- PLoS One, Vol.17(5), pp.1-30
- Audience
- Academic
- Publisher
- Public Library of Science
- Date published
- 2022
- DOI
- 10.1371/journal.pone.0268379
- ISSN
- 1932-6203
- PMID
- 35560326; PMC9106174
- Copyright note
- Copyright: © 2022 Gramotnev et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; Thompson Institute; School of Health - Psychology; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99640579202621
- Output Type
- Journal article
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