Journal article
Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease
PloS one, Vol.12(5), pp.e0175674-e0175674
2017
DOI: 10.1371/journal.pone.0175674
PMCID: PMC5435130
PMID: 28520803
Abstract
To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments.
We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition. Additionally, longitudinal structural MRI and DAT scan data were included. Univariate analyses were run initially, with false discovery rate = 0.2, to select biomarker variables for inclusion in multivariable longitudinal mixed-effect models.
By year 3, cognitive impairment was diagnosed in 15-38% participants depending on the criteria applied. Biomarkers, some longitudinal, predicting cognitive impairment in multivariable models were: (1) dopamine deficiency (decreased caudate and putamen DAT availability); (2) diffuse, cortical decreased brain volume or thickness (frontal, temporal, parietal, and occipital lobe regions); (3) co-morbid Alzheimer's disease Aβ amyloid pathology (lower CSF Aβ 1-42); and (4) genes (COMT val/val and BDNF val/val genotypes).
Cognitive impairment in PD increases in frequency 50-200% in the first several years of disease, and is independently predicted by biomarker changes related to nigrostriatal or cortical dopaminergic deficits, global atrophy due to possible widespread effects of neurodegenerative disease, co-morbid Alzheimer's disease plaque pathology, and genetic factors.
Details
- Title: Subtitle
- Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease
- Creators
- Chelsea Caspell-Garcia - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, United States of AmericaTanya Simuni - Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of AmericaDuygu Tosun-Turgut - University of California, San Francisco, San Francisco, CA, United States of AmericaI-Wei Wu - University of California, San Francisco, San Francisco, CA, United States of AmericaYu Zhang - University of California, San Francisco, San Francisco, CA, United States of AmericaMike Nalls - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States of AmericaAndrew Singleton - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States of AmericaLeslie A Shaw - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of AmericaJu-Hee Kang - Department of Pharmacology & Clinical Pharmacology, Inha University School of Medicine, Incheon, Republic of KoreaJohn Q Trojanowski - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of AmericaAndrew Siderowf - Avid Radiopharmaceuticals, Philadelphia, PA, United States of AmericaChristopher Coffey - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, United States of AmericaShirley Lasch - Institute for Neurodegenerative Disorders (IND) and Molecular NeuroImaging, LLC (MNI), New Haven CT, United States of AmericaDag Aarsland - Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, NorwayDavid Burn - Institute for Ageing and Health, Newcastle University, Newcastle, EnglandLana M Chahine - Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of AmericaAlberto J Espay - Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, United States of AmericaEric D Foster - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, United States of AmericaKeith A Hawkins - Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States of AmericaIrene Litvan - UCSD Movement Disorder Center, Department of Neurosciences, University of California San Diego, San Diego, CA, United States of AmericaIrene Richard - Departments of Neurology and Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States of AmericaDaniel Weintraub - Mental Illness Research, Education and Clinical Center (MIRECC), Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, United States of AmericaParkinson’s Progression Markers Initiative (PPMI)
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.12(5), pp.e0175674-e0175674
- DOI
- 10.1371/journal.pone.0175674
- PMID
- 28520803
- PMCID
- PMC5435130
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- P50 NS053488 / NINDS NIH HHS P30 AG010124 / NIA NIH HHS
- Language
- English
- Date published
- 2017
- Academic Unit
- Biostatistics; College of Public Health
- Record Identifier
- 9983997444002771
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