Journal article
Impact of the Dopamine System on Long‐Term Cognitive Impairment in Parkinson Disease: An Exploratory Study
Movement disorders clinical practice (Hoboken, N.J.), Vol.10(6), pp.943-955
06/2023
DOI: 10.1002/mdc3.13751
PMCID: PMC10272925
PMID: 37332638
Abstract
Background
Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD).
Objectives
We used data from a multi-site, international, prospective cohort study to explore the impact of dopamine system-related biomarkers on CI in PD.
Methods
PD participants were assessed annually from disease onset out to 7 years, and CI determined by applying cut-offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine-123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system-related biomarkers and CI, including persistent impairment.
Results
Demographic and clinical variables associated with CI were higher age, male sex, lower education, non-White race, higher depression and anxiety scores and higher MDS-UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values (P range 0.003–0.005) and higher LEDD over time (P range <0.001–0.01) were significantly associated with increased risk for CI.
Conclusions
Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically-relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course.
Details
- Title: Subtitle
- Impact of the Dopamine System on Long‐Term Cognitive Impairment in Parkinson Disease: An Exploratory Study
- Creators
- Daniel Weintraub - University of PennsylvaniaMarina Picillo - University of SalernoHyunkeun Ryan Cho - University of IowaChelsea Caspell-Garcia - University of IowaCornelis Blauwendraat - National Institute on AgingEthan G. Brown - University of California, San FranciscoLana M. Chahine - University of PittsburghChristopher S. Coffey - University of IowaRoseanne D. Dobkin - Rutgers, The State University of New JerseyTatiana Foroud - Indiana University – Purdue University IndianapolisDoug Galasko - University of California San DiegoKarl Kieburtz - University of Rochester Medical CenterKenneth Marek - Institute for Neurodegenerative DisordersKalpana Merchant - Northwestern UniversityBrit Mollenhauer - Paracelsus Elena Klinik KasselKathleen L. Poston - Stanford UniversityTanya Simuni - Northwestern UniversityAndrew Siderowf - University of PennsylvaniaAndrew Singleton - National Institute on AgingJohn Seibyl - Institute for Neurodegenerative DisordersCaroline M. Tanner - University of California, San FranciscoParkinson's Progression Markers Initiative
- Resource Type
- Journal article
- Publication Details
- Movement disorders clinical practice (Hoboken, N.J.), Vol.10(6), pp.943-955
- DOI
- 10.1002/mdc3.13751
- PMID
- 37332638
- PMCID
- PMC10272925
- NLM abbreviation
- Mov Disord Clin Pract
- ISSN
- 2330-1619
- eISSN
- 2330-1619
- Grant note
- DOI: 10.13039/100000864, name: Michael J. Fox Foundation for Parkinson's Research
- Language
- English
- Electronic publication date
- 04/10/2023
- Date published
- 06/2023
- Academic Unit
- Biostatistics
- Record Identifier
- 9984410796602771
Metrics
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