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Original research
Data-driven sequence of cognitive decline in people with Parkinson’s disease
  1. Andrew John Petkus1,
  2. Erin Donahue1,
  3. Michael W Jakowec1,
  4. Ece Bayram2,
  5. John Darrell Van Horn3,4,
  6. Irene Litvan2,
  7. Giselle M Petzinger1,
  8. Dawn M Schiehser5,6
  1. 1Department of Neurology, University of Southern California, Los Angeles, California, USA
  2. 2Department of Neurosciences, University of California San Diego, La Jolla, California, USA
  3. 3Department of Psychology, University of Virginia, Charlottesville, Virginia, USA
  4. 4School of Data Science, University of Virginia, Charlottesville, Virginia, USA
  5. 5Veterans Administration San Diego Healthcare System (VASDHS), San Diego, California, USA
  6. 6Department of Psychiatry, University of California San Diego, La Jolla, California, USA
  1. Correspondence to Dr Andrew John Petkus, Department of Neurology, University of Southern California, Los Angeles CA 90033, USA; petkus{at}usc.edu

Abstract

Background Understanding the sequential progression of cognitive impairments in Parkinson’s disease (PD) is crucial for elucidating neuropathological underpinnings, refining the assessment of PD-related cognitive decline stages and enhancing early identification for targeted interventions. The first aim of this study was to use an innovative event-based modeling (EBM) analytic approach to estimate the sequence of cognitive declines in PD. The second aim was to validate the EBM by examining associations with EBM-derived individual-specific estimates of cognitive decline severity and performance on independent cognitive screening measures.

Methods This cross-sectional observational study included 99 people with PD who completed a neuropsychological battery. Individuals were classified as meeting the criteria for mild cognitive impairment (PD-MCI) or subtle cognitive decline by consensus. An EBM was constructed to compare cognitively healthy individuals with those with PD-MCI or subtle cognitive disturbances. Multivariable linear regression estimated associations between the EBM-derived stage of cognitive decline and performance on two independent cognitive screening tests.

Results The EBM estimated that tests assessing executive function and visuospatial ability become abnormal early in the sequence of PD-related cognitive decline. Each higher estimated stage of cognitive decline was associated with approximately 0.24 worse performance on the Dementia Rating Scale (p<0.001) and 0.26 worse performance on the Montreal Cognitive Assessment (p<0.001) adjusting for demographic and clinical variables.

Conclusion Findings from this study will have important clinical implications for practitioners, on specific cognitive tests to prioritise, when conducting neuropsychological evaluations with people with PD. Results also highlight the importance of frontal–subcortical system disruption impacting executive and visuospatial abilities.

  • neuropsychology
  • Parkinson's disease
  • computational psychiatry
  • cognitive neuropsychology

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • Contributors AJP conceptualised the study, completed the data analysis and manuscript write-up and is the guarantor of the work. DMS contributed to the conceptualisation of the study, obtained funding, provided advice to the analysis plan and contributed to the manuscript write-up. GMP obtained funding and contributed to the manuscript write-up. ED contributed to the manuscript write-up. MWJ contributed to the manuscript write-up and obtained funding. EB contributed to the methodology and the manuscript write-up. JDVH provided advice on the statistical analysis and contributed to the manuscript write-up. IL contributed to the methodology and the manuscript write-up.

  • Funding This work was supported by grants from the US Department of Defense, US Army and US Army Medical Command Congressionally Directed Medical Research Programs (Grant Numbers: W81XWH18-1-0665, W81XWH18-1-0666, and W81XWH19-1-0443), Angie Proctor (Award number N/A) and Kirk Hyde (Award number N/A).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.