Evidence map›Paper›PMID 38870440›Full record

ArticleNeurology2024

The Parkinson's Disease Composite of Executive Functioning: A Measure for Detecting Cognitive Decline in Clinical Trials.

Christina B Young, Brenna Cholerton, Alena M Smith, Marian Shahid-Besanti, Carla Abdelnour, Elizabeth C Mormino, Shu-Ching Hu, Kathryn A Chung, Amie Peterson, Liana Rosenthal and 6 more

Erratum issuedAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Reflexive eye movement alterations are related to subclinical impulsive-compulsive behaviors in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Article
  7. Article
  8. Attention/Working Memory and Executive Function in Parkinson's Disease: Review, Critique, and Recommendations.Movement disorders : official journal of the Movement Disorder Society · 2025
    Review
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Christina B YoungFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0001-9535-2137
Brenna CholertonFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-2139-987X
Alena M SmithFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Marian Shahid-BesantiFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Carla AbdelnourFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-7636-9758
Elizabeth C MorminoFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-4542-6537
Shu-Ching HuFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Kathryn A ChungFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Amie PetersonFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Liana RosenthalFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Alexander PantelyatFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-6427-7485
Ted M DawsonFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Joseph QuinnFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.
Cyrus P ZabetianFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-7739-4306
Thomas J MontineFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-1346-2728
Kathleen L PostonFrom the Departments of Neurology and Neurological Sciences (C.B.Y., A.M.S., M.S.-B., C.A., E.C.M., K.L.P.) and (B.C., T.J.M.), Stanford University School of Medicine, CA; Veterans Affairs Puget Sound Health Care System (B.C., S.-C.H., C.P.Z.), Seattle; Department of Neurology (S.-C.H., C.P.Z.), University of Washington School of Medicine, Seattle; Department of Neurology (K.A.C., A. Peterson, J.Q.), Oregon Health and Science University, Portland; Portland Veterans Affairs Health Care System (K.A.C., A. Peterson, J.Q.), Oregon; Department of Neurology (L.R., A. Pantelyat, T.M.D.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0003-3424-7143

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI JUAN TRONCOSO · 2020 to 2026
$29.3M
Stanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Lisa Goldman Rosas · 2020 to 2026
$29.0M
Research Education ComponentP30AG066518 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI KEVIN M DUFF, Lisa C Silbert · 2020 to 2026
$28.6M
Udall Center Director's meeting poster awardP50NS062684 · NINDS · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2009 to 2020
$18.3M
Regional tau deposition and digital assessment of cognition in preclinical AD and MCIK99AG071837 · NIA · STANFORD UNIVERSITY · PI YOUNG, CHRISTINA B · 2022 to 2023
$256k
NIA NIH HHS K99 AG071837NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NINDS NIH HHS P50 NS062684
6 · The paper itself

Abstract

BACKGROUND AND

objectivesExecutive functioning is one of the first domains to be impaired in Parkinson disease (PD), and the majority of patients with PD eventually develop dementia. Thus, developing a cognitive endpoint measure specifically assessing executive functioning is critical for PD clinical trials. The objective of this study was to develop a cognitive composite measure that is sensitive to decline in executive functioning for use in PD clinical trials.

methodsWe used cross-sectional and longitudinal follow-up data from PD participants enrolled in the PD Cognitive Genetics Consortium, a multicenter setting focused on PD. All PD participants with Trail Making Test, Digit Symbol, Letter-Number Sequencing, Semantic Fluency, and Phonemic Fluency neuropsychological data collected from March 2010 to February 2020 were included. Baseline executive functioning data were used to create the Parkinson's Disease Composite of Executive Functioning (PaCEF) through confirmatory factor analysis. We examined the changes in the PaCEF over time, how well baseline PaCEF predicts time to cognitive progression, and the required sample size estimates for PD clinical trials. PaCEF results were compared with the Montreal Cognitive Assessment (MoCA), individual tests forming the PaCEF, and tests of visuospatial, language, and memory functioning.

resultsA total of 841 participants (251 no cognitive impairment [NCI], 480 mild cognitive impairment [MCI], and 110 dementia) with baseline data were included, of which the mean (SD) age was 67.1 (8.9) years and 270 were women (32%). Five hundred forty five PD participants had longitudinal neuropsychological data spanning 9 years (mean [SD] 4.5 [2.2] years) and were included in analyses examining cognitive decline. A 1-factor model of executive functioning with excellent fit (comparative fit index = 0.993, Tucker-Lewis index = 0.989, and root mean square error of approximation = 0.044) was used to calculate the PaCEF. The average annual change in PaCEF ranged from 0.246 points per year for PD-NCI participants who remained cognitively unimpaired to -0.821 points per year for PD-MCI participants who progressed to dementia. For PD-MCI, baseline PaCEF, but not baseline MoCA, significantly predicted time to dementia. Sample size estimates were 69%-73% smaller for PD-NCI trials and 16%-19% smaller for PD-MCI trials when using the PaCEF rather than MoCA as the endpoint. DISCUSSION: The PaCEF is a sensitive measure of executive functioning decline in PD and will be especially beneficial for PD clinical trials.

Indexed as

Cognitive DysfunctionExecutive FunctionNeuropsychological TestsParkinson DiseaseAgedClinical Trials as TopicCross-Sectional StudiesDisease ProgressionFemaleHumansLongitudinal StudiesMaleMiddle Aged

Identifiers

PMID38870440
PMCPMC11244747

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.