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Published Date: 10 January 2025

Association of Favorable Cerebrospinal Fluid Markers With Reversion of Mild Cognitive Impairment Due to Parkinson’s Disease

Cameron A. Ryczek, M.A., Rhiannon Rivas, M.A., Lea Hemphill, M.S., Zackary Zanotelli, B.A., Nicholas Renteria, B.A., Khashayar Dashtipour, M.D., and Jacob D. Jones, Ph.D. jacob.jones@csusb.eduAuthors Info & Affiliations
Publication: The Journal of Neuropsychiatry and Clinical Neurosciences
In Advance
https://doi.org/10.1176/appi.neuropsych.20240099
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Abstract

Objective:

Cognitive impairment is a common nonmotor symptom among individuals with Parkinson’s disease (PD). Although cognitive impairment generally develops progressively, individuals with PD-associated mild cognitive impairment (PD-MCI) may revert to being cognitively normal (CN), which is referred to as PD-MCI reversion. Previous studies are inconsistent in whether PD-MCI reverters are at greater risk for PD-MCI recurrence relative to CN individuals. Even less is known about how PD-MCI reverters compare with CN individuals or PD-MCI nonreverters in terms of neurodegenerative biomarkers. The authors examined group differences (CN, PD-MCI reversion, and PD-MCI nonreversion) in cerebrospinal fluid (CSF) markers of Alzheimer’s disease (AD), including amyloid beta, tau (total [t-tau] and phosphorylated [p-tau]), and alpha-synuclein.

Methods:

Data from the longitudinal international multisite Parkinson Progression Marker Initiative were used. Participants were newly diagnosed as having PD (N=430) and completed a battery of neurocognitive assessments at baseline and annual follow-ups for up to 5 years. Participants were classified as CN, PD-MCI reverters, or PD-MCI nonreverters on the basis of the first two neurocognitive assessments.

Results:

The PD-MCI nonreversion group had greater p-tau:amyloid beta and t-tau:amyloid beta ratios relative to the PD-MCI reversion group. The CN and PD-MCI reversion groups did not significantly differ in any of the CSF markers.

Conclusions:

PD-MCI reverters may have a more favorable trajectory in terms of AD pathology relative to PD-MCI nonreverters. Future studies are needed to verify whether PD-MCI reversion may represent an intermediate prognostic group between CN individuals and those with MCI nonreversion.

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Information & Authors

Information

Published In

Go to The Journal of Neuropsychiatry and Clinical Neurosciences
Go to The Journal of Neuropsychiatry and Clinical Neurosciences
The Journal of Neuropsychiatry and Clinical Neurosciences
In Advance

History

Received: 20 May 2024
Revision received: 6 August 2024
Revision received: 23 September 2024
Accepted: 8 October 2024
Published online: 10 January 2025

Keywords

  1. Cerebrospinal Fluid Markers
  2. Cognitive Disorders
  3. Mild Cognitive Impairment
  4. Parkinson’s Disease
  5. Alzheimer’s disease

Authors

Details

Cameron A. Ryczek, M.A.
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
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Rhiannon Rivas, M.A.
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
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Lea Hemphill, M.S.
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
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Zackary Zanotelli, B.A.
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
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Nicholas Renteria, B.A.
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
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Khashayar Dashtipour, M.D.
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
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Jacob D. Jones, Ph.D. jacob.jones@csusb.edu
Department of Psychology, California State University, San Bernardino (Ryczek, Rivas, Hemphill, Zanotelli, Renteria, Jones); Department of Neurology, Division of Movement Disorders, Loma Linda University Health System, Loma Linda, Calif. (Dashtipour); Center on Aging, California State University, San Bernardino (Jones).
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Notes

Send correspondence to Dr. Jones (jacob.jones@csusb.edu).

Competing Interests

Dr. Dashtipour reports serving as a consultant, speaker, or adviser for AbbVie, Acadia Pharmaceuticals, Acorda Therapeutics, Avion Pharmaceuticals, Ipsen, Neurocrine Biosciences, Revance Therapeutics, Sunovion Respiratory Development, Supernus Pharmaceuticals, and Teva Pharmaceuticals. The other authors report no financial relationships with commercial interests.

Funding Information

The study was supported by NIH (grants SC3 NS124906 and T34 GM136467 to Dr. Jones). The Parkinson’s Progression Markers Initiative, a public-private partnership, is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including Abbvie, AcureX, Aligning Science Across Parkinson’s, Allergan, Amathus Therapeutics, AskBio, Avid Radiopharmaceuticals, BIAL, Biogen, Biohaven, BioLegend, BlueRock Therapeutics, Bristol-Myers Squibb, Calico Labs, Celgene, Cerevel Therapeutics, Coave Therapeutics, DaCapo Brainscience, Denali, Edmond J. Safra Foundation, Eli Lilly, 4D Pharma, Gain Therapeutics, GE HealthCare, Genentech, GSK, Golub Capital, Handl Therapeutics, Insitro, Janssen Neuroscience, Lundbeck, Merck, Meso Scale Discovery, Mission Therapeutics, Neurocrine Biosciences, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi, Servier, Sun Pharma Advanced Research Company, Takeda, Teva, UCB, Vanqua Bio, Verily, Voyager Therapeutics, the Weston Family Foundation, and Yumanity Therapeutics.

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