Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug;8(8):1695-1708.
doi: 10.1002/acn3.51436. Epub 2021 Jul 26.

Distinct progression patterns across Parkinson disease clinical subtypes

Peter S Myers  1 , Joshua J Jackson  2 , Amber K Clover  1 , Christina N Lessov-Schlaggar  3 , Erin R Foster  1   3   4 , Baijayanta Maiti  1 , Joel S Perlmutter  1   4   5   6   7 , Meghan C Campbell  1   5
Affiliations

Distinct progression patterns across Parkinson disease clinical subtypes

Peter S Myers et al. Ann Clin Transl Neurol. 2021 Aug.

Abstract

Objective: To examine specific symptom progression patterns and possible disease staging in Parkinson disease clinical subtypes.

Methods: We recently identified Parkinson disease clinical subtypes based on comprehensive behavioral evaluations, "Motor Only," "Psychiatric & Motor," and "Cognitive & Motor," which differed in dementia and mortality rates. Parkinson disease participants ("Motor Only": n = 61, "Psychiatric & Motor": n = 17, "Cognitive & Motor": n = 70) and controls (n = 55) completed longitudinal, comprehensive motor, cognitive, and psychiatric evaluations (average follow-up = 4.6 years). Hierarchical linear modeling examined group differences in symptom progression. A three-way interaction among time, group, and symptom duration (or baseline age, separately) was incorporated to examine disease stages.

Results: All three subtypes increased in motor dysfunction compared to controls. The "Motor Only" subtype did not show significant cognitive or psychiatric changes compared to the other two subtypes. The "Cognitive & Motor" subtype's cognitive dysfunction at baseline further declined compared to the other two subtypes, while also increasing in psychiatric symptoms. The "Psychiatric & Motor" subtype's elevated psychiatric symptoms at baseline remained steady or improved over time, with mild, steady decline in cognition. The pattern of behavioral changes and analyses for disease staging yielded no evidence for sequential disease stages.

Interpretation: Parkinson disease clinical subtypes progress in clear, temporally distinct patterns from one another, particularly in cognitive and psychiatric features. This highlights the importance of comprehensive clinical examinations as the order of symptom presentation impacts clinical prognosis.

PubMed Disclaimer

Conflict of interest statement

All authors have completed the conflict of interest form and report the following financial disclosures:

Peter S. Myers received support from NINDS NS097437.

Joshua J. Jackson receives support from NINDS NS097437, NIMH AG061162‐01, NIDCD DC017522‐02S1.

Amber K. Clover received support from NINDS NS097437.

Christina N. Lessov‐Schlaggar received support from NINDS NS097437.

Erin R. Foster is funded by the National Institutes of Health (NIA R21AG063974, NIA R01AG065214, NIDDK R01DK064832) and the Advanced Research Center of the Greater St. Louis Chapter of the American Parkinson Disease Association.

Baijayanta Maiti received funding from the National Center for Advancing Translational Sciences of the National Institutes of Health KL2 TR002346, American Academy of Neurology and American Brain Foundation Clinical Research Training Fellowship in Parkinson’s disease, Parkinson Study Group/Parkinson’s Disease Foundation Mentored Clinical Research Award, Greater St. Louis Chapter of American Parkinson Disease Association and the Jo Oertli fund. He has received compensation for reviewing grants as a member of the Parkinson Study Group mentoring committee.

Joel S. Perlmutter has received research funding from National Institutes of Health NS075321, NS103957, NS107281, NS092865, U10NS077384, NS097437, U54NS116025, U19 NS110456, AG050263, AG‐64937, NS097799, NS075527, ES029524, NS109487, R61 AT010753, (NCATS, NINDS, NIA), RO1NS118146, R01AG065214, Department of Defense (DOD W81XWH‐217‐1‐0393), Michael J Fox Foundation, Barnes‐Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson disease research fund), American Parkinson Disease Association (APDA) Advanced Research Center at Washington University, Greater St. Louis Chapter of the APDA, Paula and Rodger Riney Fund, Jo Oertli Fund, Huntington Disease Society of America, Murphy Fund, and CHDI. He co‐directs the Dystonia Coalition, which received the majority of its support through the NIH (grants NS116025, NS065701 from the National Institutes of Neurological Disorders and Stroke, TR 001456 from the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences). Dr. Perlmutter has provided medical legal consultation to Wood, Cooper, and Peterson, LLC and to Simmons and Simmons LLP. He serves as Director of Medical and Scientific Advisory Committee of the Dystonia Medical Research Foundation, Chair of the Scientific Advisory Committee of the Parkinson Study Group, Chair of the Standards Committee of the Huntington Study Group (honoraria for this one), member of the Scientific Advisory Board of the APDA, Chair of the Scientific and Publication Committee for ENROLL‐HD (honoraria from this one), and member of the Education Committee of the Huntington Study Group (honoraria from this one). Dr. Perlmutter has received honoraria from CHDI, Huntington Disease Study Group, Parkinson Study Group, Beth Israel Hospital (Harvard group), U Pennsylvania, Stanford U.; Boston University.

Meghan C. Campbell receives research support from NIH (NS097437, NS075321‐02, NS097799, AG063974, AT010753‐01, AT010753‐02S1), the McDonnell Center for Systems Neuroscience, the Mallinckrodt Institute of Radiology at WUSTL, the Neurimaging Labs Innovation Award, and honoraria from the Parkinson Foundation.

Figures

Figure 1
Figure 1
Consort diagram.
Figure 2
Figure 2
Predicted change in each domain. All predictions are based on the HLM growth models. (A) Depicts change over time for each motor domain. A positive slope indicates worsening performance. (B) Depicts change over time for each cognitive domain for each group. For CDR‐SB, a positive slope indicates worsening cognitive dysfunction. For all other cognitive domains, a negative slope indicates worsening performance. (C) Depicts change over time for each psychiatric domain. A positive slope indicates worsening severity. UPDRS3‐Total, Unified Parkinson Disease Rating Scale, part 3 motor subscale; CDR‐SB, Clinical Dementia Rating evaluation, sum of boxes; PIGD, postural instability and gait disturbance; GDS, Geriatric Depression Scale; FrSBe‐A, Frontal Systems Behavior scale, apathy subscale; NPIQ, Neuropsychiatric Inventory questionnaire. &significant difference between "Motor Only" and "Psychiatric & Motor"; ¥significant difference between "Motor Only" & "Cognitive & Motor"; §significant difference between "Psychiatric & Motor" and "Cognitive & Motor." All α < 0.05.
Figure 3
Figure 3
Individual depression changes in the “Psychiatric & Motor” subtype. From baseline and last visit medication information, participants were categorized as “Initiated Tx” (individuals who started to take antidepressants during the study) and “Stable‐Discontinued Tx” (individuals whose antidepressant usage did not change between baseline and last visit and individuals who stopped taking antidepressants after the baseline visit). All α < 0.05.
Figure 4
Figure 4
Subtype‐specific symptom manifestation patterns. Based on results, motor, psychiatric, and cognitive symptom progressions are shown for each subtype, illustrating the temporal relationships of symptom manifestations. For the cognitive domain, a negative slope represents worse performance. For the motor and psychiatric domains, a positive slope represents worse performance.
See this image and copyright information in PMC

References

    1. Jankovic J, McDermott M, Carter J, et al. Variable expression of Parkinson’s disease: a base‐line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology. 1990;40(10):1529‐1534. - PubMed
    1. Nutt JG. Motor subtype in Parkinson’s disease: different disorders or different stages of disease? Mov Disord Off J Mov Disord Soc. 2016;31(7):957‐961. - PubMed
    1. Erro R, Vitale C, Amboni M, et al. The heterogeneity of early Parkinson’s disease: a cluster analysis on newly diagnosed untreated patients. PLoS One. 2013;8(8):e70244. - PMC - PubMed
    1. van Rooden SM, Colas F, Martínez‐Martín P, et al. Clinical subtypes of Parkinson’s disease. Mov Disord Off J Mov Disord Soc. 2011;26(1):51‐58. - PubMed
    1. Graham JM, Sagar HJ. A data‐driven approach to the study of heterogeneity in idiopathic Parkinson’s disease: identification of three distinct subtypes. Mov Disord Off J Mov Disord Soc. 1999;14(1):10‐20. - PubMed

Publication types