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Baroreflex-sympathoneural dysfunction characterizes at-risk individuals with preclinical central Lewy body diseases

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Clinical Autonomic Research Aims and scope Submit manuscript

A Correction to this article was published on 12 January 2023

This article has been updated

Abstract

Purpose

In central Lewy body diseases (LBDs) such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), by the time parkinsonism or cognitive dysfunction becomes manifest, substantial central neurodegeneration has already occurred. Cardiovascular autonomic biomarkers might detect preclinical central LBDs in at-risk individuals, enabling possibly effective disease-modifying treatment.

Methods

In the prospective, longitudinal PDRisk study, 59 participants provided information about family history of PD, olfactory dysfunction, dream enactment behavior, and orthostatic intolerance or hypotension at a protocol-specific website and were screened as outpatients. Thirty-four had three or more confirmed risk factors and were followed until PD was diagnosed or up to 7.5 years. Dependent measures included assessments of baroreflex-sympathoneural function, via the blood pressure recovery time (PRT) after release of the Valsalva maneuver and baroreflex areas; and baroreflex-cardiovagal function, via heart rate variability in the time and frequency domains and Valsalva baroslopes. Data were compared from groups with or without a subsequent diagnosis of a central LBD (LBD+, N = 9; LBD−, N = 25) and PDRisk participants with fewer than three confirmed risk factors (PDRisk−, N = 25).

Results

The LBD+ group had larger orthostatic falls in systolic blood pressure than did the LBD− and PDRisk− groups (p < 0.0001 each). The LBD+ group had increased PRTs (p = 0.0114 versus LBD−, p = 0.0094 versus PDRisk−) and baroreflex areas after the Valsalva maneuver (p = 0.0225 versus LBD−, p = 0.0028 versus PDRisk−), whereas the groups did not differ in indices of baroreflex-cardiovagal function.

Conclusion

Orthostatic hypotension and baroreflex-sympathoneural dysfunction characterize at-risk individuals who go on to be diagnosed with a central LBD during longitudinal follow-up.

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Data availability

Data spreadsheets from this study are available from the Corresponding Author upon written request.

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Acknowledgements

The funding organization for this study was the Division of Intramural Research (DIR), NINDS, NIH. The DIR, NINDS, NIH supported the research reported here.

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Authors and Affiliations

  1. Autonomic Medicine Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive MSC-1620, Building 10 Room 8N260, Bethesda, MD, 20892, USA

    David S. Goldstein

  2. Chaim Sheba Medical Center, Tel-Aviv University, Tel-Aviv, Israel

    Yehonatan Sharabi

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Contributions

All the authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by D.S.G. The first draft of the manuscript was written by D.S.G., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to David S. Goldstein.

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Conflict of interest

D.S.G. reports no disclosures. Yehonatan Sharabi reports no disclosures. This is not an industry-sponsored study. The authors declare that they have no conflict of interest.

Ethical approval

Participants in this study gave written informed consent to participate in IRB-approved intramural NINDS protocols. Consent for the PDRisk study was in two forms: electronic at a protocol-specific, IRB-approved website and in writing at the time of evaluation at the NIH Clinical Center. The study is listed in ClinicalTrials.gov (study NCT00775853). For comparison purposes, physiological data were culled from an ongoing database under an IRB-approved secondary research protocol (NIH Clinical Protocol 000490). Data were reviewed from all participants with PD + OH, PD without OH (PD No OH), or PAF or who were healthy volunteers (HVs) studied at the NIH Clinical Center between 1991 and 2022.

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Goldstein, D.S., Sharabi, Y. Baroreflex-sympathoneural dysfunction characterizes at-risk individuals with preclinical central Lewy body diseases. Clin Auton Res 33, 41–49 (2023). https://doi.org/10.1007/s10286-022-00912-y

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