Cardiac sympathetic degeneration informs the duration of the prodromal stage of body-first Lewy body disease
4 affiliations
- 1Lundbeck Foundation Parkinson’s Disease Research Center (PACE), Aarhus University
- 2Department of Nuclear Medicine, Aarhus University Hospital
- 3Department of Neurology, College of Medicine, The Catholic University of Korea
- 4Department of Radiology, Division of Nuclear Medicine, College of Medicine, The Catholic University of Korea
Abstract
Body-first Lewy body disease (LBD) is hypothesized to begin in the peripheral autonomic nervous system years before nigrostriatal involvement. Isolated REM sleep behaviour disorder (iRBD) is considered an early manifestation of body-first LBD but is preceded by an unknown period of peripheral autonomic degeneration. Consequently, the total duration of the prodromal phase remains unknown. We used longitudinal imaging data to model the progression of cardiac sympathetic and nigrostriatal dopaminergic degeneration and employed the resulting curves to estimate the prodromal period of body-first LBD. Cardiac sympathetic trajectories were highly consistent across two cohorts, showing rapid early decline followed by gradual slowing, reaching 50% of the normal value after ~5 years and 25% after ~10 years. Dopaminergic decline was slightly slower, reaching 50% of the normal value after ~8 years and 25% after ~15 years. iRBD patients displayed severe baseline cardiac sympathetic loss (median 21.3% of normal), but mild baseline dopaminergic deficit (median 81.5% of normal), indicating that cardiac sympathetic degeneration may precede dopaminergic nigrostriatal involvement by 8.6 years. Based on baseline dopaminergic deficits in Parkinson’s disease (PD), the combined model estimated that the prodromal phase of body-first LBD, from onset of cardiac sympathetic degeneration to predicted clinical PD diagnosis, exceeds 20 years.
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BibTeX
@article{skjærbæk2026cardiac,
title = {{Cardiac sympathetic degeneration informs the duration of the prodromal stage of body-first Lewy body disease}},
author = {Casper Skjærbæk and Ole Lajord Munk and Katrine B. Andersen and Anushree Krishnamurthy and Karoline Knudsen and Thea Lillethorup and Sang-Won Yoo and Dong-Woo Ryu and Yoonsang Oh and Seunggyun Ha and Joong-Seok Kim and Per Borghammer and Jacob Horsager},
journal = {npj Parkinson's Disease},
year = {2026},
month = jul,
doi = {10.1038/s41531-026-01455-z},
url = {https://doi.org/10.1038/s41531-026-01455-z},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cardiac sympathetic degeneration informs the duration of the prodromal stage of body-first Lewy body disease
AU - Casper Skjærbæk
AU - Ole Lajord Munk
AU - Katrine B. Andersen
AU - Anushree Krishnamurthy
AU - Karoline Knudsen
AU - Thea Lillethorup
AU - Sang-Won Yoo
AU - Dong-Woo Ryu
AU - Yoonsang Oh
AU - Seunggyun Ha
AU - Joong-Seok Kim
AU - Per Borghammer
AU - Jacob Horsager
PY - 2026
DA - 2026/07/01
JO - npj Parkinson's Disease
DO - 10.1038/s41531-026-01455-z
UR - https://doi.org/10.1038/s41531-026-01455-z
AB - Body-first Lewy body disease (LBD) is hypothesized to begin in the peripheral autonomic nervous system years before nigrostriatal involvement. Isolated REM sleep behaviour disorder (iRBD) is considered an early manifestation of body-first LBD but is preceded by an unknown period of peripheral autonomic degeneration. Consequently, the total duration of the prodromal phase remains unknown. We used longitudinal imaging data to model the progression of cardiac sympathetic and nigrostriatal dopaminergic degeneration and employed the resulting curves to estimate the prodromal period of body-first LBD. Cardiac sympathetic trajectories were highly consistent across two cohorts, showing rapid early decline followed by gradual slowing, reaching 50% of the normal value after ~5 years and 25% after ~10 years. Dopaminergic decline was slightly slower, reaching 50% of the normal value after ~8 years and 25% after ~15 years. iRBD patients displayed severe baseline cardiac sympathetic loss (median 21.3% of normal), but mild baseline dopaminergic deficit (median 81.5% of normal), indicating that cardiac sympathetic degeneration may precede dopaminergic nigrostriatal involvement by 8.6 years. Based on baseline dopaminergic deficits in Parkinson’s disease (PD), the combined model estimated that the prodromal phase of body-first LBD, from onset of cardiac sympathetic degeneration to predicted clinical PD diagnosis, exceeds 20 years.
SN - 2373-8057
ER -