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Alzheimers. Dement., Feb 2025, 21 (2) e14584 | https://doi.org/10.1002/alz.14584
Cholinergic degeneration and early cognitive signs in prodromal Lewy body dementia
Kyung Ah Woo1 Heejung Kim2,3 Ryul Kim1 Bora Jin1 Jung Hwan Shin4 Seoyeon Kim1 Yu Kyeong Kim2 Hyunwoo Nam1 Beomseok Jeon4 Jee-Young Lee1
1 Department of Neurology, Seoul Metropolitan Government–Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Dongjak-gu, Seoul, Republic of Korea
2 Department of Nuclear Medicine, Seoul Metropolitan Government–Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Dongjak-gu, Seoul, Republic of Korea
3 Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea
4 Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
Correspondence: Jee-Young Lee
1 Department of Neurology, Seoul Metropolitan Government–Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Dongjak-gu, Seoul, Republic of Korea
2 Department of Nuclear Medicine, Seoul Metropolitan Government–Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Dongjak-gu, Seoul, Republic of Korea
3 Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea
4 Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
Correspondence: Jee-Young Lee
Abstract
INTRODUCTION
Isolated REM sleep behavior disorder (iRBD) is a strong prodromal marker of Lewy body diseases (LBDs) – Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Cholinergic loss is linked to cognitive decline in these conditions, but its trajectory remains unclear.
METHODS
In a cohort of 92 iRBD participants with baseline MRI, cholinergic basal forebrain (cBF) volume was measured, with longitudinal changes analyzed in 49 with follow-up scans. Cross-sectional neuropsychological associations were examined across a broader RBD–LBD continuum, including the iRBD cohort plus 65 PD and 15 DLB patients with probable RBD.
RESULTS
cBF volume declined at comparable rates in iRBD-to-PD and iRBD-to-DLB converters, but atrophy was more severe at DLB phenoconversion. cBF atrophy correlated with attention, executive, and memory deficits. In iRBD, baseline cBF z-score < −1.0 predicted dementia (hazard ratio = 9.57, p = .009).
CONCLUSION
cBF degeneration evolves from the prodromal iRBD stage of LBDs and predicts dementia, highlighting a window for cholinergic-targeted intervention.
Isolated REM sleep behavior disorder (iRBD) is a strong prodromal marker of Lewy body diseases (LBDs) – Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Cholinergic loss is linked to cognitive decline in these conditions, but its trajectory remains unclear.
METHODS
In a cohort of 92 iRBD participants with baseline MRI, cholinergic basal forebrain (cBF) volume was measured, with longitudinal changes analyzed in 49 with follow-up scans. Cross-sectional neuropsychological associations were examined across a broader RBD–LBD continuum, including the iRBD cohort plus 65 PD and 15 DLB patients with probable RBD.
RESULTS
cBF volume declined at comparable rates in iRBD-to-PD and iRBD-to-DLB converters, but atrophy was more severe at DLB phenoconversion. cBF atrophy correlated with attention, executive, and memory deficits. In iRBD, baseline cBF z-score < −1.0 predicted dementia (hazard ratio = 9.57, p = .009).
CONCLUSION
cBF degeneration evolves from the prodromal iRBD stage of LBDs and predicts dementia, highlighting a window for cholinergic-targeted intervention.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-25)
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