Goldstein David S, Sharabi Yehonatan
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.
Chaim Sheba Medical Center, Tel-Aviv University, Tel-Aviv, Israel.
Clin Auton Res. 2023 Feb;33(1):41-49. doi: 10.1007/s10286-022-00912-y. Epub 2022 Dec 12.
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.
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).
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.
Orthostatic hypotension and baroreflex-sympathoneural dysfunction characterize at-risk individuals who go on to be diagnosed with a central LBD during longitudinal follow-up.
在诸如帕金森病（PD）和路易体痴呆（DLB）等中枢路易体疾病（LBDs）中，当帕金森综合征或认知功能障碍出现时，大量中枢神经退行性变已经发生。心血管自主神经生物标志物可能在高危个体中检测出临床前中枢LBDs，从而实现可能有效的疾病修饰治疗。
在这项前瞻性纵向PDRisk研究中，59名参与者在特定方案的网站上提供了有关PD家族史、嗅觉功能障碍、梦境行为以及体位性不耐受或低血压的信息，并作为门诊患者接受筛查。34人有三个或更多已确认的风险因素，并随访至PD被诊断或长达7.5年。相关测量包括通过瓦尔萨尔瓦动作释放后血压恢复时间（PRT）和压力反射区域评估压力反射-交感神经功能；以及通过时域和频域的心率变异性和瓦尔萨尔瓦压力斜率评估压力反射-心迷走神经功能。对随后被诊断为中枢LBD（LBD+，N = 9）或未被诊断为中枢LBD（LBD-，N = 25）的组以及风险因素少于三个的PDRisk参与者（PDRisk-，N = 25）的数据进行了比较。
LBD+组收缩压的体位性下降幅度大于LBD-组和PDRisk-组（每组p < 0.0001）。LBD+组瓦尔萨尔瓦动作后的PRT增加（与LBD-组相比，p = 0.0114；与PDRisk-组相比，p = 0.0094）以及压力反射区域增加（与LBD-组相比，p = 0.0225；与PDRisk-组相比，p = 0.0028），而压力反射-心迷走神经功能指标在各组之间没有差异。
体位性低血压和压力反射-交感神经功能障碍是在纵向随访期间继续被诊断为中枢LBD的高危个体的特征。
