Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States.
Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, United States.
Parkinsonism Relat Disord. 2018 May;50:99-103. doi: 10.1016/j.parkreldis.2018.02.003. Epub 2018 Feb 3.
Excessive daytime sleepiness is a commonly reported clinical feature of dementia with Lewy bodies (DLB) that can occur early in the disease. Cholinergic depletion is known to be severe in DLB, even when dementia severity is mild. The nucleus basalis of Meynert serves as a primary source of cortical acetylcholine, and has a role in facilitating cortical activation and arousal. We sought to determine whether daytime sleepiness at the initial evaluation of patients with DLB was associated with neuronal loss in the nucleus basalis of Meynert.
Autopsy-confirmed patients who met clinical criteria for probable DLB at their initial evaluation and who were administered the informant-completed Epworth Sleepiness Scale were included in the study (n = 40). Each patient had a dementia at baseline (80% with mild severity) and two or more features of parkinsonism, visual hallucinations, fluctuations, or probable REM sleep behavior disorder. Quantitative digital pathology of the nucleus basalis of Meynert was performed in the DLB group and in 20 non-DLB autopsy controls.
DLB had greater neuronal depletion in the nucleus basalis of Meynert (p < 0.0001) than pathologic controls. Sleepiness was present in 58% of the DLB group and those with daytime sleepiness had significantly lower neuron counts in the nucleus basalis of Meynert than their non-sleepy counterparts (p = 0.001). Regression modeling revealed that sleepiness was a stronger predictor of neuronal loss in the nucleus basalis of Meynert than visual hallucinations, fluctuations or dementia severity (p = 0.003).
Excessive daytime sleepiness in early DLB is indicative of a more profound loss of basal forebrain cholinergic integrity.
日间过度嗜睡是路易体痴呆（DLB）的一种常见临床特征，即使在痴呆严重程度较轻时，也可能在疾病早期出现。已知胆碱能缺失在 DLB 中非常严重。基底核的 Meynert 作为皮质乙酰胆碱的主要来源，在促进皮质激活和觉醒方面发挥作用。我们试图确定 DLB 患者初始评估时的日间嗜睡是否与 Meynert 基底核神经元丢失有关。
本研究纳入了在初始评估时符合可能的 DLB 临床标准且接受了 informant 完成的 Epworth 嗜睡量表评估的尸检确诊患者（n=40）。每位患者在基线时均有痴呆（80%为轻度严重程度），并且有两种或更多帕金森病特征、视觉幻觉、波动或可能的 REM 睡眠行为障碍。对 DLB 组和 20 例非 DLB 尸检对照组的 Meynert 基底核进行了定量数字病理学检查。
DLB 的 Meynert 基底核神经元缺失明显多于病理对照（p<0.0001）。在 58%的 DLB 组中存在嗜睡，且日间嗜睡者的 Meynert 基底核神经元计数明显低于无嗜睡者（p=0.001）。回归模型显示，与视觉幻觉、波动或痴呆严重程度相比，嗜睡是 Meynert 基底核神经元缺失的更强预测因子（p=0.003）。
早期 DLB 中的日间过度嗜睡表明基底前脑胆碱能完整性的丧失更为严重。
