School of Psychology and Psychiatry, Monash University, Clayton Campus, Wellington Road, Clayton, Victoria, 3800, Australia.
J Neurol. 2013 Mar;260(3):891-902. doi: 10.1007/s00415-012-6732-y. Epub 2012 Nov 20.
Hypothalamic pituitary adrenal (HPA) axis hyperactivity has been linked to learning and memory difficulties in a range of neurodegenerative and neuropsychiatric conditions. In Huntington's disease (HD), both declines in learning and memory and HPA axis dysfunction are present early in the disease. However, the relationship between specific learning and memory deficits and HPA axis functioning in HD has not been examined. The aim of this study was to investigate cortisol levels in relation to verbal learning and memory in pre-diagnosed (pre-HD) participants and patients at the early stages of diagnosed HD (early-HD). Cortisol concentration was assayed in saliva samples from 57 participants (17 early-HD, 20 pre-HD, and 20 controls) at four time-points across a 24-h period. Verbal memory was assessed using the California Verbal Learning Test-Second Edition (CVLT-II). We focused statistical analyses on the late evening cortisol concentration, and examined cortisol levels and verbal memory function in relation to diagnostic group (control, pre-HD, early-HD), and in a separate set of analyses combining pre-HD and early-HD (and excluding controls) we also examined cortisol and verbal memory performance in relation to the severity of HD-related motor signs. Of these two classification approaches, HD motor sign severity was more strongly associated with high evening cortisol levels and both reduced information encoding and memory retrieval. Separately, there was also a trend of higher cortisol levels in pre-HD. The findings suggest hypercortisolism and the underlying pathological changes may begin many years before a clinical diagnosis is made, but the memory decline associated with HPA axis disturbance may only become detectable once motor signs become pronounced.
下丘脑-垂体-肾上腺 (HPA) 轴活性亢进与一系列神经退行性和神经精神疾病中的学习和记忆困难有关。在亨廷顿病 (HD) 中，学习和记忆能力下降以及 HPA 轴功能障碍在疾病早期就存在。然而，HD 中特定学习和记忆缺陷与 HPA 轴功能之间的关系尚未得到研究。本研究旨在探讨皮质醇水平与预诊断 (HD 前) 参与者和诊断早期 HD (早期 HD) 患者的言语学习和记忆之间的关系。在 24 小时内的四个时间点，从 57 名参与者 (17 名早期 HD、20 名 HD 前和 20 名对照) 的唾液样本中检测皮质醇浓度。使用加利福尼亚言语学习测试-第二版 (CVLT-II) 评估言语记忆。我们将统计分析集中在傍晚皮质醇浓度上，并检查皮质醇水平和言语记忆功能与诊断组 (对照组、HD 前、早期 HD) 的关系，在另一组分析中，我们还将 HD 相关运动迹象的严重程度与皮质醇和言语记忆表现结合起来进行了分析。在这两种分类方法中，HD 运动迹象的严重程度与傍晚皮质醇水平升高以及信息编码和记忆检索减少的相关性更强。另外，HD 前组的皮质醇水平也有升高的趋势。研究结果表明，皮质醇过多症和潜在的病理变化可能在临床诊断前多年就开始出现，但与 HPA 轴紊乱相关的记忆下降可能仅在运动迹象明显时才变得可检测到。
