Department of Neurology and Psychiatry, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
J Alzheimers Dis. 2018;65(4):1365-1375. doi: 10.3233/JAD-180486.
Previous studies suggest that excessive cortisol levels after stroke are associated with cognitive dysfunction. However, limited data exist regarding associations between post-stroke cortisol levels, brain abnormalities, genetic factors, and cognitive outcome. We sought to study these issues in a longitudinal stroke survivors cohort.
Data from 182 cognitively intact ischemic stroke patients from the TABASCO study were available. Saliva cortisol levels (bedtime and post-awakening) and cognitive assessments were obtained on admission, and 6, 12, and 24 months thereafter. During hospitalization, patients underwent 3T MRI scans and APOE genotyping.
Higher bedtime cortisol levels immediately post-stroke were associated with larger neurological deficits (p < 0.001), brain atrophy (p = 0.025), worse white matter integrity (p = 0.003), and worse cognitive results up to 24 months post-stroke. These findings remained significant when adjusted for age, gender, education, smoking, stroke severity, apolipoprotein E4 (ApoE4) status, and body mass index. ApoE4 negatively modified the relation between cortisol and memory. As a group, participants who presented with high admission bedtime cortisol levels continued to present relatively elevated bedtime levels across all examined time-points, and this group had inferior memory and executive functioning scores compared to the lower cortisol group 24 months post-stroke (p = 0.05, p = 0.035, respectively). Post-awakening cortisol levels were not associated with neuroimaging findings or cognitive scores.
High bedtime salivary cortisol levels post-stroke may provide information about dysregulation of diurnal HPA-axis activity under acute challenge conditions, and predict worse cognitive outcome. ApoE4 genotype might modify this association. These findings call for specific stress management interventions in stroke survivors.
既往研究表明，卒中后皮质醇水平过高与认知功能障碍相关。然而，关于卒中后皮质醇水平、脑异常、遗传因素与认知结局之间的关联，目前仅有有限的数据。我们旨在通过一项卒中后幸存者的纵向队列研究来探讨这些问题。
本研究纳入了来自 TABASCO 研究的 182 例认知功能正常的缺血性卒中患者的数据。于入院时以及此后的 6、12 和 24 个月时，采集唾液皮质醇水平（睡前和觉醒后）和认知评估结果。住院期间，患者接受 3T MRI 扫描和 APOE 基因分型。
卒中后即刻较高的睡前皮质醇水平与更大的神经功能缺损（p<0.001）、脑萎缩（p=0.025）、更差的白质完整性（p=0.003）以及卒中后 24 个月时的认知结果相关。在校正年龄、性别、教育程度、吸烟状况、卒中严重程度、载脂蛋白 E4（ApoE4）状态和体重指数后，这些发现仍然具有统计学意义。ApoE4 对皮质醇与记忆之间的关系具有负性修饰作用。作为一个整体，入院时皮质醇水平较高的患者在所有检测的时间点上持续表现出相对较高的睡前皮质醇水平，与较低皮质醇组相比，该组患者在卒中后 24 个月时的记忆和执行功能评分更差（p=0.05，p=0.035）。觉醒后皮质醇水平与神经影像学结果或认知评分无关。
卒中后较高的睡前唾液皮质醇水平可能反映了急性应激条件下下丘脑-垂体-肾上腺轴日间活动的失调，并预测了更差的认知结局。ApoE4 基因型可能会修饰这种关联。这些发现呼吁对卒中幸存者进行特定的应激管理干预。
