Holleman Jasper, Adagunodo Sofia, Kåreholt Ingemar, Hagman Göran, Aspö Malin, Udeh-Momoh Chinedu T, Solomon Alina, Kivipelto Miia, Sindi Shireen
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.
Memory Clinic Zentralschweiz, Luzerner Psychiatrie, Pfaffnau-Sankt Urban, Switzerland.
BMJ Neurol Open. 2022 Oct 19;4(2):e000344. doi: 10.1136/bmjno-2022-000344. eCollection 2022.
This study aims to investigate the relationship between diurnal cortisol patterns, cognition and Alzheimer's disease (AD) biomarkers in memory clinic patients.
Memory clinic patients were recruited from Karolinska University Hospital in Sweden (n=155). Diurnal cortisol patterns were assessed using five measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime levels (AM/PM ratio) and total daily output. Cognition was measured in five domains: memory, working memory, processing speed, perceptual reasoning and overall cognition. AD biomarkers Aβ, total tau and phosphorylated tau were assessed from cerebrospinal fluid (CSF). Cognition was measured at follow-up (average 32 months) in a subsample of participants (n=57).
In assessing the associations between cortisol and cognition, higher awakening cortisol levels were associated with greater processing speed at baseline. No relationship was found between diurnal cortisol patterns and change in cognition over time or CSF AD biomarkers in the total sample. After stratification by CSF Aβ levels, higher awakening cortisol levels were associated with worse memory performance in amyloid-positive participants. In amyloid-negative participants, higher bedtime cortisol levels and a lower AM/PM ratio were associated with lower overall cognition, greater awakening cortisol levels were associated with better processing speed, and a higher AM/PM ratio was associated with better perceptual reasoning. Additionally, higher awakening cortisol levels were associated with lower CSF Aβ levels in amyloid-positive participants, while higher bedtime cortisol levels and a lower AM/PM ratio were associated with higher CSF total tau in amyloid-negative participants.
Our findings suggest that diurnal cortisol patterns are associated with cognitive function and provide new insights into the association between diurnal cortisol patterns and AD-related CSF biomarkers. Further research is needed to examine the complex relationship between cortisol, cognition and brain pathology.
本研究旨在调查记忆门诊患者的昼夜皮质醇模式、认知与阿尔茨海默病(AD)生物标志物之间的关系。
从瑞典卡罗林斯卡大学医院招募记忆门诊患者(n = 155)。使用五项指标评估昼夜皮质醇模式:觉醒水平、皮质醇觉醒反应、就寝时水平、觉醒与就寝时水平之比(上午/下午比值)和每日总分泌量。从五个领域测量认知:记忆、工作记忆、处理速度、知觉推理和整体认知。从脑脊液(CSF)中评估AD生物标志物Aβ、总tau蛋白和磷酸化tau蛋白。在参与者的一个子样本(n = 57)中进行随访(平均32个月)时测量认知。
在评估皮质醇与认知之间的关联时,较高的觉醒皮质醇水平与基线时更快的处理速度相关。在总样本中,未发现昼夜皮质醇模式与随时间变化的认知或脑脊液AD生物标志物之间存在关系。按脑脊液Aβ水平分层后,较高的觉醒皮质醇水平与淀粉样蛋白阳性参与者较差的记忆表现相关。在淀粉样蛋白阴性参与者中,较高的就寝时皮质醇水平和较低的上午/下午比值与较低的整体认知相关,较高的觉醒皮质醇水平与较好的处理速度相关,较高的上午/下午比值与较好的知觉推理相关。此外,较高的觉醒皮质醇水平与淀粉样蛋白阳性参与者较低的脑脊液Aβ水平相关,而较高的就寝时皮质醇水平和较低的上午/下午比值与淀粉样蛋白阴性参与者较高的脑脊液总tau蛋白相关。
我们的研究结果表明,昼夜皮质醇模式与认知功能相关,并为昼夜皮质醇模式与AD相关脑脊液生物标志物之间的关联提供了新的见解。需要进一步研究来检查皮质醇、认知和脑病理学之间的复杂关系。