Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type
Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type
复制标题
DOI：
10.1016/j.neurobiolaging.2014.10.031
复制
发表时间：
2015-02
影响因子：
4.2
通讯作者：
J. Popp;S. Wolfsgruber;I. Heuser;O. Peters;M. Hüll;J. Schröder;H. Möller;P. Lewczuk;A. Schneider;H. Jahn;C. Luckhaus;R. Perneczky;L. Frölich;M. Wagner;W. Maier;J. Wiltfang;J. Kornhuber;F. Jessen
中科院分区：
文献类型：
--
作者：
J. Popp;S. Wolfsgruber;I. Heuser;O. Peters;M. Hüll;J. Schröder;H. Möller;P. Lewczuk;A. Schneider;H. Jahn;C. Luckhaus;R. Perneczky;L. Frölich;M. Wagner;W. Maier;J. Wiltfang;J. Kornhuber;F. Jessen
据报道，阿尔茨海默病(AD)患者的外周和中枢神经系统皮质醇水平升高，可能反映了下丘脑-垂体-肾上腺(HPA)轴的脑成分功能障碍。然而，大脑暴露在高皮质醇浓度下也可能加速疾病进展和认知能力下降。这项研究的目的是调查HPA轴的失调是否发生在AD的早期临床阶段，以及血浆和脑脊液皮质醇水平是否与临床疾病进展相关。由德国痴呆能力网络进行的一项多中心研究收集了AD痴呆患者、轻度AD认知障碍患者(MCI-AD)、其他类型MCI患者(MCI-O)和认知正常的对照组的晨间血浆和脑脊液皮质醇浓度。对患有MCI-AD、MCI-O和AD痴呆的参与者进行了临床和神经心理学随访。AD痴呆或MCI-AD患者的脑脊液皮质醇浓度高于MCI-O或正常认知患者。在控制了可能的混杂因素后，包括脑脊液中淀粉样β1-42和总tau的测量，基线脑脊液皮质醇水平较高与MCI-AD的临床恶化和认知功能下降更快相关。这一发现表明，HPA轴的失调发生在AD的MCI阶段，可能会加速疾病的进展和认知能力的下降。
Increased peripheral and central nervous system cortisol levels have been reported in Alzheimer's disease (AD) and may reflect dysfunction of cerebral components of the hypothalamic-pituitary-adrenal (HPA) axis. However, brain exposure to high cortisol concentrations may also accelerate disease progression and cognitive decline. The objectives of this study were to investigate whether HPA-axis dysregulation occurs at early clinical stages of AD and whether plasma and CSF cortisol levels are associated with clinical disease progression. Morning plasma and CSF cortisol concentrations were obtained from the subjects with AD dementia, mild cognitive impairment of AD type (MCI-AD), MCI of other type (MCI-O), and controls with normal cognition included in a multicenter study from the German Dementia Competence Network. A clinical and neuropsychological follow-up was performed in a subgroup of participants with MCI-AD, MCI-O, and AD dementia. CSF cortisol concentrations were increased in the subjects with AD dementia or MCI-AD compared with subjects with MCI-O or normal cognition. After controlling for possible confounders including CSF measures of amyloid beta1–42 and total tau, higher baseline CSF cortisol levels were associated with faster clinical worsening and cognitive decline in MCI-AD. The findings suggest that HPA-axis dysregulation occurs at the MCI stage of AD and may accelerate disease progression and cognitive decline.