Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type.

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.

Popp J ，Wolfsgruber S ，Heuser I ，Peters O ，Hüll M ，Schröder J ，Möller HJ ，Lewczuk P ，Schneider A ，Jahn H ，Luckhaus C ，Perneczky R ，Frölich L ，Wagner M ，Maier W ，Wiltfang J ，Kornhuber J ，Jessen F ... -  《-》

Varying strength of cognitive markers and biomarkers to predict conversion and cognitive decline in an early-stage-enriched mild cognitive impairment sample.

Egli SC ，Hirni DI ，Taylor KI ，Berres M ，Regeniter A ，Gass A ，Monsch AU ，Sollberger M ... -  《-》

Incremental value of biomarker combinations to predict progression of mild cognitive impairment to Alzheimer's dementia.

Frölich L ，Peters O ，Lewczuk P ，Gruber O ，Teipel SJ ，Gertz HJ ，Jahn H ，Jessen F ，Kurz A ，Luckhaus C ，Hüll M ，Pantel J ，Reischies FM ，Schröder J ，Wagner M ，Rienhoff O ，Wolf S ，Bauer C ，Schuchhardt J ，Heuser I ，Rüther E ，Henn F ，Maier W ，Wiltfang J ，Kornhuber J ... -  《Alzheimers Research & Therapy》

Decreasing body mass index is associated with cerebrospinal fluid markers of Alzheimer's pathology in MCI and mild dementia.

Several studies have identified an association between body mass index (BMI) and the incidence and severity of Alzheimer's disease (AD) but this relationship is not fully understood. The primary objective of this study was to assess the possible association between BMI and cerebrospinal fluid (CSF) biomarkers of AD pathology in subjects with normal cognition and cognitive impairment. The secondary objective was to test whether BMI may contribute to improve the accuracy of a clinical model to predict AD pathology in memory clinic patients with cognitive impairment. One hundred and seven elderly subjects with cognitive impairment (91 memory clinic patients with mild cognitive impairment [MCI] and 16 with dementia of AD type) and 55 cognitively healthy volunteers were included in this study. All subjects received a comprehensive clinical and neuropsychological evaluation and a lumbar puncture for CSF biomarker analysis. Multiple linear regressions and receiver operating characteristic (ROC) analyses were carried out to assess the association between BMI and the CSF biomarkers of AD pathology. BMI was positively correlated with the CSF levels of Aβ42 and negatively with tau and P-tau181 in participants with cognitive impairment. The associations were independent of age, sex, educational level, type and severity of cognitive impairment, cerebrovascular risk factors and the presence of the APOEε4 allele. Furthermore, BMI significantly improved the sensitivity and specificity of a multi-factorial model to predict the presence of an AD CSF biomarker profile. Lower BMI is associated with cerebral AD pathology rather than with cognitive impairment in elderly subjects with MCI and mild dementia. Along with other clinical factors, decreasing BMI may help the clinician to identify patients with cognitive impairment due to AD.

Mathys J ，Gholamrezaee M ，Henry H ，von Gunten A ，Popp J ... -  《-》

Combining Cerebrospinal Fluid Biomarkers and Neuropsychological Assessment: A Simple and Cost-Effective Algorithm to Predict the Progression from Mild Cognitive Impairment to Alzheimer's Disease Dementia.

Mazzeo S ，Santangelo R ，Bernasconi MP ，Cecchetti G ，Fiorino A ，Pinto P ，Passerini G ，Falautano M ，Comi G ，Magnani G ... -  《-》