C-1073 (Mifepristone) in the Adjunctive Treatment of Alzheimers Disease

DeBattista, Charles; Belanoff, Joseph K.

doi:10.2174/1567205053585954

Cited by 23 publications

(16 citation statements)

References 27 publications

(30 reference statements)

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“…HSD11B1 controls tissue levels of biologically active glucocorticoids and thereby influences neuronal vulnerability. These results also point to the possibility of using RU486 in AD, because different assays show that RU486 slows the progression of cognitive decline in this disease (Belanoff et al, 2002;DeBattista and Belanoff, 2005). Figure 9.…”

Section: Discussionmentioning

confidence: 82%

Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex

Pablos¹,

Villarán²,

Argüelles³

et al. 2006

J. Neurosci.

192

176

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Inflammation could be involved in some neurodegenerative disorders that accompany signs of inflammation. However, because sensitivity to inflammation is not equal in all brain structures, a direct relationship is not clear. Our aim was to test whether some physiological circumstances, such as stress, could enhance susceptibility to inflammation in the prefrontal cortex (PFC), which shows a relative resistance to inflammation. PFC is important in many brain functions and is a target for some neurodegenerative diseases. We induced an inflammatory process by a single intracortical injection of 2 g of lipopolysaccharide (LPS), a potent proinflammogen, in nonstressed and stressed rats. We evaluated the effect of our treatment on inflammatory markers, neuronal populations, BDNF expression, and behavior of several mitogen-activated protein (MAP) kinases and the transcription factor cAMP response element-binding protein. Stress strengthens the changes induced by LPS injection: microglial activation and proliferation with an increase in the levels of the proinflammatory cytokine tumor necrosis factor-␣; loss of cells such as astroglia, seen as loss of glial fibrillary acidic protein immunoreactivity, and neurons, studied by neuronal-specific nuclear protein immunohistochemistry and GAD67 and NMDA receptor 1A mRNAs expression by in situ hybridization. A significant increase in the BDNF mRNA expression and modifications in the levels of MAP kinase phosphorylation were also found. In addition, we observed a protective effect from RU486 [mifepristone (11␤-[p-(dimethylamino)phenyl]-17␤-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one)], a potent inhibitor of the glucocorticoid receptor activation. All of these data show a synergistic effect between inflammation and stress, which could explain the relationship described between stress and some neurodegenerative pathologies.

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Section: Discussionmentioning

confidence: 82%

Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex

Pablos¹,

Villarán²,

Argüelles³

et al. 2006

J. Neurosci.

192

176

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“…Another study [27] found that oral contraceptive use was related to better cognitive performance only in univariate model. Mifepristone, a kind of emergency contraceptive, has been reported to be effective in treatment for AD in a number of clinical studies [35][36][37]. It is important to note that the particular type and duration of oral contraceptive used by participants were not collected in our study and also not reported by those epidemiological studies afore mentioned, and it is highly possible that different oral contraceptive may differ in their effect on cognitive function.…”

Section: Discussionmentioning

confidence: 86%

Reproductive History and Risk of Cognitive Impairment in Elderly Women: A Cross-Sectional Study in Eastern China

Chen

et al. 2015

JAD

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Abstract.Background: Epidemiological studies suggest that proxies of higher lifetime estrogen exposure are associated with better cognitive function in postmenopausal women, but this has not been found consistently. Objective: To determine whether reproductive history, an important modifier of estrogen exposure across the lifetime, is associated with risk of cognitive impairment in postmenopausal women. Methods: We analyzed the baseline data from Zhejiang Major Public Health Surveillance Program (ZPHS) including 4,796 postmenopausal women. Cognitive impairment was assessed through the application of Mini-Mental State Examination questionnaire. Logistic regression models, controlled for an extensive range of potential confounders, were generated to examine the associations between women's reproductive history and risk of cognitive impairment in their later life. Results: The length of reproductive period was inversely associated with risk of cognitive impairment (p = 0.001). Odds ratio (OR) of cognitive impairment were 1.316 (95% CI 1.095∼1.582) for women with 5 or more times of full-term pregnancies, compared with those with 1∼4 times of full-term pregnancies. Women without incomplete pregnancy had a significant higher risk of cognitive impairment (OR = 1.194, 95% CI 1.000∼1.429), compared with the reference (1∼2 times of incomplete pregnancies). Oral contraceptive use (OR = 0.489, 95% CI 0.263∼0.910) and intrauterine device (IUD) use (OR = 0.684, 95% CI 0.575∼0.815) were associated with significantly reduced risk of cognitive impairment. Conclusion: Our results indicated that shorter reproductive period, higher number of full-term pregnancies and no incomplete pregnancy history were associated with an increased risk of cognitive impairment. In contrast, oral contraceptive and IUD use corresponded to reduced risk of cognitive impairment.

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“…In a group of inpatients with the disorder, an opendesign, openlabel study invol ving acute augmentation (7 days) of current medications with 600 or 1200 mg RU486 daily produced significant reductions in scores on the Brief Psychiatric Rating Scale and in measures of depressive symptoms compared with baseline, although patients who received only 50 mg RU486 daily showed little or no benefit (Belanoff 2002). Similar findings were replicated in a study in which a group of patients taking neither conventional antidepressant nor antipsychotic medications received 7 days of RU486 treatment for psychotic major depression (DeBattista 2005).…”

Section: Glucocorticoid Receptor Antagonistsmentioning

confidence: 76%

“…Future therapeutic strategies that may potentially arise from these researches are briefly outlined. In addition to unipolar depression, hyper cortisolaemia has since been found in other psy chiatric illnesses, including psychotic depression, bipolar disorder, schizophrenia and Alzheimer's disease (Nelson 1997;Walder 2000;DeBattista 2005), although these abnormalities in cortisol levels have not always been found in milder depression (using ICD-10 criteria) (Cowen 2002). In severe depression, high doses of glucocorticoids have been shown to cause brief elevations in mood, suggesting that cortisol may actually be a resilience factor that the body releases to restore normal serotonergic function (Young AH 1994a).…”

Section: Discussionmentioning

confidence: 99%

Antiglucocorticoids in psychiatry

McIsaac¹,

Westrin²,

Young³

2009

Adv. psychiatr. treat

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SummarySignificant evidence has accrued suggesting that the hypothalamic–pituitary–adrenal (HPA) axis plays a role in some psychiatric disorders. This article reviews the physiology of the HPA axis, evidence of dysfunction in this axis in psychiatric illnesses and the role that this dysfunction might play in pharmacological treatment resistance. Future therapeutic strategies that may potentially arise from these researches are briefly outlined.

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C-1073 (Mifepristone) in the Adjunctive Treatment of Alzheimers Disease

Cited by 23 publications

References 27 publications

Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex

Stress Increases Vulnerability to Inflammation in the Rat Prefrontal Cortex

Reproductive History and Risk of Cognitive Impairment in Elderly Women: A Cross-Sectional Study in Eastern China

Antiglucocorticoids in psychiatry

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