RESUMO
BACKGROUND: Previous studies have shown that individuals with mood disorders have a higher prevalence of both hypercortisolemia and insulin resistance. Insulin resistance is posited to contribute to the cognitive deficits observed in individuals who have depression. However, the mechanistic relationship between cortisol and insulin within the central nervous system remains to be further elucidated. This study aimed to evaluate the effects of the antiglucocorticoid agent, mifepristone, on metabolic function and cognitive performance in individuals receiving treatment for depressive disorders who were euthymic at baseline. METHODS: Participants were administered a 600â¯mg/day dose of mifepristone for 28 days. Oral glucose tolerance tests (OGTTs) and cognitive assessments measuring verbal memory and executive functioning were administered at baseline and after 28 days of treatment. RESULTS: Improvements in attention and verbal learning were associated with reduction of fasting plasma glucose (FPG) in response to mifepristone treatment. LIMITATIONS: Limitations include the open-label design of this study and a small sample size. CONCLUSIONS: The findings from this study suggest that improvement in fasting plasma glucose levels, upon administration of mifepristone, is associated with the improvement in early input of verbal information. Further studies are warranted in order to better evaluate the use of mifepristone or other antiglucocorticoid agents in treatment of mood disorders characterized by metabolic dysfunction.
Assuntos
Glicemia/efeitos dos fármacos , Cognição/efeitos dos fármacos , Transtorno Depressivo Maior/metabolismo , Antagonistas de Hormônios/farmacologia , Mifepristona/farmacologia , Sobrepeso/metabolismo , Idoso , Atenção/efeitos dos fármacos , Glicemia/metabolismo , Transtorno Depressivo Maior/complicações , Função Executiva/efeitos dos fármacos , Feminino , Teste de Tolerância a Glucose , Humanos , Hidrocortisona/metabolismo , Masculino , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Sobrepeso/complicações , Aprendizagem Verbal/efeitos dos fármacosRESUMO
BACKGROUND: To determine the effects of memantine on cognition in a normal population of postmenopausal women with putative risk factors for Alzheimer's disease (AD) using a built-in control for the genetic risk factor for AD (apoE-epsilon4 status). METHODS: A prospective, open-label, 6-month pilot medication trial with memantine and follow-up after discontinuance conducted at the Center for Neuroscience in Women's Health, Stanford University School of Medicine. Neuropsychological data were collected on 22 community-dwelling postmenopausal women (11 apoE-epsilon4 carriers and 11 apoE-epsilon4 non-carriers) with at least one putative risk factor for AD. RESULTS: ApoE-epsilon4 status was not a significant predictor of change in neuropsychological performance. Changes associated with memantine treatment for entire sample included significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal. A positive medication effect was noted with executive functions and possibly category fluency. Trend-level improvements were seen in motor dexterity of the non-dominant hand and maintained even after drug discontinuance. CONCLUSIONS: Treatment with memantine appeared to have differential effects on cognitive performance in a population of women with putative risk factors for AD. ApoE-epsilon4 carrier status did not account for observed changes in cognition.