RESUMEN
AIM: The aim of this study was to test the efficacy and safety of mirtazapine in the treatment of sleep disorders in patients with Alzheimer's disease by means of a randomized, double-blind, placebo-controlled trial. Measurements were obtained for 7 days before intervention (baseline) and for 2 weeks after the onset of treatment. METHODS: Alzheimer's disease patients with sleep disorders (n = 24) received 15-mg mirtazapine (n = 8) or placebo (n = 16) once daily at 2100 hours for 2 weeks. Patients were evaluated with actigraphy and structured scales before and after intervention. Historical control was employed. RESULTS: Treatment with mirtazapine or placebo had no effect on cognitive and functional status as assessed by the Mini-Mental State Examination and the Katz scale, respectively. There were no differences between groups in the frequency or severity of the adverse events reported. Compared with the placebo group, mirtazapine users showed increased daytime sleepiness but no improvement in the duration or efficiency of nocturnal sleep after treatment. CONCLUSIONS: This study showed no significant therapeutic effects of 15-mg mirtazapine in community-dwelling Alzheimer's disease patients with sleep disorders. Instead, this study found evidence of worsening of daytime sleep patterns.
Asunto(s)
Enfermedad de Alzheimer/complicaciones , Antidepresivos Tricíclicos/uso terapéutico , Mianserina/análogos & derivados , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Actigrafía , Anciano , Anciano de 80 o más Años , Antidepresivos Tricíclicos/efectos adversos , Brasil , Método Doble Ciego , Femenino , Humanos , Masculino , Mianserina/efectos adversos , Mianserina/uso terapéutico , Mirtazapina , Pruebas Neuropsicológicas , Proyectos Piloto , Resultado del TratamientoRESUMEN
A circadian rhythm is a cycle of approximately 24 h, responsible for many physiological adjustments, and ageing of the circadian clock contributes to cognitive decline. Rhythmicity is severely impaired in Alzheimer disease (AD) and few therapeutic attempts succeeded in improving sleep disorders in such context. This study evaluated sleep parameters by actigraphy in 30 AD patients before and after trazodone use for 2 weeks, and we show a significant improvement in relative rhythm amplitude (RRA), compatible with a more stable daytime behavioral pattern. So, trazodone appears to produce a stabilization of the circadian rhythms in individuals with AD.
Asunto(s)
Ciclos de Actividad/efectos de los fármacos , Enfermedad de Alzheimer/tratamiento farmacológico , Trastornos del Sueño del Ritmo Circadiano/tratamiento farmacológico , Sueño/efectos de los fármacos , Trazodona/uso terapéutico , Actigrafía , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/fisiopatología , Femenino , Humanos , Masculino , Trastornos del Sueño del Ritmo Circadiano/diagnóstico , Trastornos del Sueño del Ritmo Circadiano/fisiopatología , Factores de Tiempo , Trazodona/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Single-nucleotide polymorphisms in genes encoding immunological mediators can affect the biological activity of these molecules by regulating transcription, translation, or secretion, modulating the genetic risk of inflammatory damage in Alzheimer's disease (AD). Nonetheless, the Brazilian contingent is highly admixed, and few association trials performed herein with AD patients have considered genetic ancestry estimates as co-variables when investigating markers for this complex trait. METHODS: We analyzed polymorphisms in 10 inflammatory genes and compared the genotype distribution across outpatients with late-onset AD and noncognitively impaired subjects from Midwest Brazil under a strict criterion, and controlling for ancestry heritage and ApoE genotype. RESULTS: Our findings show an almost 40% lower chance of AD (p = 0.004) among homozygotes of the IL10 -1082A allele (rs1800896). Dichotomization to ApoE and mean ancestry levels did not affect protection, except among those with greater European or minor African heritage. CONCLUSION: The IL10 locus seems to affect the onset of AD in a context sensitive to the genetic ancestry of Brazilian older adults.
Asunto(s)
Enfermedad de Alzheimer/genética , Citocinas/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/epidemiología , Brasil , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Alzheimer's disease (AD) is the most common neurodegenerative disorder with a complex genetic background. Recent genome-wide association studies (GWAS) have placed important new contributors into the genetic framework of early- and late-onset forms of this dementia. Besides confirming the major role of classic allelic variants (e.g. apolipoprotein E) in the development of AD, GWAS have thus far implicated over 20 single nucleotide polymorphisms in AD. In this review, we summarize the findings of 16 AD-based GWAS performed to date whose public registries are available at the National Human Genome Research Institute, with an emphasis on understanding whether the polymorphic markers under consideration support functional implications to the pathophysiological role of the major genetic risk factors unraveled by GWAS.