RESUMO
BACKGROUND: Delaying the transition from minimal cognitive impairment to Alzheimer's dementia is a major concern in Alzheimer's disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer's dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model. METHODS: In this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer's disease patients. The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T), Clock Drawing Test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test. RESULTS: We report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p = 0.031; dichotomized delayed Centil REY copy p = 0.002 and a tendency to improve in all the rest of them. The amyloid-beta deposition analysis showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878), while placebo-treated did increase it (p = 0.036). We did not observe significant changes in other brain areas studied. CONCLUSIONS: This study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer's dementia in patients with prodromal Alzheimer's disease. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study. TRIAL REGISTRATION: NCT01982578, registered on November 13, 2013.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/farmacologia , Cognição , Genisteína/uso terapêutico , Genisteína/farmacologia , HumanosRESUMO
BACKGROUND: A cadaveric feasibility study was carried out. Osteotomies to correct fixed sagittal imbalance are usually performed at L3/ L4. OBJECTIVE: To investigate the feasibility of S1 pedicle subtraction osteotomy to correct spinal deformity and spinopelvic parameters, achieving better results with more limited exposure. The data obtained will allow a fixation construct specific for this osteotomy to be designed. METHODS: S1 pedicle subtraction osteotomy was performed on 12 cadaveric specimens. Baseline and postprocedural computed tomography and biomechanical studies were performed. Data were analyzed with a fixation system SolidWorks model, and the redesigned fixation construct was described and analyzed with an ANSYS model. RESULTS: S1 pedicle subtraction osteotomy is technically feasible. The fixation can be achieved with L4, L5, and iliac screws connected with bars. The system can be reinforced with a polyetheretherketone cage placed anteriorly in the S1 body osteotomy site, a cross-connecting bar, a double iliac screw, or an anterior interbody cage placed at the L5-S1 disc. The fixation strength is improved by angulating the iliac rod channel 10°, adding a semi-sphere to the locking screw contact surface and 2 fins to its saddle. The redesigned construct showed suitable stress and deformation levels, achieving the expected biomechanical requirements. DISCUSSION: Compared with surgery on higher levels, S1 pedicle subtraction osteotomy allows greater correction with shorter fixation, because the osteotomy is performed at a more caudal level, modifying the spinopelvic parameters. CONCLUSIONS: S1 pedicle subtraction osteotomy is technically feasible. Finite element analysis results indicate that it has appropriate biomechanical properties.