Genistein effect on cognition in prodromal Alzheimer's disease patients. The GENIAL clinical trial

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 efective 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 defned polyphenol that acts by multimodal specifc mechanisms. Our group previously showed that genistein supplementation is efective to treat the double transgenic (APP/PS1) AD animal model. Methods: In this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the efect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer’s disease patients. The amyloidbeta deposition was analyzed using 18F-futemetamol 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 signifcant 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 signifcant 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.This work was supported by the following grants: CB16/10/00435 (CIBERFES) from Instituto de Salud Carlos III, (PID2019-110906RB-I00/ AEI/10.13039/501100011033) and RED2018-102576-T from the Spanish Ministry of Innovation and Science, PROMETEO/2019/097 from “Consellería de Innovación, Universidades, Ciencia y Sociedad Digital de la Generalitat Valen ciana” and EU Funded H2020- DIABFRAIL-LATAM (Ref: 825546), European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) and of the ERA-NET Cofund ERA-HDHL (GA N° 696295 of the EU Horizon 2020 Research and Innovation Programme) and Fundación Ramón Areces y Fundación Soria Melguizo. to J.V. and Grant PID2020-113839RB-I00 funded by MCIN/ AEI/10.13039/501100011033, PCIN-2017-117 of the Ministry of Economy and Competitiveness, and the EU Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ (JPI HDHL INTIMIC-085) to CB. We also acknowledge funding from the Spanish Ministry of Science, Innovation, and Universities (RTI2018099200-B-I00), the Generalitat of Catalonia, Agency for management of University and Research Grants (2017SGR696) and the Department of Health (SLT002/16/00250) to RP. Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-fnanced with ERDF funds (OP ERDF of Comunitat Valenciana 2014-2020). M.J. is a “Serra Hunter” Fellow

Genistein effect on cognition in prodromal Alzheimer's disease patients : the GENIAL clinical trial

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

Implantación y certificación de un sistema de gestión de i+d+i según norma UNE 166002:2006 en la Fundación Instituto Valenciano de Tecnología ( Invate)

Proyecto ConfidencialSantabárbara Gómez, JM. (2008). Implantación y certificación de un sistema de gestión de i+d+i según norma UNE 166002:2006 en la Fundación Instituto Valenciano de Tecnología ( Invate). http://hdl.handle.net/10251/34238.Archivo delegad

Do dietary patterns determine levels of vitamin B6, folate, and vitamin B12 intake and corresponding biomarkers in European adolescents? The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study

OBJECTIVES: To determine dietary patterns (DPs) and explain the highest variance of vitamin B6, folate, and B12 intake and related concentrations among European adolescents. METHODS: A total of 2173 adolescents who participated in the Healthy Lifestyle in Europe by Nutrition in Adolescence study met the eligibility criteria for the vitamin B intake analysis (46% boys) and 586 adolescents for the biomarkers analysis (47% boys). Two non-consecutive, 24-h, dietary recalls were used to assess the mean intakes. Concentrations were measured by chromatography and immunoassay testing. A reduced rank regression was applied to elucidate the combined effect of food intake of vitamin B and related concentrations. RESULTS: The identified DPs (one per vitamin B intake and biomarker and by sex) explained a variability between 34.2% and 23.7% of the vitamin B intake and between 17.2% and 7% of the biomarkers. In the reduced rank regression models, fish, eggs, cheese, whole milk and buttermilk intakes were loaded positively for vitamin B intake in both sexes; however, soft drinks and chocolate were loaded negatively. For the biomarkers, a higher variability was observed in the patterns in terms of food loads such as alcoholic drinks, sugars, and soft drinks. Some food items were loaded differently between intakes and biomarkers such as fish products, which was loaded positively for intakes but negatively for plasma folate in girls. CONCLUSIONS: The identified DPs explained up to 34.2% and 17.2% of the variability of the vitamin B intake and plasma concentrations, respectively, in European adolescents. Further studies are needed to elucidate the factors that determine such patterns