Genistein effect on cognition in prodromal Alzheimer's disease patients. The GENIAL clinical trial
Por:
Viña J, Escudero J, Baquero M, Cebrián M, Carbonell-Asíns JA, Muñoz JE, Satorres E, Meléndez JC, Ferrer-Rebolleda J, Cózar-Santiago MDP, Santabárbara-Gómez JM, Jové M, Pamplona R, Tarazona-Santabalbina FJ and Borrás C
Publicada:
4 nov 2022
Ahead of Print:
4 nov 2022
Resumen:
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.
Filiaciones:
Viña J:
Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, and CIBERFES, Insitute of Health Research-INCLIVA, Avenida Blasco Ibáñez 15, 46010, Valencia, Spain
Escudero J:
Hospital General of Valencia, Av. Tres Cruces 2, ES, 46014, Valencia, Spain
Baquero M:
Neurology Unit, University and Polytechnic Hospital La Fe, Valencia, Spain
Cebrián M:
Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, and CIBERFES, Insitute of Health Research-INCLIVA, Avenida Blasco Ibáñez 15, 46010, Valencia, Spain
Carbonell-Asíns JA:
Department of Bioinformatics and Biostatistics, Insitute of Health Research-INCLIVA, Valencia, Spain
Muñoz JE:
Pharmacy Department, Hospital Clínico Universitario de Valencia/INCLIVA Health Research Institute, Valencia, Spain
Satorres E:
Department of Developmental Psychology, Faculty of Psychology, University of Valencia, ES 46002, Valencia, Spain
Meléndez JC:
Department of Developmental Psychology, Faculty of Psychology, University of Valencia, ES 46002, Valencia, Spain
Ferrer-Rebolleda J:
Nuclear Medicine Department, Ascires Biomedical Group, Valencia, Spain
Cózar-Santiago MDP:
Nuclear Medicine Department, Ascires Biomedical Group, Valencia, Spain
Santabárbara-Gómez JM:
Nuclear Medicine Department, Ascires Biomedical Group, Valencia, Spain
Jové M:
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), E-25198, Lleida, Spain
Pamplona R:
Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), E-25198, Lleida, Spain
:
Department of Geriatrics, La Ribera Hospital, Alcira, Valencia, Spain
Borrás C:
Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, and CIBERFES, Insitute of Health Research-INCLIVA, Avenida Blasco Ibáñez 15, 46010, Valencia, Spain.
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