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

BackgroundDelaying the transition from minimal cognitive impairment to Alzheimers dementia is a major concern in Alzheimers 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 Alzheimers 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. MethodsIn 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 early symptomatic Alzheimers patients. 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. ResultsWe 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 was analyzed using 18F-flutemetamol uptake which 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 ConclusionsThis study shows that genistein may have a role in therapeutics to delay the onset of Alzheimers dementia in patients with mild cognitive impairment. 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 registrationNCT01982578