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Abstract 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.

Abstract Background Understanding the anatomy of the facial alveolar bone (FAB), provides a prognostic tool for estimating the degree of dimensional ridge alterations after tooth extraction. This systematic review and meta-analysis aims to determine the FAB thickness and modifying factors of anterior maxillary teeth measured by CBCT scans. A secondary objective was to assess the facial distance from the cementoenamel junction (CEJ) to the bone crest. Methods An electronic search was made of Medline, Embase, Web of Science, Cochrane Library and Google Scholar up to December 2019. Studies that analyze and quantitatively compare FAB thickness at maxillary teeth by CBCT scans were included. The methodological quality of the included studies was appraised using the ROBINS-I tool and the overall meta-evidence certainty using the GRADE approach. A single means random-effects meta-analysis was performed to obtain the weighted mean for 95% confidence interval. A meta-regression of covariates and subgroup analysis was conducted. The nullity Qh test and I2 index for heterogeneity was estimated. Results 2560 potentially relevant articles were recorded from which 29 studies were selected for the qualitative analysis, including 17,321 teeth. Seventeen studies considered the facial bone crest, and 12 the CEJ as a reference point for their measurements. Mean FAB thickness was ≤ 1 mm in maxillary incisors and canines (0.75–1.05 mm) and 1–2 mm in premolars. Patients over 50 years of age, females and thin gingival phenotype was associated with thinner FAB at some apico-coronal locations of maxillary incisors and canines. The geographical setting was an effect modifier that could explain up to 87% of the heterogeneity in FAB thickness, being Asian populations that showed the lowest FAB thickness values. The CEJ-bone crest distance was 2–2.5 mm in all teeth analyzed. Population over 50 years of age exhibited greater CEJ-bone crest distances, and males also showed a trend for greater distance. Evidence certainty has shown moderate quality in most analysis subsets. Conclusions Facial alveolar bone at anterior maxillary teeth is thin, heterogeneous in width along its apico-coronal dimensions, and increases in thickness in maxillary premolars. The CEJ-bone crest distance presented homogeneous and similar values in all teeth analyzed.