Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study.

I-Chen Li,Yu-Wen Chen,David Pei-Cheng Lin,Chin-Chu Chen,Chuan-Han Lin,Tsung-Han Lu,Wan-Ping Chen,Han-Hsin Chang,Li-Ya Lee,Yen-Po Chen

doi:10.3389/fnagi.2020.00155

Abstract

ObjectiveTo investigate the efficacy and safety of three H. erinaceus mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer’s Disease (AD).MethodsThis study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period.ResultsAfter 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1–40 over the study period. Using diffusion tensor imaging, the mean apparent diffusion coefficient (ADC) values from the arcuate fasciculus region in the dominant hemisphere significantly increased in the placebo group while no significant difference was found in the EAHE group in comparison to their baselines. Moreover, ADC values from the parahippocampal cingulum region in the dominant hemisphere significantly decreased in the EAHE group whereas no significant difference was found in the placebo group when compared to their baselines. Lastly, except for four subjects who dropped out of the study due to abdominal discomfort, nausea, and skin rash, no other adverse events were reported.ConclusionThree 350 mg/g EAHE capsules intervention for 49 weeks demonstrated higher CASI, MMSE, and IADL scores and achieved a better contrast sensitivity in patients with mild AD when compared to the placebo group, suggesting that EAHE is safe, well-tolerated, and may be important in achieving neurocognitive benefits.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04065061.

Highlights

The pace of population aging across the world over the past halfcentury is increasing dramatically, triggering a Silver Tsunami of chronic age-related diseases
EAHE mycelia was grown in a submerged liquid medium comprised of 0.25 % yeast extract, 4.5% glucose, 0.5% soybean powder, 0.25 % peptone, and 0.05 % MgSO4 with an initial pH set to 4.5 at 26◦C for 5 days
A total of 68 participants who had been diagnosed with mild Alzheimer’s Disease (AD) were recruited in this study

Summary

Introduction

The pace of population aging across the world over the past halfcentury is increasing dramatically, triggering a Silver Tsunami of chronic age-related diseases. Among these diseases, Alzheimer’s Disease (AD) is the fifth-leading cause of death among adults aged 65 years and older and is a leading cause of disability and morbidity (Alzheimer’s Association, 2019). There has been a shift in the clinical research field, with the focus to develop safe and effective interventions in early and presymptomatic AD stages (Graham et al, 2017). Several prevention trials have been carried out and shown promising results, suggesting the potential feasibility of implementing non-pharmacological approaches, including dietary interventions (Ngandu et al, 2015; Andrieu et al, 2017)

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