Exploring lnflammasome/Cytokine/lnsulin cascade as converging landscape for AD, Schizophrenia(SCHIZO);and COVID-19 syndrome: synthesis of evidence and Post-hoc analysis of Ginsana-115 RCT in treatment-resistant-schizophrenia

Abstract

Background:COVID-19 pandemic calls into question whether AD and Very-late-onset­ schizophrenia-like psychosis (VLOSL): "dementia praecox" have higher COVID-19 risk and whether lnflammasome-Cytokine-insulin signaling casade (IFCI) mediates the dementia and psychosis link.Our objective is : 1) to conduct Pub-med search for IFCI) in AD, VLOSL and COVID-10 burden; 2a)to conduct post-hoc RCT analysis of Ginseng effect regarding cognitive impairment correlates with insulin resistance(IR) and cardio-metabolic risks (CMR) in schizophrenia Result: In Part1: our Pubmed search concludes Dementia syndrome carries higher mortality risk. A meta-analysis of 634,338 COVID-19 patients from 16 studies reveals that schizophrenia, and dementia, significantly increased risk of COVID-19 mortality and severity. Cardio-metabolic risk factors modify the link. A large Swedish cohort study and systematic review of 17studies found evidence of VLOSL carries higher risk of dementia. Aberrant IFCI correlated with COVID-19 severity. Effect sizes cannot be calculated due to sample heterogeneity. In Part 2: post-hoc analysis of Ginsana-115 (Boehringer-lngelheim-Pharmaton,Switzerland) of 8-week placebo­ controlled parallel group design in TRS subjects . Log-lR(insulin resistance) scores significantly correlated with spatial processing (p=0.017). Framingham-Risk-score correlated inversely with visual perception p = 0.040) and spatial processing (p=0.029) and neurocognitive index (p=0.090). Systolic blood pressure (sBP) correlated significantly and inversely with visual perception (p=0.032),speed (p=0.010),, spatial processing (p=0.034), HDL correlated with memory score:p=0.008. Brief­ Psychiatric-Rating-Scale:BPRS correlated significantly with executive reasoning ( p=0.047),memory (p=0.021), and mental inflexibility (p=0.026). Ginsana-115 at 100-mg/200-mg significantly reduced FRS by 24.1% compared with 16.1%(P<0.05) and systolic blood pressure (P<0.05) and significantly improved lipid profile in raising HDL and lowering LDL. Ginsana-115: 100 mg and 200 mg oral dosage, significantly improved negative symptom of apathy akin to AD. Conclusion: IFCI) appears to link COVID-19 syndrome, VLOSL overlapping with AD. L. Ginsana-115 effects in TRS highlight the therapeutic strategy of Diet, drug leads and Exercise targeting specifically IFCL·Iandscape in COVID-19 syndrome, AD and VLOSL.