The APOE4 genotype is the strongest genetic risk factor for Alzheimer’s disease (AD) and also for earlier stages like mild Cognitive Impairment (MCI).1 Evidence suggests that APOE4 genotype influences cognition even in pre-MCI state such as subjective cognitive impairment (SCI).2 Systemic and central metabolic dysfunction associated with this neuropathology is evident often decades before any symptoms appear.3APOE4 carriers also present with a distinct gut-microbial diversity which potentially contributes to the pathological metabolic effects of APOE4 genotype.3–7. The gene discussed is APOE; the disease is Cognitive impairment.