The investigators propose a proof of concept RCT (randomized clinical trial), testing the efficacy of intranasal insulin (INI) with semaglutide, a combination therapy with strong biological plausibility to benefit impaired cognition through vascular mechanisms, in older adults with MetS (metabolic syndrome) and MCI (Mild Cognitive Impairment), who are enriched for cerebrovascular disease and at high dementia risk. The study will focus on cognitive and biological outcomes, allowing identification of relevant mechanisms.
Inclusion Criteria: * Diagnosis of MCI (based on a MOCA \<27 and a clinical dementia rating scale \[CDR\] score of 0.5 representing questionable dementia). * Diagnosis of MetS -requiring a) abdominal obesity (waist circumference \>102cm for men and \>88cm for women), and b) glucose intolerance (fasting glucose\>110 mg/dL) and at least one of the following-c) dyslipidemia (high triglycerides \[\>150 mg/dL\] and low HDL \[\<40mg/dL for men and \<50 mg/dL for women\]), or d) elevated blood pressure (\>130/\>85 mmHg). * Fluent in Hebrew * The study requires an active study partner Exclusion Criteria: * Diabetes (of any type) * Taking medications that may affect glucose metabolism (including a GLP-1RA). * Diagnosis of dementia and its subtypes, conditions that may directly affect cognition, * short life expectancy or a medical condition that precludes consistent participation in the study, * contraindications to either insulin or Semaglutide. * Medications that may affect glucose metabolism such as corticosteroids.