Public Health

Area of Science:

• Neuroscience
• Metabolic Disorders
• Pharmacology

Background:

• Older adults with metabolic syndrome (MetS) and mild cognitive impairment (MCI) face cognitive decline.
• Intranasal insulin (INI) and semaglutide show promise for cerebrovascular and insulin signaling pathways.
• Combining INI and semaglutide may offer synergistic cognitive benefits.

Purpose of the Study:

• To assess the feasibility of combining intranasal insulin (INI) with oral semaglutide in older adults with MetS and MCI.
• To explore the efficacy of this combination on cognitive function and neurobiological markers.
• To lay the groundwork for a large-scale randomized clinical trial.

Main Methods:

• A randomized, double-blind, placebo-controlled feasibility trial involving 80 participants aged >60 years with MetS and MCI.
• Four treatment arms: INI/oral semaglutide, intranasal placebo/oral semaglutide, INI/oral placebo, intranasal placebo/oral placebo for 12 months.
• Feasibility assessed by ease of use, adherence, and safety; efficacy by cognitive tests and neuroimaging biomarkers.

Main Results:

• Data collection ongoing since March 2024; 19 participants randomized to date.
• Screening identified challenges in meeting MCI and MetS criteria.
• Randomized participants (N=19) are aged ~67 years, with obesity (BMI 32.8), mild cognitive impairment (MMSE 25.0), and controlled HbA1c (5.6%).

Conclusions:

• This feasibility study is expected to support a larger trial on INI and semaglutide for cognitive enhancement.
• The combination targets key pathways in cognitive decline, offering a potential new therapy for MetS patients at high dementia risk.
• This approach addresses an understudied population with significant unmet needs.