Frazier · Experimental neurology 2019 · narrative review · n=?

Broadening the definition of brain insulin resistance in aging and Alzheimer's disease.

Cited 72 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and mechanistic discussion with preliminary preclinical molecular observations.

PubMed 30576640 · doi:10.1016/j.expneurol.2018.12.007 · record verified 2026-08-29

What was done

The authors reviewed the literature on brain insulin sensitivity, decreased insulin receptor density and function in aging and Alzheimer's disease, and the therapeutic rationale for intranasal insulin administration. They also summarized initial results from molecular experiments designed to evaluate insulin receptor activation and its signaling effects on neuronal glucose uptake.

What was found

The abstract reports no quantitative data or specific numerical endpoints. It describes qualitative findings: brain cells express functional insulin receptors, receptor number and signaling decline in aging and Alzheimer's disease models, intranasal insulin administration improves learning and memory measures across animal models and humans, and insulin mediates brain glucose metabolism partially via alterations in glucose transporters.

Why it matters

Clarifying how insulin signaling impacts neuronal glucose metabolism helps explain whether therapeutic approaches like intranasal insulin act by overcoming receptor dysfunction, replacing deficient central insulin, or bypassing transport deficits.

Limits

The abstract provides no sample sizes, specific study designs, or quantitative metrics. Direct cellular and metabolic measures of insulin action remain sparse in aged and Alzheimer's disease models, leaving the exact mechanism of intranasal insulin's cognitive effects unresolved.

Cited by