# Insulin Resistance as a Shared Pathophysiological Driver in Neurological Disorders: a Narrative Review

## TL;DR

This review explores how insulin resistance in the brain contributes to various neurological disorders and suggests that metabolic interventions could help manage these conditions.

## Contribution

The paper highlights insulin resistance as a unifying pathophysiological mechanism across multiple neurological disorders and proposes metabolism-based interventions as a novel therapeutic approach.

## Key findings

- Central insulin resistance disrupts brain energy metabolism and promotes neuroinflammation, contributing to diseases like Alzheimer’s and Parkinson’s.
- Nutrition- and metabolism-based interventions may restore insulin sensitivity and reduce neurobiological vulnerability.
- Neuroimaging and biomarker studies support the link between impaired insulin signaling and cognitive and affective dysfunction.

## Abstract

Insulin resistance has traditionally been viewed as a peripheral metabolic abnormality; however, accumulating evidence indicates that impaired insulin signaling within the central nervous system plays a critical role in the pathogenesis of multiple neurological disorders. The purpose of this narrative review is to synthesize current evidence supporting insulin resistance as a shared pathophysiological driver across neurodegenerative, neurological, and neuropsychiatric conditions, and to evaluate the potential of nutrition- and metabolism-based interventions as modulatory strategies.

Recent human and experimental studies demonstrate that central insulin resistance disrupts brain energy metabolism, promotes neuroinflammation, impairs synaptic plasticity, and alters neuronal network stability. These mechanisms contribute to disease onset and progression in Alzheimer’s disease, Parkinson’s disease, epilepsy, and mood disorders. Advances in neuroimaging, cerebrospinal fluid biomarkers, and molecular profiling have strengthened the link between impaired insulin signaling and cognitive, behavioral, and affective dysfunction. In parallel, emerging evidence suggests that dietary patterns, energy restriction, ketogenesis, and lifestyle interventions can partially restore insulin sensitivity, improve metabolic flexibility, and mitigate neurobiological vulnerability.

Insulin resistance should be regarded not merely as a comorbid metabolic condition, but as an active disease-modifying factor in a broad spectrum of neurological disorders. Targeting insulin signaling pathways through personalized nutritional and metabolic interventions represents a promising, modifiable strategy for prevention and adjunctive management. Future research integrating metabolic phenotyping with neurological outcomes will be essential to translate these insights into clinical practice.