Insulin-like Growth Factor 1 Impact on Alzheimer’s Disease: Role in Inflammation, Stress, and Cognition

Alzheimer’s disease (AD) is a leading cause of dementia, characterized by multifactorial interactions involving genetic, inflammatory, and metabolic dysregulation. Insulin-like growth factor 1 (IGF-I) plays a critical role in maintaining brain homeostasis through neurogenesis, synaptogenesis, and neuroprotection. However, disruptions in IGF-I signaling have been implicated in hallmark AD processes such as beta-amyloid accumulation, glucose metabolism disturbances, oxidative stress, chronic inflammation, and neuronal death. This review aims to comprehensively analyze the mechanisms by which IGF-I influences AD pathology, emphasizing its potential as both an early detection biomarker and a therapeutic target. By synthesizing clinical and preclinical study findings, we explore how chronic stress, systemic inflammation, and lifestyle factors disrupt IGF-I pathways, accelerating cognitive and social impairments. Special attention is given to high-level cognitive processes, including executive functions and social cognition, which are particularly vulnerable to these disruptions. Highlighting the interplay between IGF-I, neuroinflammation, and stress, this work underscores the need for affordable and accessible diagnostic tools and therapeutic strategies. This review contributes to a deeper understanding of IGF-I’s multifaceted role in AD, offering new insights for addressing the growing global burden of dementia.