High‑fat diet and cognitive dysfunction: Mechanistic insights into diet‑induced neurodegeneration (Review)

Cognitive impairment encompasses a spectrum of neurological deficits affecting memory, attention, executive function and other higher‑order cognitive processes. Increasing attention has been paid to modifiable lifestyle factors that influence its onset and progression. Among these, chronic high‑fat diet (HFD) consumption has emerged as a significant and potentially reversible risk factor for cognitive decline. Both epidemiological and experimental studies have consistently linked HFD‑particularly diets rich in saturated fatty acids‑to impairments in memory, attention and executive functions. Mechanistically, HFD induces neuroinflammation, oxidative stress, insulin resistance and gut microbiota dysbiosis, which collectively disrupt synaptic plasticity and neuronal survival. Individual susceptibility factors such as age, sex and the presence of the apolipoprotein E ε4 allele may further exacerbate these pathological effects. This review also highlights promising intervention strategies, including adherence to Mediterranean or Dietary Approaches to Stop Hypertension dietary patterns, regular physical exercise, pharmacological approaches and gut microbiota modulation. A comprehensive understanding of these multifactorial pathways is essential for developing targeted preventive and therapeutic interventions to mitigate HFD‑associated neurodegeneration.