Potential Mechanisms of Chlorogenic Acid in Cognitive Impairment: A Comprehensive Review

Cognitive impairment (CI) is a clinical syndrome primarily affecting cognitive functions such as learning, memory, perception, and problem-solving. Its causes are heterogeneous, including neurological, psychiatric, metabolic, vascular, toxicological, and age-related factors. Currently, no specific and effective pharmacological therapies are available for CI in clinical practice. As one of the most abundant dietary polyphenols, chlorogenic acid (CGA) displays diverse biological effects and has recently garnered growing interest within cognitive neuroscience. This review summarizes the mechanisms by which CGA ameliorates cognitive impairment, encompassing neuroprotection, modulation of the gut–brain axis, inhibition of neuroinflammation, inhibition of oxidative stress, promotion of autophagy, inhibition of apoptosis, and suppression of amyloid-β (Aβ) formation. The signaling pathways implicated include activation of the PKC, Nrf2/PPAR and Nrf2/ARE pathways, as well as inhibition of the TLR4/NF-κB, mTOR/TFEB, p38 MAPK, and JNK/c-Jun pathways. This article provides an overview of current advancements in CGA, addressing its chemical attributes, dietary origins, drug metabolism, and the mechanistic basis for its efficacy in neurodegenerative diseases.