Cold exposure induced cognitive impairment: A systematic review

Extreme cold exposure has emerged as a significant global public health challenge to cognitive function among populations such as military personnel, polar workers, and residents of high-latitude regions. However, the complex mechanisms underlying cold environment-induced cognitive impairment remain to be systematically elucidated. This systematic review synthesizes the effects of cold exposure (CE) on cognitive function and the potential biological mechanisms involved. CE impairs cognition through four interconnected pathways: neuroendocrine dysregulation, oxidative stress, neuroinflammation, and mitochondrial dysfunction. The dual dysregulation of the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-thyroid axis constitutes the core neuroendocrine mechanism, wherein excessive glucocorticoids mediate hippocampal structural damage through mitochondrial reactive oxygen species bursts, autophagic dysregulation, and synaptic plasticity impairment. Oxidative stress is characterized by ROS accumulation and a collapse of antioxidant defenses, with time-dependent decompensation of the Nrf2 pathway exacerbating lipid peroxidation and oxidative modification of synaptic proteins. Neuroinflammation features hippocampal microglial activation and a positive feedback loop involving the HMGB1-NLRP3 inflammasome, driving the cascade release of pro-inflammatory cytokines such as interleukin-1 and tumor necrosis factor-α. Mitochondrial dysfunction manifests as suppressed biogenesis, imbalanced dynamics (Drp1-mediated excessive fission), and decreased oxidative phosphorylation efficiency, leading to neuronal energy crisis and apoptosis. These four pathways amplify each other through positive feedback cycles, ultimately culminating in synaptic plasticity collapse and hippocampal-dependent memory deficits. Based on these mechanisms, this review proposes comprehensive protective strategies, including cold acclimatization training, pharmacological interventions, and targeted therapies. Current research faces challenges such as high heterogeneity in exposure parameters, lack of core body temperature monitoring, and insufficient mechanistic validation. Future efforts should establish standardized research paradigms, quantitatively delineate the relationship between CE intensity/duration and neural injury, and explore precision intervention targets based on the neuroendocrine-immune-metabolic interaction network, thereby providing theoretical foundations and practical approaches for brain health protection in extreme environments.