Peripheral blood biomarkers and mild behavioral impairment in mild cognitive impairment: Clinical correlations and mechanistic insights.

In the context of global aging, mild behavioral impairment (MBI) is present in 48.9% of patients with mild cognitive impairment (MCI). MBI, a neurobehavioral syndrome in the elderly, is an independent risk factor for cognitive decline and is closely related to peripheral blood biomarkers associated with Alzheimer's disease, offering new diagnostic and interventional avenues for early MCI. To summarize evidence on peripheral blood biomarkers related to MBI and their underlying mechanisms involving neuroinflammation, tau pathology, and oxidative stress, a systematic review of studies published between 2015 and 2024 was conducted. MBI is closely associated with peripheral blood biomarker changes. Neuroinflammatory markers like glial fibrillary acidic protein and neurofilament light indicate astrocyte activation and neural circuit disruption, with glial fibrillary acidic protein levels correlating with impulse dyscontrol scores. Chitinase-3-like protein 1, a marker of blood-brain barrier integrity, exacerbates neuroinflammation and is linked to depressive symptoms and hippocampal atrophy. Elevated phosphorylated tau proteins in blood correlate with brain tau deposition, increasing the risk of MBI and impairing cognition. Oxidative stress markers damage neurons and disrupt neurotransmission, and concurrent alterations in malondialdehyde and superoxide dismutase levels significantly elevate the risk of MBI. The correlation between MBI and biomarkers offers new diagnostic and interventional directions for early MCI. Future research should standardize MBI assessment, conduct longitudinal studies, explore biomarker-MBI relationships, investigate psychosocial impacts, and develop advanced detection methods.