Core Viewpoint - The study reveals that exosomes derived from macrophage-derived foam cells in atherosclerotic plaques exacerbate ischemic white matter injury and vascular cognitive impairment by transmitting metabolic defects to microglia [2][5][10]. Group 1: Research Findings - Atherosclerosis (AS) is identified as an independent risk factor for vascular cognitive impairment (VCI), with unclear mechanisms [2]. - The research team discovered that exosomes in the circulation of AS patients worsen ischemic white matter injury and VCI [5]. - Foam cells produce exosomes that target microglia in the central nervous system, transmitting oxidative stress imbalance and metabolic defects through the miR-101-3p-Nrf2-Slc2a1 signaling axis [5][7]. Group 2: Potential Therapeutic Targets - The study confirms that inhibiting miR-101-3p or activating Nrf2 can counteract the effects of atherosclerotic exosomes and improve vascular cognitive impairment [6][7]. - The findings suggest a long-distance connection between peripheral macrophages and microglia, providing new insights and potential therapeutic targets for atherosclerosis-induced vascular cognitive impairment [3][10].