Unraveling Pathophysiological Link Between Mitophagy Pathway and Vascular Dementia

Context: Vascular dementia (VaD) is the second most common type of dementia after Alzheimer’s disease worldwide. Vascular dementia is a neurodegenerative disorder characterized by gradual cognitive impairment. Ischemic and hemorrhagic strokes result in VaD, markedly distributing cerebral blood flow and decreasing patients’ cognitive and memory performance. Due to their high energy demands, neurons are more sensitive to cellular architecture changes and exposed to mitochondrial stress than other cell types. Mitochondrial dysfunction and selective autophagy of mitochondria, known as mitophagy, are associated with VaD. This review aims to elucidate the association between mitophagy and VaD. Evidence Acquisition: This review was conducted independently by at least two researchers dominant in various VaD studies. We searched databases including Elsevier, Google Scholar, and PubMed using the terms ‘vascular dementia’, ‘vascular cognitive impairment’, and ‘mitophagy’. We evaluated 70 articles on the relationship between VaD and mitophagy and interpreted the results. Adobe Photoshop 2022 was used for drawing figures by researchers. Results: The autophagy process plays a protective role in experimental VaD models via preserving vascular integrity and the structure of the blood-brain barrier, upregulating occludin and claudin protein expressions, reducing oxidative stress, and decreasing cognitive dysfunction. Some studies claim that autophagy could have adverse effects in a time-dependent manner against neuronal injury. Prolonged autophagy and overexpressed autophagic proteins induce ischemic injury and cause neuronal cells to undergo apoptotic cell death. Conclusions: Although there are limited studies on the activation of mitophagy-related pathways in VaD, and the definitive role of mitophagy in neuronal healing is unclear, further research is needed to elucidate mitophagy pathways in neurons.