Hypotension with neurovascular changes and cognitive dysfunction: An epidemiological, pathobiological, and treatment review

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  Figure 1. (A) Mechanisms of cognitive impairment caused by hypotension. Brain atrophy and infarcts, cause neuronal loss and brain dysfunction. In addition, infarcts disrupt brain connectivity and reduce network efficiency. Damage to white matter lesions also degrades connectivity. Increased oxidative stress promotes Aβ deposition and tau hyperphosphorylation. (B) The clearance pathways of Aβ and tau. Aβ and tau in brain can be eliminated by various kinds of clearance mechanisms. Intracellular Aβ and tau are mainly degraded via UPS and autophagy-lysosome. Extracellular Aβ and tau can be degraded by glial phagocytosis and proteases secreted by neurons and astrocytes. Extracellular Aβ and tau in ISF can be transported into blood via the blood-brain barrier or into lymph by perivascular drainage and glymphatic drainage. Extracellular Aβ and tau in CSF can be removed to blood via the blood- CSF barrier or to lymph by lymphatic drainage via perineural space and meningeal lymphatic vessels. And then by CSF absorption, Aβ and tau in CSF can be transported into blood via arachnoid villi and the blood-CSF barrier, and also into cervical lymph nodes via meningeal lymphatic vessels as well as…

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  Figure 2. Role and mechanism of hypotension in neuronal damage. Hypotension leads to brain dysfunction through hypoxia-ischemia, as well as increase in Aβ production because of increased APP processing by secretase enzymes, and promote the activation of glial cells, the release of inflammatory factors, and cause cerebral vascular contraction, thus further aggravating cerebral hypoperfusion. Excessive amyloid deposition promotes tau hyperphosphorylation, ultimately leading to neuronal damage. AA: Arachidonic acid; Aβ: Amyloid-β; APP: Amyloid precursor protein; BACE: β-site APP cleaving enzyme; sAPPβ: Soluble peptide APPβ; C99: Transmembrane 99-residue C-terminal fragment; AICD: Amyloid precursor protein intracellular domain; NF-κB: Nuclear factor kappa-B; GSK-3β: Glycogen synthase kinase 3β; NFT: Neurofibrillary tangles; PI3K: Phosphatidylinositol-3 kinase; PKC: Protein kinase C; PLA2: Phospholipase A2; PP2A: Protein phosphatase 2A; I2PP2A: PP2A inhibitor 2; Ca2+: Calcium ion.