CNS Neurosci Ther. 2026 Aug;32(8):e71089. doi: 10.1002/cns.71089.
ABSTRACT
BACKGROUND: Chronic cerebral hypoperfusion (CCH) is a major hemodynamic substrate of vascular cognitive impairment and vascular dementia, yet effective therapies with multi-target neuroprotective potential remain limited. CCH triggers a complex pathological cascade characterized by neurovascular dysfunction, white matter injury, neuroinflammation, oxidative stress, and synaptic impairment.
METHODS: In this review, we summarize the major pathophysiological mechanisms of CCH and discuss current evidence supporting neuromodulation as a promising therapeutic strategy. We focus primarily on central stimulation modalities, including repetitive transcranial magnetic stimulation, transcranial electrical stimulation, photobiomodulation, and ultrasound-based neuromodulation, while also addressing selected peripheral physical modulation approaches and emerging multimodal combination strategies.
RESULTS: Available evidence suggests that these interventions may mitigate hypoperfusion-related brain injury and cognitive impairment by targeting multiple pathophysiological mechanisms, ultimately restoring synaptic plasticity and promoting circuit- and network-level recovery. We further discuss current challenges to clinical translation, including limited deep-target engagement, insufficient individualized dosing, and the underuse of rhythm-based biomarkers.
CONCLUSION: Neuromodulation holds promise as a mechanistically informed and multi-target neuroprotective strategy for CCH-related cognitive impairment.
PMID:42605969 | DOI:10.1002/cns.71089