Neuromodulation Techniques in Chronic Cerebral Hypoperfusion: Mechanisms and Therapeutic Advances.

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.