Extracellular vesicles in vascular cognitive impairment and dementia: a neurovascular evidence map for patient stratification and clinical translation

Vascular cognitive impairment and dementia (VCID) comprises distinct syndromes caused by cerebrovascular injury and mixed vascular-neurodegenerative pathology. Extracellular vesicles (EVs), including small EV-enriched preparations, are being investigated as biomarkers and therapeutic products. We performed a structured narrative review and an expanded PubMed search through 8 October 2026, incorporating exosome, microvesicle and microparticle terminology. The revision search retrieved 140 records; representative evidence tables summarize 13 preclinical therapeutic studies and 10 human biomarker studies. We organize the evidence by EV preparation, neurovascular unit mechanism, clinical phenotype and development pathway. Therapeutic evidence remains predominantly preclinical. Human studies include exploratory cohorts and studies with separate validation datasets or longitudinal follow-up, but prospective clinical utility remains unestablished. Differences in EV separation, characterization, purity and cellular attribution limit cross-study comparison. We propose five evidence domains covering biological rationale, technical control, phenotype-relevant translation, clinical validation and prospective evaluation. This author-developed map integrates existing EV, biomarker and VCID development principles. It has not undergone consensus development, inter-rater reliability testing or prospective validation, and does not assign readiness scores or mandate sequential progression. Its intended use is to make evidence gaps explicit and connect candidate assays or products to defined patient populations, outcomes and safety requirements.