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In this review, we introduce a temporal framework to explore how early immune system activation and interactions at neurovascular-immune interfaces pave the way to cognitive impairment. The overall paradigm suggests that prohypertensive stimuli induce mechanical stress and systemic inflammatory responses that shift peripheral and meningeal immune effector mechanisms toward a proinflammatory state. Neurovascular-immune interfaces in the brain include a dysfunctional blood-brain barrier, crossed by peripheral immune cells; the perivascular space, in which macrophages respond to cerebrospinal fluid- and blood-derived immune regulators; and the meningeal immune reservoir, particularly T cells. Immune responses at these interfaces bridge peripheral and neurovascular unit inflammation, directly contributing to impaired brain perfusion, clearance of toxic metabolites, and synaptic function. We propose that deep immunophenotyping in biofluids together with advanced neuroimaging could aid in the translational determination of sequential immune and brain endotypes specific to arterial hypertension. This could close knowledge gaps on how and when immune system activation transits into neurovascular dysfunction and cognitive impairment. In the future, targeting specific immune mechanisms could prevent and halt hypertension disease progression before clinical symptoms arise, addressing the need for new interventions against one of the leading threats to cognitive health.<\/jats:p>","DOI":"10.1152\/ajpcell.00219.2024","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T11:00:32Z","timestamp":1730718032000},"page":"C1577-C1590","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Immune system activation and cognitive impairment in arterial hypertension"],"prefix":"10.1152","volume":"327","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4439-4374","authenticated-orcid":false,"given":"Stefanie","family":"Schreiber","sequence":"first","affiliation":[{"name":"Department of Neurology, Otto von Guericke University Magdeburg, Magdeburg, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Helmholtz 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