Hypertension as a Major Risk Factor in Alzheimer’s Disease: Mechanisms, Interactions and Therapeutic Perspectives

Enshe Jiang,1,2 Sami Ullah,3 Irum Waheed,3 Jinqian Han,4 Xiaoguang Zhang1 1Department of Neurosurgery, The First Affiliated Hospital of Henan University, Henan University, Kaifeng, People’s Republic of China; 2Institute of Nursing and Health, Henan University, Kaifeng, People’s Republic of China; 3School of Life Sciences, Henan University, Kaifeng, People’s Republic of China; 4Department of Nursing Science, University of Malaya, Kuala Lumpur, MalaysiaCorrespondence: Jinqian Han, Department of Nursing Science, University of Malaya, Kuala Lumpur, Malaysia, Email [email protected] Xiaoguang Zhang, Department of Neurosurgery, The First Affiliated Hospital of Henan University, Henan University, Kaifeng, People’s Republic of China, Email [email protected]: Alzheimer’s disease (AD) and hypertension (HTN) are closely related pathophysiological pathways that have a major impact on cognitive impairment in later life. Chronic high blood pressure exacerbates neurodegenerative processes by accelerating cerebrovascular dysfunction, impairing the clearance of amyloid-β (Aβ), promoting tau pathology and causing microvascular damage. Through mechanisms such as endothelial dysfunction, blood-brain barrier (BBB) disruption, white matter hyperintensities, cerebral microbleeds, and decreased cerebral perfusion, midlife HTN is consistently a strong predictor of late-life dementia. Neuropathological and biomarker analyses demonstrate that HTN is strongly linked to tau burden, neuronal death, and regional brain atrophy, even in the presence of continuous amyloid deposition. Experimental evidence showing that HTN enhances Aβ deposition, neuroinflammation, and small vessel disease, all of which contribute to cognitive decline, thereby supporting the vascular theory of AD. Antihypertensive medications, particularly those that target the renin-angiotensin system, have promising neuroprotective benefits and somewhat lower the prevalence of dementia. This review suggests that controlling blood pressure throughout life could significantly reduce the global incidence of dementia. In addition to being a major vascular risk factor, HTN also acts as a separate accelerator of neurodegeneration linked to AD. This highlights the need for early detection and continuous blood pressure medication as practical, scalable preventive measures. Keywords: hypertension, Alzheimer’s disease, neuropathology, clinical biomarkers