Hypertension-induced cognitive impairment: from pathophysiology to public health

Abstract

Hypertension affects two-thirds of people aged >60 years and significantly increases the risk of both vascular cognitive impairment and Alzheimer’s disease. Hypertension compromises the structural and functional integrity of the cerebral microcirculation, promoting microvascular rarefaction, cerebromicrovascular endothelial dysfunction and neurovascular uncoupling, which impair cerebral blood supply. In addition, hypertension disrupts the blood–brain barrier, promoting neuroinflammation and exacerbation of amyloid pathologies. Ageing is characterized by multifaceted homeostatic dysfunction and impaired cellular stress resilience, which exacerbate the deleterious cerebromicrovascular effects of hypertension. Neuroradiological markers of hypertension-induced cerebral small vessel disease include white matter hyperintensities, lacunar infarcts and microhaemorrhages, all of which are associated with cognitive decline. Use of pharmaceutical and lifestyle interventions that reduce blood pressure, in combination with treatments that promote microvascular health, have the potential to prevent or delay the pathogenesis of vascular cognitive impairment and Alzheimer’s disease in patients with hypertension.

Abstract

Hypertension and ageing have deleterious effects on the cerebral microcirculation that can lead to cognitive dysfunction. This Review discusses cerebrovascular maladaptation to hypertension and microvascular contributions to hypertension-induced cognitive impairment in ageing, as well as the role of hypertension in the pathogenesis of Alzheimer’s disease.

Key points

• Hypertension is associated with ageing and significantly increases the risk of vascular cognitive impairment and Alzheimer’s disease.

• In older individuals, hypertension leads to maladaptation of the cerebral circulation, resulting in dysregulation of cerebral blood flow, microvascular rarefaction, blood–brain barrier disruption, oxidative stress and impaired neurovascular coupling.

• Hypertension causes pathological alterations in cerebral microvessels that damage microvascular structure, network architecture and function, and contribute to the genesis of cerebral microhaemorrhages, lacunar infarcts and white matter injury; these factors are associated with cognitive decline.

• Potential mechanisms by which hypertension could exacerbate the progression of Alzheimer’s disease include increased oxidative microvascular damage, brain inflammation and blood–brain barrier disruption, as well as impaired glymphatic (also known as glial-lymphatic) clearance of amyloid-β.

• Use of pharmaceutical and/or lifestyle interventions that reduce blood pressure in combination with treatments that promote microvascular health could potentially prevent or delay cognitive decline in patients with hypertension.