Visit-to-Visit Blood Pressure Variability and Alzheimer’s Disease: Links and Risks

Abstract

While hypertension has been shown to be a risk factor for vascular dementia, several studies have also demonstrated that hypertension also increases the risk of Alzheimer's disease (AD). Although the relationship between visit-to-visit blood pressure variability (VVV) and cognitive impairment, including AD, have been provided, the mechanisms remain poorly understood. This review paper focuses on the relationship of VVV with AD and summarizes the pathophysiology underlying that relationship, which appears to be mediated by arterial stiffness.

Visit‐to‐visit variability in blood pressure and Alzheimer's disease

“…Oligaemia can increase brain amyloidogenesis by enhancing expression and processing of Aβ precursor protein, activate microglia, impair neuronal protein synthesis, and cause neuronal damage and cellular death, particularly in the most vulnerable areas such as the hippocampi, which are among the sites to be affected earlier and at a higher degree in AD. High visit‐to‐visit BPV can also determine ischemic changes in small vessels attributable to cerebral hypoperfusion during low‐BP periods . Notably, the shift in the limits of cerebral autoregulation toward upper levels, which is common in elderly individuals or patients with long‐lasting hypertension, makes cerebral blood flow highly dependent on systemic BP and amplifies the detrimental effects of its fluctuations…”

“…Visit‐to‐visit BPV is an upstream determinant of artery remodeling, and high fluctuations of BP levels have been independently associated with arterial stiffness . Increased large artery stiffness provides direct harmful effects on structure and function of cerebral penetrating arteries . BPV could cause a “tsunami effect” towards the cerebral parenchyma leading to cerebral small vessel diseases, including silent infarcts, white matter hyperintensities, and microbleeds, which contribute to reactive gliosis, synaptic and neuronal dysfunction, and disruption of brain structure and functional connectivity, either dependently or independently from the Aβ pathway …”

“…Notably, AD‐related changes progress through the brain in a hierarchical sequence that starts in the mesiotemporal cortex and progressively invades the frontal, temporal, and parietal lobes. The early involvement by neurofibrillary tangles of the insular cortex, which is part of the cortical network implied in the central control of autonomic nervous system, may likely contribute to the impairment of cardioregulatory functions . Hence, BP instability may partly reflect and represent an epiphenomenon and a marker of AD pathology, even in subclinical stages.…”

Long Sleep Duration: An Epiphenomenon or a Risk for Dementia?

“…9 In light of this background, arterial stiffness and BP variability may be pivotal moderators for the relationship between long sleep duration and dementia risk. 10 The cerebral small vessels that rise directly from large vessels would be fragile with regard to the greater BP variability that long sleep duration partly causes. If the large vessels became stiffer, the effect of BP variability on small vessels would be greater, resulting in silent cerebral ischemia or microbleeds.…”

Reply to “Long sleep duration: An epiphenomenon or a risk for dementia?”

“…Thus, arterial stiffness may be a common pathophysiology in the relationships between VVV and AD and VaD. 10 There have been few reports assessing a mechanism underlying the relationship between long sleep duration and risk of dementia. The data presented herein could make an important contribution, if a clear pathophysiology was provided.…”