Impact of impaired cerebral blood flow autoregulation on cognitive impairment

Abstract

Although the causes of cognitive impairment are multifactorial, emerging evidence indicates that cerebrovascular dysfunction plays an essential role in dementia. One of the most critical aspects of cerebrovascular dysfunction is autoregulation of cerebral blood flow (CBF), mainly mediated by the myogenic response, which is often impaired in dementia individuals with comorbidities, such as diabetes and hypertension. However, many unsolved questions remain. How do cerebrovascular networks coordinately modulate CBF autoregulation in health and disease? Does poor CBF autoregulation have an impact on cognitive impairment, and what are the underlying mechanisms? This review summarizes the cerebral vascular structure and myogenic (a three-phase model), metabolic (O2, CO2, adenosine, and H+), and endothelial (shear stress) factors in the regulation of CBF; and the consequences of CBF dysautoregulation. Other factors contributing to cerebrovascular dysfunction, such as impaired functional hyperemia and capillary abnormalities, are included as well. Moreover, this review highlights recent studies from our lab in terms of novel mechanisms involved in CBF autoregulation and addresses a hypothesis that there is a three-line of defense for CBF autoregulation in the cerebral vasculature.

Longitudinal Characterization of Cerebral Hemodynamics in the TgF344-AD Rat Model of Alzheimer’s Disease

“…Brain hypoperfusion could be attributed to impaired cerebral hemodynamics, BBB leakage, and NVU dysfunction. 4,61 We found that the MR of the MCA and PA was intact in AD rats at 3 months of age, similar to what was seen in WT rats. AD rats started to lose the vasoconstrictive response to pressures at 4 months in both the MCA and PA.…”

“…Changes in cerebral VSMC functional contractility could affect the MR of cerebral vasculature and CBF autoregulation associated with AD/ADRD 57,61,62 . We compared the contractile capability of VSMCs isolated from MCAs of AD and WT rats.…”

Cerebral small vessel disease pathology in COVID-19 patients: A systematic review

“…This ensures prevention of high pressure reaching the distal microcirculation, protecting against the detrimental effects of rapid changes in blood pressure, enabling the endothelium to locally regulate blood flow at the microvascular level ( Toth et al, 2017 ). Impairment of cerebral autoregulation, seen in comorbidities commonly associated with vascular cognitive impairment and dementia (i.e., hypertension, diabetes) may also contribute to impairment of NVC due to hypoperfusion or elevated arterial pressure in the distal microcirculation, potentially causing CSVD pathologies of ischemic lesions and microbleeds, respectively ( Wang et al, 2022 ). Moreover, CSVD is associated with impaired NVC ( Moretti and Caruso, 2020 ) and is strongly linked to COVID-19, as is evidenced in this systematic review.…”

Role ofDusp5 KO on Vascular Properties of Middle Cerebral Artery in Rats

“…1 Importantly, emerging research suggests a connection between vascular aging and neurodegenerative conditions like AD/ADRD. 49 The compromised blood flow to the brain due to vascular aging may play a role in the development and progression of cognitive decline and neurodegeneration. 3, 33 Understanding the intricate relationship between vascular aging, hemodynamics, and neurological health is crucial for developing targeted interventions to mitigate the risks associated with aging and promote overall vascular and cognitive well-being.…”