Hypertension impairs neurovascular coupling and promotes microvascular injury: role in exacerbation of Alzheimer’s disease

Csiszár, Anna; Tarantini, Stefano; Fülöp, Gábor; Kiss, Tamás; Valcarcel‐Ares, Marta Noa; Galván, Verónica; Ungvári, Zoltán; Yabluchanskiy, Andriy

doi:10.1007/s11357-017-9991-9

Cited by 80 publications

(89 citation statements)

References 189 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In conclusion, there is substantial evidence about the link between blood pressure and cognitive functioning. The effects of high blood pressure on the functional and structural integrity of the cerebral microcirculation could explain this relationship [107]. Exposure to elevated blood pressure promotes oxidative stress and microvascular lesions [107].…”

Section: Discussionmentioning

confidence: 99%

“…The effects of high blood pressure on the functional and structural integrity of the cerebral microcirculation could explain this relationship [107]. Exposure to elevated blood pressure promotes oxidative stress and microvascular lesions [107]. Furthermore, it appears to be related to alterations in the permeability of the encephalic blood barrier [108].…”

Section: Discussionmentioning

confidence: 99%

“…However, vascular alterations could cause neuroinflammation, micro-haemorrhages and alterations in capillarization of brain tissue (cerebral-microvascular rarefaction) that contribute to changes in cerebral blood flow [109]. These dysfunctions can further alter the neurovascular coupling response, i.e., the ability to self-regulate blood flow based on neural metabolic demand [107]. The consequences of these structural and functional changes, in particular of cerebral blood flow, could be responsible for the cognitive impairment associated with the increase in blood pressure.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Blood Pressure on Cognitive Performance: A Systematic Review

Forte

Pascalis

Favieri

et al. 2019

JCM

View full text Add to dashboard Cite

Background: High blood pressure has been associated with an increased risk of developing cognitive impairment. However, this relationship is unclear. This study aims to systematically review the effects of blood pressure on executive functioning, language, memory, attention and processing speed. Methods: The review process was conducted according to the PRISMA-Statement, using the PubMed, PsycINFO, PsycARTICLES and MEDLINE databases. Restrictions were made by selecting studies, which included one or more cognitive measures and reported blood pressure recordings. Studies that included participants with medical conditions or people diagnosed with dementia, psychiatric disorders, stroke and head trauma were excluded. The review allows selecting fifty studies that included 107,405 participants. The results were reported considering different cognitive domains separately: global cognitive functioning, attention, processing speed, executive functions, memory and visuospatial abilities. Results: Higher blood pressure appears to influence cognitive performance in different domains in the absence of dementia and severe cardiovascular diseases, such as strokes. This relationship seems to be independent of demographic factors (gender and education), medical co-morbidity (diabetes), and psychiatric disorders (depression). Furthermore, it presents different patterns considering ageing. In the elderly, a sort of "cardiovascular paradox" is highlighted, which allows considering higher blood pressure as a protective factor for cognitive functioning. Conclusions: The results underline that higher blood pressure is associated with a higher risk of cognitive decline in people without dementia or stroke. These findings highlight the need to introduce early management of blood pressure, even in the absence of clinical hypertension, to prevent the risk of a decline of cognitive functioning typically associated with ageing. into dementia. Given the progressive ageing of the world population, the challenge of modern science is highlighted the factors associated with the evolution of cognitive impairment.Cognitive impairment appears to be amplified by several factors as the habit of smoking cigarettes [13,14], chronic use of alcohol [15], poor eating habits and obesity [16,17], inadequate exercise [18], chronic stress [19] or by some pathologies such as diabetes mellitus [20] or depression [21]. Moreover, the risk of cognitive impairment appears to increase in the presence of cardiovascular disorders, such as high blood pressure, cardiomyopathies, arteriosclerosis, cerebral infarcts and strokes [22]. Many studies have shown an association between vascular ageing indices, such as stiffness of the arteries and dysfunction of small vessels and cognitive decline [23]. The exposure to high blood pressure would damage the cerebral microcirculation, causing cognitive impairments [23].The mechanisms that can explain the relationship between high blood pressure and cognitive impairment are not wholly known. Some studies have shown associations be...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Blood Pressure on Cognitive Performance: A Systematic Review

Forte

Pascalis

Favieri

et al. 2019

JCM

View full text Add to dashboard Cite

show abstract

“…Vascular contributions to cognitive impairment and dementia (VCID) in aging have garnered much interest in the past decade (Corriveau et al 2016;Csiszar et al 2017;Gorelick et al 2011;Snyder et al 2015;Toth et al 2017;Tucsek et al 2017). There are numerous agerelated vascular pathologies underlying VCID.…”

Section: Introductionmentioning

confidence: 99%

Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice

et al. 2017

Self Cite

View full text Add to dashboard Cite

There is correlative evidence that impaired cerebral blood flow (CBF) regulation, in addition to promoting cognitive impairment, is also associated with alterations in gait and development of falls in elderly people. CBF is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism becomes progressively impaired with age. To establish a direct cause-andeffect relationship between impaired NVC and gait abnormalities, we induced neurovascular uncoupling pharmacologically in young C57BL/6 mice by inhibiting the synthesis of vasodilator mediators involved in NVC. Treatment of mice with the epoxygenase inhibitor MSPPOH, the NO synthase inhibitor L-NAME, and the COX inhibitor indomethacin significantly decreased NVC mimicking the aging phenotype. Pharmacologically induced neurovascular uncoupling significantly decreased the dynamic gait parameter duty cycle, altered footfall patterns, and significantly increased phase dispersion, indicating impaired interlimb coordination. Impaired NVC also tended to increase gait variability. Thus, selective experimental disruption of NVC causes subclinical gait abnormalities, supporting the importance of CBF in both cognitive function and gait regulation.

show abstract

“…However, when cognitive demand exceeds these compensatory mechanisms, performance becomes impaired (Cabeza et al, ). Because cerebrovascular dysfunction plays a critical role in the pathogenesis of age‐related neurodegenerative disorders, including AD (Csiszar et al, ; Lin et al, , ; Van Skike et al, ), and manifests early in disease progression (Iturria‐Medina, Sotero, Toussaint, Mateos‐Perez, & Evans, ), it is important to investigate the mechanisms underlying cognitive decline and brain vascular deterioration driven by nonpathologic aging.…”

Section: Introductionmentioning

confidence: 99%

mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging

Skike

Lin

Burbank³

et al. 2019

Aging Cell

Self Cite

View full text Add to dashboard Cite

Cerebrovascular dysfunction and cognitive decline are highly prevalent in aging, but the mechanisms underlying these impairments are unclear. Cerebral blood flow decreases with aging and is one of the earliest events in the pathogenesis of Alzheimer's disease (AD). We have previously shown that the mechanistic/mammalian target of rapamycin (mTOR) drives disease progression in mouse models of AD and in models of cognitive impairment associated with atherosclerosis, closely recapitulating vascular cognitive impairment. In the present studies, we sought to determine whether mTOR plays a role in cerebrovascular dysfunction and cognitive decline during normative aging in rats. Using behavioral tools and MRI-based functional imaging, together with biochemical and immunohistochemical approaches, we demonstrate that chronic mTOR attenuation with rapamycin ameliorates deficits in learning and memory, prevents neurovascular uncoupling, and restores cerebral perfusion in aged rats. Additionally, morphometric and biochemical analyses of hippocampus and cortex revealed that mTOR drives age-related declines in synaptic and vascular density during aging. These data indicate that in addition to mediating AD-like cognitive and cerebrovascular deficits in models of AD and atherosclerosis, mTOR drives cerebrovascular, neuronal, and cognitive deficits associated with normative aging. Thus, inhibitors of mTOR may have potential to treat age-related cerebrovascular dysfunction and cognitive decline. Since treatment of age-related cerebrovascular dysfunction in older adults is expected to prevent further deterioration of cerebral perfusion, recently identified as a biomarker for the very early (preclinical) stages of AD, mTOR attenuation may potentially block the initiation and progression of AD. K E Y W O R D Saging, brain vasculature, cerebral blood flow, cognitive decline, functional MRI, mTOR

show abstract

Hypertension impairs neurovascular coupling and promotes microvascular injury: role in exacerbation of Alzheimer’s disease

Cited by 80 publications

References 189 publications

Effects of Blood Pressure on Cognitive Performance: A Systematic Review

Effects of Blood Pressure on Cognitive Performance: A Systematic Review

Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice

mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging

Contact Info

Product

Resources

About