Association of arterial stiffness with progression of subclinical brain and cognitive disease

Tsao, Connie W.; Himali, Jayandra J.; Beiser, Alexa; Larson, Martin G.; DeCarli, Charles; Vasan, Ramachandran S.; Mitchell, Gary F.; Seshadri, Sudha

doi:10.1212/wnl.0000000000002368

Cited by 101 publications

(82 citation statements)

References 40 publications

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“…Multivariable models adjusted for vascular and cognitive risk factors showed that a higher CFPWV was related to lower memory scores but was not related to processing speed or executive function. Previous research suggests that vascular injury and ischemia of the brain manifest preferentially as a decline of executive function and processing speed rather than memory [28,29,30,31,32]. In our study, however, we found the strongest relations between aortic stiffness (CFPWV) and memory.…”

Section: Aortic Stiffness Cerebrovascular Damage and Memorycontrasting

confidence: 80%

“…Recently, aortic stiffness has been associated with an increased risk for damage to microvascular structure and function of various target organs, including the kidneys and brain [9,24,25,26,27,28]. Several factors, including blood-brain barrier and endothelial dysfunction, hypertension, hypercholesterolemia, diabetes mellitus, and smoking, contribute to cerebral SVD in older adults; however, the mechanisms by which aortic stiffness leads to cognitive dysfunction are complex and still incompletely understood.…”

Section: Aortic Stiffness Cerebrovascular Damage and Memorymentioning

confidence: 99%

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Aortic Stiffness, Cerebrovascular Dysfunction, and Memory

Cooper

Mitchell

2016

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Background: Aortic stiffness is associated with cardiovascular and cerebrovascular events and cognitive decline. This mini-review focuses on relations of aortic stiffness with microvascular dysfunction and discusses the contribution of abnormal pulsatile hemodynamics to cerebrovascular damage and cognitive decline. We also provide a rationale for considering aortic stiffness as a putative and important contributor to memory impairment in older individuals. Summary: Aging is associated with stiffening of the aorta but not the muscular arteries, which reduces wave reflection and increases the transmission of pulsatility into the periphery. Aortic stiffening thereby impairs a protective mechanism that shields the peripheral microcirculation from excessive pulsatility within downstream target organs. Beyond midlife, aortic stiffness increases rapidly and exposes the cerebral microcirculation to abnormal pulsatile mechanical forces that are associated with microvascular damage and remodeling in the brain. Aortic stiffening and high-flow pulsatility are associated with alterations in the microvasculature of the brain; however, a mechanistic link between aortic stiffness and memory has not been established. We showed that in a community-based sample of older individuals, cerebrovascular resistance and white matter hyperintensities - markers of cerebrovascular remodeling and damage - mediated the relation between higher aortic stiffness and lower performance on memory function tests. These data suggest that microvascular and white matter damage associated with excessive aortic stiffness contribute to impaired memory function with advancing age. Key Messages: Increasing evidence suggests that vascular etiologies - including aortic stiffness and microvascular damage - contribute to memory impairment and the pathogenesis of dementia, including Alzheimer's disease. Interventions that reduce aortic stiffness may delay memory decline among older individuals.

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Section: Aortic Stiffness Cerebrovascular Damage and Memorycontrasting

confidence: 80%

Section: Aortic Stiffness Cerebrovascular Damage and Memorymentioning

confidence: 99%

Aortic Stiffness, Cerebrovascular Dysfunction, and Memory

Cooper

Mitchell

2016

Pulse

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“…For example, pulse pressure, a measure of arterial stiffening, which increases with age and exposure to hypertension [145], can be used as an additional method to quantify the effects of vascular pathology resulting from chronic hypertension. Elevations in pulse pressure have been associated with cognitive impairment [189,190], cognitive decline [190], cerebral small vessel disease [127,191], and Alzheimer’s disease biomarkers [192]. Compared to BP, pulse pressure is believed to more precisely quantify the exposure of target organs such as the brain to potentially harmful pulsatile energy resulting from arterial stiffening [193].…”

Section: Discussionmentioning

confidence: 99%

Defining the Relationship Between Hypertension, Cognitive Decline, and Dementia: a Review

2017

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Hypertension is a highly prevalent condition which has been established as a risk factor for cardiovascular and cerebrovascular disease. Although the understanding of the relationship between cardiocirculatory dysfunction and brain health has improved significantly over the last several decades, it is still unclear whether hypertension constitutes a potentially treatable risk factor for cognitive decline and dementia. While it is clear that hypertension can affect brain structure and function, recent findings suggest that the associations between blood pressure and brain health are complex and, in many cases, dependent on factors such as age, hypertension chronicity, and antihypertensive medication use. Whereas large epidemiological studies have demonstrated a consistent association between high midlife BP and late-life cognitive decline and incident dementia, associations between late-life blood pressure and cognition have been less consistent. Recent evidence suggests that hypertension may promote alterations in brain structure and function through a process of cerebral vessel remodeling, which can lead to disruptions in cerebral autoregulation, reductions in cerebral perfusion, and limit the brain’s ability to clear potentially harmful proteins such as β-amyloid. The purpose of the current review is to synthesize recent findings from epidemiological, neuroimaging, physiological, genetic, and translational research to provide an overview of what is currently known about the association between blood pressure and cognitive function across the lifespan. In doing so, the current review also discusses the results of recent randomized controlled trials of antihypertensive therapy to reduce cognitive decline, highlights several methodological limitations, and provides recommendations for future clinical trial design.

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“…The relationship between vascular health and brain anatomy has been previously investigated using systemic (largely peripheral) measures of arterial status (Beauchet et al, 2013; Jochemsen et al, 2015; Rabkin, 2012; Raz et al, 2008; Singer et al, 2014; Tsao et al, 2016). However, there is now considerable evidence that the cerebrovascular system may present specific alterations and pathologies with aging, which are somewhat independent of those observed in the rest of the body.…”

Section: Discussionmentioning

confidence: 99%

“…Although cross-sectional analyses revealed a negative correlation between carotid distension and total gray matter volume (and also a positive correlation with increased white matter lesion volume), these findings did not reach significance in a prospective analysis after a 4-year follow-up. Similarly, a large sample (N=1,223) study of older adults failed to find an association between various peripheral stiffness measures (inverse-transformed carotid-femoral pulse wave velocity, central pulse pressure, and mean arterial pressure) and brain anatomy as a whole (Tsao et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Individual differences in regional cortical volumes across the life span are associated with regional optical measures of arterial elasticity

et al. 2017

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Aging is often accompanied by changes in brain anatomy and cerebrovascular health. However, the specific relationship between declines in regional cortical volumes and loss of cerebral arterial elasticity is less clear, as only global or very localized estimates of cerebrovascular health have been available. Here we employed a novel tomographic optical method (pulse-DOT) to derive local estimates of cerebral arterial elasticity and compared regional volumetric estimates (obtained with FreeSurfer) with optical arterial elasticity estimates from the same regions in 47 healthy adults (aged 18–75). Between-subject analyses revealed a global correlation between cortical volume and cortical arterial elasticity, which was a significant mediator of the association between age and cortical volume. Crucially, a novel within-subject analysis highlighted the spatial association between regional variability in cortical volumes and arterial elasticity in the same regions. This association strengthened with age. Gains in the predictability of cortical volumes from arterial elasticity data were obtained by sharpening the resolution up to individual cortical regions. These results indicate that some of the variance of sub-clinical age-related brain atrophy is associated with differences in the status of cerebral arteries, and can help to explain the unique patterns of brain atrophy found within each individual.

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Association of arterial stiffness with progression of subclinical brain and cognitive disease

Cited by 101 publications

References 40 publications

Aortic Stiffness, Cerebrovascular Dysfunction, and Memory

Aortic Stiffness, Cerebrovascular Dysfunction, and Memory

Defining the Relationship Between Hypertension, Cognitive Decline, and Dementia: a Review

Individual differences in regional cortical volumes across the life span are associated with regional optical measures of arterial elasticity

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