Life‐course blood pressure in relation to brain volumes

Power, Melinda C.; Schneider, Andrea L.C.; Wruck, Lisa; Griswold, Michael; Coker, Laura H.; Alonso, Álvaro; Jack, Clifford R.; Knopman, David S.; Mosley, Thomas H.; Gottesman, Rebecca F.

doi:10.1016/j.jalz.2016.03.012

Cited by 62 publications

(57 citation statements)

References 32 publications

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“…The notion that cardiovascular disease during midlife influences late-life neurologic outcomes has been borne out in recent epidemiological literature 19,20 . Although we found associations between midlife CRP levels and late-life white matter structural abnormalities that were independent of midlife cardiovascular disease, it remains possible that these associations are mediated, at least in part, by interim cardiovascular disease occurring after midlife.…”

Section: Discussionmentioning

confidence: 99%

Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease

Walker

Power

Hoogeveen

et al. 2017

Stroke

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Background and Purpose It is currently unclear whether midlife systemic inflammation promotes the development of white matter (WM) abnormalities and small vessel disease in the elderly. We examined the association of midlife systemic inflammation with late-life white matter hyperintensity (WMH) volume, deep and periventricular WM microstructural integrity (fractional anisotropy [FA], mean diffusivity [MD]), cerebral infarcts and microbleeds in a biracial prospective cohort study. Methods Linear and logistic regression examined the relation between midlife high-sensitivity C-reactive protein (CRP), a non-specific marker of inflammation, and brain MRI markers assessed 21 years later in the Atherosclerosis Risk in Communities Study. Results We included 1,485 participants (baseline age 56(5), 28% African American). After adjusting for demographic factors and cardiovascular disease, each standard deviation (SD) increase in midlife CRP was associated with lower FA (−0.09 SD; 95% CI:−0.15, −0.02) and greater MD (0.08 SD; 95% CI:0.03, 0.15) in deep WM, and lower FA (−0.07 SD; 95% CI:−0.13, 0.00) in periventricular WM. We found stronger associations between CRP and periventricular WM microstructural integrity among African American participants (p-interaction=.011). While an association between higher CRP levels and greater WMH volume was found only among APOE ε4-positive participants in our primary analysis (0.14 SD; 95% CI:0.01, 0.26; p-interaction=.028), this relationship extended to the entire sample after accounting for differential attrition. Midlife CRP was not associated with the presence of cerebral infarcts or microbleeds in late-life. Conclusions Our findings support the hypothesis that midlife systemic inflammation may promote the development of chronic microangiopathic structural WM abnormalities in the elderly.

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Section: Discussionmentioning

confidence: 99%

Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease

Walker

Power

Hoogeveen

et al. 2017

Stroke

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“…Chronic hypertension also compromises blood-brain barrier (BBB) integrity, leading to both cerebral edema and the introduction of systemic elements into the brain parenchyma [49]. Hypertension recorded 15 years prior has been associated with smaller brain volumes in areas typically affected by AD such as the hippocampus [50]. Our group has observed that an increased resting-state cardiac rate pressure product as a surrogate of myocardial oxygen use has a small to moderate correlation with neocortical amyloidosis in midlife adults with preclinical AD [51].…”

Section: Hypertension/hypotensionmentioning

confidence: 99%

Pathophysiologic relationship between Alzheimer's disease, cerebrovascular disease, and cardiovascular risk: A review and synthesis

Santos

Snyder

et al. 2017

Alz & Dem Diag Ass & Dis Mo

325

263

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As the population ages due to demographic trends and gains in life expectancy, the incidence and prevalence of dementia increases, and the need to understand the etiology and pathogenesis of dementia becomes ever more urgent. Alzheimer's disease (AD), the most common form of dementia, is a complex disease, the mechanisms of which are poorly understood. The more we learn about AD, the more questions are raised about our current conceptual models of disease. In the absence of a cure or the means by which to slow disease progress, it may be prudent to apply our current knowledge of the intersection between AD, cardiovascular disease, and cerebrovascular disease to foster efforts to delay or slow the onset of AD. This review discusses our current understanding of the epidemiology, genetics, and pathophysiology of AD, the intersection between AD and vascular causes of dementia, and proposes future directions for research and prevention.

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“…In elderly populations, low SBP [116,117] and low DBP [117,118] have been associated with reduced brain volume and cortical thickness, suggesting that the relationship between BP and brain volume may age-dependent [15,119,120]. A pattern of hypertension in midlife followed by hypotension in late-life appears to be especially harmful [34], particularly in brain regions affected in the earliest phase of Alzheimer’s disease [121]. …”

Section: Pathophysiology Of Hypertension As It Relates To Cognitive Dmentioning

confidence: 99%

“…Not only do these vascular changes shift the cerebral autoregulatory curve in a manner which reduces resting cerebral blood flow, but the brain also becomes more susceptible to hypoperfusion during periods of low systemic BP [152] or during periods of normal BP in chronically hypertensive individuals [153]. These hypertension-induced changes to cerebral autoregulation and perfusion may explain why individuals with chronic hypertension in midlife and low BP in late-life show significant reductions in brain volume [34,121] and greater levels of cognitive deficits [101]. …”

Section: Pathophysiology Of Hypertension As It Relates To Cognitive Dmentioning

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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Life‐course blood pressure in relation to brain volumes

Cited by 62 publications

References 32 publications

Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease

Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease

Pathophysiologic relationship between Alzheimer's disease, cerebrovascular disease, and cardiovascular risk: A review and synthesis

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

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