Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and Memory

Cooper, Leon N.; Woodard, Todd; Sigurðsson, Sigurður; Buchem, Mark A. van; Torjesen, Alyssa A.; Inker, Lesley A.; Aspelund, Thor; Eiríksdóttir, Guðný; Harris, Tamara B.; Gudnason, Vilmundur; Launer, Lenore J.; Mitchell, Gary F.

doi:10.1161/hypertensionaha.115.06398

Cited by 118 publications

(98 citation statements)

References 40 publications

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“…Decreasing DBP from midlife to later life may be linked to cerebral hypoperfusion 33, 34. Decreasing DBP from midlife on is also a likely consequence of aortic stiffening, which contributes to cognitive decline 29, 35. We observed that the effect size of higher midlife PP levels on cognitive decline in later life was larger than that associated with higher SBP or with lower DBP.…”

Section: Discussionmentioning

confidence: 60%

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Long‐Term Blood Pressure Level and Variability From Midlife to Later Life and Subsequent Cognitive Change: The ARIC Neurocognitive Study

Yano

Griswold

Wang

et al. 2018

JAHA

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BackgroundTo understand how blood pressure (BP) from midlife and beyond is related to cognition in older age, a lifespan approach is needed. We assessed the associations of BP levels and variability from midlife on with subsequent cognitive change.Methods and ResultsThe ARIC (Atherosclerosis Risk in Communities) Study participants underwent 4 clinic BP measurements (visit 1, 2, 3, and 4 BPs) between 1987 and 1998, and their mean levels and average real variability (ARV) were assessed as exposures. A global cognitive z score, estimated from the Delayed Word Recall Test, Digit Symbol Substitution Test, and Word Fluency Test scores, was calculated at 1996 to 1998 (visit 4) and 2011 to 2013 (visit 5). Among 11 408 participants (mean age, 54 years; 56% women; 21% black race), mean systolic BP (SBP)/diastolic BP (DBP) level was 123/72 mm Hg, and ARVSBP/ARVDBP was 11/7 mm Hg. With linear mixed models, 1‐SD increases of ARVSBP (standardized regression coefficient [95% confidence interval], −0.03 [−0.04 to −0.01] points) and ARVDBP (standardized regression coefficient [95% confidence interval], −0.02 [−0.03 to −0.002] points; both P<0.05), but not mean SBP or DBP levels, were associated with lower global cognitive z scores at visit 4. In contrast, mean SBP (standardized regression coefficient [95% confidence interval], −0.04 [−0.06 to −0.02] points) or DBP (standardized regression coefficient [95% confidence interval], 0.04 [0.02–0.06] points; both P<0.001) level, but not ARVSBP or ARVDBP, was associated with change in global cognitive z scores from visits 4 to 5.ConclusionsGreater visit‐to‐visit SBP or DBP variability from midlife on is modestly associated with lower cognitive function, whereas higher mean SBP and lower DBP levels from midlife to later life are modestly associated with cognitive decline in later life.

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Section: Discussionmentioning

confidence: 60%

“…A common cause may lead to both higher long‐term SBP variability and lower cognitive function. For example, adverse stressors (eg, psychosocial stress and sleep deprivation), large‐artery (aortic) stiffness, and lower socioeconomic status could lead to both increased long‐term SBP variability and lower cognitive function 19, 20, 28, 29…”

Section: Discussionmentioning

confidence: 99%

Long‐Term Blood Pressure Level and Variability From Midlife to Later Life and Subsequent Cognitive Change: The ARIC Neurocognitive Study

Yano

Griswold

Wang

et al. 2018

JAHA

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“…4 In this regard, elevated aortic stiffness and pulsatility are hypothesized to contribute, in part, to declines in cognitive performance with aging by promoting the development of subcortical white matter hyperintensities via increased cerebrovascular remodeling and resistance. 12,13 In addition, the link between age-related aortic stiffness and pulsatility with cerebral blood flow (CBF) and cerebrovascular reactivity, defined as the ability to augment brain blood flow in response to a vasodilatory stimulus, remains relatively unexplored. Experimentally, cerebrovascular reactivity is quantified by measuring cerebrovascular reserve (CVR) in response to a physiological or pharmacological stimuli, such as CO 2 or acetazolamide (ACZ), a carbonic anhydrase inhibitor.…”

mentioning

confidence: 99%

Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans

DuBose¹,

Ponto²,

Moser³

et al. 2018

Hypertension

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Abstract-Greater aortic stiffness and pulse pressure are associated with cerebrovascular remodeling, reduced white matter microstructure, and cognitive performance with aging in humans. However, it is unclear whether aortic stiffness and pulse pressure are associated with reduced basal global cerebral blood flow (CBF) and cerebrovascular reserve among older adults. Global CBF was quantified in 205 adults (range, 19-87 years; mean±SE: 30.6±1.3 years) using quantitative [ 15 O] water brain positron emission tomography imaging. In a subset of older adults (n=24; 70.0±2.0 years), aortic stiffness (carotid femoral pulse wave velocity) and cerebrovascular reserve (change in global CBF after intravenous infusion of acetazolamide) were assessed. In the entire cohort, global CBF was lower in older compared with young adults (36.5±1.1 versus 50.5±0.7 mL/min per 100 mL; P<0.001). Global CBF was higher in young women compared with young men (51.0±0.30 versus 47.4±0.03 mL/min per 100 mL; P<0.001) but did not differ between older women and men (P=0.63). In older adults, greater carotid femoral pulse wave velocity was associated with lower cerebrovascular reserve (r=−0.68; P=0.001 adjusted for age, sex, and mean arterial pressure) but not global CBF (r=0.13; P=0.60). Brachial pulse pressure was not associated with lower cerebrovascular reserve (r=−0.37; P=0.159) when adjusted for age and sex. These data indicate that the age-related increases in aortic stiffness may contribute, in part, to the brain's impaired ability to augment blood flow in response to a stimulus with aging in humans. (Hypertension. 2018;72:476-482.

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“…Earlier, there have been reports on repeated episodes of microvascular cerebral ischemia/hypoperfusion and impaired cerebral vasoreactivity amplified by blood pressure variability. In older adults from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 8 cerebral microvascular remodeling and parenchymal damage (cerebrovascular resistance and WMH) were the inferred mechanisms that mediated the associations between cf-PWV and memory. There is a reasonable evidence that high blood pressure is mechanistically involved in CSVD.…”

Section: De Buyzere Stiff Arteries and Brain Aging In The Young 491mentioning

confidence: 99%

Young Adults With Stiff Arteries

Buyzere

2016

Hypertension

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T he arterial system gradually stiffens because of the time integrated and shared effects of several traditional risk indicators. In clinical practice, this detrimental process can be monitored noninvasively by the carotid-femoral pulse wave velocity (cf-PWV), which is considered the "gold standard" methodology for the stiffness of the thoracic and abdominal aorta. PWV improved cardiovascular risk prediction when added to standard risk factors including systolic blood pressure in several community-based samples including the Framingham Heart Study.Stiffening of the arterial wall is increasingly considered as a hallmark of unsuccessful aging and shifted our interest to interactions between the fields of arterial stiffening and hypertension and the fields of subtle brain damage and mild cognitive impairment/dementia on the other side. A decade of intensive research linked increased cf-PWV with a higher prevalence and extent of brain lesions on nuclear magnetic resonance imaging (MRI) and lower cognitive scores on a whole array of neuropsychological tests, however, with varying degrees of uncertainty.In the meta-analysis by van Sloten et al, 1 41 arterial stiffness studies with cognition-related outcomes showed considerable heterogeneity. Some of the studies showed significant associations with cognitive impairment but many associations were relatively weak. The weakest evidence is expected for less specific and less precise measurements of cognitive function (eg, scrutinizing Mini-Mental Status Examination). Relative strength of the associations might have been weakened by competing conditions, such as atherothrombosis and neurodegenerative diseases.Hajjar et al 2 demonstrated that PWV is superior to elevated blood pressure in predicting hypertension-related cognitive decline. Higher PWV was associated with a steeper decline in executive, memory, and working memory scores after appropriate adjustments. PWV increased the explained variance of the association between hypertension and executive function from 1% to 10%.In the same meta-analysis by van Sloten et al 1 on 23 studies, greater stiffness was associated more convincingly with markers of cerebral small vessel disease (CSVD) with odds ratios all around 1.30 per 1 SD increase in the cross-sectional analyses: 1.30 for white matter hyperintensities (WMH), 1.32 for cerebral microbleeds, and 1.29 for cerebral infarcts. Of interest, the Framingham Heart Study 3 confirmed significant associations between cf-PWV and lower total cerebral brain volume, greater WMH volume, and greater prevalence of silent cerebral infarcts. Nonetheless, a word of caution might be in place as in a more recent study 4 of elderly without cognitive impairment the significance for a crude analysis between cf-PWV and WMH was lost after adjustment for common cardiovascular covariates.The large majority of these studies targeted elderly individuals because arterial stiffness, cognitive decline, and brain damage are traditionally viewed as inherent to irreversible processes of aging. Foci of ongo...

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Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and Memory

Cited by 118 publications

References 40 publications

Long‐Term Blood Pressure Level and Variability From Midlife to Later Life and Subsequent Cognitive Change: The ARIC Neurocognitive Study

Long‐Term Blood Pressure Level and Variability From Midlife to Later Life and Subsequent Cognitive Change: The ARIC Neurocognitive Study

Higher Aortic Stiffness Is Associated With Lower Global Cerebrovascular Reserve Among Older Humans

Young Adults With Stiff Arteries

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