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

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 [15O]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.

SUBMITTER: DuBose LE

PROVIDER: S-EPMC6261448 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

DuBose Lyndsey E LE Boles Ponto Laura L LL Moser David J DJ Harlynn Emily E Reierson Leah L Pierce Gary L GL

Hypertension (Dallas, Tex. : 1979) 20180618 2

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 [<sup>15</sup>O]water brain positron ...[more]

PMID: 29915015

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Project description:BACKGROUND:Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults. METHODS:Vanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (n=155; age, 72±7 years; 59% male) or mild cognitive impairment (n=115; age, 73±7 years; 57% male). Aortic pulse wave velocity (PWV; meters per second) was quantified from cardiac magnetic resonance. Resting CBF (milliliters per 100 g per minute) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudocontinuous arterial spin labeling magnetic resonance imaging. Linear regression models related aortic PWV to regional CBF, adjusting for age, race/ethnicity, education, Framingham Stroke Risk Profile (diabetes mellitus, smoking, left ventricular hypertrophy, prevalent cardiovascular disease, atrial fibrillation), hypertension, body mass index, apolipoprotein E4 ( APOE ?4) status, and regional tissue volume. Models were repeated testing PWV× APOE ?4 interactions. Sensitivity analyses excluded participants with prevalent cardiovascular disease and atrial fibrillation. RESULTS:Among participants with normal cognition, higher aortic PWV related to lower frontal lobe CBF (?=-0.43; P=0.04) and higher CVR in the whole brain (?=0.11; P=0.02), frontal lobes (?=0.12; P<0.05), temporal lobes (?=0.11; P=0.02), and occipital lobes (?=0.14; P=0.01). Among APOE ?4 carriers with normal cognition, findings were more pronounced with higher PWV relating to lower whole-brain CBF (?=-1.16; P=0.047), lower temporal lobe CBF (?=-1.81; P=0.004), and higher temporal lobe CVR (?=0.26; P=0.08), although the last result did not meet the a priori significance threshold. Results were similar in sensitivity models. Among participants with mild cognitive impairment, higher aortic PWV related to lower CBF in the occipital lobe (?=-0.70; P=0.02), but this finding was attenuated when participants with prevalent cardiovascular disease and atrial fibrillation were excluded. Among APOE ?4 carriers with mild cognitive impairment, findings were more pronounced with higher PWV relating to lower temporal lobe CBF (?=-1.20; P=0.02). CONCLUSIONS:Greater aortic stiffening relates to lower regional CBF and higher CVR in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer's disease. Central arterial stiffening may contribute to reductions in regional CBF despite preserved cerebrovascular reserve capacity.

Project description:Cerebral blood flow (CBF) becomes pulsatile in response to the pulsatile change in perfusion pressure that is regulated by cerebrovascular impedance. In this study, we aimed to characterize age-related differences in cerebrovascular impedance across the adult lifespan. Carotid artery pressure [(CAP), via applanation tonometry] and CBF velocity (CBFV) in the middle cerebral artery (via transcranial Doppler) were measured in 148 healthy adults (21-79 yr, 62% women). Cerebrovascular impedance was quantified using transfer function analysis. Coherence between changes in CBFV and CAP was >0.90 in the frequency range of 0.78-2.73 Hz, suggesting a linear dynamic relationship between these two variables. Impedance modulus at the first harmonics (0.78-1.56 Hz) of CBFV and CAP oscillations (Z1), reflecting mainly heart rate frequency, was 20% higher in the old (>64 yr, P = 0.002) and 13% higher in the middle-aged (45-64 yr, P = 0.08) than in young individuals (<45 yr). In addition, Z1 was 24% higher in men than in women (P < 0.001). Multiple linear regression analysis revealed that Z1 is negatively associated with systolic (β = -0.470), diastolic (β = -0.418), pulsatile (β = -0.374), and mean CBFV (β = -0.473; P < 0.001 for all) after adjustment for age, sex, and body mass index (BMI). These results suggest that older age and male sex are associated with higher cerebrovascular impedance than young individuals, which may contribute to brain hypoperfusion.NEW & NOTEWORTHY Impedance modulus at the first harmonics of cerebral blood flow velocity (CBFV) and carotid artery pressure oscillations (Z1) was higher in the old (>64 yr) than in the young individuals (<45 yr), and it was higher in men than in women. Z1 is negatively associated with CBFV after adjustment for age, sex, and body mass index. Increases in cerebrovascular impedance with age may buffer systemic arterial pressure fluctuations at the cost of increased brain hypoperfusion risk.

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

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

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