Sex moderations in the relationship between aortic stiffness, cognition, and cerebrovascular reactivity in healthy older adults.
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ABSTRACT:
SUBMITTER: Sabra D
PROVIDER: S-EPMC8478243 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC6394409 | biostudies-literature
Project description:BackgroundPerivascular spaces on brain magnetic resonance imaging (MRI) may indicate poor fluid drainage in the brain and have been associated with numerous neurological conditions. Cerebrovascular reactivity (CVR) is a marker of cerebrovascular function and represents the ability of cerebral blood vessels to regulate cerebral blood flow in response to vasodilatory or vasoconstrictive stimuli. We aimed to examine whether pathological widening of the perivascular space in older adults may be associated with deficits in CVR.MethodsIndependently living older adults free of dementia or clinical stroke were recruited from the community and underwent brain MRI. Pseudo-continuous arterial spin labeling MRI quantified whole brain cerebral perfusion at rest and during CVR to hypercapnia and hypocapnia induced by visually guided breathing exercises. Perivascular spaces were visually scored using existing scales.ResultsThirty-seven independently living older adults (mean age = 66.3 years; SD = 6.8; age range 55-84 years; 29.7% male) were included in the current analysis. Multiple linear regression analysis revealed a significant negative association between burden of perivascular spaces and global CVR to hypercapnia (B = -2.0, 95% CI (-3.6, -0.4), p = .015), adjusting for age and sex. Perivascular spaces were not related to CVR to hypocapnia.DiscussionPerivascular spaces are associated with deficits in cerebrovascular vasodilatory response, but not vasoconstrictive response. Enlargement of perivascular spaces could contribute to, or be influenced by, deficits in CVR. Additional longitudinal studies are warranted to improve our understanding of the relationship between cerebrovascular function and perivascular space enlargement.
| S-EPMC10033456 | biostudies-literature
Project description:OBJECTIVE:To test the hypothesis that aerobic exercise is associated with improvements in cognition and cerebrovascular regulation, we enrolled 206 healthy low-active middle-aged and older adults (mean ± SD age 65.9 ± 6.4 years) in a supervised 6-month aerobic exercise intervention and assessed them before and after the intervention. METHODS:The study is a quasi-experimental single group pre/postintervention study. Neuropsychological tests were used to assess cognition before and after the intervention. Transcranial Doppler ultrasound was used to measure cerebral blood flow velocity. Cerebrovascular regulation was assessed at rest, during euoxic hypercapnia, and in response to submaximal exercise. Multiple linear regression was used to examine the association between changes in cognition and changes in cerebrovascular function. RESULTS:The intervention was associated with improvements in some cognitive domains, cardiorespiratory fitness, and cerebrovascular regulation. Changes in executive functions were negatively associated with changes in cerebrovascular resistance index (CVRi) during submaximal exercise (β = -0.205, p = 0.013), while fluency improvements were positively associated with changes in CVRi during hypercapnia (β = 0.106, p = 0.03). CONCLUSION:The 6-month aerobic exercise intervention was associated with improvements in some cognitive domains and cerebrovascular regulation. Secondary analyses showed a novel association between changes in cognition and changes in cerebrovascular regulation during euoxic hypercapnia and in response to submaximal exercise.
| S-EPMC7357295 | biostudies-literature
Project description: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.
| S-EPMC6261448 | biostudies-literature
Project description:BackgroundElevated blood pressure (BP) variability is predictive of increased risk for stroke, cerebrovascular disease, and other vascular brain injuries, independent of traditionally studied average BP levels. However, no studies to date have evaluated whether BP variability is related to diminished cerebrovascular reactivity, which may represent an early marker of cerebrovascular dysfunction presaging vascular brain injury.MethodsThe present study investigated BP variability and cerebrovascular reactivity in a sample of 41 community-dwelling older adults (mean age 69.6 [SD 8.7] years) without a history of dementia or stroke. Short-term BP variability was determined from BP measurements collected continuously during a 5-minute resting period followed by cerebrovascular reactivity during 5-minute hypocapnia and hypercapnia challenge induced by visually guided breathing conditions. Cerebrovascular reactivity was quantified as percent change in cerebral perfusion by pseudo-continuous arterial spin labeling (pCASL)-MRI per unit change in end-tidal CO2.ResultsElevated systolic BP variability was related to lower whole brain cerebrovascular reactivity during hypocapnia (ß = -0.43 [95% CI -0.73, -0.12]; P = 0.008; adjusted R2 =.11) and hypercapnia (ß = -0.42 [95% CI -0.77, -0.06]; P = 0.02; adjusted R2 = 0.19).ConclusionsFindings add to prior work linking BP variability and cerebrovascular disease burden and suggest BP variability may also be related to prodromal markers of cerebrovascular dysfunction and disease, with potential therapeutic implications.
| S-EPMC9793985 | biostudies-literature
Project description:Although cerebrovascular factors are the second leading cause of cognitive impairment and dementia in elderly, the precise spatial and temporal trajectories of vascular decline in aging have not been fully characterized. With an advanced cerebrovascular reactivity (CVR) MRI technique that specifically informs vascular stiffness and dilatory ability of cerebral vessels, we present four-year longitudinal CVR data measured in 116 healthy individuals (20-88 years of age). Our data revealed a spatial heterogeneity in vascular decline in aging (p?=?0.003), in that temporal lobe showed the fastest rate of longitudinal CVR decline, followed by parietal and frontal lobes. The rate of CVR decline was also age-dependent. Middle age, not older age, manifested the fastest rate of longitudinal CVR decline (p?<?0.05). Longitudinal changes in CVR were associated with changes in processing speed (p?=?0.031) and episodic memory (p?=?0.022), but not with working memory or reasoning. The rate of longitudinal CVR change was not different between hypertensive and normotensive participants. However, cross-sectionally, individuals with hypertension revealed in a lower CVR compared to normotensive participants (p?=?0.016). These findings help elucidate age-related decline in brain hemodynamics and support CVR as a non-invasive biomarker in evaluating cerebrovascular conditions in elderly individuals.
| S-EPMC5949266 | biostudies-literature
Project description:A high sodium (Na+ ) meal impairs peripheral vascular function. In rodents, chronic high dietary Na+ impairs cerebral vascular function, and in humans, habitual high dietary Na+ is associated with increased stroke risk. However, the effects of acute high dietary Na+ on the cerebral vasculature in humans are unknown. The purpose of this study was to determine if acute high dietary Na+ impairs cerebrovascular reactivity in healthy adults. Thirty-seven participants (20F/17M; 25 ± 5 years; blood pressure [BP]: 107 ± 9/61 ± 6 mm Hg) participated in this randomized, cross-over study. Participants were given a low Na+ meal (LSM; 138 mg Na+ ) and a high Na+ meal (HSM; 1,495 mg Na+ ) separated by ≥ one week. Serum Na+ , beat-to-beat BP, middle cerebral artery velocity (transcranial Doppler), and end-tidal carbon dioxide (PET CO2 ) were measured pre- (baseline) and 60 min post-prandial. Cerebrovascular reactivity was assessed by determining the percent change in middle cerebral artery velocity to hypercapnia (via 8% CO2 , 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Peripheral vascular function was measured using brachial artery flow-mediated dilation (FMD). Changes in serum Na+ were greater following the HSM (HSM: Δ1.6 ± 1.2 mmol/L vs. LSM: Δ0.7 ± 1.2 mmol/L, p < .01). Cerebrovascular reactivity to hypercapnia (meal effect: p = .41) and to hypocapnia (meal effect: p = .65) were not affected by the HSM. Contrary with previous findings, FMD was not reduced following the HSM (meal effect: p = .74). These data suggest that a single high Na+ meal does not acutely impair cerebrovascular reactivity, and suggests that despite prior findings, a single high Na+ meal does not impair peripheral vascular function in healthy adults.
| S-EPMC7547584 | biostudies-literature
Project description:Aortic stiffness is associated with cognitive decline. Here, we examined the association between carotid-femoral pulse wave velocity and cognitive function and investigated whether cerebrovascular remodeling and parenchymal small vessel disease damage mediate the relation. Analyses were based on 1820 (60% women) participants in the Age, Gene/Environment Susceptibility-Reykjavik Study. Multivariable linear regression models adjusted for vascular and demographic confounders showed that higher carotid-femoral pulse wave velocity was related to lower memory score (standardized β: -0.071±0.023; P=0.002). Cerebrovascular resistance and white matter hyperintensities were each associated with carotid-femoral pulse wave velocity and memory (P<0.05). Together, cerebrovascular resistance and white matter hyperintensities (total indirect effect: -0.029; 95% CI, -0.043 to -0.017) attenuated the direct relation between carotid-femoral pulse wave velocity and memory (direct effect: -0.042; 95% CI, -0.087 to 0.003; P=0.07) and explained ≈41% of the observed effect. Our results suggest that in older adults, associations between aortic stiffness and memory are mediated by pathways that include cerebral microvascular remodeling and microvascular parenchymal damage.
| S-EPMC4679440 | biostudies-literature
Project description:In conventional neuroimaging, cerebrovascular reactivity (CVR) is quantified primarily using the blood-oxygenation level-dependent (BOLD) functional MRI (fMRI) signal, specifically, as the BOLD response to intravascular carbon dioxide (CO2) modulations, in units of [%?BOLD/mmHg]. While this method has achieved wide appeal and clinical translation, the tolerability of CO2-related tasks amongst patients and the elderly remains a challenge in more routine and large-scale applications. In this work, we propose an improved method to quantify CVR by exploiting intrinsic fluctuations in CO2 and corresponding changes in the resting-state BOLD signal (rs-qCVR). Our rs-qCVR approach requires simultaneous monitoring of PETCO2, cardiac pulsation and respiratory volume. In 16 healthy adults, we compare our quantitative CVR estimation technique to the prospective CO2-targeting based CVR quantification approach (qCVR, the "standard"). We also compare our rs-CVR to non-quantitative alternatives including the resting-state fluctuation amplitude (RSFA), amplitude of low-frequency fluctuation (ALFF) and global-signal regression. When all subjects were pooled, only RSFA and ALFF were significantly associated with qCVR. However, for characterizing regional CVR variations within each subject, only the PETCO2-based rs-qCVR measure is strongly associated with standard qCVR in 100% of the subjects (p?0.1). In contrast, for the more qualitative CVR measures, significant within-subject association with qCVR was only achieved in 50-70% of the subjects. Our work establishes the feasibility of extracting quantitative CVR maps using rs-fMRI, opening the possibility of mapping functional connectivity and qCVR simultaneously.
| S-EPMC5148619 | biostudies-literature
Project description:BACKGROUND:Aortic valve replacement (AVR) for calcific aortic stenosis is associated with high rates of perioperative stroke and silent cerebral infarcts on diffusion-weighted magnetic resonance imaging (MRI), but cognitive outcomes in elderly AVR patients compared with individuals with cardiac disease who do not undergo surgery are uncertain. METHODS:One hundred ninety AVR patients (mean age 76 ± 6 years) and 198 non-surgical participants with cardiovascular disease (mean age 74 ± 6 years) completed comprehensive cognitive testing at baseline (preoperatively) and 4 to 6 weeks and 1 year postoperatively. Surgical participants also completed perioperative stroke evaluations, including postoperative brain MRI. Mixed model analyses and reliable change scores examined cognitive outcomes. Stroke outcomes were evaluated in participants with and without postoperative cognitive dysfunction. RESULTS:From reliable change scores, only 12.4% of the surgical group demonstrated postoperative cognitive dysfunction at 4 to 6 weeks and 7.5% at 1 year. Although the surgical group had statistically significantly lower scores in working memory/inhibition 4 to 6 weeks after surgery, the groups did not differ at 1 year. In surgical participants, postoperative cognitive dysfunction was associated with a greater number (p < 0.01) and larger total volume (p < 0.01) of acute cerebral infarcts on MRI. CONCLUSIONS:In high-risk, aged participants undergoing surgical AVR for aortic stenosis, postoperative cognitive dysfunction was surprisingly limited and was resolved by 1 year in most. Postoperative cognitive dysfunction at 4 to 6 weeks was associated with more and larger acute cerebral infarcts.
| S-EPMC6382522 | biostudies-literature