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Cerebral blood flow (CBF) decreases across the adult lifespan; however, more studies are needed to understand the underlying mechanisms. This study measured CBF and cerebrovascular resistance (CVR) using a multimodality approach in 185 healthy adults (21–80 years). Color-coded duplex ultrasonography and phase-contrast MRI were used to measure CBF, CBF velocity, and vessel diameters of the internal carotid (ICA) and vertebral arteries (VA). MRI arterial spin labeling was used to measure brain perfusion. Transcranial Doppler was used to measure CBF velocity at the middle cerebral artery. Structural MRI was used to measure brain volume. CBF was presented as total blood flow (mL/min) and normalized CBF (nCBF, mL/100g/min). Mean arterial pressure was measured to calculate CVR. Age was associated with decreased CBF by ∼3.5 mL/min/year and nCBF by ∼0.19 mL/100g/min/year across the methods. CVR increased by ∼0.011 mmHg/mL/100g/min/year. Blood flow velocities in ICA and VA decreased with age ranging from 0.07–0.15 cm/s/year, while the vessel diameters remained similar among age groups. These findings suggest that age-related decreases in CBF can be attributed mainly to decreases in blood flow velocity in the large cerebral arteries and that increased CVR likely reflects the presence of cerebral vasoconstrictions in the small cerebral arterioles and/or capillaries.

Older adults have higher cerebrovascular impedance than young individuals which may contribute to chronic brain hypoperfusion. Besides, middle-aged athletes exhibit lower cerebrovascular impedance than their sedentary peers. We examined whether aerobic exercise training (AET) reduces cerebrovascular impedance in sedentary older adults. We conducted a proof-of-concept trial that randomized 73 older adults to 1 yr of AET (

The impact of aerobic exercise training (AET) on cerebral blood flow (CBF) regulation remains inconclusive. This study investigated the effects of one-year progressive, moderate-to-vigorous AET on CBF, central arterial stiffness, and cognitive performance in cognitively normal older adults. Seventy-three older adults were randomly assigned to AET or stretching-and-toning (SAT, active control) intervention. CBF was measured with 2D duplex ultrasonography. Central arterial stiffness, measured by carotid β-stiffness index, was assessed with the ultrasonography and applanation tonometry. Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by CBF. A cognitive battery was administered with a focus on memory and executive function. Cardiorespiratory fitness was measured by peak oxygen consumption ([Formula: see text]O2peak). One-year AET increased [Formula: see text]O2peak and CBF and decreased CVR and carotid β-stiffness index. In the AET group, improved [Formula: see text]O2peak was correlated with increased CBF (r = 0.621, p = 0.001) and decreased CVR (r = −0.412, p = 0.037) and carotid β-stiffness index (r = −0.478, p = 0.011). Further, increased Woodcock-Johnson recall score was associated with decreased CVR (r = −0.483, p = 0.012) and carotid β-stiffness index (r = −0.498, p = 0.008) in AET group (not in SAT group). In conclusion, one-year progressive, moderate-to-vigorous aerobic exercise training increased CBF and decreased carotid arterial stiffness and CVR which were associated with improved memory function in cognitively normal older adults.

We examined whether the efficacy of steady-state cerebral autoregulation (CA) is reduced in older adults with amnestic mild cognitive impairment (aMCI), a prodromal stage of clinical Alzheimer disease (AD). Forty-two patients with aMCI and 24 cognitively normal older adults (NC) of similar age, sex, and education underwent stepwise decreases and increases in mean arterial pressure (MAP) induced by intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Changes in cerebral blood flow (CBF) were measured repeatedly in the internal carotid and vertebral artery. Linear mixed modeling, including random effects of both individual intercept and regression slope, was used to quantify the MAP-CBF relationship accounting for nonindependent, repeated CBF measures. Changes in end-tidal CO(2) (EtCO(2)) associated with changes in MAP were also included in the model to account for their effects on CBF. Marginal mean values of MAP were reduced by 13–14 mmHg during sodium nitroprusside and increased by 20–24 mmHg during phenylephrine infusion in both groups with similar doses of drug infusion. A steeper slope of changes in CBF in response to changes in MAP was observed in aMCI relative to NC, indicating reduced efficacy of CA (MAP × Group, P = 0.040). These findings suggest that cerebrovascular dysfunction may occur early in the development of AD. NEW & NOTEWORTHY Cerebral autoregulation is a fundamental regulatory mechanism to protect brain perfusion against changes in blood pressure that, if impaired, may contribute to the development of Alzheimer’s disease. Using a linear mixed model, we demonstrated that the efficacy of cerebral autoregulation, assessed during stepwise changes in arterial pressure, was reduced in individuals with amnestic mild cognitive impairment, a prodromal stage of Alzheimer’s disease. These findings support the hypothesis that cerebrovascular dysfunction may be an important underlying pathophysiological mechanism for the development of clinical Alzheimer’s disease.

Background: Central arterial stiffness and brain hypoperfusion are emerging risk factors of Alzheimer’s disease (AD). Aerobic exercise training (AET) may improve central arterial stiffness and brain perfusion. Objective: To investigate the effects of AET on central arterial stiffness and cerebral blood flow (CBF) in patients with amnestic mild cognitive impairment (MCI), a prodromal stage of AD. Methods: This is a proof-of-concept, randomized controlled trial that assigned 70 amnestic MCI patients into a 12-month program of moderate-to-vigorous AET or stretching-and-toning (SAT) intervention. Carotid β-stiffness index and CBF were measured by color-coded duplex ultrasonography and applanation tonometry. Total CBF was measured as the sum of CBF from both the internal carotid and vertebral arteries, and divided by total brain tissue mass assessed with MRI to obtain normalized CBF (nCBF). Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Changes in cardiorespiratory fitness were measured by peak oxygen uptake (VO2peak). Results: Total 48 patients (29 in SAT and 19 in AET) were completed one-year training. AET improved VO2peak, decreased carotid β-stiffness index and CBF pulsatility, and increased nCBF. Changes in VO2peak were associated positively with changes in nCBF (r = 0.388, p = 0.034) and negatively with carotid β-stiffness index (r = –0.418, p = 0.007) and CBF pulsatility (r = –0.400, p = 0.014). Decreases in carotid β-stiffness were associated with increases in cerebral perfusion (r = –0.494, p = 0.003). AET effects on cognitive performance were minimal compared with SAT. Conclusion: AET reduced central arterial stiffness and increased CBF which may precede its effects on neurocognitive function in patients with MCI.

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 (Z(1)), 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 (64 yr) than in the young individuals (

Background Increased risk for the future development of Alzheimer disease begins as early as midlife. Algorithm-based scores, such as the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) dementia risk score, and the Framingham general cardiovascular disease (CVD) risk score, have been used to determine future risk for the development of cognitive decline and dementia. We evaluated the association between neuroimaging and cognitive measures with the 2 risk scores in middle-aged, cognitively intact adults (49±6 y). Methods In a cohort of 132 participants collected in 2014, magnetic resonance imaging was used to determine measures of cortical thickness in a priori regions of interest and a neuropsychological battery to assess memory and executive function. Results The CAIDE dementia risk score was significantly and inversely associated with the cortical thickness of the parahippocampal (r=-0.266; P=0.002) and superior frontal gyrus (r=-0.261; P=0.002) despite a considerable percentage of individuals (99.3%) at low risk for CVD. There was a significant negative association between CAIDE and memory (r=-0.251; P=0.003). Framingham general CVD score was not associated with brain structure or cognitive function. Conclusions These results indicate that the CAIDE dementia risk score is associated with cortical thickness and cognitive function at midlife in a low-risk population. These data provide insight into subclinical structural and functional changes occurring during midlife associated with future risk for the development of dementia.

Background: Central arterial stiffness is an emerging risk factor of age-related cognitive impairment and Alzheimer’s disease (AD). However, the underlying pathophysiological mechanisms remain unclear. Objective: We tested the hypothesis that carotid arterial stiffness is associated with reduced cerebral blood flow (CBF) and increased cerebrovascular resistance (CVR) in patients with amnestic mild cognitive impairment (MCI), a prodromal stage of AD. Methods: Fifty-four patients with amnestic MCI and 24 cognitively normal subjects (CN) of similar age and sex to MCI patients underwent measurements of CBF and carotid β-stiffness index using ultrasonography and applanation tonometry. Total CBF was measured as the sum of CBF from both the internal carotid and vertebral arteries, and divided by total brain tissue mass (assessed with MRI) to obtain normalized CBF (nCBF). Results: Relative to CN subjects, MCI patients showed lower nCBF (53.3 ± 3.2 vs 50.4±3.4 mL/100 g/min, P < 0.001) and higher CVR (0.143 ± 0.019 vs 0.156 ± 0.023 mmHg/mL/min, P < 0.015). Multiple linear regression analysis showed that nCBF was negatively associated with carotid β-stiffness index (B = -0.822, P < 0.001); CVR was positively associated with carotid systolic pressure (B = 0.001, P < 0.001) after adjustment for age, sex, body mass index, and MCI status. Conclusion: These findings suggest that carotid artery stiffening may contribute at least in part to the reduced nCBF and increased CVR in patients with MCI associated with augmented carotid arterial pulsatility.

BACKGROUND Vascular dysfunction has been implicated in the onset and progression of Alzheimer's disease (AD), yet the relationship of arterial stiffening with brain amyloid-β (Aβ) burden in at risk patients is unclear. OBJECTIVE We aimed to determine the relationship of aortic and carotid arterial stiffening with Aβ burden in patients with amnestic mild cognitive impairment (aMCI), a proposed transitional stage between normal aging and AD. METHODS Thirty-two older adults with aMCI underwent 18Florbetapir PET amyloid imaging to ascertain Aβ burden via standardized uptake value ratio (SUVR). Carotid-femoral pulse wave velocity (cfPWV), which reflects aortic stiffness, and carotid β stiffness index and distensibility, which reflect local cerebral arterial stiffness, thus having direct impact on the cerebral circulation, were measured using applanation tonometry and ultrasonography. RESULTS Region-of-interest based analysis showed that precuneus and mean cortex Aβ SUVR were correlated positively with carotid β stiffness index and negatively with carotid distensibility after adjusting for age, sex, mean arterial pressure (MAP), pulse pressure (PP), and APOE4 status. Whole-brain voxel-wise analysis showed that Aβ SUVR was positively correlated with carotid β stiffness index, and negatively with carotid distensibility at the precuneus/cingulate gyrus after multiple comparison correction. cfPWV was not correlated with Aβ SUVR. CONCLUSIONS Carotid rather than aortic stiffening was independently associated with brain Aβ burden in patients with aMCI after adjusting for age, sex, MAP, PP, and APOE4 status. These findings provide evidence that arterial stiffening, particularly carotid artery stiffening, may contribute to AD pathology in patients with aMCI.

Sex differences in cerebral white matter (WM) aging have been debated extensively over the past two decades without unequivocal resolution. We aimed to determine if the effects of age and arterial stiffness on white matter (WM) microstructure differ between sexes. Artery elasticity via carotid artery compliance (CAC) and WM diffusion metrics via diffusion tensor image derived fractional anisotropy (FA) and mean diffusivity (MD) were measured in 155 (87 females) middle-aged (40–62 years) adults. Males demonstrated poorer water diffusion metrics in WM than women in the corpus callosum body, cingulum, and cingulum (hippocampal). Age and CAC had greater effects on WM water diffusion in males than females in midlife independent of education and cardiovascular risk factors. Sex moderated age (cingulum FA, cingulum (hippocampal) MD, and uncinate MD, all p

Intact memory and problem solving are key to functional independence and quality of life in older age. Considering the unprecedented demographic shift toward a greater number of older adults than children in the United States in the next few decades, it is critically important for older adults to maintain work productivity and functional independence for as long as possible. Implementing early interventions focused on modifiable risk factors for cognitive decline at midlife is a strategy with the highest chance of success at present, bearing in mind the current lack of dementia cures. We present a selective, narrative review of evidence linking nutrition, body composition, vascular health, and brain function in midlife to highlight the phenotypic heterogeneity of obesity-related brain vulnerability and to endorse the development of individually tailored lifestyle modification plans for primary prevention of cognitive decline.

Objective The purpose of this study was to examine the relationship between dynapenia and metabolic risk factors in obese and nonobese older adults. Methods A total of 1453 men and women (age ≥70 years) from the Lifestyle Interventions and Independence for Elders (LIFE) Study were categorized as (1) nondynapenic/nonobese (NDYN-NO), (2) dynapenic/nonobese (DYN-NO), (3) nondynapenic/obese (NDYN-O), or (4) dynapenic/obese (DYN-O), based on muscle strength (Foundation for the National Institute of Health criteria) and body mass index. Dependent variables were blood lipids, fasting glucose, blood pressure, presence of at least 3 metabolic syndrome (MetS) criteria, and other chronic conditions. Results A significantly higher likelihood of having abdominal obesity criteria in NDYN-NO compared with DYN-NO groups (55.6 vs 45.1%, P ≤ .01) was observed. Waist circumference also was significantly higher in obese groups (DYN-O = 114.0 ± 12.9 and NDYN-O = 111.2 ± 13.1) than in nonobese (NDYN-NO = 93.1 ± 10.7 and DYN-NO = 92.2 ± 11.2, P ≤ .01); and higher in NDYN-O compared with DYN-O ( P = .008). Additionally, NDYN-O demonstrated higher diastolic blood pressure compared with DYN-O (70.9 ± 10.1 vs 67.7 ± 9.7, P ≤ .001). No significant differences were found across dynapenia and obesity status for all other metabolic components ( P > .05). The odds of having MetS or its individual components were similar in obese and nonobese, combined or not with dynapenia (nonsignificant odds ratio [95% confidence interval]). Conclusion Nonobese dynapenic older adults had fewer metabolic disease risk factors than nonobese and nondynapenic older adults. Moreover, among obese older adults, dynapenia was associated with lower risk of meeting MetS criteria for waist circumference and diastolic blood pressure. Additionally, the presence of dynapenia did not increase cardiometabolic disease risk in either obese or nonobese older adults.

Summary Objective Growing prevalence of neuropathology and cognitive impairment are emerging consequences of the obesity epidemic. Adiposity indices used in examining the relationships between obesity, neuropathology, and cognition vary substantially in the literature leading to incongruent findings. Our aim was to determine the anthropometric measures most strongly associated with early white matter disease and cognitive function at midlife. Method Multiple adiposity indices were measured in 126 adults aged 40–62 who also completed a magnetic resonance imaging (MRI) scan to quantify white matter disease and a cognitive test battery. Anthropometric indices of obesity were compared to image-based estimates of visceral adipose tissue with dual-energy X-ray absorptiometry (DEXA) as predictors of current white matter disease and cognitive function. We also explored sex as a potential moderator of these relationships. Results Waist circumference (WC) was most strongly correlated with DEXA estimates of visceral adipose tissue ( r =0.871, p β =0.231, p =0.034), percent body fat ( β =0.230, p =0.045), and VAT ( β =0.247, p =0.027) significantly predicted subclinical white matter hyperintensities in the absence of cognitive impairment after accounting for age, sex, years of education, and cardiovascular risk factors. Sex was not a significant moderator of any of the observed relationships. Conclusions Of the anthropometric indices used in this study, WC, BF, and VAT successfully predicted subclinical white matter disease in cognitively normal adults at midlife. Increasing VAT may independently insidiously affect cerebral white matter prior to detectable cognitive changes, necessitating early intervention.

There is a well-conceived notion that rate of recovery from strenuous exercise gets slower with age. However, it is unclear whether older adults who exercise habitually demonstrate slower rates of recovery. We determined whether older adults who are physically active demonstrate slower rates of recovery from unaccustomed strenuous exercise compared with younger peers. Healthy young sedentary (n=10, 28±2 years), young endurance-trained (n=15, 27±2 years), and older endurance-trained (n=14, 58±2 years) men and women were studied. Participants performed 45 min of downhill running at 65% of their maximal oxygen consumption. Visual analog pain scores of muscle groups increased at 24, 48, and 72 h in all three groups (p

BACKGROUND: Metabolic syndrome (MetS) adversely affects the vasculature and cerebral white matter (CWM) integrity. Arterial stiffening has been associated with diminished CWM integrity. Physical activity (PA) can ameliorate components of MetS and subsequently affect arterial stiffening and CWM integrity. Our aim was to determine the role of PA on mitigating the adverse influence of MetS on arterial stiffness and CWM integrity. METHODS: In a cross-sectional study design, sixty-six middle-aged adults (40–62 years) composed of 18 sedentary MetS (Sed MetS), 21 physically active MetS (Active MetS), and 27 healthy individuals absent of MetS risk factors were studied. Carotid artery stiffness was assessed via simultaneous ultrasound and tonometry. CWM integrity was measured using diffusion tensor imaging (DTI) through metrics of fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: Carotid β-stiffness index in Active MetS was lower than Sed MetS but was not different from Healthy controls (6.6±1.5, 7.7±2.1, and 5.6±1.6 au, p=0.001). CWM integrity was significantly greater in Active MetS subjects compared to Sed MetS subjects but statistically equal to Healthy controls in the anterior limb of the internal capsule, and splenium of the corpus callosum, uncinate fasciculus, and superior corona radiata (all p

Objectives Excessive visceral fat is associated with greater metabolic fluctuation and increased risk for dementia in older adults. The aim of the current study is to directly determine the impact of central adiposity on brain structure at midlife by examining the thickness of the cerebral cortex. Methods High-resolution magnetization-prepared rapid acquisition gradient-echo images were obtained from 103 participants aged 40 to 60 years (mean [standard deviation] = 49.63 [6.47] years) on a 3-T Siemens Skyra scanner. Visceral fat was measured using dual-energy x-ray absorptiometry. Results Individuals with higher visceral fat mass and volume had significantly thicker cortex in the right posterior cingulate gyrus (β = 0.29 [p = .019] and β = 0.31 [p = .011], respectively), controlling for age, systolic blood pressure, total cholesterol level, and blood glucose level. Conclusions Visceral fat was significantly associated with thicker cortex in the posterior cingulate gyrus. Although future studies are necessary, these results indicate that central adiposity is associated with significant metabolic changes that impinge upon the central nervous system in middle age.

Background and aims: The relation between adiposity and arterial stiffness remains controversial. We determined whether abdominal and visceral adipose tissue may be a better predictor of arterial stiffness than general obesity in middle-aged adults. Methods and results: A total of 146 participants (76 men, 70 women; 50 years) were studied. The automatic vascular screening device (Omron VP-1000plus) was used to measure blood pressure simultaneously in the arms and ankles and to determine arterial stiffness by pulse wave velocity (PWV). Using multiple linear regressions, the relations between indicators of obesity and arterial stiffness were examined after adjustment for confounders. Both carotid-femoral PWV and brachial-ankle PWV were significantly associated with BMI (both P < 0.05) but not with body fat percentage. Measures of abdominal obesity, including waist circumference and visceral fat mass (via DXA), were strongly associated with PWV and remained positively associated with arterial stiffness after adjustment for age and gender. Cardiovascular fitness as assessed by maximal oxygen consumption was related to body fat percentage but not with visceral fat. More favorable cardiovascular health profile was associated with both lower visceral fat mass and PWV (both P < 0.001). Conclusion: Abdominal obesity and visceral fat are associated with large artery stiffness. These findings support the importance of adiposity measures as a risk factor for arterial stiffening in middle-aged adults.

Hispanics are at increased risk of acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health to measures of cerebral gray matter integrity, 60 middle-aged Hispanic and non-Hispanic Caucasian participants were matched across age, gender, years of education, and mental status. Arterial stiffness was characterized via β-stiffness index and carotid-femoral pulse-wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non-Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (p=0.04) with concurrently lower language (p=0.02), memory (p=0.03), and attention-executive functioning (p=0.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics.

Purpose: Ischemic preconditioning (IPC) has been used to protect myocardial cells against ischemia- reperfusion injury and is recently utilized for improving exercise performance. It is unknown whether remote IPC (RIPC) to tissues not involved in exercise can induce similar exercise improvements and what "dose" of IPC is necessary to induce exercise performance benefits. This study determined if unilateral and bilateral upper limb RIPC improves lower body anaerobic power output. Methods: Using two randomized, sham-controlled, crossover study designs, we studied 43 recreationally-active adults. For study 1, unilateral RIPC was used, while for study 2, the ischemic stimuli was increased to bilateral occlusion. After either the RIPC or sham control treatment, subjects completed four 30 s Wingate anaerobic tests on a Monark cycle ergometer with 2 min passive rest between trials. Results: In the unilateral occlusion trial, peak power, mean power, and fatigue index were not different between the two conditions at every Wingate test. In the bilateral occlusion trial, mean power was greater in the RIPC condition during the first Wingate test compared with the sham control (both p

Objective: We determined if transcranial color-coded Doppler derived hemodynamics are associated with MRI-based cerebral blood flow (CBF) in regions clinically important to dementia in healthy middle-aged adults. Approach: In 30 subjects (18m/12f; age = 52 ± 1 years), blood flow velocity (BFV) and cerebrovascular conductance (CVC) were measured with transcranial color-coded Doppler (TCCD) at the middle cerebral artery (MCA) and cerebral blood flow (CBF) was assessed with arterial spin labeled perfusion MRI. Main results: BFV and CVC were associated with hippocampus (r = 0.58 and r = 0.61, both p < 0.01) and occipitoparietal (r = 0.50 and r = 0.58, both p < 0.01) CBF. CVC was further associated with posterior cingulate CBF (r = 0.58 p < 0.01). Independent of age and sex, BFV and CVC were associated with hippocampus (r = 0.59 and r = 0.55, both p < 0.003) and occipitoparietal (r = 0.50 and r = 0.57, both p < 0.01) CBF. CVC was independently associated with posterior cingulate CBF (r = 0.38, p = 0.049). Significance: TCCD-measured BFV and CVC of the MCA are indicators of cerebral perfusion to clinically valuable brain regions in healthy middle-aged adults. TCCD may not be a good indicator of blood flow to cerebral white matter.

BACKGROUND Individuals with metabolic syndrome (MetS) exhibit reduced cerebral blood flow. The mechanisms of this reduction remain unknown but arterial stiffening has been implicated as a contributor. We determined if MetS was associated with reduced cerebral blood flow at midlife, and if so, whether arterial stiffness was responsible for mediating their relation. METHODS Middle-aged (40–60 years) community dwelling adults (n = 83) were studied. MetS score was calculated for each subject. Middle cerebral artery hemodynamics was measured using transcranial Doppler ultrasound. Indices of aortic, systemic, and carotid artery stiffness were derived. RESULTS Subjects had subclinical MetS pathology (MetS score = 19.8 ± 10.4) that was inversely associated with cerebrovascular conductance (CVC: r = −0.261, P = 0.02). Carotid-femoral pulse wave velocity (cfPWV) (r = −0.188, P = 0.09), brachial-ankle pulse wave velocity (baPWV) (r = −0.161, P = 0.15), and carotid artery distensibility (r = −0.10, P = 0.37) abrogated the direct association of MetS score and CVC, demonstrating full mediation. Nonparametric bootstrapping further indicated significant indirect effects of cfPWV, baPWV, and carotid artery distensibility, fully mediating reductions of CVC exerted from sublcinical MetS. Carotid artery distensibility demonstrated the greatest effect on CVC (B = −0.0019, SE = 0.0012, −0.0050 to −0.0002 95% confidence interval). CONCLUSIONS Arterial stiffness, particularly the stiffness of the carotid artery, mediated reductions in CVC related to MetS.

The aging U.S. population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion-tensor imaging in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N = 168) between the ages of 40-62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full-tensor, high-dimension normalization, and tract-based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL-cholesterol. Post hoc analysis revealed that greater waist circumference was associated with lower axial diffusivity, indicating lower parallel diffusion; lower radial diffusivity, indicating lower perpendicular diffusion; and lower mean diffusivity, indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain. Hum Brain Mapp 38:3337-3344, 2017. © 2017 Wiley Periodicals, Inc.

Objective: Arterial stiffness is associated with cognitive decline and may serve as an early marker of brain vulnerability. In search of potential early intervention targets, the present study examined the neural correlates of working memory in relation to arterial stiffness in middle-aged, cognitively healthy adults. Methods: Twenty-eight adults, ages 40- 60 years, completed a 2-Back verbal working memory task during fMRI. Arterial stiffness was measured using the 􀀁- stiffness index via simultaneous ultrasound and applanation tonometry on the carotid artery. Mean task-related activation intensity was determined for 12 a priori regions of interest (ROI). Statistical analyses included partial correlations, controlling for hypertension status and antihypertensive medication. Results: Arterial stiffness was correlated negatively with task-related activation in 3 ROIs: left precentral gyrus/BA 6 (r=-0.64, p Conclusions: Greater arterial stiffness was significantly associated with decreased task-related brain activation during a verbal working memory task, possibly reflecting increased vulnerability for cognitive impairment. Arterial stiffness should be investigated further as an early marker of cognitive risk and a potential target for early intervention.

Background Excessive adipose tissue, particularly with a centralized distribution, propagates hormonal and metabolic disturbance. The detrimental effects of adiposity may extend beyond the periphery and target the central nervous system, increasing vulnerability to cognitive decline. The aim of current study was to determine how central adiposity impacts the brain at midlife by examining the blood oxygen level-dependent (BOLD) response to a challenging cognitive task. Methods Seventy-three adults, aged 40-60 years, completed a 2-Back verbal working memory task during functional magnetic resonance imaging (fMRI). Central adiposity was assessed with waist circumference. The association between waist circumference and task-related activation in a priori regions of interest was modeled using bootstrapping regression models corrected for multiple-comparisons. Results Larger waist circumference was associated with diminished working-memory-related BOLD response in the right superior frontal gyrus (β=-0.008, p=0.001, 95% CI: -0.012 - -0.004) and left middle frontal gyrus (β=-0.009, p=0.002, 95% CI: -0.015 - -0.003), statistically adjusting for age, sex, systolic blood pressure, and total cholesterol. Reduced task-related activation in the right superior frontal gyrus (r=-0.369, p=0.002) and left middle frontal gyrus (r=-0.266, p=0.025) were related to slower reaction time on the task, controlling for age and education. Conclusions Larger waist circumference predicted alterations in the BOLD response that coupled with decrements in task performance. While future studies are necessary, the results suggest that similar to its role in the periphery, central adiposity may be a robust predictor of metabolic and hormonal alterations that impinge upon central nervous system functioning.

BACKGROUND: Excessive adipose tissue, particularly with a central distribution, consists of visceral fat, which is metabolically active and could impinge upon central nervous system functioning. The aim of the current study was to examine levels of visceral adiposity in relation to key cerebral metabolite ratios localized in the occipitoparietal grey matter. METHODS: Seventy-three adults, aged between 40–60 years, underwent structural magnetic resonance imaging and single voxel (1)H Magnetic Resonance Spectroscopy ((1)H MRS). Visceral fat was assessed using Dual Energy X Ray Absorptiometry (DXA). RESULTS: Individuals with higher visceral fat mass and volume had significantly lower ratios of N-acetyl-aspartate to total creatine (phosphocreatine+creatine, PCr+Cr) (NAA/PCr+Cr) (β = −0.29, p=0.03, β = −0.28, p=0.04). They also had significantly higher ratios of myo-inositol to total creatine (mI/PCr+Cr ) (β = 0.36, p=0.01, β = 0.36, p=0.01). Visceral fat mass and volume were not significantly related to ratios of glutamate to total creatine (Glu/PCr+Cr). CONCLUSIONS: Visceral fat was associated with lower NAA/PCr+Cr ratio and higher mI/PCr+Cr ratios. While future studies are necessary, these results indicate central adiposity is associated with metabolic changes that could impinge upon the central nervous system in middle age.

Objective.Arthritis and its associated joint pain act as significant barriers for adults attempting to perform land-based physical activity. Swimming can be an ideal form of exercise for patients with arthritis. Yet there is no information on the efficacy of regular swimming exercise involving patients with arthritis. The effect of a swimming exercise intervention on joint pain, stiffness, and physical function was evaluated in patients with osteoarthritis (OA).Methods.Using a randomized study design, 48 sedentary middle-aged and older adults with OA underwent 3 months of either swimming or cycling exercise training. Supervised exercise training was performed for 45 min/day, 3 days/week at 60–70% heart rate reserve for 12 weeks. The Western Ontario and McMaster Universities Arthritis Index was used to measure joint pain, stiffness, and physical limitation.Results.After the exercise interventions, there were significant reductions in joint pain, stiffness, and physical limitation accompanied by increases in quality of life in both groups (all p < 0.05). Functional capacity as assessed by maximal handgrip strength, isokinetic knee extension and flexion power (15–30% increases), and the distance covered in the 6-min walk test increased (all p < 0.05) in both exercise groups. No differences were observed in the magnitude of improvements between swimming and cycling training.Conclusion.Regular swimming exercise reduced joint pain and stiffness associated with OA and improved muscle strength and functional capacity in middle-aged and older adults with OA. Additionally, the benefits of swimming exercise were similar to the more frequently prescribed land-based cycling training. Trial registration: clinicaltrials.govNCT01836380.

Background: Hispanics are at least 1.5 times more likely at any age past 55 years to have mild cognitive impairment and manifest dementia symptoms 7 years earlier than non-Hispanic Caucasians. Regional cerebral hypoperfusion has been implicated as an initial event in the pathogenesis of dementia. Aim: To compare cerebral perfusion in brain regions known to be susceptible to vascular related hypoperfusion in Hispanic and non-Hispanic Caucasian adults. Methods: Apparently healthy middle-aged Hispanic (n=16) and non-Hispanic Caucasian (n=16) subjects were matched across age, gender, years of education, and cognitive status. Arterial spin labeled perfusion magnetic resonance imaging (ASL-MRI) estimated cerebral blood flow in a priori brain regions of interest. Results: Mean cerebral perfusion was significantly lower in the Hispanic cohort than matched non-Hispanic Caucasian peers in the right (38±32 vs. 76±22 ml/100 g/min, p=0.005) and left centrum semiovale (39±32 vs. 72±31 ml/100 g/min, p=0.047). These differences remained significant even after controlling for blood pressure (p

This 3-year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of life. Our findings reinforce the importance of preserving muscle health with advancing age. INTRODUCTION: The age-associated loss of skeletal muscle quantity and function are critical determinants of independent physical functioning in later life. Longitudinal studies investigating how decrements in muscle components of sarcopenia impact fear of falling (FoF) and quality of life (QoL) in older adults are lacking. METHODS: Twenty-six healthy older subjects (age, 74.1 +/- 3.7; Short Physical Performance Battery (SPPB) score >/=10) and 22 mobility-limited older subjects (age, 77.2 +/- 4.4; SPPB score

Evan P Pasha1, Andreana P Haley2 and Hirofumi Tanaka1* 1Cardiovascular Aging Research Laboratory, Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, TX, USA 2Department of Psychology, The University of Texas at Austin, Austin, TX, USA *Corresponding author: Hirofumi Tanaka, Ph.D, Department of Kinesiology and Health Education, 2109 San Jacinto Blvd, University of Texas at Austin, Austin, TX 78712, USA, Tel: 512-232-4801; Fax: 512-471-0946; E-mail: htanaka@austin.utexas.edu

This longitudinal study examined the major physiological mechanisms that determine the age-related loss of lower extremity muscle power in two distinct groups of older humans. We hypothesized that after ~3 years of follow-up, mobility-limited older adults (mean age: 77.2 ± 4, n = 22, 12 females) would have significantly greater reductions in leg extensor muscle power compared to healthy older adults (74.1 ± 4, n = 26, 12 females).Mid-thigh muscle size and composition were assessed using computed tomography. Neuromuscular activation was quantified using surface electromyography and vastus lateralis single muscle fibers were studied to evaluate intrinsic muscle contractile properties.At follow-up, the overall magnitude of muscle power loss was similar between groups: mobility-limited: -8.5 % vs. healthy older: -8.8 %, P0.8. Mobility-limited elders had significant reductions in muscle size (-3.8 %, P0.01) and strength (-5.9 %, P0.02), however, these parameters were preserved in healthy older (P ≥ 0.7). Neuromuscular activation declined significantly within healthy older, but not in mobility-limited participants. Within both groups, the cross-sectional areas of type I and IIA muscle fibers were preserved while substantial increases in single fiber peak force (30 %), peak power (200 %) and unloaded shortening velocity (50 %) were elicited at follow-up.Different physiological mechanisms contribute to the loss of lower extremity muscle power in healthy older and mobility-limited older adults. Neuromuscular changes may be the critical early determinant of muscle power deficits with aging. In response to major whole muscle decrements, major compensatory mechanisms occur within the contractile properties of surviving single muscle fibers in an attempt to restore overall muscle power and function with advancing age.

One of the most fundamental adaptive physiological events is the response of skeletal muscle to high-intensity resistance exercise, resulting in increased protein synthesis and ultimately larger muscle mass. However, muscle growth in response to contraction is attenuated in older humans. Impaired contractile-induced muscle growth may contribute to sarcopenia: the age-associated loss of muscle mass and function that is manifested by loss of strength, contractile capacity, and endurance. We hypothesized that the storage of ceramide would be increased in older individuals and this would be associated with increases in NFκB signaling and a decreased anabolic response to exercise. To test this hypothesis we measured ceramides at rest and anabolic and NFκB signaling after an acute bout of high-intensity resistance exercise in young and older males. Using lipidomics analysis we show there was a 156% increase in the accumulation of C16:0-ceramide ( P < 0.05) and a 30% increase in C20:0-ceramide ( P < 0.05) in skeletal muscle with aging, although there was no observable difference in total ceramide. C16:0-ceramide content was negatively correlated ( P = 0.008) with lower leg lean mass. Aging was associated with a ∼60% increase in the phosphorylation of the proinflammatory transcription factor NFκB in the total and nuclear cell fractions ( P < 0.05). Furthermore, there was an attenuated activation of anabolic signaling molecules such as Akt ( P < 0.05), FOXO1 ( P < 0.05), and S6K1 ( P < 0.05) after an acute bout of high-intensity resistance exercise in older males. We conclude that ceramide may have a significant role in the attenuation of contractile-induced skeletal muscle adaptations and atrophy that is observed with aging.