Purpose: Previous studies report memory and functional connectivity of memory systems improve acutely after a single aerobic exercise session or with training, suggesting the acute effects of aerobic exercise may reflect initial changes that adapt over time. In this trial, for the first time, we test the proof-of-concept of whether the acute and training effects of aerobic exercise on working memory and brain network connectivity are related in the same participants.Methods: Cognitively normal older participants (N=34) were enrolled in a randomized clinical trial (NCT02453178). Participants completed fMRI resting state and a face working memory Nback task acutely after light and moderate intensity exercise and after a 12-week aerobic training intervention.Results: Functional connectivity did not change more after moderate compared with light intensity training. However, both training groups showed similar changes in cardiorespiratory fitness (maximal exercise oxygen uptake, VO 2 peak), limiting group-level comparisons. Acute effects of moderate intensity aerobic exercise on hippocampal-cortical connections in the default network predicted training enhancements in the same connections. Working memory also

Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk.

Muscle sympathetic neural activity (MSNA) influences the mechanical properties (i.e., vascular smooth muscle tone and stiffness) of peripheral arteries, but it remains controversial whether MSNA contributes to stiffness of central arteries such as the aorta and carotids. We examined whether elevated MSNA (age-related) would be independently associated with greater stiffness of central [carotid-femoral pulse wave velocity (PWV)] and peripheral (carotid-brachial PWV) arteries, in addition to lower carotid compliance coefficient (CC), in healthy men and women (n=88, age:19-73 years, 52%men). Also, we examined whether acute elevations in MSNA without increases in mean arterial pressure (MAP) using graded levels of lower body negative pressure (LBNP) would augment central and peripheral artery stiffness in young (YG, n=15, 60%men) and middle-age/older adults (MA/O, n=14, 43%men). Resting MSNA burst frequency (bursts•min −1) was significantly correlated with carotid-femoral PWV (R=0.44, P<0.001), carotid-brachial PWV (R=0.32, P=0.003), and carotid CC (R=0.28, P=0.01) after controlling for sex, MAP, heart rate, and waist-to-hip ratio (central obesity), but these correlations were abolished after further controlling for age (all P>0.05). In YG and MA/O adults, MSNA was elevated during LBNP (P<0.001) and produced significant increases in carotid-femoral PWV (YG:Δ+1.3±0.3 vs. MA/ O:Δ+1.0±0.3 m•s −1 , P=0.53) and carotid-brachial PWV (YG: Δ+0.7±0.3 vs. MA/O: Δ+0.7±0.5 m•s −1 , P=0.92), whereas carotid CC during LBNP was significantly reduced in YG but not MA/O (YG:Δ-0.04 ±0.01 vs. MA/O:Δ0.001±0.008 mm 2 •mmHg −1 , P<0.01). Collectively, these data demonstrate the influence of MSNA on central artery stiffness and its potential contribution to age-related increases in stiffness of both peripheral and central arteries.

Experiments were conducted to measure the extent of contractile changes during phasic activity of different motor units. Motor units of cat medial gastrocnemius were isolated and classified by their mechanical properties as fast and fatigable (FF), fast and fatigue resistant (FR), or slow (S). Single stimuli interpolated between stimulus trains of the fatigue test produced twitches whose shapes were measured at different times during this test. After 30 seconds of fatigue testing, twitch contraction times of 33% of FF units fell into the slow range, i.e., 5 of 17 units had become slower than the fastest slow units. Mean twitch contraction time of FF units increased by 11.8 msec, whereas that of S units decreased by 16.2 msec. We conclude that the mechanical properties of rested motor units change markedly with use and are a poor index for determining the contractile speed of active muscles.

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.

Aging is associated with increased carotid artery stiffness, a predictor of incident stroke, and reduced cognitive performance and brain white matter integrity (WMI) in humans. Therefore, we hypothesized that higher carotid stiffness/lower compliance would be independently associated with slower processing speed, higher working memory cost, and lower WMI in healthy middle-aged/older (MA/O) adults. Carotid β-stiffness ( < 0.001) was greater and compliance ( < 0.001) was lower in MA/O ( = 32; 64.4 ± 4.3 yr) vs. young ( = 19; 23.8 ± 2.9 yr) adults. MA/O adults demonstrated slower processing speed (27.4 ± 4.6 vs. 35.4 ± 5.0 U/60 s, < 0.001) and higher working memory cost (-15.4 ± 0.14 vs. -2.2 ± 0.05%, < 0.001) vs. young adults. Global WMI was lower in MA/O adults ( < 0.001) and regionally in the frontal lobe ( = 0.020) and genu ( = 0.009). In the entire cohort, multiple regression analysis that included education, sex, and body mass index, carotid β-stiffness index (B = -0.53 ± 0.15 U, = 0.001) and age group (B = -4.61 ± 1.7, = 0.012, adjusted = 0.4) predicted processing speed but not working memory cost or WMI. Among MA/O adults, higher β-stiffness (B = -0.60 ± 0.18, = 0.002) and lower compliance (B = 0.93 ± 0.26, = 0.002) were associated with slower processing speed but not working memory cost or WMI. These data suggest that greater carotid artery stiffness is independently and selectively associated with slower processing speed but not working memory among MA/O adults. Carotid artery stiffening may modulate reductions in processing speed earlier than working memory with healthy aging in humans. Previously, studies investigating the relation between large elastic artery stiffness, cognition, and brain structure have focused mainly on aortic stiffness in aged individuals with cardiovascular disease risk factors and other comorbidities. This study adds to the field by demonstrating that the age-related increases in carotid artery stiffness, but not aortic stiffness, is independently and selectively associated with slower processing speed but not working memory among middle-aged/older adults with low cardiovascular disease risk factor burden.

Background Women with a history of preeclampsia (hxPE) exhibit sustained arterial stiffness and elevated blood pressure (BP) postpartum. Aortic stiffness and 24-hour BP variability (BPV) are associated with age-related cognitive decline. Although hxPE is related to altered cognitive function, the association between aortic stiffness and BPV with cognitive performance in young women with hxPE has not been investigated. The objectives of this study were to 1) test whether cognitive performance is lower in young women with hxPE and 2) determine whether aortic stiffness and BPV are associated with cognitive performance independent of 24-hour average BP. Methods Women with hxPE (N=23) and healthy pregnancy controls (N=38) were enrolled 1-3 years postpartum. Cognitive performance was assessed in domains of memory, processing speed and executive function. 24-hour ambulatory BP monitoring and carotid-femoral pulse wave velocity (cfPWV) were used to measure BPV and aortic stiffness, respectively. Results Women with hxPE had slower processing speed (-0.56±0.17 versus 0.34±0.11 Z-score, P&lt;0.001) and lower executive function (-0.43±0.14 versus 0.31±0.10 Z-score, P=0.004) compared with controls independent of education, whereas memory did not differ. BPV and cfPWV (adjusted for BP) did not differ between women with hxPE and controls. Greater diastolic BPV was associated with lower executive function independent of 24-hour average BP and education in women with hxPE (r = -0.48, P=0.03) but not controls (r = 0.15, P=0.38). Conclusions Select cognitive functions are reduced postpartum in young women with a recent hxPE and linked with elevated 24-hour diastolic BPV.

Context Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-age and older (MA/O) men is associated with increased CVD risk. Objectives We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. Design Cross-sectional. Participants Fifty-eight healthy, non-smoking men categorized as young (N=20; age: 29±4 years, testosterone: 500±58 ng/dL), MA/O with higher testosterone (N=20; age: 60±6 years, testosterone: 512±115 ng/dL), and MA/O lower testosterone (N=18; age 59±8 years, testosterone: 269±48 ng/dL). Main Outcome Measures Brachial artery flow-mediated dilation (FMDBA) measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status [TAS] and oxidized low-density lipoprotein [LDL] cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. RESULTS: During saline, FMDBA was reduced in MA/O compared to young, regardless of testosterone status (P&lt;0.001). FMDBA was reduced in MA/O lower testosterone (3.7±2.0%) compared to MA/O higher testosterone (5.7±2.2%, p=0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3±1.6%, p=0.022) in MA/O lower testosterone but had no effect in young (P=0.992) or MA/O higher testosterone (P=0.250). FMDBA correlated with serum testosterone (r=0.45, p&lt;0.001), IL-6 (r=-0.41, P=0.002), and CRP (r=-0.28, P=0.041). Conclusions Healthy MA/O men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.