Central arterial stiffness, brain white matter hyperintensity and total brain volume across the adult lifespan.

OBJECTIVES: Mounting evidence suggests that central arterial stiffening is associated with brain ageing in older adults. The purpose of this study was to determine the associations of age with carotid arterial stiffness and carotid-femoral pulse wave velocity (cfPWV), both measurements of central arterial stiffness, the relationship between age-related arterial stiffness, brain white matter hyperintensity (WMH) and total brain volume (TBV), and whether effects of central arterial stiffness on WMH volume and TBV are mediated by pulsatile cerebral blood flow (CBF). METHODS: One hundred and seventy-eight healthy adults (21-80 years) underwent measurements of central arterial stiffness using tonometry and ultrasonography, WMH and TBV via MRI, and pulsatile CBF at the middle cerebral artery via transcranial Doppler. RESULTS: Advanced age was associated with increases in both carotid arterial stiffness and cfPWV, increases in WMH volume and decreases in TBV (all P  < 0.01). Multiple linear regression analysis showed that carotid ß-stiffness was positively associated with WMH volume (B = 0.015, P  = 0.017) and cfPWV negatively with TBV (B = -0.558, P  < 0.001) after adjustment for age, sex and arterial pressure. Pulsatile CBF mediates the associations between carotid ß-stiffness and WMH (95% confidence interval: 0.0001-0.0079). CONCLUSION: These findings suggest that age-related central arterial stiffness is associated with increased WMH volume and decreased TBV, which is likely mediated by increased arterial pulsation.

Cerebral blood flow and cerebrovascular resistance across the adult lifespan: A multimodality approach.

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.

One-year aerobic exercise increases cerebral blood flow in cognitively normal older adults.

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 ß-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 (V˙O2peak). One-year AET increased V˙O2peak and CBF and decreased CVR and carotid ß-stiffness index. In the AET group, improved V˙O2peak was correlated with increased CBF (r = 0.621, p = 0.001) and decreased CVR (r = -0.412, p = 0.037) and carotid ß-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 ß-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.

Arterial Aging and Cerebrovascular Function: Impact of Aerobic Exercise Training in Older Adults.

Advanced age is the major risk factor for dementia including Alzheimer's disease. The clinical effects of recently developed anti-amyloid therapy for Alzheimer's disease were modest and the long-term outcome is unknown. Thus, an in-depth understanding of the mechanisms of brain aging is essential to develop preventive interventions to maintain cognitive health in late life. Mounting evidence suggests that arterial aging manifested as increases in central arterial stiffness is associated closely with cerebrovascular dysfunction and brain aging while improvement of cerebrovascular function with aerobic exercise training contributes to brain health in older adults. We summarized evidence in this brief review that 1) increases in central arterial stiffness and arterial pulsation with age are associated with increases in cerebrovascular resistance, reduction in cerebral blood flow, and cerebrovascular dysfunction, 2) aerobic exercise training improves cerebral blood flow by modifying arterial aging as indicated by reductions in cerebrovascular resistance, central arterial stiffness, arterial pulsation, and improvement in cerebrovascular function, and 3) improvement in cerebral blood flow and cerebrovascular function with aerobic exercise training may lead to improvement in cognitive function. These findings highlight the associations between arterial aging and cerebrovascular function and the importance of aerobic exercise in maintaining brain health in older adults.

Aerobic exercise training reduces cerebrovascular impedance in older adults: a 1-year randomized controlled trial.

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 (n = 36) or stretching and toning (SAT, n = 37) interventions. Cerebrovascular impedance was estimated from simultaneous recordings of carotid artery pressure (CAP) via applanation tonometry and cerebral blood flow velocity (CBFV) in the middle cerebral artery via transcranial Doppler using transfer function analysis. Fifty-six participants completed 1-yr interventions, and 41 of those completed cerebrovascular impedance measurements. AET group showed a significant increase in V̇o2peak after the intervention [estimated marginal mean (95% confidence interval); from 22.8 (21.6 to 24.1) to 24.9 (23.6 to 26.2) mL·kg-1·cm-1, P < 0.001], but not SAT [from 21.7 (20.5 to 22.9) to 22.3 (21.1 to 23.7) mL·kg-1·cm-1, P = 0.114]. Coherence between changes in CBFV and CAP was >0.90 in the frequency range of 0.78-3.12 Hz. The averaged cerebrovascular impedance modulus (Z) in this frequency range decreased after 1-yr AET [from 1.05 (0.96 to 1.14) to 0.95 (0.92 to 1.06) mmHg·s·cm-1, P = 0.023], but not SAT [from 0.96 (0.87 to 1.04) to 1.01 (0.92 to 1.10) mmHg·s·cm-1, P = 0.138]. Reductions in Z were correlated positively with reductions in carotid pulse pressure (r = 0.628, P = 0.004) and inversely with mean CBFV (r = -0.563, P = 0.012) in the AET group. One-year AET reduces cerebrovascular impedance in older adults, which may benefit brain perfusion.NEW & NOTEWORTHY Estimation of cerebrovascular impedance is essential for understanding dynamic cerebral blood flow regulation. This randomized controlled trial demonstrated that aerobic exercise training reduced cerebrovascular impedance in older adults, which may benefit brain perfusion.

Statin contribution to middle cerebral artery blood flow velocity in older adults at risk for dementia.

PURPOSE: It is plausible that statins could improve cerebral blood flow through pleiotropic mechanisms. The purpose of this investigation was to assess the contribution of statins to cerebrovascular variables in older adults with dyslipidemia and familial history of dementia. Furthermore, we explored the interaction between statin use and sex due to prevalent bias in statin trials. METHODS: Middle cerebral artery blood flow velocity (MCAv) was measured using transcranial Doppler ultrasound. Continuous supine rest recordings lasted 8 min. Participants included in analyses were statin (n = 100) or non-statin users (n = 112). RESULTS: MCAv and cerebrovascular conductance were significantly higher in statin users (p = 0.047; p = 0.04), and pulsatility index (PI) was significantly lower in statin users (p < 0.01). An interaction effect between statin use and sex was present for PI (p = 0.02); female statin users had significantly lower cerebrovascular resistance than the other three groups. CONCLUSION: In this cross-sectional analysis, statin use was positively associated with cerebrovascular variables in older adults at risk for dementia. Female statin users had significantly higher resting MCAv and cerebrovascular conductance than female non-statin users. The greatest contribution of statin use was the association with reduced cerebrovascular resistance. Given that cerebrovascular dysregulation is one of the earliest changes in Alzheimer's disease and related dementia pathology, targeting the cerebrovasculature with statins may be a promising prevention strategy.

Aerobic exercise training and neurocognitive function in cognitively normal older adults: A one-year randomized controlled trial.

BACKGROUND: Current evidence is inconsistent on the benefits of aerobic exercise training for preventing or attenuating age-related cognitive decline in older adults. OBJECTIVE: To investigate the effects of a 1-year progressive, moderate-to-high intensity aerobic exercise intervention on cognitive function, brain volume, and cortical thickness in sedentary but otherwise healthy older adults. METHODS: We randomized 73 older adults to a 1-year aerobic exercise or stretching-and-toning (active control) program. The primary outcome was a cognitive composite score calculated from eight neuropsychological tests encompassing inductive reasoning, long-term and working memory, executive function, and processing speed. Secondary outcomes were brain volume and cortical thickness assessed by MRI, and cardiorespiratory fitness measured by peak oxygen uptake (VO2 ). RESULTS: One-year aerobic exercise increased peak VO2 by ∼10% (p < 0.001) while it did not change with stretching (p = 0.241). Cognitive composite scores increased in both the aerobic and stretching groups (p < 0.001 for time effect), although no group difference was observed. Total brain volume (p < 0.001) and mean cortical thickness (p = 0.001) decreased in both groups over time, while the reduction in hippocampal volume was smaller in the stretching group compared with the aerobic group (p = 0.040 for interaction). Across all participants, improvement in peak VO2 was positively correlated with increases in cognitive composite score (r = 0.282, p = 0.042) and regional cortical thickness at the inferior parietal lobe (p = 0.016). CONCLUSIONS: One-year aerobic exercise and stretching interventions improved cognitive performance but did not prevent age-related brain volume loss in sedentary healthy older adults. Cardiorespiratory fitness gain was positively correlated with cognitive performance and regional cortical thickness.

Carotid Arterial Compliance and Aerobic Exercise Training in Chronic Traumatic Brain Injury: A Pilot Study.

OBJECTIVE: Decreased carotid arterial compliance (CAC) is associated with cerebral microvascular damage, cerebral blood flow (CBF) dysregulation, and increased risk for stroke and dementia, which are reported to be prevalent after traumatic brain injury (TBI). However, the effect of TBI on CAC has not been reported. The purposes of this pilot study were to (1) compare CAC between participants with chronic traumatic brain injury (cTBI) and age-matched healthy control (HC) subjects and (2) to examine whether CAC changed after 3 months of exercise training in those with cTBI. SETTING: Community based. PARTICIPANTS: Nineteen participants with cTBI (6-72 months postinjury) and 19 HC matched for age and sex were tested at baseline. The same cTBI cohort was enrolled in a proof-of-concept randomized controlled exercise training program to investigate the effects of 3 months of aerobic exercise training (AET) or nonaerobic stretching and toning (SAT) on cerebrovascular parameters. DESIGN: Cross-sectional study and randomized controlled trial. MAIN MEASURES: CAC was measured by tonometry and ultrasonography at the common carotid artery; CBF was measured by ultrasonography at the bilateral internal carotid and vertebral arteries, and pulsatile CBF was measured by transcranial Doppler ultrasonography at the middle cerebral arteries. Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by total CBF. RESULTS: Relative to HC, the participants with cTBI had lower CAC (0.10 ± 0.03 vs 0.12 ± 0.03 mm 2 /mm Hg, P = .046) and higher CVR (0.17 ± 0.03 vs 0.15 ± 0.03 mm Hg/mL/min, P = .028). CAC tended to increase after AET compared with SAT ( P = .080). Increases in CAC were associated with decreased pulsatile CBF ( r = -0.689, P = .003). CONCLUSION: These findings suggest that the individuals with cTBI have decreased CAC, which may potentially be improved by AET.

Resting-state functional MRI signal fluctuation amplitudes are correlated with brain amyloid-ß deposition in patients with mild cognitive impairment.

Mounting evidence suggests that amyloid-ß (Aß) and vascular etiologies are intertwined in the pathogenesis of Alzheimer's disease (AD). Blood-oxygen-level-dependent (BOLD) signals, measured by resting-state functional MRI (rs-fMRI), are associated with neuronal activity and cerebrovascular hemodynamics. Nevertheless, it is unclear if BOLD fluctuations are associated with Aß deposition in individuals at high risk of AD. Thirty-three patients with amnestic mild cognitive impairment underwent rs-fMRI and AV45 PET. The AV45 standardized uptake value ratio (AV45-SUVR) was calculated using cerebral white matter as reference, to assess Aß deposition. The whole-brain normalized amplitudes of low-frequency fluctuations (sALFF) of local BOLD signals were calculated in the frequency band of 0.01-0.08 Hz. Stepwise increasing physiological/vascular signal regressions on the rs-fMRI data examined whether sALFF-AV45 correlations were driven by vascular hemodynamics, neuronal activities, or both. We found that sALFF and AV45-SUVR were negatively correlated in regions of default-mode and visual networks (precuneus, angular, lingual and fusiform gyri). Regions with higher sALFF had less Aß accumulation. Correlated cluster sizes in MNI space (r ≈ -0.47) were reduced from 3018 mm3 to 1072 mm3 with stronger cardiovascular regression. These preliminary findings imply that local brain blood fluctuations due to vascular hemodynamics or neuronal activity can affect Aß homeostasis.

Midlife aerobic exercise and dynamic cerebral autoregulation: associations with baroreflex sensitivity and central arterial stiffness.

Midlife aerobic exercise may significantly impact age-related changes in the cerebro- and cardiovascular regulations. This study investigated the associations of midlife aerobic exercise with dynamic cerebral autoregulation (dCA), cardiovagal baroreflex sensitivity (BRS), and central arterial stiffness. Twenty middle-aged athletes (MA) who had aerobic training for >10 yr were compared with 20 young (YS) and 20 middle-aged sedentary (MS) adults. Beat-to-beat cerebral blood flow velocity, blood pressure (BP), and heart rate were measured at rest and during forced BP oscillations induced by repeated sit-stand maneuvers at 0.05 Hz. Transfer function analysis was used to calculate dCA and BRS parameters. Carotid distensibility was measured by ultrasonography. MA had the highest peak oxygen uptake (V̇o2peak) among all groups. During forced BP oscillations, MS showed lower BRS gain than YS, but this age-related reduction was absent in MA. Conversely, dCA was similar among all groups. At rest, BRS and dCA gains at low frequency (∼0.1 Hz) were higher in the MA than in MS and YS groups. Carotid distensibility was similar between MA and YS groups, but it was lower in the MS. Across all subjects, V̇o2peak was positively associated with BRS gains at rest and during forced BP oscillations (r = 0.257∼0.382, P = 0.003∼0.050) and carotid distensibility (r = 0.428∼0.490, P = 0.001). Furthermore, dCA gain at rest and carotid distensibility were positively correlated with BRS gain at rest in YS and MA groups (all P < 0.05). These findings suggest that midlife aerobic exercise improves central arterial elasticity and BRS, which may contribute to cerebral blood flow (CBF) regulation through dCA.NEW & NOTEWORTHY Middle-aged athletes (MA) showed intact dynamic cerebral autoregulation (dCA) during sit-stand maneuvers when compared with young (YS) and middle-aged sedentary (MS) adults. Conversely, MA showed the significant attenuation of age-related carotid distensibility and baroreflex sensitivity (BRS) impairments. In MA and YS groups, BRS was positively associated with dCA gain at rest and carotid distensibility. Our findings suggest that midlife aerobic exercise improves BRS by reducing central arterial stiffness, which contributes to CBF regulation through dCA.

Hippocampal and rostral anterior cingulate blood flow is associated with affective symptoms in chronic traumatic brain injury.

OBJECTIVE: The purpose of this study was to assess cerebral blood flow (CBF) and its association with self-reported symptoms in chronic traumatic brain injury (TBI). PARTICIPANTS: Sixteen participants with mild to severe TBI and persistent self-reported neurological symptoms, 6 to 72 months post-injury were included. For comparison, 16 age- and gender-matched healthy normal control participants were also included. MAIN MEASURES: Regional CBF and brain volume were assessed using pseudo-continuous Arterial Spin Labeling (PCASL) and T1-weighted data respectively. Cognitive function and self-reported symptoms were assessed in TBI participants using the national institutes of health (NIH) Toolbox Cognition Battery and Patient-Reported Outcome Measurement Information System respectively. Associations between CBF and cognitive function, symptoms were assessed. RESULTS: Global CBF and regional brain volumes were similar between groups, but region of interest (ROI) analysis revealed lower CBF bilaterally in the thalamus, hippocampus, left caudate, and left amygdala in the TBI group. Voxel-wise analysis revealed that CBF in the hippocampus, parahippocampus, rostral anterior cingulate, inferior frontal gyrus, and other temporal regions were negatively associated with self-reported anger, anxiety, and depression symptoms. Furthermore, region of interest (ROI) analysis revealed that hippocampal and rostral anterior cingulate CBF were negatively associated with symptoms of fatigue, anxiety, depression, and sleep issues. CONCLUSION: Regional CBF deficit was observed in the group with chronic TBI compared to the normal control (NC) group despite similar volume of cerebral structures. The observed negative correlation between regional CBF and affective symptoms suggests that CBF-targeted intervention may potentially improve affective symptoms and quality of life after TBI, which needs to be assessed in future studies.

One-year aerobic exercise altered cerebral vasomotor reactivity in mild cognitive impairment.

The purpose of this study was to test the hypothesis that changes in cerebral vasomotor reactivity (CVMR) after 1-yr aerobic exercise training (AET) are associated with cognitive performances in individuals with amnestic mild cognitive impairment (MCI). Seventy sedentary patients with amnestic MCI were randomized to 1-yr moderate-to-vigorous intensity AET or stretching and toning (SAT) interventions. Cerebral blood flow velocity (CBFV) with transcranial Doppler, mean arterial pressure (MAP) with finapres plethysmograph, and EtCO2 with capnography were measured during hyperventilation (hypocapnia) and a modified rebreathing protocol (hypercapnia) to assess CVMR. Cerebrovascular conductance index (CVCi) was calculated by CBFV/MAP, and CVMR by ΔCBFV/ΔEtCO2 and ΔCVCi/ΔEtCO2. Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Cardiorespiratory fitness was assessed by peak oxygen uptake (V̇o2peak). A total of 37 patients (19 in SAT and 18 in AET) completed 1-yr interventions and CVMR assessments. AET improved V̇o2peak, increased hypocapnic CVMR, but decreased hypercapnic CVMR. The effects of AET on cognitive performance were minimal when compared with SAT. Across both groups, there was a negative correlation between changes in hypocapnic and hypercapnic CVMRs in CBFV% and CVCi% (r = -0.741, r = -0.725, P < 0.001). Attenuated hypercapnic CVMR, but not increased hypocapnic CVMR, was associated with improved cognitive test scores in the AET group. In conclusion, 1-yr AET increased hypocapnic CVMR and attenuated hypercapnic CVMR which is associated cognitive performance in patients with amnestic MCI.NEW & NOTEWORTHY One-year moderate-to-vigorous intensity aerobic exercise training (AET) improved cardiorespiratory fitness (V̇o2peak), increased hypocapnic cerebral vasomotor reactivity (CVMR), whereas it decreased hypercapnic CVMR when compared with stretching and toning in patients with amnestic mild cognitive impairment (MCI). Furthermore, changes in hypercapnic CVMR with AET were correlated with improved memory and executive function. These findings indicate that AET has an impact on cerebrovascular function which may benefit cognitive performance in older adults who have high risk of Alzheimer's disease.

Acute Effects of Short-Term Warm Water Immersion on Arterial Stiffness and Central Hemodynamics.

Warm water immersion (WWI) has a potentially favorable effect on vascular health. However, the effects of short-term WWI on vascular function and central hemodynamics remain unclear. The present study aimed to determine the acute effects of short-term WWI on arterial stiffness and central hemodynamics in healthy men. Ten healthy men (27-57 years, 44 ± 12 years of mean age) underwent 5-min WWI (40-41°C) at the heart level. Systemic hemodynamics and tympanic temperature were monitored during WWI. Furthermore, pulse wave velocity (PWV) and aortic hemodynamics were measured before and 10 min after WWI. Cardiac output (CO) (via the Modelflow method) increased (P = 0.037), whereas tympanic temperature did not change (P = 0.879) during WWI. After 5-min WWI, heart rate (HR) and brachial diastolic blood pressure (BP) were significantly decreased. Aortic and leg PWV were decreased by 7.5 and 3.1%, respectively (P = 0.006 and P = 0.040). Femoral arterial blood flow was increased by 45.9% (P = 0.002), and leg vascular resistance was decreased by 29.1% (P < 0.001). Regarding central hemodynamic variables (estimated by general transfer function), aortic BP and augmentation index (AIx) did not change significantly, but the subendocardial viability ratio (SEVR), an index of coronary perfusion, was increased (P = 0.049). Our results indicate that a short-term WWI acutely improves aortic and peripheral arterial stiffness and coronary perfusion. Further studies to determine the interaction between the residual effect of a single bout of short-term WWI and chronic change (e.g., adaptation) in arterial stiffness and central hemodynamics are needed.

One-Year Aerobic Exercise Reduced Carotid Arterial Stiffness and Increased Cerebral Blood Flow in Amnestic Mild Cognitive Impairment.

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 ß-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 ß-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 ß-stiffness index (r = -0.418, p = 0.007) and CBF pulsatility (r = -0.400, p = 0.014). Decreases in carotid ß-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.

A proof-of-concept trial of a community-based aerobic exercise program for individuals with traumatic brain injury.

Objective: To assess the feasibility of conducting an aerobic exercise training study in a community setting for individuals with traumatic brain injury (TBI)Methods: This is a prospective, randomized, and controlled study. Nine participants (three moderate-to-severe and six mild TBI) were randomized to a community-based 3-month individualized aerobic exercise training program (AET). Seven participants (four moderate-to-severe, three mild TBI) were randomized to a stretching and toning program (SAT). Cardiorespiratory fitness (CRF) level was assessed with peak oxygen uptake (VO2peak) testing.Results: After 3 months of training, the AET trended toward improved VO2peak when compared with the SAT group (8% vs - 4%, p = .059) with a large effect size of 1.27. Only 50% of participants in the AET group completed more than 70% of the assigned exercise sessions. No adverse events were reported. Both the AET and SAT groups reported small improvements in self-reported mood symptoms, including depression, anxiety, and anger.Conclusions: It is feasible to conduct an exercise training study and improve CRF for persons with TBI in community settings with structured exercise protocols. However, exploring methods to enhance adherence is crucial for future exercise clinical trials to improve brain health in this population.

Midlife aerobic exercise and brain structural integrity: Associations with age and cardiorespiratory fitness.

Lower midlife physical activity is associated with higher risk of neurodegenerative disease in late life. However, it remains unknown whether physical exercise and fitness are associated with brain structural integrity during midlife. The purpose of this study was to compare brain structures between middle-aged aerobically trained adults (MA), middle-aged sedentary (MS), and young sedentary (YS) adults. Thirty MA (54±4 years), 30 MS (54±4 years), and 30 YS (32±6 years) participants (50% women) underwent measurements of brain volume, cortical thickness, and white matter (WM) fiber integrity using MRI. MA participants had aerobic training for 24.8±9.6 years and the highest cardiorespiratory fitness level (i.e., peak oxygen uptake: VO2peak) among all groups. Global WM integrity, as assessed with fractional anisotropy (FA) from diffusion tensor imaging, was lower in the MS compared with the YS group. However, global FA in the MA group was significantly higher than that in the MS group (P<0.05) and at a similar level to the YS group. Furthermore, tract-based spatial statistical analysis demonstrated that FA in the anterior, superior, and limbic WM tracts (e.g., the genu of the corpus callosum, superior longitudinal fasciculus, uncinate fasciculus) was higher in the MA compared with MS groups, and positively associated with VO2peak, independently from age and sex. From cortical thickness analysis, MS and MA participants showed thinner prefrontal and parieto-temporal areas than the YS group. On the other hand, the MA group exhibited thicker precentral, postcentral, pericalcarine, and lateral occipital cortices than the MS and YS groups. But, the insula and right superior frontal gyrus showed thinner cortical thickness in the MA compared with the MS groups. Collectively, these findings suggest that midlife aerobic exercise is associated with higher WM integrity and greater primary motor and somatosensory cortical thickness.

Older age and male sex are associated with higher cerebrovascular impedance.

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 (ß = -0.470), diastolic (ß = -0.418), pulsatile (ß = -0.374), and mean CBFV (ß = -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.

Effects of short-term warm water immersion on cardiac baroreflex sensitivity in healthy men.

Warm water immersion (WWI) causes dizziness presumably due to a substantial drop of blood pressure. The aim of this study was to elucidate the effects of short-term WWI on cardiac baroreflex sensitivity (BRS) and the contribution of arterial stiffness to the cardiac BRS. Twelve apparent healthy men (44 ± 12 years) performed the single stand-up test after 5-min sitting in the bathtub without (Control) and with 41 °C warm water at the heart level (WWI). Cardiac BRS gain was evaluated by R-R interval response to the standing-induced drop of systolic blood pressure. In addition, before and 10 min after the single stand-up test, carotid arterial ß-stiffness index was evaluated in the supine rest. BRS gain was blunted (2.9 ± 1.6 vs. 1.8 ± 1.1 ms/mmHg, P = 0.005), whereas ß-stiffness index was not changed significantly after WWI. BRS gain correlated with ß-stiffness index before (r = - 0.626, P = 0.028) and after WWI (r = - 0.672, P = 0.015). ANCOVA revealed that these slopes of linear regression lines remained unchanged after WWI (P = 0.350). These results indicate that a short-term WWI acutely deteriorates cardiac BRS. Individuals with stiffer arteries are relatively more susceptible to WWI because of their poor baseline BRS, which might be one of the causes of bathing-related falling in elderly persons as well as frailty.

Middle-aged endurance athletes exhibit lower cerebrovascular impedance than sedentary peers.

Because elevated hemodynamic pulsatility could be mechanical stress against the brain, the dampening function of central and cerebral arteries is crucial. Regular endurance exercise training favorably restores the deteriorated dampening function of the aorta and carotid arteries in older populations, yet its effect on cerebrovascular dampening function remains unknown. To address this question, we compared cerebrovascular impedance, a frequency-domain relationship of the cerebral pressure and flow, in 21 middle-aged masters athletes who have been engaged in endurance training and races for >10 yr (MA, 53 ± 4 yr) with sedentary 21 age-matched (MS, 53 ± 5 yr) and 21 young (YS, 29 ± 6 yr) individuals. Using transfer function analysis, cerebrovascular impedance was computed from the simultaneously recorded carotid artery pressure (CAP, via applanation tonometry) and middle cerebral artery blood flow velocity (CBFV, via transcranial Doppler). In the frequency range of 0.78-3.12 Hz, coherence between pulsatile changes in CAP and CBFV was higher than 0.90 in all groups. All subjects exhibited the highest impedance modulus in the range of the first harmonic oscillations (0.78-1.56 Hz) mainly originating from cardiac ejection. Impedance modulus in this range was significantly lower in the MA than MS groups (0.88 ± 0.24 vs. 1.15 ± 0.29 mmHg·s/cm, P = 0.011) and equivalent to the YS (0.92 ± 0.30 mmHg·s/cm). Among middle-aged subjects, higher impedance modulus was correlated with lower mean CBFV (r = -0.776, P < 0.001) and cerebral cortical perfusion evaluated by MRI (r = -0.371, P = 0.015). These results suggest that middle-aged endurance athletes exhibited the significantly lower modulus of cerebrovascular impedance, which is associated with higher CBFV and cerebral cortical perfusion.NEW & NOTEWORTHY Impedance modulus in the range of first harmonic oscillations (0.78-1.56 Hz), which reflects heart rate at rest, was lower in middle-aged endurance athletes than in age-matched sedentary peers and was similar to young individuals. Prolonged endurance training is associated with the improved cerebrovascular dampening function in middle-aged adults. Lower cerebrovascular impedance modulus may contribute to maintaining brain perfusion in midlife.

Cerebral Vasomotor Reactivity in Amnestic Mild Cognitive Impairment.

BACKGROUND: Cerebral blood flow (CBF) is sensitive to changes in arterial CO2, referred to as cerebral vasomotor reactivity (CVMR). Whether CVMR is altered in patients with amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer disease (AD), is unclear. OBJECTIVE: To determine whether CVMR is altered in aMCI and is associated with cognitive performance. METHODS: Fifty-three aMCI patients aged 55 to 80 and 22 cognitively normal subjects (CN) of similar age, sex, and education underwent measurements of CBF velocity (CBFV) with transcranial Doppler and end-tidal CO2 (EtCO2) with capnography during hypocapnia (hyperventilation) and hypercapnia (rebreathing). Arterial pressure (BP) was measured to calculate cerebrovascular conductance (CVCi) to normalize the effect of changes in BP on CVMR assessment. Cognitive function was assessed with Mini-Mental State Examination (MMSE) and neuropsychological tests focused on memory (Logical Memory, California Verbal Learning Test) and executive function (Delis-Kaplan Executive Function Scale; DKEFS). RESULTS: At rest, CBFV and MMSE did not differ between groups. CVMR was reduced by 13% in CBFV% and 21% in CVCi% during hypocapnia and increased by 22% in CBFV% and 20% in CVCi% during hypercapnia in aMCI when compared to CN (all p < 0.05). Logical Memory recall scores were positively correlated with hypocapnia (r = 0.283, r = 0.322, p < 0.05) and negatively correlated with hypercapnic CVMR measured in CVCi% (r = -0.347, r = -0.446, p < 0.01). Similar correlations were observed in D-KEFS Trail Making scores. CONCLUSION: Altered CVMR in aMCI and its associations with cognitive performance suggests the presence of cerebrovascular dysfunction in older adults who have high risks for AD.