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.

Association of Dementia and Vascular Risk Scores With Cortical Thickness and Cognition in Low-risk Middle-aged Adults.

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.

Recovery from Strenuous Downhill Running in Young and Older Physically Active Adults.

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<0.05), and changes in the muscular pain scale of the legs was smaller in the older trained group than in the young trained group. Maximum isometric strengths at 90° decreased in all groups at 24 h, but the recovery rates were not different at 72 h among the groups. Plasma creatine kinase activity and myoglobin concentration increased at 24 h following downhill running and returned to baseline at 48 h in both the young and older trained groups. The present findings are not consistent with the prevailing notion that older trained adults have a slower rate of recovery from strenuous exercise.

Abdominal obesity and white matter microstructure in midlife.

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.

Higher visceral fat is associated with lower cerebral N-acetyl-aspartate ratios in middle-aged adults.

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. Seventy-three adults, aged between 40 and 60 years, underwent structural magnetic resonance imaging and single voxel 1H Magnetic Resonance Spectroscopy (1H MRS). Visceral fat was assessed using Dual Energy X Ray Absorptiometry (DXA). 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) (ß = -0.29, p = 0.03, ß = -0.28, p = 0.04). They also had significantly higher ratios of myo-inositol to total creatine (mI/PCr + Cr ) (ß = 0.36, p = 0.01, ß = 0.36, p = 0.01). Visceral fat mass and volume were not significantly related to ratios of glutamate to total creatine (Glu/PCr + Cr). 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.

Central Adiposity and Cortical Thickness in Midlife.

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 (ß = 0.29 [p = .019] and ß = 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.

Longitudinal decline of lower extremity muscle power in healthy and mobility-limited older adults: influence of muscle mass, strength, composition, neuromuscular activation and single fiber contractile properties.

PURPOSE: 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). METHODS: 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. RESULTS: At follow-up, the overall magnitude of muscle power loss was similar between groups: mobility-limited: -8.5 % vs. healthy older: -8.8 %, P > 0.8. Mobility-limited elders had significant reductions in muscle size (-3.8 %, P < 0.01) and strength (-5.9 %, P < 0.02), 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. CONCLUSION: 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.

Patients with amnestic mild cognitive impairment have higher cerebrovascular impedance than cognitively normal older adults.

Brain hypoperfusion is associated with cognitive impairment. Higher cerebrovascular impedance modulus (Z) may contribute to brain hypoperfusion. We tested hypotheses that patients with amnestic mild cognitive impairment (aMCI) (i.e., those who have a high risk of developing Alzheimer's disease) have higher Z than age-matched cognitively normal individuals, and that high Z is correlated with brain hypoperfusion. Fifty-eight patients with aMCI (67 ± 7 yr) and 25 cognitively normal subjects (CN, 65 ± 6 yr) underwent simultaneous measurements of carotid artery pressure (CAP, via applanation tonometry) and middle cerebral arterial blood velocity (CBV, via transcranial Doppler). Z was quantified using cross-spectral and transfer function analyses between dynamic changes in CBV and CAP. Patients with aMCI exhibited higher Z than NC (1.18 ± 0.34 vs. 1.01 ± 0.35 mmHg/cm/s, P = 0.044) in the frequency range from 0.78 to 4.29 Hz. The averaged Z in the frequency range (0.78-3.13 Hz) of high coherence (>0.9) was inversely correlated with total cerebral blood flow measured with 2-D Doppler ultrasonography normalized by the brain tissue mass (via structural MRI) across both patients with aMCI and NC (r = -0.311, P = 0.007), and in patients with aMCI alone (r = -0.306, P = 0.007). Our findings suggest that patients with aMCI have higher cerebrovascular impedance than cognitively normal older adults and that increased cerebrovascular impedance is associated with brain hypoperfusion.NEW & NOTEWORTHY This is the first study to compare cerebrovascular impedance between patients with amnestic mild cognitive impairment (aMCI) and age-matched cognitively normal individuals. Patients with aMCI had higher cerebrovascular impedance modulus than age-matched cognitively normal individuals, which was correlated with brain hypoperfusion. These results suggest the presence of cerebrovascular dysfunction in the dynamic regulation of cerebral blood flow in older adults who have high risks of Alzheimer's disease.

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.

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.

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.

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.

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.

Carotid Arterial Stiffness and Cerebral Blood Flow in Amnestic Mild Cognitive Impairment.

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 ß-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 ß-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.

Carotid Stiffness is Associated with Brain Amyloid-ß Burden in Amnestic Mild Cognitive Impairment.

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-ß (Aß) burden in at risk patients is unclear. OBJECTIVE: We aimed to determine the relationship of aortic and carotid arterial stiffening with Aß 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 Aß burden via standardized uptake value ratio (SUVR). Carotid-femoral pulse wave velocity (cfPWV), which reflects aortic stiffness, and carotid ß 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 Aß SUVR were correlated positively with carotid ß 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 Aß SUVR was positively correlated with carotid ß stiffness index, and negatively with carotid distensibility at the precuneus/cingulate gyrus after multiple comparison correction. cfPWV was not correlated with Aß SUVR. CONCLUSIONS: Carotid rather than aortic stiffening was independently associated with brain Aß 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.

Steady-state cerebral autoregulation in older adults with amnestic mild cognitive impairment: linear mixed model analysis.

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 CO2 (EtCO2) 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.

Associations of carotid arterial compliance and white matter diffusion metrics during midlife: modulation by sex.

Sex differences in cerebral white matter (WM) aging have been debated extensively over the past 2 decades without unequivocal resolution. We aimed to determine if the effects of age and arterial stiffness on 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 < 0.05) and CAC (cingulum FA, p < 0.05) related reductions in regional WM diffusion metrics. CAC mediated age-related associations in regional WM diffusion metrics (cingulum FA, cingulum MD, superior corona radiata MD, and uncinate MD, all p < 0.05) in males but not in females. Age and CAC were associated with WM diffusion metrics independent of cardiovascular risk factors. These associations appear to be stronger in males than in females.

Physical activity mitigates adverse effect of metabolic syndrome on vessels and brain.

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. 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). Carotid ß-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 < 0.05). Middle-aged individuals with MetS who habitually perform PA demonstrated lower arterial stiffness and more favorable CWM integrity than their sedentary peers, indicating that PA may be effective in mitigating the adverse effects of MetS on the vasculature and brain at midlife.

Phenotypic heterogeneity of obesity-related brain vulnerability: one-size interventions will not fit all.

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.