Evan Pasha

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 (&bgr; = 0.29 [p = .019] and &bgr; = 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.

Central adiposity and the functional magnetic resonance imaging response to cognitive challenge

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 the 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. 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 to −0.004) and left middle frontal gyrus (β=−0.009, P=0.002, 95% CI: −0.015 to −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.

Improved Function and Reduced Pain after Swimming and Cycling Training in Patients with Osteoarthritis

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.gov NCT01836380.

Visceral adiposity predicts subclinical white matter hyperintensities in middle-aged adults

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<0.001). Increasing WC (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.

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.

Impacts of Metabolic Syndrome Scores on Cerebrovascular Conductance Are Mediated by Arterial Stiffening

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.

Vascular Function, Cerebral Cortical Thickness, and Cognitive Performance in Middle-Aged Hispanic and Non-Hispanic Caucasian Adults

Hispanics are at increased risk for acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health with measures of cerebral gray matter integrity, 60 middle‐aged Hispanic and non‐Hispanic Caucasian participants were matched across age, sex, years of education, and mental status. Arterial stiffness was characterized by 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=.04) with concurrently lower language (P=.02), memory (P=.03), and attention‐executive functioning (P=.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics.

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.

Transcranial Doppler of the middle cerebral artery indicates regional gray matter cerebral perfusion

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.

Midlife Arterial Stiffness and Brain Activation During Working Memory Task

Objective: Arterial stiffness is associated with cognitive decline and may serve as an early marker of brain vul- nerability. 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, con- trolling 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<0.001), left precentral/middle frontal gyrus (r=-0.62, p=0.001) and left superior parietal lobule/BA 7 (r=-0.48, p=0.013). There was also a negative association be- tween arterial stiffness and task-related activation in the right superior frontal gyrus/BA 6 (r=-0.45, p=0.023). Conclu- sions: 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.