Publications by authors named "Owen Carmichael"

130 Publications

Practical application of in vivo MRI-based brown adipose tissue measurements in infants.

Obesity (Silver Spring) 2021 Oct;29(10):1676-1683

Pennington Biomedical Research Center, Baton Rouge, Louisana, USA.

Objective: The role of brown adipose tissue (BAT) in infant metabolism remains poorly understood, primarily because of the inherent limitation of positron emission tomography/computed tomography imaging to measure BAT, which is not suitable for infants. The aims of this method development study were to assess the feasibility, intra-rater reliability, interscan repeatability, and physiological relevance of measuring BAT in infants using magnetic resonance imaging (MRI).

Methods: A total of 10 nonsedated infants (mean age, 22.6 [1.3] days old) completed two 3-T MRI exams using chemical-shift-encoded water-fat scans 6.2 (2.8) days apart. Candidate BAT voxels in the supraclavicular region were identified based on fat signal fraction (FSF). The volumes of BAT depots were manually traced, and FSF was calculated. Whole-body fat mass was determined using dual-energy x-ray absorptiometry.

Results: Images were successfully obtained from 19 of 20 (95%) attempted scans. The mean BAT volume was 5.41 (SD 1.1) cm , and the mean FSF was 16.41% (SD 3.3%). Intra-rater analysis showed good reliability with no systemic bias (proportional bias for volume: p = 0.19; FSF: p = 0.30). Test-retest for interscan repeatability was good (intraclass correlation coefficients for volume: 0.92, p = 0.001 and intraclass correlation coefficients for FSF: 0.93, p < 0.001). FSF was inversely related to fat-free mass (r = -0.69, p = 0.03).

Conclusions: This method development study supports the use of MRI to obtain reliable and quantitative measurements of BAT volume in infants.
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http://dx.doi.org/10.1002/oby.23237DOI Listing
October 2021

Beliefs, Understanding, and Barriers Related to Dementia Research Participation Among Older African Americans.

Alzheimer Dis Assoc Disord 2021 Sep 6. Epub 2021 Sep 6.

Department of Psychology Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA.

Background: United States Census Bureau projects African Americans (AAs) will be one of the fastest growing populations over the next 30 years. Research suggests they are at higher risk for developing dementia. It is important to know about AA adults' beliefs about, and knowledge of, dementia; and how these beliefs and knowledge impact participation in dementia research.

Methods: Four focus groups were completed with 51 older AA adults (76.5% female; mean age=68) in Baton Rouge, Louisiana to examine understanding of dementia and barriers influencing willingness to participate in a clinical trial on dementia risk reduction.

Findings: Participants exhibited awareness of several risk and protective factors related to dementia, including family history of dementia, lack of cognitive engagement, and sedentary lifestyles. They were willing to participate in interventions to lower the risk of developing dementia. Barriers to participation included invasive procedures, pharmaceutical interventions, mistrust of investigators, inadequate compensation, and long study duration.

Discussion: Given the high relevance of dementia research to older AAs, their knowledge of dementia, and their willingness to participate in dementia research once barriers are addressed, it is imperative to continue to identify and remediate factors contributing to the poor representation of AAs in dementia research.
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http://dx.doi.org/10.1097/WAD.0000000000000476DOI Listing
September 2021

Effects of testosterone administration on fMRI responses to executive function, aggressive behavior, and emotion processing tasks during severe exercise- and diet-induced energy deficit.

Neuroimage 2021 Nov 20;243:118496. Epub 2021 Aug 20.

Military Nutrition Division, US Army Research Institute of Environmental Medicine (USARIEM), Natick, MA, USA.

Background: Clinical administration of testosterone is widely used due to a variety of claimed physical and cognitive benefits. Testosterone administration is associated with enhanced brain and cognitive function, as well as mood, in energy-balanced males, although such relationships are controversial. However, the effects of testosterone administration on the brains of energy-deficient males, whose testosterone concentrations are likely to be well below normal, have not been investigated.

Methods: This study collected functional magnetic resonance imaging (fMRI) data from 50 non-obese young men before (PRE) and shortly after (POST) 28 days of severe exercise-and-diet-induced energy deficit during which testosterone (200 mg testosterone enanthate per week in sesame oil, TEST) or placebo (sesame seed oil only, PLA) were administered. Scans were also collected after a post-energy-deficit weight regain period (REC). Participants completed five fMRI tasks that assessed aspects of: 1) executive function (Attention Network Task or ANT; Multi-Source Interference Task or MSIT; AXE Continuous Processing Task or AXCPT); 2) aggressive behavior (Provoked Aggression Task or AGG); and 3) latent emotion processing (Emotional Face Processing or EMO).

Results: Changes over time in task-related fMRI activation in a priori defined task-critical brain regions during performance of 2 out of 5 tasks were significantly different between TEST and PLA, with TEST showing greater levels of activation during ANT in the right anterior cingulate gyrus at POST and during MSIT in several brain regions at REC. Changes over time in objective task performance were not statistically significant; testosterone-treated volunteers had greater self-reported anger during AGG at POST.

Conclusions: Testosterone administration can alter some aspects of brain function during severe energy deficit and increase levels of anger.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118496DOI Listing
November 2021

Legacy of a 10-Year Multidomain Lifestyle Intervention on the Cognitive Trajectories of Individuals with Overweight/Obesity and Type 2 Diabetes Mellitus.

Dement Geriatr Cogn Disord 2021 19;50(3):237-249. Epub 2021 Aug 19.

Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Introduction: Weight loss and increased physical activity interventions are commonly recommended for individuals with type 2 diabetes (T2D) and overweight or obesity. We examined the impact of randomization to an intensive lifestyle intervention (ILI) on trajectories of cognitive function over 10 years in a cohort of participants in a randomized clinical trial who had T2D and overweight/obesity at baseline.

Methods: Participants aged 45-76 years were enrolled in 2001-2004 and were randomized to the ILI or a diabetes support and education (DSE) condition. Cognitive function was assessed in 3,938 participants at up to 4 time points 8-18 years after randomization. General linear mixed effects models examined cognitive trajectories over time. Subgroup analyses focused on sex, individuals with baseline body mass index >30, those carrying the APOE ε4 allele, and those with a baseline history of cardiovascular disease (CVD).

Results: Overall, there were no differences in the rate of cognitive decline by intervention arm. Subgroup analyses showed that participants who had a baseline history of CVD and were randomized to the ILI arm of the study performed significantly worse on the Stroop Color Word Test than those in the DSE arm.

Discussion/conclusions: The ILI did not result in preserved cognitive function or slower rates of cognitive decline in this cohort of individuals who had T2D and were overweight or obese at baseline.
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http://dx.doi.org/10.1159/000517160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530880PMC
August 2021

The effects of the form of sugar (solid vs. beverage) on body weight and fMRI activation: A randomized controlled pilot study.

PLoS One 2021 17;16(5):e0251700. Epub 2021 May 17.

Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, United States of America.

Objective: To test if sugar sweetened beverages (SSBs) and sugar sweetened solids (SSSs) have differential effects on body weight and reward processing in the brain.

Methods: In a single blind randomized controlled pilot trial (RCT), twenty participants with BMI between 20 and 40 kg/m2 were randomized to consume a 20 fluid ounce soda (SSB, 248 kcal) or the equivalent in solid form (SSS; similar to thick gelatin or gummy candy) daily. At baseline and day 28, fasting body weight and fed-state BOLD fMRI of the brain were assessed. Differences in fMRI signals between views of low-fat (LF (<30%)) high sugar (HS (>30%)) food, and non-food images were calculated in brain regions implicated in energy homeostasis, taste, and reward.

Results: All participants in the SSB (6F 4M; 8 Caucasian; 36±14 y, 28.2±5.5 kg/m2; Mean±SD) and SSS (3F 7M; 6 Caucasian; 39±12; 26.3±4.4) groups completed the study. Weight change was 0.27±0.78 kg between SSB and SSS participants. Changes in the fMRI response to LF/HS foods in reward, homeostatic and taste regions tended to not be different between the groups over the four weeks. However, activation of the right substantia nigra increased following the SSB but decreased activation following the SSS in response to LF/HS foods over 28 days (-0.32±0.12). Ratings of wanting for LF/HS foods were correlated with activation in several brain regions, including the OFC.

Conclusions: Change in weight was modest between the groups in this study. Daily consumption of a SSB over 28 days led to mixed responses to LF/HS foods in areas of the brain associated with reward. Ratings of wanting are correlated with fMRI activation inside an MRI scanner.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251700PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128228PMC
October 2021

Does the impact of intensive lifestyle intervention on cognitive function vary depending baseline level of frailty? An ancillary study to the Action for Health in Diabetes (Look AHEAD) Trial.

J Diabetes Complications 2021 05 16;35(5):107909. Epub 2021 Mar 16.

Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, One Medical Center Blvd, Winston-Salem, NC 27101, United States of America; Department of Biostatistics and Data Science, Wake Forest School of Medicine, One Medical Center Blvd, Winston-Salem, NC 27101, United States of America. Electronic address:

Aims: To assess whether there is an opportune window when intensive lifestyle intervention (ILI) benefits cognitive function.

Methods: Standardized cognitive assessments were collected following ≥8 years of either ILI or a control condition of diabetes support and education (DSE) in 3708 individuals, ages 45-76 years at enrollment, with type 2 diabetes and overweight or obesity. Frailty index (FI) scores were used to group individuals at baseline into tertiles according to their age-related health status. Linear models were used to describe intervention adherence and cognitive function, with interaction terms to examine the consistency of relationships among tertiles.

Results: Worse baseline FI scores were associated with poorer subsequent performance in tests of attention, processing speed, and executive function. No differences in any measure of cognitive function were observed between intervention groups within any FI tertile (all p > 0.10). Among individuals with worse baseline FI scores, weight gain was associated with poorer global cognitive function among participants assigned to DSE. There was no association between weight changes and cognitive function among participants assigned to ILI.

Conclusions: Among adults with type 2 diabetes and overweight/obesity, we found no evidence that there is a window of opportunity based on FI when ILI benefits cognitive function.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.107909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046723PMC
May 2021

Neuroimaging, Behavioral, and Gait Correlates of Fall Profile in Older Adults.

Front Aging Neurosci 2021 18;13:630049. Epub 2021 Feb 18.

Biomedical Imaging Center, Pennington Biomedical Research Center, Baton Rouge, LA, United States.

Prior research has suggested that measurements of brain functioning and performance on (tasks which require simultaneous performance) are promising candidate predictors of fall risk among older adults. However, no prior study has investigated whether brain function measurements during dual task performance could improve prediction of fall risks and whether the type of subtasks used in the dual task paradigm affects the strength of the association between fall characteristics and dual task performance. In this study, 31 cognitively normal, community-dwelling older adults provided a self-reported fall profile (number of falls and fear of falling), completed a gait dual task (spell a word backward while walking on a GaitRite mat), and completed a supine dual task (rhythmic finger tapping with one hand while completing the AX continuous performance task (AX-CPT) with the other hand) during functional magnetic resonance imaging (fMRI). Gait performance, AX-CPT reaction time and accuracy, finger tapping cadence, and brain functioning in finger-tapping-related and AX-CPT-related brain regions all showed declines in the dual task condition compared to the single task condition. Dual-task gait, AX-CPT and finger tapping performance, and brain functioning were all independent predictors of fall profile. No particular measurement domain stood out as being the most strongly associated measure with fall variables. Fall characteristics are determined by multiple factors; brain functioning, motor task, and cognitive task performance in challenging dual-task conditions all contribute to the risk of falling.
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http://dx.doi.org/10.3389/fnagi.2021.630049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935539PMC
February 2021

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.

Nat Commun 2020 09 22;11(1):4796. Epub 2020 Sep 22.

Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
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http://dx.doi.org/10.1038/s41467-020-18367-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508833PMC
September 2020

Estrogen, brain structure, and cognition in postmenopausal women.

Hum Brain Mapp 2021 01 10;42(1):24-35. Epub 2020 Sep 10.

Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA.

Declining estrogen levels before, during, and after menopause can affect memory and risk for Alzheimer's disease. Undesirable side effects of hormone variations emphasize a role for hormone therapy (HT) where possible benefits include a delay in the onset of dementia-yet findings are inconsistent. Effects of HT may be mediated by estrogen receptors found throughout the brain. Effects may also depend on lifestyle factors, timing of use, and genetic risk. We studied the impact of self-reported HT use on brain volume in 562 elderly women (71-94 years) with mixed cognitive status while adjusting for aforementioned factors. Covariate-adjusted voxelwise linear regression analyses using a model with 16 predictors showed HT use as positively associated with regional brain volumes, regardless of cognitive status. Examinations of other factors related to menopause, oophorectomy and hysterectomy status independently yielded positive effects on brain volume when added to our model. One interaction term, HTxBMI, out of several examined, revealed significant negative association with overall brain volume, suggesting a greater reduction in brain volume than BMI alone. Our main findings relating HT to regional brain volume were as hypothesized, but some exploratory analyses were not in line with existing hypotheses. Studies suggest lower levels of estrogen resulting from oophorectomy and hysterectomy affect brain volume negatively, and the addition of HT modifies the relation between BMI and brain volume positively. Effects of HT may depend on the age range assessed, motivating studies with a wider age range as well as a randomized design.
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http://dx.doi.org/10.1002/hbm.25200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721237PMC
January 2021

Molecular correlates of MRS-based phosphocreatine muscle resynthesis rate in healthy adults.

NMR Biomed 2021 01 1;34(1):e4402. Epub 2020 Sep 1.

Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.

Dynamic phosphorus MRS ( P-MRS) is a method used for in vivo studies of skeletal muscle energetics including measurements of phosphocreatine (PCr) resynthesis rate during recovery of submaximal exercise. However, the molecular events associated with the PCr resynthesis rate are still under debate. We assessed vastus lateralis PCr resynthesis rate from P-MRS spectra collected from healthy adults as part of the CALERIE II study (caloric restriction), and assessed associations between PCr resynthesis and muscle mitochondrial signature transcripts and proteins (NAMPT, NQO1, PGC-1α, and SIRT1). Regression analysis indicated that higher concentration of nicotinamide phosphoribosyltransferase (NAMPT) protein, a mitochondrial capacity marker, was associated with faster PCr resynthesis. However, PCr resynthesis was not associated with greater physical fitness (VO peak) or messenger ribonucleic acid levels of mitochondrial function markers such as NQO1, PGC-1α, and SIRT1, suggesting that the impact of these molecular signatures on PCr resynthesis may be minimal in the context of an acute exercise bout. Together, these findings suggest that P-MRS based PCr resynthesis may represent a valid non-invasive surrogate marker of mitochondrial NAMPT in human skeletal muscle.
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http://dx.doi.org/10.1002/nbm.4402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491428PMC
January 2021

Long-term Change in Physiological Markers and Cognitive Performance in Type 2 Diabetes: The Look AHEAD Study.

J Clin Endocrinol Metab 2020 12;105(12)

Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.

Context: The effects of physiological improvements on cognitive function among persons with type 2 diabetes mellitus (T2DM) are not fully understood.

Objective: To determine whether improvements in physiological markers (body weight, blood sugar control, and physical activity) during intensive lifestyle intervention (ILI) are associated with enhancements in cognitive function in older adults with T2DM.

Design: Multisite randomized controlled trial.

Setting: Academic research centers.

Patients Or Other Participants: Participants were aged 45-76 years, with T2DM.

Intervention: The Action for Health in Diabetes (Look AHEAD) study, a randomized, controlled clinical trial of ILI.

Main Outcome Measure: Two to 3 cognitive assessments were collected from 1089 participants, the first and last occurring a mean (standard deviation) of 8.6 (1.0) and 11.5 (0.7) years after enrollment.

Results: Greater improvement in blood sugar control was associated with better cognitive scores (fasting glucose and Rey Auditory Verbal Learning Test [AVLT]: P = 0.0148; fasting glucose and Digit Symbol Coding (DSC): P = 0.0360; HbA1C and DSC: P = 0.0477); but weight loss had mixed associations with cognitive scores (greater body mass index [BMI] reduction and worse AVLT overall: P = 0.0053; and greater BMI reduction and better DSC scores among those overweight but not obese at baseline: P = 0.010). Associations were strongest among those who were overweight (not obese) at baseline, and among those with a history of cardiovascular disease (CVD) at baseline.

Conclusions: Improvements in glycemic control, but not necessarily weight status, during ILI may be associated with better subsequent cognitive performance. These associations may differ by adiposity and CVD history.
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http://dx.doi.org/10.1210/clinem/dgaa591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566388PMC
December 2020

Validation of the Activity Preference Assessment: a tool for quantifying children's implicit preferences for sedentary and physical activities.

Int J Behav Nutr Phys Act 2020 08 24;17(1):108. Epub 2020 Aug 24.

University of Leeds, Leeds, England, UK.

Background: High levels of sedentary behavior and low physical activity are associated with poor health, and the cognitive determinants of these behaviors in children and adolescents are not well understood. To address this gap, we developed a novel, non-verbal, computer-based assessment to quantify the degree to which youth prefer to be sedentary relative to physically active in their leisure time.

Methods: The Activity Preference Assessment (APA) uses a forced-choice paradigm to understand implicit decision-making processes when presented with common sedentary and physical activities. The APA bias score ranges from - 100 to + 100, with positive scores indicating a relative preference for sedentary activities, and negative scores representing a preference for physical activities. In 60 children ages 8-17 years, we assessed the validity of this behavioral task against a free-choice play observation, accelerometry-measured activity, anthropometrics and body composition, and cardiorespiratory fitness. We explored neighborhood, family, and individual-level factors that may influence implicit activity preferences. Test-retest reliability was assessed over one week.

Results: The majority of children (67%) preferred sedentary relative to physical activities. APA bias scores were positively associated with sedentary time during free-choice play. In girls, bias scores were negatively associated with average daily MVPA. APA bias scores were positively associated with body fat and negatively associated with cardiorespiratory fitness. These findings were independent of age, sex, and race/ethnicity. Neighborhood access to physical activity spaces, the number of people in the home, perceived physical self-competence (e.g., coordination, strength), and self-reported depressive symptoms were associated with activity preferences. The intra-class correlation for test-retest reliability was r = 0.59.

Conclusions: The APA shows promise as a novel tool for quantifying children's relative preference for sedentary versus physical activities. Implicit bias scores from the APA are clinically meaningful, as shown by significant associations with adiposity and cardiorespiratory fitness. Future longitudinal studies should examine the directionality of the association between preferences and health markers, and the degree to which implicit activity preferences are modifiable. Importantly, the task only takes an average of 10 min to complete, highlighting a potential role as an efficient screening tool for the propensity to be sedentary versus physically active.

Trial Registration: ClinicalTrials.gov NCT03624582 .
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http://dx.doi.org/10.1186/s12966-020-01014-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444062PMC
August 2020

Left Ventricular Mass Index Is Associated With Cognitive Function in Middle-Age: Bogalusa Heart Study.

Circ Cardiovasc Imaging 2020 08 10;13(8):e010335. Epub 2020 Aug 10.

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.

Background: Elevated cardiovascular disease risk factor burden is a recognized contributor to poorer cognitive function; however, the physiological mechanisms underlying this association are not well understood. We sought to assess the potential mediation effect of left ventricular (LV) remodeling on the association between lifetime systolic blood pressure and cognitive function in a community-based cohort of middle-aged adults.

Methods: Nine hundred sixty participants of the Bogalusa Heart Study (59.2% women, 33.8% black, aged 48.4±5.1 years) received 2-dimensional echocardiography to quantify relative wall thickness, LV mass, and diastolic and systolic LV function; and a standardized neurocognitive battery to assess memory, executive functioning, and language processing. Multivariable linear regression assessed the association of cardiac structure and function with a global composite cognitive function score, adjusting for traditional cardiovascular disease risk factors. Mediation analysis assessed the effect of LV mass index on the association between lifetime systolic blood pressure burden and cognitive function.

Results: There were 233 (24.3%) and 136 (14.2%) individuals with concentric LV remodeling and concentric LV hypertrophy, respectively. Each g/m increment in LV mass index was associated with a 0.03 standardized unit decrement in global cognitive function (=0.03). Individuals with concentric LV remodeling and isolated diastolic dysfunction had the poorest cognitive function, and a greater ratio between early mitral inflow velocity and early diastolic mitral annular velocity (E/e') was associated with poorer cognitive function, even after adjustment for LV mass index (B=-0.12; =0.03). A total of 18.8% of the association between lifetime systolic blood pressure burden and midlife cognitive function was accounted for by LV mass index.

Conclusions: Cardiac remodeling partially mediates the association between lifespan systolic blood pressure burden and adult cognition in individuals without dementia or clinical cardiovascular disease. Slowing or reversing the progression of cardiac remodeling in middle-age may be a novel therapeutic approach to prevent cognitive decline.
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http://dx.doi.org/10.1161/CIRCIMAGING.119.010335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428065PMC
August 2020

White matter atrophy in cerebral amyloid angiopathy.

Neurology 2020 08 1;95(5):e554-e562. Epub 2020 Jul 1.

From the Hemorrhagic Stroke Research Program, Stroke Research Center, Department of Neurology (P.F., Y.D.R., S.J.V.V., S.M.-R., F.I.K., E.G., K.M.S., A.V., S.M.G., M.E.G.), and Division of Neurocritical Care and Emergency Neurology (J.N.G., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Objective: We postulated that cerebral amyloid angiopathy (CAA) is associated with white matter atrophy (WMA) and that WMA can be related to cognitive changes in CAA.

Methods: White matter volume expressed as percent of intracranial volume (pWMV) of prospectively enrolled patients without dementia diagnosed with probable CAA was compared to age-matched healthy controls (HC) and patients with Alzheimer disease (AD). Cognitive scores were also sought to understand the potential effects of WMA on cognitive function.

Results: Patients with CAA (n = 72) had significantly lower pWMV (27.97% ± 2.63) when compared to age-matched HC (n = 72; mean difference [MD], 2.38%; < 0.0001) and patients with AD (n = 72; MD, 1.57%; < 0.0001). Differences were most pronounced in the posterior occipital regions in both comparisons. When comparisons were restricted to groups of patients with CAA but no intracerebral hemorrhage (n = 32) or hypertension (n = 32), and age-matched HC and AD, the significant differences were unaltered. Within the CAA cohort, higher age, lobar microbleed counts, and presence of hypertension were associated with lower pWMV ( = 0.0007, = 0.031, and = 0.003, respectively). All associations remained independent in multivariable analyses. Within the CAA cohort, higher pWMV independently correlated with better scores of executive function.

Conclusions: Patients with CAA show WMA when compared to age-matched HC and patients with AD. WMA independently correlates with the number of lobar microbleeds, a marker of CAA severity. Consistent spatial patterns of WMA especially in posterior regions might be related to CAA. The association between WMA and measures of executive function suggests that WMA might represent an important mediator of CAA-related neurologic dysfunction.
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http://dx.doi.org/10.1212/WNL.0000000000010017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455340PMC
August 2020

Do menopausal status and APOE4 genotype alter the long-term effects of intensive lifestyle intervention on cognitive function in women with type 2 diabetes mellitus?

Neurobiol Aging 2020 08 8;92:61-72. Epub 2020 Apr 8.

Columbia University Medical Center, New York, NY, USA.

In the Look AHEAD trial, randomization to Intensive Lifestyle Intervention (ILI) or Diabetes Support and Education (DSE) did not result in differences in cognitive outcomes. However, menopause and APOE genotype are factors that affect the response to this intervention. The effect of this intervention on a single cognitive assessment was examined in 3 groups of women: premenopausal or <5 years postmenopausal (N = 594), within 5-10 years (n = 388), and ≥10 years postmenopausal (n = 963), and as a function of continuous years since menopause. The late postmenopausal group in the ILI had worse composite z-scores compared to those in the DSE, whereas the younger premenopausal or early postmenopausal women in the ILI had better composite z-scores than the DSE. A significant interaction between years since menopause and intervention arm, but not baseline age, was observed on executive function domains. ILI appeared only to benefit cognitive function among non-APOE4 carriers during premenopause or early postmenopause. These findings emphasize the importance of assessing menopause and APOE status to understand how weight loss impacts cognition.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269875PMC
August 2020

A Pilot Study of Cardiorespiratory Fitness, Adiposity, and Cardiometabolic Health in Youth With Overweight and Obesity.

Pediatr Exerc Sci 2020 04 25;32(3):124-131. Epub 2020 Apr 25.

Pennington Biomedical Research Center.

Objective: To conduct a preliminary assessment of the relationships between cardiorespiratory fitness, adiposity, and cardiometabolic health using gold standard measures in diverse youth ranging from overweight to severe obesity.

Methods: Twenty of 30 participants (mean [SD]; age 13.2 [1.8] y, 55% female, 45% African American) met the criteria for VO2peak during a graded cycle ergometer test to volitional fatigue. The body composition was measured by dual-energy X-ray absorptiometry (percentage of body fat, fat mass index, and fat-free mass) and magnetic resonance imaging (abdominal visceral and subcutaneous [SAT] adipose tissue). The VO2peak was expressed relative to fat-free mass. Fasting lipid levels, glycemic biomarkers, and vital signs were examined individually and used in a composite cardiometabolic risk score. Accelerometer-measured physical activity and sedentary time were included as covariates.

Results: VO2peak was negatively associated with abdominal SAT (r = -.49, P < .05), but not visceral adipose tissue or markers of cardiometabolic health. The association between SAT and VO2peak was partly explained by habitual sedentary time.

Conclusions: We demonstrated a significant negative association between cardiorespiratory fitness and SAT in a diverse group of high-risk youth. The inclusion of rigorous, laboratory-based measures and youth with severe obesity extends the previous work in pediatric populations.
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http://dx.doi.org/10.1123/pes.2019-0192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606316PMC
April 2020

Automated White Matter Hyperintensity Segmentation Using Bayesian Model Selection: Assessment and Correlations with Cognitive Change.

Neuroinformatics 2020 06;18(3):429-449

Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.

Accurate, automated white matter hyperintensity (WMH) segmentations are needed for large-scale studies to understand contributions of WMH to neurological diseases. We evaluated Bayesian Model Selection (BaMoS), a hierarchical fully-unsupervised model selection framework for WMH segmentation. We compared BaMoS segmentations to semi-automated segmentations, and assessed whether they predicted longitudinal cognitive change in control, early Mild Cognitive Impairment (EMCI), late Mild Cognitive Impairment (LMCI), subjective/significant memory concern (SMC) and Alzheimer's (AD) participants. Data were downloaded from the Alzheimer's disease Neuroimaging Initiative (ADNI). Magnetic resonance images from 30 control and 30 AD participants were selected to incorporate multiple scanners, and were semi-automatically segmented by 4 raters and BaMoS. Segmentations were assessed using volume correlation, Dice score, and other spatial metrics. Linear mixed-effect models were fitted to 180 control, 107 SMC, 320 EMCI, 171 LMCI and 151 AD participants separately in each group, with the outcomes being cognitive change (e.g. mini-mental state examination; MMSE), and BaMoS WMH, age, sex, race and education used as predictors. There was a high level of agreement between BaMoS' WMH segmentation volumes and a consensus of rater segmentations, with a median Dice score of 0.74 and correlation coefficient of 0.96. BaMoS WMH predicted cognitive change in: control, EMCI, and SMC groups using MMSE; LMCI using clinical dementia rating scale; and EMCI using Alzheimer's disease assessment scale-cognitive subscale (p < 0.05, all tests). BaMoS compares well to semi-automated segmentation, is robust to different WMH loads and scanners, and can generate volumes which predict decline. BaMoS can be applicable to further large-scale studies.
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http://dx.doi.org/10.1007/s12021-019-09439-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338814PMC
June 2020

Pattern of regional white matter hyperintensity volume in mild cognitive impairment subtypes and associations with decline in daily functioning.

Neurobiol Aging 2020 02 2;86:134-142. Epub 2019 Nov 2.

Department of Psychiatry, University of California, San Diego, CA, USA; Psychology Service, VA San Diego Healthcare System, San Diego, CA, USA.

White matter hyperintensities (WMHs), a marker of small-vessel cerebrovascular disease, increase risk for mild cognitive impairment (MCI). Less is known about whether regional WMHs distinguish MCI subtypes and predict decline in everyday functioning. About 618 Alzheimer's Disease Neuroimaging Initiative participants (301 cognitively normal [CN]; 232 amnestic MCI [aMCI]; 85 nonamnestic MCI [naMCI]) underwent neuropsychological testing, MRI, and assessment of everyday functioning. aMCI participants showed greater temporal (p = 0.002) and occipital WMHs (p = 0.030) relative to CN whereas naMCI participants had greater frontal (p = 0.045), temporal (p = 0.003), parietal (p = 0.018), and occipital (p < 0.001) WMH compared with CN. Relative to those with aMCI, individuals with naMCI showed greater occipital WMH (p = 0.013). Greater WMH in temporal (p = 0.001) and occipital regions (p = 0.006) was associated with faster decline in everyday functioning across the sample. Temporal lobe WMHs were disproportionately associated with accelerated functional decline among naMCI (p = 0.045). Regional WMH volumes vary across cognitive groups and predict functional decline. Cerebrovascular markers may help identify individuals at risk for decline and distinguish subtypes of cognitive impairment.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995428PMC
February 2020

Total body skeletal muscle mass estimated by magnetic resonance imaging and creatine (methyl-d ) dilution in athletes.

Scand J Med Sci Sports 2020 Mar 12;30(3):421-428. Epub 2019 Nov 12.

Centre for Human & Applied Physiological Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

Creatine dilution (D -cr) is a technique for estimating total skeletal muscle mass (SMM) with practical utility, but has not been applied in athletic populations where body composition may differ to that in the normal population. This study aimed to assess the agreement between SMM derived from both D -cr and that obtained from whole-body magnetic resonance imaging (MRI) in 15 male and 5 female national level kayakers (stature: 182.0 ± 13.1 and 170.0 ± 9.0 cm; body mass: 80.6 ± 9.9 and 66.4 ± 6.0 kg; V̇O peak: 56.5 ± 7.0 and 49.6 ± 4.4 mL kg  min , mean ± SD). SMM was determined following 60 mg of dosed D -cr and analysis of expelled urine collected on four subsequent days for creatine, creatinine, D -cr, and D -creatinine using liquid chromatography/mass spectroscopy. SMM was then estimated by assuming a creatine pool size of 4.3 g/kg. During the same time period, a whole-body MRI was undertaken to derive SMM from the analysis of multiple slices taken across the body. A strong positive correlation (F = 74.32; R = 0.90; P < .0001) between the two methods was observed, but the D -cr SMM was found to be significantly higher (43.3 ± 6.8 kg) when compared with MRI (36.3 ± 5.8 kg, P < .0001). However, the difference between the methods was removed when a higher intramuscular creatine pool (5.1 g/kg) was assumed. These data show that D -cr has potential utility in athletes, as referenced against MRI, but show that assumptions regarding creatine pool size need to be carefully considered.
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http://dx.doi.org/10.1111/sms.13585DOI Listing
March 2020

Genetic architecture of subcortical brain structures in 38,851 individuals.

Nat Genet 2019 11 21;51(11):1624-1636. Epub 2019 Oct 21.

Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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http://dx.doi.org/10.1038/s41588-019-0511-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055269PMC
November 2019

Brain functional differences in visuo-motor task adaptation between dominant and non-dominant hand training.

Exp Brain Res 2019 Dec 21;237(12):3109-3121. Epub 2019 Sep 21.

Fine Motor Control and Learning Laboratory, School of Kinesiology, Louisiana State University, Baton Rouge, LA, 70803, USA.

Although learning and adapting to visuo-motor tasks is critical to child development and health conditions requiring rehabilitation, the neural processes involved in learning a new visuo-motor task and adapting it to novel conditions such as execution with an untrained limb are not fully understood. Therefore, we trained 27 healthy, right-hand-dominant individuals aged 18-35 years to perform a multidirectional point-to-point visually rotated aiming task with a joystick during functional magnetic resonance imaging, with 13 participants learning the task with the dominant (D) and 14 with the non-dominant (ND) hand. All individuals performed the task with the trained and untrained hand before and after training. As expected, performance of both the trained and the untrained hand improved significantly over the course of task acquisition. Brain functional changes associated with adaptation to the demands of the task, and execution differed significantly between D and ND groups. In particular, the ND group showed greater recruitment of visual and motor regions (left middle occipital and left precentral gyri) than the D group during task acquisition. In addition, the D group exhibited greater recruitment of motor planning regions (left precuneus) that contribute to performance with the trained hand, even after bilateral transfer-switching from the trained to non-trained hand. The D group showed more persistence of activation in sensorimotor regions-greater activation when returning to the rotated task after a switching to a simpler, non-rotated aiming task for a short interval. Finally, the D group showed more activation after-effects-increases in simpler task activation after training on the visually rotated task. The findings suggest that brain functional changes associated with adaptation to a visuo-motor skill may differ substantially depending on whether the dominant or non-dominant hand is trained, with non-dominant-hand training associated with greater activation during acquisition, and dominant-hand training associated with greater activation during bilateral transfer, persistence, and after-effects.
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http://dx.doi.org/10.1007/s00221-019-05653-5DOI Listing
December 2019

Brain MRI findings related to Alzheimer's disease in older African American adults.

Prog Mol Biol Transl Sci 2019 15;165:3-23. Epub 2019 May 15.

Pennington Biomedical Research Center, Baton Rouge, LA, United States.

Although a substantial body of research has identified brain MRI measures as important markers of Alzheimer's disease (AD) risk, progression, and treatment response, most of that research has been performed in non-Hispanic white American populations, leading to questions about the utility of the brain MRI measures among individuals of other races or ethnicities. African American individuals in particular are under-represented in AD research, and may exhibit differences in prevalence of AD risk factors, prevalence of AD, incidence of AD, the clinical course of cognitive decline, and AD neuropathology, each of which could influence the utility of brain MRI markers. Unfortunately, while current evidence suggests that African Americans exhibit poorer brain health late in life based on brain MRI measurements, several other aspects of brain MRI markers in this population are unclear, including trajectories of brain MRI markers leading up to old age, relationships between traditional brain health risk factors and brain MRI findings, and the status of brain MRI markers as correlates of cognitive impairment. This unclear state of affairs highlights the urgency of future research in which large numbers of older African American adults contribute longitudinal brain MRI measurements concurrent with clinical, cognitive, and molecular biomarker measurements, ideally in the context of AD preventive or therapeutic trials.
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http://dx.doi.org/10.1016/bs.pmbts.2019.04.002DOI Listing
April 2020

Effects of testosterone supplementation on body composition and lower-body muscle function during severe exercise- and diet-induced energy deficit: A proof-of-concept, single centre, randomised, double-blind, controlled trial.

EBioMedicine 2019 Aug 27;46:411-422. Epub 2019 Jul 27.

Louisiana State University's Pennington Biomedical Research Centre, Baton Rouge, LA, USA.

Background: Severe energy deficits during military operations, produced by significant increases in exercise and limited dietary intake, result in conditions that degrade lean body mass and lower-body muscle function, which may be mediated by concomitant reductions in circulating testosterone.

Methods: We conducted a three-phase, proof-of-concept, single centre, randomised, double-blind, placebo-controlled trial (CinicalTrials.gov, NCT02734238) of non-obese men: 14-d run-in, free-living, eucaloric diet phase; 28-d live-in, 55% exercise- and diet-induced energy deficit phase with (200 mg testosterone enanthate per week, Testosterone, n = 24) or without (Placebo, n = 26) exogenous testosterone; and 14-d recovery, free-living, ad libitum diet phase. Body composition was the primary end point; secondary endpoints included lower-body muscle function and health-related biomarkers.

Findings: Following energy deficit, lean body mass increased in Testosterone and remained stable in Placebo, such that lean body mass significantly differed between groups [mean difference between groups (95% CI), 2.5 kg (3.3, 1.6); P < .0001]. Fat mass decreased similarly in both treatment groups [0.2 (-0.4, 0.7), P = 1]. Change in lean body mass was associated with change in total testosterone (r = 0.71, P < .0001). Supplemental testosterone had no effect on lower-body muscle function or health-related biomarkers.

Interpretation: Findings suggest that supplemental testosterone may increase lean body mass during short-term severe energy deficit in non-obese, young men, but it does not appear to attenuate lower-body functional decline.

Funding: Collaborative Research to Optimize Warfighter Nutrition projects I and II, Joint Program Committee-5, funded by the US Department of Defence.
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http://dx.doi.org/10.1016/j.ebiom.2019.07.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711889PMC
August 2019

Examining Relationships between Multiple Self-Reported Sleep Measures and Gait Domains in Cognitively Healthy Older Adults.

Gerontology 2020 9;66(1):47-54. Epub 2019 May 9.

Institute for Dementia Research and Prevention, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

Background: Gait-related changes in older adulthood may be related to changes in cognition (e.g., executive functioning), and recent work suggests that different self-reported measures of sleep may be tied to contrasting aspects of executive functioning. However, the relationship between these self-reported sleep measures and gait domains has not been explored. Such an investigation would be useful in helping to determine which older adults might exhibit changes in gait as well as experience other gait-associated changes (e.g., increased fall risk).

Objective: To examine associations between different aspects of self-reported sleep and gait domains in a sample of cognitively healthy older adults.

Method: A total of 423 older adults (mean age 69.9 years, range 50-92) completed self-report measures of sleep quality, daytime sleepiness, and sleep-related distress. The participants also completed an objective, electronic measure of both single-task and dual-task gait (i.e., GAITRite). Principal component analyses were used to elucidate the solution for each gait condition, and multiple linear regression was used to examine the contributions of sleep measures to variability in gait performance.

Results: A 5-component solution of the single-task condition and a 4-component solution of the dual-task condition were identified. Multiple linear regressions revealed that a poorer sleep quality was associated with greater single-task and dual-task asymmetry. Greater daytime sleepiness was associated with increased dual-task gait variability and postural control. After controlling for the effects of other facets of sleep, sleep-related distress was not associated with any gait domain.

Conclusions: Among cognitively healthy older adults,sleep quality and daytime sleepiness, but not sleep-related distress, are associated with aspects of gait. Patients who report these symptoms should be assessed and monitored for possible changes in gait.
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http://dx.doi.org/10.1159/000499737DOI Listing
August 2020

High-Normal Adolescent Fasting Plasma Glucose Is Associated With Poorer Midlife Brain Health: Bogalusa Heart Study.

J Clin Endocrinol Metab 2019 10;104(10):4492-4500

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana.

Context: It is unclear how adolescent glycemic status relates to brain health in adulthood.

Objective: To assess the association between adolescent fasting plasma glucose (FPG) and MRI-based brain measures in midlife.

Design: Between 1973 and 1992, the Bogalusa Heart Study (BHS) collected FPG from children, 3 to 18 years old, and followed up between 1992 and 2018. Cognitive tests and brain MRI were collected in 2013 to 2016 and 2018.

Setting: Observational longitudinal cohort study.

Participants: Of 1298 contacted BHS participants, 74 completed screening, and 50 completed MRI.

Main Outcome Measures: Mean FPG per participant at ages <20, 20 to 40, and over 40 years old; brain white matter hyperintensity (WMH) volume, gray matter volume, and functional MRI (fMRI) activation to a Stroop task; tests of logical and working memory, executive function, and semantic fluency.

Results: At MRI, participants were middle aged (51.3 ± 4.4 years) and predominantly female (74%) and white (74%). Mean FPG was impaired for zero, two, and nine participants in pre-20, 20 to 40, and over-40 periods. The pre-20 mean FPG above the pre-20 median value (i.e., above 83.5 mg/dL) was associated with greater WMH volume [mean difference: 0.029% of total cranial volume, CI: (0.0059, 0.052), P = 0.015] and less fMRI activation [-1.41 units (-2.78, -0.05), P = 0.043] on midlife MRI compared with below-median mean FPG. In controlling for over-40 mean FPG status did not substantially modify the associations. Cognitive scores did not differ by pre-20 mean FPG.

Conclusions: High-normal adolescent FPG may be associated with preclinical brain changes in midlife.
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http://dx.doi.org/10.1210/jc.2018-02750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736207PMC
October 2019

Sex-Related Differences in Brain Volumes and Cerebral Blood Flow Among Overweight and Obese Adults With Type 2 Diabetes: Exploratory Analyses From the Action for Health in Diabetes Brain Magnetic Resonance Imaging Study.

J Gerontol A Biol Sci Med Sci 2020 03;75(4):771-778

Biomedical Imaging Center, Pennington Biomedical Research Center, Baton Rouge, LA.

Background: Sex may be an important modifier of brain health in response to risk factors. We compared brain structure and function of older overweight and obese women and men with type 2 diabetes mellitus.

Methods: Cross-sectional cognitive assessments and magnetic resonance images were obtained in 224 women and 95 men (mean age 69 years) with histories of type 2 diabetes mellitus and overweight or obesity. Prior to magnetic resonance images, participants had completed an average of 10 years of random assignment to either multidomain intervention targeting weight loss or a control condition of diabetes support and education. Total (summed gray and white) matter volumes, white matter hyperintensity volumes, and cerebral blood flow across five brain regions of interest were analyzed using mixed-effects models.

Results: After covariate adjustment, women, compared with men, averaged 10.9 [95% confidence interval 3.3, 18.5; ≈1%] cc greater summed region of interest volumes and 1.39 [0.00002, 2.78; ≈54%] cc greater summed white matter hyperintensity volumes. Sex differences could not be attributed to risk factor profiles or intervention response. Their magnitude did not vary significantly with respect to age, body mass index, intervention assignment, or APOE-ε4 genotype. Sex differences in brain magnetic resonance images outcomes did not account for the better levels of cognitive functioning in women than men.

Conclusions: In a large cohort of older overweight or obese adults with type 2 diabetes mellitus, differences in brain volumes and white matter disease were apparent between women and men, but these did not account for a lower prevalence of cognitive impairment in women compared with men in this cohort.

Trial Registration: NCT00017953.
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http://dx.doi.org/10.1093/gerona/glz090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205422PMC
March 2020

Magnetic resonance elastography of the brain: A study of feasibility and reproducibility using an ergonomic pillow-like passive driver.

Magn Reson Imaging 2019 06 8;59:68-76. Epub 2019 Mar 8.

School of Computer Science and Technology, Xidian University, Xi'an, Shaanxi, 710071, China. Electronic address:

Magnetic resonance elastography (MRE) can be used to noninvasively resolve the displacement pattern of induced mechanical waves propagating in tissue. The goal of this study is to establish an ergonomically flexible passive-driver design for brain MRE, to evaluate the reproducibility of MRE tissue-stiffness measurements, and to investigate the relationship between tissue-stiffness measurements and driver frequencies. An ergonomically flexible passive pillow-like driver was designed to induce mechanical waves in the brain. Two-dimensional finite-element simulation was used to evaluate mechanical wave propagation patterns in brain tissues. MRE scans were performed on 10 healthy volunteers at mechanical frequencies of 60, 50, and 40 Hz. An axial mid-brain slice was acquired using an echo-planar imaging sequence to map the displacement pattern with the motion-encoding gradient along the through-plane (z) direction. All subjects were scanned and rescanned within 1 h. The Wilcoxon signed-rank test was used to test for differences between white matter and gray matter shear-stiffness values. One-way analysis of variance (ANOVA) was used to test for differences between shear-stiffness measurements made at different frequencies. Scan-rescan reproducibility was evaluated by calculating the within-subject coefficient of variation (CV) for each subject. The finite-element simulation showed that a pillow-like passive driver is capable of efficient shear-wave propagation through brain tissue. No subjects complained about discomfort during MRE acquisitions using the ergonomically designed driver. The white-matter elastic modulus (mean ± standard deviation) across all subjects was 3.85 ± 0.12 kPa, 3.78 ± 0.15 kPa, and 3.36 ± 0.11 kPa at frequencies of 60, 50, and 40 Hz, respectively. The gray-matter elastic modulus across all subjects was 3.33 ± 0.14 kPa, 2.82 ± 0.16 kPa, and 2.24 ± 0.14 kPa at frequencies of 60, 50, and 40 Hz, respectively. The Wilcoxon signed-rank test confirmed that the shear stiffness was significantly higher in white matter than gray matter at all three frequencies. The ranges of within-subject coefficients of variation for white matter, gray matter, and whole-brain shear-stiffness measurements for the three frequencies were 1.8-3.5% (60 Hz), 4.7-6.0% (50 Hz), and 3.7-4.1% (40 Hz). An ergonomic pneumatic pillow-like driver is feasible for highly reproducible in vivo evaluation of brain-tissue shear stiffness. Brain-tissue shear-stiffness values were frequency-dependent, thus emphasizing the importance of standardizing MRE acquisition protocols in multi-center studies.
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http://dx.doi.org/10.1016/j.mri.2019.03.009DOI Listing
June 2019

Vascular Burden Score Impacts Cognition Independent of Amyloid PET and MRI Measures of Alzheimer's Disease and Vascular Brain Injury.

J Alzheimers Dis 2019 ;68(1):187-196

UC Davis Department of Neurology and Center for Neuroscience, Davis, CA, USA.

Background/objective: To determine the impact of vascular burden on rates of decline in episodic memory and executive function. We hypothesize that greater vascular burden will have an additive negative impact on cognition after accounting for baseline cognitive impairment, positron emission tomography (PET) amyloid burden, and magnetic resonance imaging (MRI) measures.

Methods: Individuals were followed an average of 5 years with serial cognitive assessments. Predictor variables include vascular burden score (VBS), quantitative brain MRI assessment, and amyloid imaging. Subjects consisted of 65 individuals, 53% of whom were male, aged 73.2±7.2 years on average with an average of 15.5±3.3 years of educational achievement.

Results: Baseline cognitive impairment was significantly associated poorer episodic memory (p < 0.0001), smaller hippocampal volume (p < 0.0001), smaller brain volume (p = 0.0026), and greater global Pittsburg Imaging Compound B (PiB) index (p = 0.0008). Greater amyloid burden was associated with greater decline in episodic memory over time (β= -0.20±0.07, p < 0.005). VBS was significantly associated with the level of executive function performance (β= -0.14±0.05, p < 0.005) and there was a significant negative interaction between VBS, cognitive impairment, and PiB index (β= -0.065±0.03, p = 0.03).

Conclusions: Our results find a significant influence of VBS independent of standard MRI measures and cerebral amyloid burden on executive function. In addition, VBS reduced the amount of cerebral amyloid burden needed to result in cognitive impairment. We conclude that the systemic effects of vascular disease as reflected by the VBS independently influence cognitive ability.
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http://dx.doi.org/10.3233/JAD-180965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615551PMC
June 2020

Sex-related differences in the prevalence of cognitive impairment among overweight and obese adults with type 2 diabetes.

Alzheimers Dement 2018 09 5;14(9):1184-1192. Epub 2018 Jul 5.

Departments of Epidemiology and Neurology, Mayo Clinic, Rochester, MN, USA.

Introduction: Type 2 diabetes mellitus and obesity may increase risks for cognitive decline as individuals age. It is unknown whether this results in different prevalences of cognitive impairment for women and men.

Methods: The Action for Health in Diabetes, a randomized controlled clinical trial of a 10-year intensive lifestyle intervention, adjudicated cases of cross-sectional cognitive impairment (mild cognitive impairment or dementia) 10-13 years after enrollment in 3802 individuals (61% women).

Results: The cross-sectional prevalences of cognitive impairment were 8.3% (women) and 14.8% (men): adjusted odds ratio 0.55, 95% confidence interval [0.43, 0.71], P < .001. Demographic, clinical, and lifestyle risk factors varied between women and men but did not account for this difference, which was limited to individuals without apolipoprotein E (APOE)-ε4 alleles (interaction P = .034).

Conclusions: Among overweight and obese adults with type 2 diabetes mellitus, traditional risk factors did not account for the lower prevalence of cognitive impairment observed in women compared with men.
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http://dx.doi.org/10.1016/j.jalz.2018.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338071PMC
September 2018

Pedometer-assessed steps per day as a predictor of cognitive performance in older adults.

Neuropsychology 2018 Nov 6;32(8):941-949. Epub 2018 Aug 6.

Institute for Dementia Research and Prevention.

Objective: To examine associations between pedometer-assessed daily steps and several domains of cognitive functioning in cognitive healthy older adults.

Method: A total of 582 cognitively healthy older adults enrolled in a longitudinal aging study completed the Uniform Data Set (UDS) neuropsychological battery ( = 374) or the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; = 208) and were asked to wear a pedometer for 1 week.

Results: Bivariate correlations revealed associations between average daily steps and attention, executive functioning, language, and memory on one or both cognitive batteries. Multiple regression analyses controlling for demographic, health, and mobility variables demonstrated a significant relationship between average daily steps and the executive functioning composite of the UDS battery and average daily steps and the attention index of the RBANS battery. Both of these composites include measures of processing speed and, therefore, the most robust link between daily steps and cognition may be its association with processing speed.

Conclusions: Step counts as measured by a pedometer, a simple and inexpensive measure of daily physical activity, are robustly associated with aspects of cognition. As pedometer-based interventions have shown success in increasing daily physical activity in older adults, a greater number of future studies should consider measuring cognitive outcomes of these interventions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000487DOI Listing
November 2018
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