Harmonized Multisite MRI-Based Quantification of Human Liver Fat and Stiffness: A Pilot Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments. PURPOSE/HYPOTHESIS: The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors. STUDY TYPE: Cohort. SUBJECTS: Four community-dwelling adults with obesity. FIELD STRENGTH/SEQUENCE: 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE. ASSESSMENT: Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing. STATISTICAL TESTS: Linear regression in MATLAB, ICC analyses using SAS 9.4, one-sided 95% confidence intervals for the ICC. RESULTS: PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF. CONCLUSIONS: We demonstrated harmonization of PDFF, MRS, and MRE-based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

Effect of renin-angiotensin system antihypertensive medication use on cognitive function in diabetes mellitus with obesity or overweight: An ancillary study to the Action for Health in Diabetes (Look AHEAD) trial.

AIM: To determine whether antihypertensive medication (AHM) acting through the renin angiotensin system (RAS-AHM), compared with other AHM, can mitigate effects on cognitive function and risk for impairment in a population with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This secondary analysis of the randomized controlled Action for Health in Diabetes (Look AHEAD) study included 712 community-dwelling participants who were followed over 15 years. Logistic regression was used to relate RAS-AHM use to cognitive impairment, and linear regression was used to relate RAS-AHM use to domain-specific cognitive function after adjusting for potential confounders. RESULTS: A total of 563 individuals reported RAS-AHM use and 149 reported other-AHM use during the study. RAS-AHM users have college or higher education (53%), had higher baseline glycated haemoglobin (57 mmol/mol), and reported higher diabetes medication use (86%), while other-AHM users were more likely to be White (72%), obese (25%) and to have cardiovascular history (19%). RAS-AHM use was not associated with a reduced risk of dementia compared with other-AHM use. We did observe better executive function (Trail Making Test, part B, P < 0.04), processing speed (Digit Symbol Substitution Test, P < 0.004), verbal memory (Rey Auditory Verbal Learning Test-delayed recall, P < 0.005), and composite score (P < 0.008) among RAS-AHM users compared with other-AHM users. CONCLUSION: In this sample of adults with T2DM, free of dementia at baseline, we observed a slower decline in processing speed, executive function, verbal memory, and composite score among RAS-AHM users.

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

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.

Impact of COVID-19 Pandemic on Research Participation Among Older African Americans.

COVID-19 represents the newest health disparity faced by African Americans (AA). This study assessed the impact of COVID-19 on barriers and willingness to participate in research among older AAs. An online survey was sent to a nationwide sample of 65- to 85-year-old AAs between January and February 2021. Constant comparison analysis was used to extract themes. A total of 624 older AAs completed the survey. Approximately 40% of participants were willing to engage in virtual or in-person research. Of the individuals who were willing to participate in research, >50% were willing to engage in a spectrum of activities from group discussions to group exercise. Research participation themes related to logistics, technology, pandemic fears, and privacy or security. Older AAs face new research barriers that can be overcome through data use transparency and technology resources. This information can be used to encourage dementia research engagement among older AAs despite the pandemic.

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

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.

Estrogen, brain structure, and cognition in postmenopausal women.

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.

Molecular correlates of MRS-based 31 phosphocreatine muscle resynthesis rate in healthy adults.

Dynamic phosphorus MRS (31 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 31 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 (VO2 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 31 P-MRS based PCr resynthesis may represent a valid non-invasive surrogate marker of mitochondrial NAMPT in human skeletal muscle.

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

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.

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

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 .

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

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.

Total body skeletal muscle mass estimated by magnetic resonance imaging and creatine (methyl-d3 ) dilution in athletes.

Creatine dilution (D3 -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 D3 -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; V̇O2 peak: 56.5 ± 7.0 and 49.6 ± 4.4 mL kg-1  min-1 , mean ± SD). SMM was determined following 60 mg of dosed D3 -cr and analysis of expelled urine collected on four subsequent days for creatine, creatinine, D3 -cr, and D3 -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 D3 -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 D3 -cr has potential utility in athletes, as referenced against MRI, but show that assumptions regarding creatine pool size need to be carefully considered.

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

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.

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

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.

Validation of T1w-based segmentations of white matter hyperintensity volumes in large-scale datasets of aging.

INTRODUCTION: Fluid-attenuated Inversion Recovery (FLAIR) and dual T2w and proton density (PD) magnetic resonance images (MRIs) are considered to be the optimum sequences for detecting white matter hyperintensities (WMHs) in aging and Alzheimer's disease populations. However, many existing large multisite studies forgo their acquisition in favor of other MRI sequences due to economic and time constraints. METHODS: In this article, we have investigated whether FLAIR and T2w/PD sequences are necessary to detect WMHs in Alzheimer's and aging studies, compared to using only T1w images. Using a previously validated automated tool based on a Random Forests classifier, WMHs were segmented for the baseline visits of subjects from ADC, ADNI1, and ADNI2/GO studies with and without T2w/PD and FLAIR information. The obtained WMH loads (WMHLs) in different lobes were then correlated with manually segmented WMHLs, each other, age, cognitive, and clinical measures to assess the strength of the correlations with and without using T2w/PD and FLAIR information. RESULTS: The WMHLs obtained from T1w-Only segmentations correlated with the manual WMHLs (ADNI1: r = .743, p < .001, ADNI2/GO: r = .904, p < .001), segmentations obtained from T1w + T2w + PD for ADNI1 (r = .888, p < .001) and T1w + FLAIR for ADNI2/GO (r = .969, p < .001), age (ADNI1: r = .391, p < .001, ADNI2/GO: r = .466, p < .001), and ADAS13 (ADNI1: r = .227, p < .001, ADNI2/GO: r = .190, p < 0.001), and NPI (ADNI1: r = .290, p < .001, ADNI2/GO: r = 0.144, p < .001), controlling for age. CONCLUSION: Our results suggest that while T2w/PD and FLAIR provide more accurate estimates of the true WMHLs, T1w-Only segmentations can still provide estimates that hold strong correlations with the actual WMHLs, age, and performance on various cognitive/clinical scales, giving added value to datasets where T2w/PD or FLAIR are not available.

Baseline connectome modular abnormalities in the childhood phase of a longitudinal study on individuals with chromosome 22q11.2 deletion syndrome.

Occurring in at least 1 in 3,000 live births, chromosome 22q11.2 deletion syndrome (22q11DS) produces a complex phenotype that includes a constellation of medical complications such as congenital cardiac defects, immune deficiency, velopharyngeal dysfunction, and characteristic facial dysmorphic features. There is also an increased incidence of psychiatric diagnosis, especially intellectual disability and ADHD in childhood, lifelong anxiety, and a strikingly high rate of schizophrenia spectrum disorders, which occur in around 30% of adults with 22q11DS. Using innovative computational connectomics, we studied how 22q11DS affects high-level network signatures of hierarchical modularity and its intrinsic geometry in 55 children with confirmed 22q11DS and 27 Typically Developing (TD) children. Results identified 3 subgroups within our 22q11DS sample using a K-means clustering approach based on several midline structural measures-of-interests. Each subgroup exhibited distinct patterns of connectome abnormalities. Subtype 1, containing individuals with generally healthy-looking brains, exhibited no significant differences in either modularity or intrinsic geometry when compared with TD. By contrast, the more anomalous 22q11DS Subtypes 2 and 3 brains revealed significant modular differences in the right hemisphere, while Subtype 3 (the most anomalous anatomy) further exhibited significantly abnormal connectome intrinsic geometry in the form of left-right temporal disintegration. Taken together, our findings supported an overall picture of (a) anterior-posteriorly differential interlobar frontotemporal/frontoparietal dysconnectivity in Subtypes 2 and 3 and (b) differential intralobar dysconnectivity in Subtype 3. Our ongoing studies are focusing on whether these subtypes and their connnectome signatures might be valid biomarkers for predicting the degree of psychosis-proneness risk found in 22q11DS. Hum Brain Mapp 39:232-248, 2018. © 2017 Wiley Periodicals, Inc.

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

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.

Performance comparison of 10 different classification techniques in segmenting white matter hyperintensities in aging.

INTRODUCTION: White matter hyperintensities (WMHs) are areas of abnormal signal on magnetic resonance images (MRIs) that characterize various types of histopathological lesions. The load and location of WMHs are important clinical measures that may indicate the presence of small vessel disease in aging and Alzheimer's disease (AD) patients. Manually segmenting WMHs is time consuming and prone to inter-rater and intra-rater variabilities. Automated tools that can accurately and robustly detect these lesions can be used to measure the vascular burden in individuals with AD or the elderly population in general. Many WMH segmentation techniques use a classifier in combination with a set of intensity and location features to segment WMHs, however, the optimal choice of classifier is unknown. METHODS: We compare 10 different linear and nonlinear classification techniques to identify WMHs from MRI data. Each classifier is trained and optimized based on a set of features obtained from co-registered MR images containing spatial location and intensity information. We further assess the performance of the classifiers using different combinations of MRI contrast information. The performances of the different classifiers were compared on three heterogeneous multi-site datasets, including images acquired with different scanners and different scan-parameters. These included data from the ADC study from University of California Davis, the NACC database and the ADNI study. The classifiers (naïve Bayes, logistic regression, decision trees, random forests, support vector machines, k-nearest neighbors, bagging, and boosting) were evaluated using a variety of voxel-wise and volumetric similarity measures such as Dice Kappa similarity index (SI), Intra-Class Correlation (ICC), and sensitivity as well as computational burden and processing times. These investigations enable meaningful comparisons between the performances of different classifiers to determine the most suitable classifiers for segmentation of WMHs. In the spirit of open-source science, we also make available a fully automated tool for segmentation of WMHs with pre-trained classifiers for all these techniques. RESULTS: Random Forests yielded the best performance among all classifiers with mean Dice Kappa (SI) of 0.66±0.17 and ICC=0.99 for the ADC dataset (using T1w, T2w, PD, and FLAIR scans), SI=0.72±0.10, ICC=0.93 for the NACC dataset (using T1w and FLAIR scans), SI=0.66±0.23, ICC=0.94 for ADNI1 dataset (using T1w, T2w, and PD scans) and SI=0.72±0.19, ICC=0.96 for ADNI2/GO dataset (using T1w and FLAIR scans). Not using the T2w/PD information did not change the performance of the Random Forest classifier (SI=0.66±0.17, ICC=0.99). However, not using FLAIR information in the ADC dataset significantly decreased the Dice Kappa, but the volumetric correlation did not drastically change (SI=0.47±0.21, ICC=0.95). CONCLUSION: Our investigations showed that with appropriate features, most off-the-shelf classifiers are able to accurately detect WMHs in presence of FLAIR scan information, while Random Forests had the best performance across all datasets. However, we observed that the performances of most linear classifiers and some nonlinear classifiers drastically decline in absence of FLAIR information, with Random Forest still retaining the best performance.

White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy.

This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aß42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aß42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV.

Our aim was to examine the clinical relevance of white matter hyperintensities (WMH) in HIV. We used an automated approach to quantify WMH volume in HIV seropositive (HIV+; n = 65) and HIV seronegative (HIV-; n = 29) adults over age 60. We compared WMH volumes between HIV+ and HIV- groups in cross-sectional and multiple time-point analyses. We also assessed correlations between WMH volumes and cardiovascular, HIV severity, cognitive scores, and diffusion tensor imaging variables. Serostatus groups did not differ in WMH volume, but HIV+ participants had less cerebral white matter (mean: 470.95 [43.24] vs. 497.63 [49.42] mL, p = 0.010). The distribution of WMH volume was skewed in HIV+ with a high proportion (23%) falling above the 95th percentile of WMH volume defined by the HIV- group. Serostatus groups had similar amount of WMH volume growth over time. Total WMH volume directly correlated with measures of hypertension and inversely correlated with measures of global cognition, particularly in executive functioning, and psychomotor speed. Greater WMH volume was associated with poorer brain integrity measured from diffusion tensor imaging (DTI) in the corpus callosum and sagittal stratum. In this group of HIV+ individuals over 60, WMH burden was associated with cardiovascular risk and both worse diffusion MRI and cognition. The median total burden did not differ by serostatus; however, a subset of HIV+ individuals had high WMH burden.