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1.
Neuroinformatics ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062817

RESUMO

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.

2.
Neurobiol Aging ; 86: 134-142, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31791658

RESUMO

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.

3.
Gerontology ; 66(1): 47-54, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31071713

RESUMO

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.

4.
Exp Brain Res ; 237(12): 3109-3121, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542802

RESUMO

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.

5.
EBioMedicine ; 46: 411-422, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31358477

RESUMO

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.


Assuntos
Composição Corporal/efeitos dos fármacos , Dieta , Suplementos Nutricionais , Exercício , Músculos/efeitos dos fármacos , Músculos/metabolismo , Testosterona/administração & dosagem , Adolescente , Adulto , Biomarcadores , Peso Corporal/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Estudo de Prova de Conceito , Adulto Jovem
6.
Neuropsychology ; 32(8): 941-949, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30080077

RESUMO

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 (n = 374) or the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; n = 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).


Assuntos
Actigrafia , Cognição/fisiologia , Exercício/fisiologia , Desempenho Psicomotor/fisiologia , Actigrafia/instrumentação , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Atenção , Função Executiva , Feminino , Avaliação Geriátrica , Nível de Saúde , Humanos , Linguagem , Estudos Longitudinais , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos
7.
Front Psychol ; 9: 17, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29434559

RESUMO

Food image fMRI paradigms are used widely for investigating the neural basis of ingestive behavior. However, these paradigms have not been validated in terms of ingestive behavior constructs, engagement of food-relevant neural systems, or test-retest reliability, making the generalizability of study findings unclear. Therefore, we validated the Macronutrient Picture System (MaPS) (McClernon et al., 2013), which includes food images from the six categories represented in the Geiselman Food Preference Questionnaire (FPQ) (Geiselman et al., 1998). Twenty-five healthy young adults (n = 21 female, mean age = 20.6 ± 1.1 years, mean BMI = 22.1 ± 1.9 kg/m2) rated the MaPS images in terms of visual interest, appetitive quality, nutrition, emotional valence, liking, and frequency of consumption, and completed the FPQ. In a second study, 12 individuals (n=8 female, mean age = 25.0 ± 6.5 years, mean BMI = 28.2 ± 8.7 kg/m2) viewed MaPS and control images (vegetables and non-food) during two separate 3T BOLD fMRI scans after fasting overnight. Intuitively, high fat/high sugar (HF/HS) and high fat/high complex carbohydrate (HF/HCCHO) images achieved higher liking and appetitive ratings, and lower nutrition ratings, than low fat/low complex carbohydrate/high protein (LF/LCHO/HP) images on average. Within each food category, FPQ scores correlated strongly with MaPS image liking ratings (p < 0.001). Brain activation differences between viewing images of HF/HS and vegetables, and between HF/HCCHO and vegetables, were seen in several reward-related brain regions (e.g., putamen, insula, and medial frontal gyrus). Intra-individual, inter-scan agreement in a summary measure of brain activation differences in seven reward network regions of interest was high (ICC = 0.61), and was even higher when two distinct sets of food images with matching visual ratings were shown in the two scans (ICC = 0.74). These results suggest that the MaPS provides valid representation of food categories and reliably activates food-reward-relevant neural systems.

8.
Hum Brain Mapp ; 39(3): 1093-1107, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29181872

RESUMO

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.


Assuntos
Envelhecimento , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética , Substância Branca/diagnóstico por imagem , Idoso , Envelhecimento/patologia , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Encéfalo/patologia , Conjuntos de Dados como Assunto , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Reconhecimento Automatizado de Padrão , Substância Branca/patologia
9.
Neurobiol Aging ; 63: 22-32, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29220823

RESUMO

Age is not only the greatest risk factor for Alzheimer's disease (AD) but also a key modifier of disease presentation and progression. Here, we investigate how longitudinal atrophy patterns vary with age in mild cognitive impairment (MCI) and AD. Data comprised serial longitudinal 1.5-T magnetic resonance imaging scans from 153 AD, 339 MCI, and 191 control subjects. Voxel-wise maps of longitudinal volume change were obtained and aligned across subjects. Local volume change was then modeled in terms of diagnostic group and an interaction between group and age, adjusted for total intracranial volume, white-matter hyperintensity volume, and apolipoprotein E genotype. Results were significant at p < 0.05 with family-wise error correction for multiple comparisons. An age-by-group interaction revealed that younger AD patients had significantly faster atrophy rates in the bilateral precuneus, parietal, and superior temporal lobes. These results suggest younger AD patients have predominantly posterior progressive atrophy, unexplained by white-matter hyperintensity, apolipoprotein E, or total intracranial volume. Clinical trials may benefit from adapting outcome measures for patient groups with lower average ages, to capture progressive atrophy in posterior cortices.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/patologia , Hipocampo/patologia , Substância Branca/patologia , Idoso , Doença de Alzheimer/diagnóstico por imagem , Apolipoproteínas E/genética , Atrofia , Disfunção Cognitiva/patologia , Progressão da Doença , Feminino , Genótipo , Hipocampo/diagnóstico por imagem , Humanos , Angiografia por Ressonância Magnética , Masculino , Tamanho do Órgão , Substância Branca/diagnóstico por imagem
10.
Neuroimage ; 157: 233-249, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28602597

RESUMO

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.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Conjuntos de Dados como Assunto , Feminino , Humanos , Processamento de Imagem Assistida por Computador/normas , Imagem por Ressonância Magnética/normas , Masculino
11.
Artigo em Inglês | MEDLINE | ID: mdl-28620356

RESUMO

Stimulating increased thermogenic activity in adipose tissue is an important biological target for obesity treatment, and label-free imaging techniques with the potential to quantify stimulation-associated biochemical changes to the adipose tissue are highly sought after. In this study, we used spatially resolved Fourier transform infrared (FTIR) imaging to quantify biochemical changes caused by cold exposure in the brown and subcutaneous white adipose tissues (BAT and s-WAT) of 6 week-old C57BL6 mice exposed to 30°C (N = 5), 24°C (N = 5), and 10°C (N = 5) conditions for 10 days. Fat exposed to colder temperatures demonstrated greater thermogenic activity as indicated by increased messenger RNA expression levels of a panel of thermogenic marker genes including uncoupling protein 1 (UCP-1) and Dio2. Protein to lipid ratio, calculated from the ratio of the integrated area from 1,600 to 1,700 cm-1 (amide I) to the integrated area from 2,830 to 2,980 cm-1 (saturated lipids), was elevated in 10°C BAT and s-WAT compared to 24°C (p = 0.004 and p < 0.0001) and 30°C (p = 0.0033 and p < 0.0001). Greater protein to lipid ratio was associated with greater UCP-1 expression level in the BAT (p = 0.021) and s-WAT (p = 0.032) and greater Dio2 expression in s-WAT (p = 0.033). The degree of unsaturation, calculated from the ratio of the integrated area from 2,992 to 3,020 cm-1 (unsaturated lipids) to the integrated area from 2,830 to 2,980 cm-1 (saturated lipids), showed stepwise decreases going from colder-exposed to warmer-exposed BAT. Complementary 1H NMR measurements confirmed the findings from this ratio in BAT. Principal component analysis applied to FTIR spectra revealed pronounced differences in overall spectral characteristics between 30, 24, and 10°C BAT and s-WAT. Spatially resolved FTIR imaging is a promising technique to quantify cold-induced biochemical changes in BAT and s-WAT in a label-free manner.

12.
Contemp Clin Trials ; 58: 47-57, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28479217

RESUMO

BACKGROUND: The physiological consequences of severe energy deficit include hypogonadism and the loss of fat-free mass. Prolonged energy deficit also impacts physical performance, mood, attentiveness, and decision-making capabilities. This study will determine whether maintaining a eugonadal state during severe, sustained energy deficit attenuates physiological decrements and maintains mental performance. This study will also assess the effects of normalizing testosterone levels during severe energy deficit and recovery on gut health and appetite regulation. METHODS: Fifty physically active men will participate in a 3-phase, randomized, placebo-controlled study. After completing a 14-d, energy-adequate, diet acclimation phase (protein: 1.6g∙kg-1∙d-1; fat: 30% total energy intake), participants will be randomized to undergo a 28-d, 55% energy deficit phase with (DEF+TEST: 200mg testosterone enanthate per week) or without (DEF) exogenous testosterone. Diet and physical activity will be rigorously controlled. Recovery from the energy deficit (ad libitum diet, no testosterone) will be assessed until body mass has been recovered within ±2.5% of initial body mass. Body composition, stable isotope methodologies, proteomics, muscle biopsies, whole-room calorimetry, molecular biology, activity/sleep monitoring, personality and cognitive function assessments, functional MRI, and comprehensive biochemistries will be used to assess physiological and psychological responses to energy restriction and recovery feeding while volunteers are in an expected hypogonadal versus eugonadal state. DISCUSSION: The Optimizing Performance for Soldiers (OPS) study aims to determine whether preventing hypogonadism will mitigate declines in physical and mental function that typically occur during prolonged energy deficit, and the efficacy of testosterone replacement on recovery from severe underfeeding. TRIAL REGISTRATION: NCT02734238.


Assuntos
Androgênios/farmacologia , Metabolismo Energético/efeitos dos fármacos , Fadiga Mental/tratamento farmacológico , Militares , Músculo Esquelético/efeitos dos fármacos , Testosterona/análogos & derivados , Adolescente , Adulto , Apetite , Biomarcadores , Índice de Massa Corporal , Pesos e Medidas Corporais , Cognição/efeitos dos fármacos , Exercício , Microbioma Gastrointestinal/fisiologia , Humanos , Masculino , Músculo Esquelético/fisiologia , Determinação da Personalidade , Projetos de Pesquisa , Sono/efeitos dos fármacos , Testosterona/farmacologia , Adulto Jovem
13.
IEEE Trans Med Imaging ; 36(8): 1758-1768, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28422655

RESUMO

Segmentation and volumetric quantification of white matter hyperintensities (WMHs) is essential in assessment and monitoring of the vascular burden in aging and Alzheimer's disease (AD), especially when considering their effect on cognition. Manually segmenting WMHs in large cohorts is technically unfeasible due to time and accuracy concerns. Automated tools that can detect WMHs robustly and with high accuracy are needed. Here, we present and validate a fully automatic technique for segmentation and volumetric quantification of WMHs in aging and AD. The proposed technique combines intensity and location features frommultiplemagnetic resonance imaging contrasts and manually labeled training data with a linear classifier to perform fast and robust segmentations. It provides both a continuous subject specific WMH map reflecting different levels of tissue damage and binary segmentations. Themethodwas used to detectWMHs in 80 elderly/AD brains (ADC data set) as well as 40 healthy subjects at risk of AD (PREVENT-AD data set). Robustness across different scanners was validated using ten subjects from ADNI2/GO study. Voxel-wise and volumetric agreements were evaluated using Dice similarity index (SI) and intra-class correlation (ICC), yielding ICC=0.96 , SI = 0.62±0.16 for ADC data set and ICC=0.78 , SI=0.51±0.15 for PREVENT-AD data set. The proposed method was robust in the independent sample yielding SI=0.64±0.17 with ICC=0.93 for ADNI2/GO subjects. The proposed method provides fast, accurate, and robust segmentations on previously unseen data from different models of scanners, making it ideal to study WMHs in large scale multi-site studies.


Assuntos
Doença de Alzheimer , Humanos , Imagem por Ressonância Magnética , Análise de Regressão , Substância Branca
14.
Neuroimage Clin ; 14: 166-173, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28180075

RESUMO

The purpose of this study was to determine whether white matter microstructure measured by diffusion magnetic resonance imaging (dMRI) provides independent information about baseline level or change in executive function (EF) or memory (MEM) in older adults with and without cognitive impairment. Longitudinal data was acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study from phases GO and 2 (2009-2015). ADNI participants included were diagnosed as cognitively normal (n = 46), early mild cognitive impairment (MCI) (n = 48), late MCI (n = 29), and dementia (n = 39) at baseline. We modeled the association between dMRI-based global white matter mean diffusivity (MD) and baseline level and change in EF and MEM composite scores, in models controlling for baseline bilateral hippocampal volume, regional cerebral FDG PET metabolism and global cerebral AV45 PET uptake. EF and MEM composite scores were measured at baseline, 6, 12, 24 and 36 months. In the baseline late MCI and dementia groups, greater global MD was associated with lesser baseline EF, but not EF change nor MEM baseline or change. As expected, lesser hippocampal volume and lesser FDG PET metabolism was associated with greater rates of EF and MEM decline. In ADNI-GO/2 participants, white matter integrity provided independent information about current executive function, but was not sensitive to future cognitive change. Since individuals experiencing executive function declines progress to dementia more rapidly than those with only memory impairment, better biomarkers of future executive function decline are needed.


Assuntos
Envelhecimento , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Demência/diagnóstico por imagem , Função Executiva/fisiologia , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Análise de Componente Principal , Análise de Regressão
15.
J Neurovirol ; 23(3): 422-429, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28101804

RESUMO

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.


Assuntos
Córtex Cerebral/patologia , Corpo Caloso/patologia , Infecções por HIV/patologia , Hipertensão/patologia , RNA Viral/sangue , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/virologia , Cognição/fisiologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/virologia , Estudos Transversais , Imagem de Tensor de Difusão , Função Executiva/fisiologia , Feminino , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/virologia , HIV-1/patogenicidade , HIV-1/fisiologia , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/virologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Índice de Gravidade de Doença , Substância Branca/diagnóstico por imagem , Substância Branca/virologia
16.
Hippocampus ; 27(3): 249-262, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27933676

RESUMO

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.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Idoso , Envelhecimento/patologia , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Atrofia/diagnóstico por imagem , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Progressão da Doença , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão , Fragmentos de Peptídeos/líquido cefalorraquidiano
17.
Neurobiol Aging ; 48: 48-52, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27639120

RESUMO

Cross-sectional studies show that elevated cerebral amyloid is associated with greater white-matter hyperintensity (WMH) burden in cognitively normal (CN) older adults. However, the relative time courses of amyloid and WMH accrual are unclear. To address this, we tested the associations between known WMH correlates-age, hypertension, and amyloid-with WMH accrual rate. We used brain magnetic resonance imaging to measure WMH change in 112 CN Alzheimer's Disease Neuroimaging Initiative (GO/2) participants over a 2-year period. A linear mixed effects model assessed baseline cerebrospinal fluid amyloid beta (Aß) 1-42, hypertension, age, and their interactions, as predictors of greater WMH accrual. Greater amyloid burden was associated with greater WMH accrual over time. Those with hypertension showed a stronger association between greater amyloid burden and WMH accrual rate. Greater age was not significantly associated with greater WMH accrual in this model. Although the direction of the relationship cannot be tested in this model, CN individuals harboring cerebral amyloid had greater accrual of WMH over a 2-year period after accounting for hypertension and age. Impaired amyloid clearance and cerebral small vessel disease may both underlie the more rapid emergence of WM lesions. The role of cerebral amyloid burden in white-matter injury should thus be considered as a relevant factor when WMHs are detected clinically.


Assuntos
Envelhecimento/metabolismo , Envelhecimento/patologia , Proteínas Amiloidogênicas/metabolismo , Cognição/fisiologia , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Idoso , Envelhecimento/psicologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Hipertensão , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Substância Branca/patologia , Substância Branca/fisiopatologia
18.
J Alzheimers Dis ; 52(2): 719-29, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26967227

RESUMO

BACKGROUND: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer's disease (AD). In assessing physical activity, caloric expenditure is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual. OBJECTIVE: To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons. METHODS: All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older. We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain. Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent. RESULTS: Higher energy output, from a variety of physical activity types, was associated with larger GM volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis. CONCLUSION: Increasing energy output from a variety of physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status.


Assuntos
Envelhecimento/fisiologia , Encéfalo/diagnóstico por imagem , Exercício/fisiologia , Substância Cinzenta/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Envelhecimento/psicologia , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/fisiopatologia , Substância Cinzenta/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Atividades de Lazer , Estudos Longitudinais , Imagem por Ressonância Magnética , Tamanho do Órgão , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Estados Unidos
19.
J Psychiatry Neurosci ; 41(3): 203-13, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26599134

RESUMO

BACKGROUND: Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an elevated risk for schizophrenia, which increases with history of childhood anxiety. Altered hippocampal morphology is a common neuroanatomical feature of 22q11.2DS and idiopathic schizophrenia. Relating hippocampal structure in children with 22q11.2DS to anxiety and impaired cognitive ability could lead to hippocampus-based characterization of psychosis-proneness in this at-risk population. METHODS: We measured hippocampal volume using a semiautomated approach on MRIs collected from typically developing children and children with 22q11.2DS. We then analyzed hippocampal morphology with Localized Components Analysis. We tested the modulating roles of diagnostic group, hippocampal volume, sex and age on local hippocampal shape components. Lastly, volume and shape components were tested as covariates of IQ and anxiety. RESULTS: We included 48 typically developing children and 69 children with 22q11.2DS in our study. Hippocampal volume was reduced bilaterally in children with 22q11.2DS, and these children showed greater variation in the shape of the anterior hippocampus than typically developing children. Children with 22q11.2DS had greater inward deformation of the anterior hippocampus than typically developing children. Greater inward deformation of the anterior hippocampus was associated with greater severity of anxiety, specifically fear of physical injury, within the 22q11.2DS group. LIMITATIONS: Shape alterations are not specific to hippocampal subfields. CONCLUSION: Alterations in the structure of the anterior hippocampus likely affect function and may impact limbic circuitry. We suggest these alterations potentially contribute to anxiety symptoms in individuals with 22q11.2DS through modulatory pathways. Altered hippocampal morphology may be uniquely linked to anxiety risk factors for schizophrenia, which could be a powerful neuroanatomical marker of schizophrenia risk and hence protection.


Assuntos
Ansiedade/diagnóstico por imagem , Síndrome de DiGeorge/diagnóstico por imagem , Síndrome de DiGeorge/psicologia , Hipocampo/diagnóstico por imagem , Adolescente , Criança , Feminino , Hipocampo/crescimento & desenvolvimento , Humanos , Processamento de Imagem Assistida por Computador , Inteligência , Testes de Inteligência , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão , Prognóstico , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Caracteres Sexuais
20.
Front Aging Neurosci ; 7: 221, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26648866

RESUMO

In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of amyloid burden and VRFs with WMH burden in CN elderly individuals with low to moderate vascular risk. Participants (n = 150) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) received fluid attenuated inversion recovery (FLAIR) MRI at study entry. Total WMH volume was calculated from FLAIR images co-registered with structural MRI. Amyloid burden was determined by cerebrospinal fluid Aß1-42 levels. Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation. We tested ridge regression models for independent associations and interactions of elevated blood pressure (BP) and amyloid to total WMH volume. We found that greater amyloid burden and a clinical history of hypertension were independently associated with greater WMH volume. In addition, elevated BP modified the association between amyloid and WMH, such that those with either current or past evidence of elevated BP had greater WMH volumes at a given burden of amyloid. These findings are consistent with the hypothesis that cerebral amyloid accumulation and VRFs are independently associated with clinically latent white matter damage represented by WMHs. The potential contribution of amyloid to WMHs should be further explored, even among elderly individuals without cognitive impairment and with limited VRF exposure.

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