White matter lesions and brain gray matter volume in cognitively normal elders

Cerebral white matter lesions (WMLs) reflect small vessel disease, are common in elderly individuals, and are associated with cognitive impairment. We sought to determine the relationships between WMLs, age, gray matter (GM) volume, and cognition in the Cardiovascular Health Study (CHS). From the Cardiovascular Health Study we selected 740 cognitively normal controls with a 1.5 T magnetic resonance imaging (MRI) scan of the brain and a detailed diagnostic evaluation. WML severity was determined using a standardized visual rating system. GM volumes were analyzed using voxel-based morphometry implemented in the Statistical Parametric Mapping software. WMLs were inversely correlated with GM volume, with the greatest volume loss in the frontal cortex. Age-related atrophy was observed in the hippocampus and posterior cingulate cortex. Regression analyses revealed links among age, APOE*4 allele, hypertension, WMLs, GM volume, and digit symbol substitution test scores. Both advancing age and hypertension predict higher WML load, which is itself associated with GM atrophy. Longitudinal data are needed to confirm the temporal sequence of events leading to a decline in cognitive function.     

White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis

ObjectiveDespite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations.MethodsTwenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls.ResultsFocal and/or diffuse hyperintense signals in the cerebral white matter were present in most (85%) patients. Cerebellar atrophy was common (62%), present from the age of 5 years. Progression was observed in two out of 6 patients with follow-up scans. Cortical atrophy (62%) and corpus callosum thinning (23%) were already present in a 13-month-old child. The presence of low T₂ signal intensity in basal ganglia and thalami was excluded by the normalized signal intensity profiling. The enlargement of perivascular spaces in white matter (38%), widening of perioptic CSF spaces (62%), and enlargement of cisterna magna (85%) were also observed. Diploic space thickening (100%), mucosal thickening (69%) and sinus hypoplasia (54%) were the most frequent non-CNS abnormalities.ConclusionWhite matter changes and cerebellar atrophy are proposed to be the characteristic brain MRI features of AM. The previously reported decreased T₂ signal intensity in basal ganglia and thalami was not detected in this quantitative study. Rather, this relative MR appearance seems to be related to the diffuse high T₂ signal in the adjacent white matter and not the gray matter iron deposition that has been hypothesized.     

未服药的强迫障碍患者脑灰质体积异常的MRI研究

目的:应用脑磁共振成像(MRI)基于体素的形态测量学(VBM)比较未服药的强迫障碍患者脑灰质体积与正常人群间的差异,并探讨强迫障碍患者脑灰质体积的改变与临床现象之间的相关性。方法:纳入符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的20例未服药的强迫障碍门诊患者,以及20名性别、年龄和受教育程度相匹配的健康对照。所有被试均接受头部磁共振扫描。采用VBM的分析方法,比较强迫障碍患者与健康对照之间脑灰质体积的差异。采用耶鲁-布郎强迫量表(Y-BOCS)、汉密顿抑郁量表(HAM D)、汉密顿焦虑量表(HAM A)评估临床症状。在控制焦虑、抑郁症状的前提下,分析强迫障碍患者异常的脑灰质体积与临床现象之间的关系。结果:与对照组相比,强迫障碍组的眶额回、颞上回、颞下回、小脑、楔前叶、辅助运动区及中央后回的灰质体积减少(P0.05,Al-phaSim校正);眶额回灰质体积的减少与Y-BOCS量表总分呈负相关(r=-0.49,P0.05)。结论:本研究结果提示眶额-纹状体-丘脑环路中的眶额回在强迫障碍的发生中起重要的作用,其他脑区如颞叶和小脑灰质体积减少,可能也参与了强迫障碍的发生。     

An MRI study of age-related white and gray matter volume changes in the rhesus monkey

We applied the automated MRI segmentation technique Template Driven Segmentation (TDS) to dual-echo spin echo (DE SE) images of eight young (5–12 years), six middle-aged (16–19 years) and eight old (24–30 years) rhesus monkeys. We analyzed standardized mean volumes for 18 anatomically defined regions of interest (ROI's) and found an overall decrease from young to old age in the total forebrain (5.01%), forebrain parenchyma (5.24%), forebrain white matter (11.53%), forebrain gray matter (2.08%), caudate nucleus (11.79%) and globus pallidus (18.26%). Corresponding behavioral data for five of the young, five of the middle-aged and seven of the old subjects on the Delayed Non-matching to Sample (DNMS) task, the Delayed-recognition Span Task (DRST) and the Cognitive Impairment Index (CII) were also analyzed. We found that none of the cognitive measures were related to ROI volume changes in our sample size of monkeys.     

胎儿孤立性单侧侧脑室扩张对脑实质体积影响的MRI研究

目的 研究不同程度单侧侧脑室扩张对脑实质体积的影响并探讨其对胎儿诊疗的临床价值。方法 收集经超声证实的孤立性单侧侧脑室扩张的胎儿,行胎儿颅脑1.5T MR扫描。测量扩张侧及正常侧的侧脑室宽度、相邻外侧脑实质厚度、侧脑室体积、大脑半球体积,并计算脑实质体积。每隔1月随访侧脑室宽度随孕周的变化情况。结果 最终纳入研究的23～31孕周的孤立性单侧侧脑室扩张胎儿共49例,按扩张程度分为3组：轻度扩张组12例、中度扩张组27例、重度扩张组10例。对比研究结果如下：(1) 3组病例的扩张侧与正常侧比较,扩张侧邻近脑实质厚度减小,脑实质体积未见明显差异;(2) 3组病例间的扩张侧侧脑室宽度、体积及大脑半球体积均存在差异（P<0.05）,扩张侧脑实质厚度及体积未见明显差异;(3)随访发现轻中度扩张组侧脑室宽度逐渐减小者占76%,重度扩张组流产率达80%。结论孤立性单侧侧脑室扩张对脑实质的体积没有影响,轻中度扩张胎儿预后好,这为侧脑室扩张胎儿的评估、预后和干预提供了重要影像学信息。     

Associations of dietary markers with brain volume and connectivity: A systematic review of MRI studies

The high prevalence of unhealthy dietary patterns and related brain disorders, such as dementia, emphasizes the importance of research that examines the effect of dietary factors on brain health. Identifying markers of brain health, such as volume and connectivity, that relate to diet is an important first step towards understanding the lifestyle determinants of healthy brain ageing. We conducted a systematic review of 52 studies (total n = 21,221 healthy participants aged 26–80 years, 55 % female) that assessed with a range of MRI measurements, which brain areas, connections, and cerebrovascular factors were associated with dietary markers.We report associations between regional brain measures and dietary health.Collectively, lower diet quality was related to reduced brain volume and connectivity, especially in white and grey matter of the frontal, temporal and parietal lobe, cingulate, entorhinal cortex and the hippocampus. Associations were also observed in connecting fibre pathways and in particular the default-mode, sensorimotor and attention networks.However, there were also some inconsistencies in research methods and findings. We recommend that future research use more comprehensive and consistent dietary measures, more representative samples, and examine the role of key subcortical regions previously highlighted in relevant animal work.     

Gray matter density and white matter integrity in pianists' brain: a combined structural and diffusion tensor MRI study

The current study combined structural magnetic resonance imaging (sMRI) and diffusion tensor MRI (DT-MRI) to investigate both gray matter density (GMD) and white matter integrity (WMI) in 18 pianists and 21 age-matched non-musicians. The pianists began their piano training at a mean age of 12. Voxel-based morphometry of the sMRI data showed that the pianists had higher GMD in the left primary sensorimotor cortex and right cerebellum. Voxel-based analysis of the DT-MRI data showed that pianists had higher fractional anisotropy (FA) (indicating higher WMI) in the right posterior limb of the internal capsule. The sMRI and DT-MRI results indicate that both the GMD and WMI of pianists may exhibit movement-related increases during adolescence or even early adulthood compared with non-musicians.     

Preservation of cognitive and functional ability as markers of longevity

Longevity is a complex biological process for which the phenotypes have not been established. Preservation of cognitive and physical function may be important and preservation of these functions is, in part, inherited. We investigated the relation between rate of change in cognitive and functional abilities in probands and risk of death in their siblings. Probands were classified as showing no decline, slow, medium, or rapid rate of decline, based on the slope of change in cognitive and physical/functional factors over three or more assessments. Siblings of probands who did not decline on measures of memory, visuospatial/cognitive function or ADL skills were approximately half as likely to die as siblings of probands who had the most rapid decline. The reduction in risk of death in siblings of probands who did not decline in was primarily observed among siblings of probands who were older than 75 years, suggesting that genetic influences on life span may be greater at older ages. There was no association between probands' rate of change in language, IADL skills, upper or lower extremity mobility and risk of death in siblings. The results of the present study identify phenotypes associated with preserved cognitive and functional abilities which may serve as markers for longevity.     

Elevated high-density-lipoprotein cholesterol and normal triglycerides as markers of longevity

Summary Serum cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides of 85 year old home-living persons were compared to those of controls and of patients who had severe coronary artery disease (CAD) at an early age. Eightyfive-year-olds had higher serum HDL cholesterol than controls and patients with CAD. Patients with severe CAD had higher serum total cholesterol and serum triglycerides and lower HDL-cholesterol than other groups. When 85-year-old persons were divided into quintiles according to serum HDL cholesterol, women with highest HDL cholesterol had lowest mortality, men with lowest HDL cholesterol had highest mortality. We conclude that elevated HDL cholesterol is correlating with longevity and low HDL cholesterol with CAD at an early age.Abbreviations HDL high density lipoprotein - CAD coronary artery disease     

White matter injury in the immature brain: role of interleukin-18

Inflammation is likely to be important in the pathophysiology of white matter damage in the immature brain. In order to investigate the involvement of interleukin (IL)-18, we subjected 9-day-old IL-18-deficient and wild-type (WT) mice to hypoxia-ischemia (HI) (unilateral carotid ligation and exposure to 10% oxygen) and white matter injury was evaluated after 3 days by immunostaining for myelin basic protein (MBP) and neurofilament (NF). The immunoreactivity of MBP was significantly higher by 92, 49 and 21%, respectively, in subcortical white matter, striatum and thalamus in IL-18-deficient mice versus WT mice following HI. Similarly, there was a more pronounced immunoreactivity of NF by 78% in the subcortical white matter in IL-18 KO versus WT mice. IL-18 was expressed by astrocytes and microglia, whereas the IL-18 receptor was mainly found in astrocytes localized in and around the subventricular white matter. Taken together, these results indicate that release of IL-18 may play an important role in the development of white matter injury in the neonatal brain.     

Age-related gray matter volume changes in the brain during non-elderly adulthood

Previous magnetic resonance imaging (MRI) studies described consistent age-related gray matter (GM) reductions in the fronto-parietal neocortex, insula and cerebellum in elderly subjects, but not as frequently in limbic/paralimbic structures. However, it is unclear whether such features are already present during earlier stages of adulthood, and if age-related GM changes may follow non-linear patterns at such age range. This voxel-based morphometry study investigated the relationship between GM volumes and age specifically during non-elderly life (18-50 years) in 89 healthy individuals (48 males and 41 females). Voxelwise analyses showed significant (p < 0.05, corrected) negative correlations in the right prefrontal cortex and left cerebellum, and positive correlations (indicating lack of GM loss) in the medial temporal region, cingulate gyrus, insula and temporal neocortex. Analyses using ROI masks showed that age-related dorsolateral prefrontal volume decrements followed non-linear patterns, and were less prominent in females compared to males at this age range. These findings further support for the notion of a heterogeneous and asynchronous pattern of age-related brain morphometric changes, with region-specific non-linear features.     

Blastocyst environment and its influence on offspring cardiovascular health: the heart of the matter

The development of adult-onset diseases such as type II diabetes, obesity and cardiovascular disease is traditionally attributed to adult lifestyle characteristics such as a lack of physical exercise, poor diet and smoking. However, evidence from both human and animal model studies has demonstrated that environmental factors such as an imbalance or reduction in maternal nutrition during gestation can have adverse effects on offspring metabolism and cardiovascular health. The severity and nature of the phenotypic changes induced in offspring is influenced by the period of gestation manipulated. In particular, the mammalian preimplantation embryo in different animal models displays particular sensitivity to environmental factors, either in vivo (maternal diet) or in vitro (embryo culture) that is associated with the onset of cardiovascular dysfunction in adult life. The detailed mechanisms by which environmental conditions can alter postnatal cardiovascular physiology are poorly understood. However, various factors including endothelial function, vascular responsiveness, the renin-angiotensin system, kidney structure and early postnatal growth dynamics have all been recognize as potential contributors. Here, we review the relationship between preimplantation embryo environment and postnatal cardiovascular disease risk, and consider biochemical, molecular, genetic and physiological pathways implicated in this association.     

Sirt3与心血管疾病和长寿关系的研究进展

Sirt3是一种依赖NAD+的去乙酰化酶。它与线粒体多种生物功能紧密相连,其中包括营养素氧化、ATP生成、活性氧自由基(ROS)清除及线粒体稳态等。Sirt3在心血管疾病的发生和发展中扮演重要角色,人类寿命延长与Sirt3也密切相关。     

Physical activity intensity and surrogate markers for cardiovascular health in adolescents

We examined the impact of physical activity (PA) on surrogate markers of cardiovascular health in adolescents. 52 healthy students (28 females, mean age 14.5 ± 0.7 years) were investigated. Microvascular endothelial function was assessed by peripheral arterial tonometry to determine reactive hyperemic index (RHI). Vagal activity was measured using 24 h analysis of heart rate variability [root mean square of successive normal-to-normal intervals (rMSSD)]. Exercise testing was performed to determine peak oxygen uptake ( $ \dot{V}{\text{O}}_{{2{\text{ peak}}}} $ ) and maximum power output. PA was assessed by accelerometry. Linear regression models were performed and adjusted for age, sex, skinfolds, and pubertal status. The cohort was dichotomized into two equally sized activity groups (low vs. high) based on the daily time spent in moderate-to-vigorous PA (MVPA, 3,000–5,200 counts^.min^?1, model 1) and vigorous PA (VPA, >5,200 counts^.min^?1, model 2). MVPA was an independent predictor for rMSSD (β = 0.448, P = 0.010), and VPA was associated with maximum power output (β = 0.248, P = 0.016). In model 1, the high MVPA group exhibited a higher vagal tone (rMSSD 49.2 ± 13.6 vs. 38.1 ± 11.7 ms, P = 0.006) and a lower systolic blood pressure (107.3 ± 9.9 vs. 112.9 ± 8.1 mmHg, P = 0.046). In model 2, the high VPA group had higher maximum power output values (3.9 ± 0.5 vs. 3.4 ± 0.5 W kg^?1, P = 0.012). In both models, no significant differences were observed for RHI and $ \dot{V}{\text{O}}_{{ 2 {\text{ peak}}}} $ . In conclusion, in healthy adolescents, PA was associated with beneficial intensity-dependent effects on vagal tone, systolic blood pressure, and exercise capacity, but not on microvascular endothelial function.     

Effects of transcytolemmal water exchange on the assessment of myocardial extracellular volume with cardiovascular MRI

Quantitative analysis of the myocardial interstitial space is gaining increased interest as a biomarker in the MRI and clinical cardiovascular communities. To investigate the effect of water exchange on the calculation of myocardial extracellular volume (ECV), we employed two tissue models: the standard ECV two‐point model (SM) and the shutter speed model (SSM). Twenty individuals (18 men and two women; age 61.9 ± 10.3 years) underwent MRI at 1.5 T with pre‐contrast and post‐contrast dynamic T₁ quantification. Means, standard deviations and ranges for SM and SSM model parameters were calculated. Infarct and viable myocardial model parameters as well as apparent ECV values calculated with the SM and SSM were statistically compared. Viable ECV^SM remained temporally constant (27.3–28.0%: P = 0.5) and infarcted myocardial ECV^SM changed significantly (49.3–58.8%; P < 0.001), reaching a steady‐state value after 15 min. The intracellular lifetime of water was three times greater in infarcted myocardium when compared with viable myocardium (τ_i: 66.6 ± 115 versus 208.7 ± 72.7 ms) and accompanied a twofold increase in ECV (ECV^SSM: 30.3 ± 11.1 versus 71.0 ± 13.1%; P < 0.001). There was a consistent significant difference in ECV values of infarcted myocardium at different timepoints between the SM and SSM, but not viable myocardium, presumably due to slower water exchange. In summary, we found a significant change in apparent ECV and water exchange in infarcted myocardium when compared with viable myocardium. This was visualized by changes in dynamic contrast enhanced curve shapes and quantified using the SSM as not only an increase in apparent ECV but also a decrease in water exchange. Copyright © 2016 John Wiley & Sons, Ltd.     

White matter pathway supporting phonological encoding in speech production: a multi-modal imaging study of brain damage patients

In speech production, an important step before motor programming is the retrieval and encoding of the phonological elements of target words. It has been proposed that phonological encoding is supported by multiple regions in the left frontal, temporal and parietal regions and their underlying white matter, especially the left arcuate fasciculus (AF) or superior longitudinal fasciculus (SLF). It is unclear, however, whether the effects of AF/SLF are indeed related to phonological encoding for output and whether there are other white matter tracts that also contribute to this process. We comprehensively investigated the anatomical connectivity supporting phonological encoding in production by studying the relationship between the integrity of all major white matter tracts across the entire brain and phonological encoding deficits in a group of 69 patients with brain damage. The integrity of each white matter tract was measured both by the percentage of damaged voxels (structural imaging) and the mean fractional anisotropy value (diffusion tensor imaging). The phonological encoding deficits were assessed by various measures in two oral production tasks that involve phonological encoding: the percentage of nonword (phonological) errors in oral picture naming and the accuracy of word reading aloud with word comprehension ability regressed out. We found that the integrity of the left SLF in both the structural and diffusion tensor imaging measures consistently predicted the severity of phonological encoding impairment in the two phonological production tasks. Such effects of the left SLF on phonological production remained significant when a range of potential confounding factors were considered through partial correlation, including total lesion volume, demographic factors, lesions on phonological-relevant grey matter regions, or effects originating from the phonological perception or semantic processes. Our results therefore conclusively demonstrate the central role of the left SLF in phonological encoding in speech production.     

White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults

We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (Aβ₄₂ and Aβ₄₂/p-Tau₁₈₁) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower WM integrity in the same portion of the fornix was also associated with reduced performance on the Digit Symbol test. Subsequent exploratory voxelwise analyses indicated a positive correlation between CSF Aβ₄₂/p-Tau₁₈₁ and WM integrity in bilateral portions of the fornix, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in the corpus callosum and left inferior longitudinal fasciculus. Our results link lower WM microstructural integrity in CN older adults with CSF biomarkers of Alzheimer's disease and suggest that this association in the fornix may be independent of volumetric measures.     

正常人抽象图片记忆刺激的脑fMRI实验研究

目的：运用功能磁共振成像（fMRI）研究志愿者抽象图片记忆提取时的脑内活动区情况及其年龄差异。方法：以3个年龄组共20名健康志愿者作为研究对象，运用单次激发GRE-EPI扫描采集fMRI图像，以抽象图片记忆的提取为刺激。用SPM软件对fMRI图像和T1W解剖图像进行融合，并对脑内活动区进行分析。结果：青年组正确率最高，儿童组次之，老年组最低。青年组在提取时在内侧颞叶有较强的激活区，而老年组内侧颞叶的激活强度较弱，但其它脑区的激活范围更广，儿童组则在内侧颞叶激活较弱，脑区的激活范围也不广。结论：脑记忆功能随着年龄而变化，在青年组，主导记忆功能的主要结构海马及其内侧颞叶功能最强；由于老年组的记忆力下降，其与记忆功能相关的结构功能减弱，但皮质及其它结构功能明显增强，儿童组则处在发育阶段。     

Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging

With age, the brain undergoes both structural and functional alterations, probably resulting in reported cognitive declines. Relatively few investigations have sought to identify those areas that remain intact with aging, or undergo the least deterioration, which might underlie cognitive preservations. Our aim here was to establish a comprehensive profile of both structural and functional changes in the aging brain, using up-to-date voxel-based methodology (i.e. optimized voxel-based morphometry (VBM) procedure; resting-state (18)FDG-PET with correction for partial volume effects (PVE)) in 45 optimally healthy subjects aged 20-83 years. Negative and positive correlations between age and both gray matter (GM) volume and (18)FDG uptake were assessed. The frontal cortex manifested the greatest deterioration, both structurally and functionally, whereas the anterior hippocampus, the thalamus and (functionally) the posterior cingulate cortex were the least affected. Our results support the developmental theory which postulates that the first regions to emerge phylogenetically and ontogenetically are the most resistant to age effects, and the last ones the most vulnerable. Furthermore, the lesser affected anterior hippocampal region, together with the lesser functional alteration of the posterior cingulate cortex, appear to mark the parting of the ways between normal aging and Alzheimer's disease, which is characterized by early and prominent deterioration of both structures.     

White matter microstructure and longitudinal relaxation time anisotropy in human brain at 3 and 7 T

A high degree of structural order by white matter (WM) fibre tracts creates a physicochemical environment where water relaxations are rendered anisotropic. Recently, angularly dependent longitudinal relaxation has been reported in human WM. We have characterised interrelationships between T1 relaxation and diffusion MRI microstructural indices at 3 and 7 T. Eleven volunteers consented to participate in the study. Multishell diffusion MR images were acquired with b-values of 0/1500/3000 and 0/1000/2000 s/mm² at 1.5 and 1.05 mm³ isotropic resolutions at 3 and 7 T, respectively. DTIFIT was used to compute DTI indices; the fibre-to-field angle (θ_FB) maps were obtained using the principal eigenvector images. The orientations and volume fractions of multiple fibre populations were estimated using BedpostX in FSL, and the orientation dispersion index (ODI) was estimated using the NODDI protocol. MP2RAGE was used to acquire images for T1 maps at 1.0 and 0.9 mm³ isotropic resolutions at 3 and 7 T, respectively. At 3 T, T1 as a function of θ_FB in WM with high fractional anisotropy and one-fibre orientation volume fraction or low ODI shows a broad peak centred at 50^o, but a flat baseline at 0^o and 90^o. The broad peak amounted up to 7% of the mean T1. At 7 T, the broad peak appeared at 40^o and T1 in fibres running parallel to B0 was longer by up to 75 ms (8.3% of the mean T1) than in those perpendicular to the field. The peak at 40^o was approximately 5% of mean T1 (i.e., proportionally smaller than that at 54^o at 3 T). The data demonstrate T1 anisotropy in WM with high microstructural order at both fields. The angular patterns are indicative of the B0-dependency of T1 anisotropy. Thus myelinated WM fibres influence T1 contrast both by acting as a T1 contrast agent and rendering T1 dependent on fibre orientation with B0.