Tract-specific fractional anisotropy predicts cognitive outcome in a community sample of middle-aged participants with white matter lesions

Cerebral white matter lesions (WMLs) have been consistently related to cognitive dysfunction but the role of white matter (WM) damage in cognitive impairment is not fully determined. Diffusion tensor imaging is a promising tool to explain impaired cognition related to WMLs. We investigated the separate association of high-grade periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) with fractional anisotropy (FA) in middle-aged individuals. We also assessed the predictive value to cognition of FA within specific WM tracts associated with high-grade WMLs. One hundred participants from the Barcelona-AsIA Neuropsychology Study were divided into groups based on low- and high-grade WMLs. Voxel-by-voxel FA were compared between groups, with separate analyses for high-grade PVHs and DWMHs. The mean FA within areas showing differences between groups was extracted in each tract for linear regression analyses. Participants with high-grade PVHs and participants with high-grade DWMHs showed lower FA in different areas of specific tracts. Areas showing decreased FA in high-grade DWMHs predicted lower cognition, whereas areas with decreased FA in high-grade PVHs did not. The predictive value to cognition of specific WM tracts supports the involvement of cortico-subcortical circuits in cognitive deficits only in DWMHs.     

半自动MRI定量方法测定脑白质高信号体积与病变定性评分的相关性

背景：在磁共振T2加权像和液体衰减反转恢复像中脑白质病变表现为白质高信号,目前对脑白质高信号体积、部位与认知功能损害的关系仍存在争议。 目的：以头颅磁共振对皮质下缺血性脑血管病患者白质高信号进行定量和定性测定,分析高信号体积和部位与认知损害的关系。 设计、时间及地点：于2007-12/2008-09在河北省人民医院神经内科完成。 对象：依据影像学诊断标准确定皮质下缺血性脑血管病53例,记录症状和体征,并进行神经心理学评估。 方法：采用美国GE公司生产的半自动1.5T MRI机对患者行头MRI扫描,定量测定脑白质高信号体积,并结合脑白质病变定性评分。 主要观察指标：分析皮质下缺血性脑血管病患者脑白质高信号体积与评分的相关性,以及白质病变与认知损害的关系。 结果：脑白质高信号体积和评分高度相关（rs=0.989, P < 0.001）,两者呈曲线关系。分层多元线性回归分析显示,白质高信号体积、白质高信号总评分的变化可以分别解释简明精神状态检查评分改变的10.5%和6.8%,前者较后者能更敏感地预测简明精神状态检查评分变化。不同区域脑白质病变中,仅基底核区白质高信号评分与简明精神状态检查评分有关（t=-2.126, P=0.039）,其他各区域白质高信号评分均非简明精神状态检查评分独立预测指标。 结论：脑白质高信号体积与评分均可应用于脑白质病变的测定,前者测定较脑白质高信号评分更敏感;皮质下缺血性脑血管病患者认知功能损害随着脑白质病变的增多,尤其是基底核区白质病变的增多而加重。     

The age‐related white matter changes scale correlates with cognitive impairment

Background and purpose: Age‐related white matter changes (ARWMC) are closely associated with cognitive impairment. Although the ARWMC scale has been widely used to grade white matter changes (WMC) severity, the correlation between this scale and cognitive impairment has not been studied. We aimed to validate the ARWMC scale against cognition in patients with stroke. Methods: We determined the severity of WMC for 172 patients with stroke on MRI by volumetric quantification and the ARWMC scale. Two scores (total score and global score) were derived from the ARWMC scale. We assessed executive function and global cognition using the Mattis dementia rating scale‐initiation/perseveration subset (MDRS I/P) and mini‐mental state examination (MMSE), respectively. We investigated the association between the three WMC measures (volume, total score, and global score) and clinical variables with cognitive impairment using multivariate regression analysis. Results: Even after adjusting for other clinical variables, total score and global score of ARWMC scale were independently associated with MDRS I/P (beta = ?0.248, P = 0.001 and beta = ?0.218, P = 0.005, respectively) and MMSE (adjusted odds ratio 1.181, 95%CI [1.038–1.343] and adjusted odds ratio 1.740, 95%CI [1.063–2.847], respectively). Conclusion: The ARWMC scale correlates well with cognitive impairment in patients with stroke.     

Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research

Subcortical ischemic white matter injury(SIWMI), pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging, is a common cause of cognitive decline in elderly. Despite its high prevalence, it remains unknown how various components of the white matter degenerate in response to chronic ischemia.This incomplete knowledge is in part due to a lack of adequate animal model. The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components. The SIWMI animal models are categorized into 1) chemically induced SIWMI models, 2) vascular occlusive SIWMI models, and 3) SIWMI models with comorbid vascular risk factors. Chemically induced models display consistent lesions in predetermined areas of the white matter, but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities. Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified. When combined with comorbid vascular risk factors(specifically hypertension), however, they can produce progressive and definitive white matter lesions including diffuse rarefaction, demyelination, loss of oligodendrocytes, and glial activation, which are by far the closest to those found in human white matter hyperintensities lesions. However, considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models. In the meantime, in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury. Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities.     

轻度认知功能障碍与脑白质弥散张量成像的相关性研究

目的通过磁共振弥散张量成像研究不同区域脑白质损害与轻度认知功能(MCI)的关系。方法纳入2015年7月至2016年2月我院的住院患者56例为研究对象,其中MCI组34例,认知功能正常组22例。所有研究对象进行一般情况检查,完成神经心理学量表检测。通过头颅磁共振弥散张量成像(DTI)检查对不同脑区白质纤维进行部分各向异性(FA)值测量。结果 MCI组患者与认知功能正常组相比,右侧额叶FA值(0.335±0.068)、左侧颞叶白质FA值(0.391±0.032)及胼胝体膝部FA值(0.658±0.053)降低,差异具有统计学意义(P0.05)。将上述FA值和MMSE、Mo CA量表中各认知域进行典型相关分析,结果显示右侧额叶白质FA值与注意与计算力呈正相关,左侧颞叶白质和胼胝体膝部FA值与记忆力呈正相关(P0.05)。结论 MCI患者注意与计算力的障碍可能与右侧额叶白质损害有关,而左侧颞叶白质及胼胝体膝部白质的损害可能导致早期的记忆障碍。DTI可能成为超早期识别与诊断MCI的新方法。     

Mild cognitive impairment in Parkinson's disease is associated with a distributed pattern of brain white matter damage

This study assesses the patterns of gray matter (GM) and white matter (WM) damage in patients with Parkinson's disease and mild cognitive impairment (PD‐MCI) compared with healthy controls and cognitively unimpaired PD patients (PD‐Cu). Three‐dimensional T1‐weighted and diffusion tensor (DT) magnetic resonance imaging (MRI) scans were obtained from 43 PD patients and 33 healthy controls. Cognition was assessed using a neuropsychological battery. Tract‐based spatial statistics was applied to compare DT MRI indices between groups on a voxel‐by‐voxel basis. Voxel‐based morphometry was performed to assess GM atrophy. Thirty PD patients were classified as MCI. Compared with healthy controls, PD‐Cu and PD‐MCI patients did not have GM atrophy. No region of WM damage was found in PD‐Cu patients when compared with healthy controls. Relative to healthy controls and PD‐Cu patients, PD‐MCI patients showed a distributed pattern of WM abnormalities in the anterior and superior corona radiata, genu, and body of the corpus callosum, and anterior inferior fronto‐occipital, uncinate, and superior longitudinal fasciculi, bilaterally. Subtle cognitive decline in PD is associated with abnormalities of frontal and interhemispheric WM connections, and not with GM atrophy. DT MRI might contribute to the identification of structural changes in PD‐MCI patients prior to the development of dementia. Hum Brain Mapp 35:1921–1929, 2014. © 2013 Wiley Periodicals, Inc.     

抑郁症患者脑白质变化初步研究

目的：利用能够提示脑白质纤维完整性的磁共振弥散张量成像（DTI）探讨首发和复发重性抑郁症患者脑白质纤维的变化及其差异。方法：20例重性抑郁症患者（首发9例，复发11例）和20名正常对照者均经常规磁共振成像（MRI）平扫，未发现异常者继续进行DTI和结构MRI（3D）扫描，基于像素的全脑分析技术对DTI数据进行分析。结果：与对照组相比较，抑郁症组白质纤维结构在双侧额中回、右顶下小叶及双侧脑岛等区域白质的各向异性值（FA）显著降低（各脑区P均〈0.001，cluster〉30像素）;与首发抑郁症患者相比较，复发抑郁症患者右侧额上回、右顶叶、中央前回、中央后回及右顶下小叶等区域FA值降低更为显著（各脑区P均〈0.001，cluster〉10像素）。结论：重性抑郁症患者存在脑白质异常，抑郁反复发作会导致脑白质损害进一步加重。     

The effect of white matter signal abnormalities on default mode network connectivity in mild cognitive impairment

Regions within the default mode network (DMN) are particularly vulnerable to Alzheimer's disease pathology and mechanisms of DMN disruption in mild cognitive impairment (MCI) are still unclear. White matter lesions are presumed to be mechanistically linked to vascular dysfunction whereas cortical atrophy may be related to neurodegeneration. We examined associations between DMN seed‐based connectivity, white matter lesion load, and cortical atrophy in MCI and cognitively healthy controls. MCI showed decreased functional connectivity (FC) between the precuneus‐seed and bilateral lateral temporal cortex (LTC), medial prefrontal cortex (mPFC), posterior cingulate cortex, and inferior parietal lobe compared to those with controls. When controlling for white matter lesion volume, DMN connectivity differences between groups were diminished within bilateral LTC, although were significantly increased in the mPFC explained by significant regional associations between white matter lesion volume and DMN connectivity only in the MCI group. When controlling for cortical thickness, DMN FC was similarly decreased across both groups. These findings suggest that white matter lesions and cortical atrophy are differentially associated with alterations in FC patterns in MCI. Associations between white matter lesions and DMN connectivity in MCI further support at least a partial but important vascular contribution to age‐associated neural and cognitive impairment.     

脑白质损害的认知功能研究

目的 :观察脑白质损害 (WML )与事件相关电位 P30 0变化关系 ,探讨 WML在认知功能降低中的作用。方法 :35例经 MRI证实的 WML ,进行影像学、简易智能状态检测 (MMSE)和事件相关电位 P30 0测定 ,依据 WML体积将其分为轻度 (<5 cm3)、中度 (5～ 15 cm3)和重度 (>15 cm3) ,并对 WML与 P30 0潜伏期变化进行相关分析。结果 :轻度 WML 11例 ,中度 17例 ,重度 7例 ,主要表现为 T2和质子密度加权像上高信号 ,分布在脑室周围、半卵园中心及皮层下白质。轻度及中度 WML时 MMSE测定值无降低 ,重度 WML时 MMSE也只降低为 2 6 .9。随 WML的程度加重 ,P30 0潜伏期延长越明显 ,相关分析提示两者具有正相关。结论 :观察老年性 WML主要依靠 T2像或质子密度加权像。MMSE在反应 WML导致的认知功能障碍时不够敏感。 WML能引起事件相关电位 P30 0延长 ,其损害程度与 P30 0潜伏期变化呈正相关。     

White matter lesion severity is associated with reduced cognitive performances in patients with normal CSF Abeta42 levels

Objective – To identify possible associations between white matter lesions (WML) and cognition in patients with memory complaints, stratified in groups with normal and low cerebrospinal fluid (CSF) Aβ42 values. Material and Methods – 215 consecutive patients with subjective memory complaints were retrospectively included. Patients were stratified into two groups with normal (n = 127) or low (n = 88) CSF Aβ42 levels (cut‐off is 450 ng/l). Cognitive scores from the Mini‐Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat) were used as continuous dependent variables in linear regression. WML load was used as a continuous independent variable and was scored with a visual rating scale. The regression model was corrected for possible confounding factors. Results – WML were significantly associated with MMSE and all Cognistat subscores except language (repetition and naming) and attention in patients with normal CSF Aβ42 levels. No significant associations were observed in patients with low CSF Aβ42. Conclusions – WML were associated with affection of multiple cognitive domains, including delayed recall and executive functions, in patients with normal CSF Aβ42 levels. The lack of such associations for patients with low CSF Aβ42 (i.e. with evidence for amyloid deposition), suggests that amyloid pathology may obscure cognitive effects of WML.     

Depression in late life, cognitive decline and white matter pathology in two clinico-pathologically investigated cases

CASE REPORTS: We report two cases of late life depression who became progressively more resistant to treatment, developed cognitive impairment, and began to exhibit neurological abnormalities and evidence of vascular disease. A discussion of the clinical features of the cases is accompanied by reports of neuropathology and neuroimaging findings. Extensive white matter lesions were present on computed tomography in both patients, and basal ganglia infarcts were seen in one. Neuropathology revealed evidence of cerebral atrophy, demyelination and white matter lesions in addition to cerebrovascular and generalised vascular disease. Neither patient exhibited Alzheimer pathology outwith the norm for their age. We believe this to be the first report of neuropathological findings in depression with white matter changes. LITERATURE REVIEW: The pathological basis of white matter lesions and their relationship to depression, its age of onset and clinical features is addressed in relation to the cases described. Pathological investigation of white matter lesions has not previously been carried out in depression and hypotheses regarding their nature in this illness are based on extrapolation from research in a variety of other disorders. The association of depression with vascular risk factors is considered, as is the relationship between depression and cognitive deficits. There is a need for further investigation in this area.     

T2 relaxation time of the normal-appearing white matter is related to the cognitive status in cerebral small vessel disease

Previous diffusion tensor imaging (DTI) studies indicate that impaired microstructural integrity of the normal-appearing white matter (NAWM) is related to cognitive impairment in cerebral small vessel disease (SVD). This study aimed to investigate whether quantitative T₂ relaxometry is a suitable imaging biomarker for the assessment of tissue changes related to cognitive abnormalities in patients with SVD. 39 patients and 18 age-matched healthy control subjects underwent 3 T magnetic resonance imaging (MRI) with T2-weighted multiple spin echo sequences for T₂ relaxometry and DTI sequences, as well as comprehensive cognitive assessment. Averaged quantitative T₂, fractional anisotropy (FA) and mean diffusivity (MD) were determined in the NAWM and related to cognitive parameters controlling for age, normalized brain volume, white matter hyperintensity volume and other conventional SVD markers. In SVD patients, quantitative T₂ values were significantly increased compared to controls (p = 0.002) and significantly negatively correlated with the global cognitive performance (r= –0.410, p = 0.014) and executive function (r= –0.399, p = 0.016). DTI parameters did not correlate with cognitive function. T₂ relaxometry of the NAWM seems to be sensitive to microstructural tissue damage associated with cognitive impairment in SVD and might be a promising imaging biomarker for evaluation of disease progression and possible effects of therapeutic interventions.     

Diffusion-weighted magnetic resonance imaging of white matter in bipolar disorder: a pilot study

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (MRI) has shown increased sensitivity in detecting brain white matter disease compared to traditional T2-weighted MRI. Diffusion-weighted imaging (DWI) can quantitatively assess the microstructural integrity of white matter using the average apparent diffusion coefficient (ADC(av)), a measure of the extent to which water molecules move freely within tissue. On the basis of numerous studies suggesting white matter disease in bipolar patients, particularly patients with more severe illness, this study aimed to test the utility of DWI in assessing the white matter integrity of bipolar patients with severe illness. METHODS: The existing MRI scans of eight bipolar patients and eight age-matched controls with neurological illness were examined retrospectively. ADC(av) values for pixels within white matter regions of interest (ROIs) were calculated and used to plot ADC(av) frequency histograms for each ROI. Mean ADC(av) values for the two groups were then compared by ANCOVA. RESULTS: The bipolar mean ADC(av) (0.855 +/- 0.051 x 10(-3) mm2/s) for combined white matter ROIs significantly exceeded that of controls (0.799 +/- 0.046 x 10(-3) mm2/s), while covarying for age (F = 4.47, df = 3, p = 0.025). CONCLUSIONS: This is the first report of an elevated ADC(av) in the white matter of a group of patients with bipolar disorder. In this group of patients with severe illness, increased white matter ADC(av) suggests microstructural changes consistent with decreased white matter integrity. DWI may be an additional, useful tool to assess white matter abnormalities in bipolar disorder.