Regional White Matter Signal Abnormalities and Cognitive Correlates Among Geriatric Patients with Treated Cardiovascular Disease

The purpose of this study was to investigate the relations between regional white matter signal abnormalities (WMSA) and cognitive functioning among individuals being treated for cardiovascular risk factors and/or clinical events. Forty-one participants with cardiovascular disease underwent a comprehensive neuropsychological assessment and MRI. Total WMSAs were quantified using a semi-automated thresholding technique. Unique to this study, total WMSA volume was divided into three separate anatomically related regions: WMSA in the periventricular (PERIWMSA) region, WMSA adjacent to subcortical nuclei (SUBWMSA), and WMSA in the deep white matter (DEEPWMSA). A ratio of these measures to total cerebral brain volume was compared to cognitive measures assessing attention, executive functioning, psychomotor speed, immediate and delayed memory, language, and visuospatial functioning. PERIWMSA, SUBWMSA, and total WMSA were significantly associated with performance on measures of attention/processing speed. No other significant relationships between WMSA and cognition were noted. Secondary analyses suggested that PERIWMSA volume was increased in individuals with clinical evidence of atherosclerosis. These results emphasize the utility of studying the associations between regional WMSA and cognitive/functional performance in patients undergoing cardiovascular treatment.     

Regional White Matter Scaling in the Human Brain

Anatomical organization of the primate cortex varies as a function of total brain size, where possession of a larger brain is accompanied by disproportionate expansion of associative cortices alongside a relative contraction of sensorimotor systems. However, equivalent scaling maps are not yet available for regional white matter anatomy. Here, we use three large-scale neuroimaging datasets to examine how regional white matter volume (WMV) scales with interindividual variation in brain volume among typically developing humans (combined N = 2391: 1247 females, 1144 males). We show that WMV scaling is regionally heterogeneous: larger brains have relatively greater WMV in anterior and posterior regions of cortical white matter, as well as the genu and splenium of the corpus callosum, but relatively less WMV in most subcortical regions. Furthermore, regions of positive WMV scaling tend to connect previously-defined regions of positive gray matter scaling in the cortex, revealing a coordinated coupling of regional gray and white matter organization with naturally occurring variations in human brain size. However, we also show that two commonly studied measures of white matter microstructure, fractional anisotropy (FA) and magnetization transfer (MT), scale negatively with brain size, and do so in a manner that is spatially unlike WMV scaling. Collectively, these findings provide a more complete view of anatomic scaling in the human brain, and offer new contexts for the interpretation of regional white matter variation in health and disease.SIGNIFICANCE STATEMENT Recent work has shown that, in humans, regional cortical and subcortical anatomy show systematic changes as a function of brain size variation. Here, we show that regional white matter structures also show brain-size related changes in humans. Specifically, white matter regions connecting higher-order cortical systems are relatively expanded in larger human brains, while subcortical and cerebellar white matter tracts responsible for unimodal sensory or motor functions are relatively contracted. This regional scaling of white matter volume (WMV) is coordinated with regional scaling of cortical anatomy, but is distinct from scaling of white matter microstructure. These findings provide a more complete view of anatomic scaling of the human brain, with relevance for evolutionary, basic, and clinical neuroscience.     

Transient Cognitive Impairment and White Matter Hyperintensities in Severely Depressed Older Patients Treated With Electroconvulsive Therapy

BackgroundAlthough electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LLD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function during and after ECT.MethodsA total of 80 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electroconvulsive Therapy study were examined. Magnetic resonance imaging scans were acquired before ECT. Overall brain morphology (white and grey matter) was evaluated using visual rating scales. Cognitive functioning before, during, and after ECT was measured using the Mini Mental State Examination (MMSE). A linear mixed-model analysis was performed to analyze the association between structural brain alterations and cognitive functioning over time.ResultsPatients with moderate to severe white matter hyperintensities (WMH) showed significantly lower MMSE scores than patients without severe WMH (F(1,75.54) = 5.42, p = 0.02) before, during, and post-ECT, however their trajectory of cognitive functioning was similar as no time × WMH interaction effect was observed (F(4,65.85) = 1.9, p = 0.25). Transient cognitive impairment was not associated with medial temporal or global cortical atrophy (MTA, GCA).ConclusionAll patients showed a significant drop in cognitive functioning during ECT, which however recovered above baseline levels post-ECT and remained stable until at least 6 months post-ECT, independently of severity of WMH, GCA, or MTA. Therefore, clinicians should not be reluctant to start or continue ECT in patients with severe structural brain alterations.     

脑白质病变临床特点与白质传导束关系研究进展

脑白质病变(WML)是脑小血管病的一种,与年龄、高血压等血管危险因素相关。WML与脑卒中、记忆、语言、步态及情绪等有密切联系,而且其进展预示着临床预后较差。利用MR微细结构成像技术了解到脑白质传导束的病变与其多样化的临床表现相关。MRI技术为WML的病理生理机制提供了依据,为进一步了解WML多样化临床表现提供了新视角。     

Prestroke Statins,Progression of White Matter Hyperintensities,and Cognitive Decline in Stroke Patients with Confluent White Matter Hyperintensities

Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n?=?100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale–initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n?=?51) had less WMH volume progression (1.54?±?4.52 cm³ vs 5.01?±?6.00 cm³, p?=?0.02) compared with the prestroke nonstatin use group (n?=?30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β?=?–0.31, p?=?0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale–initiation/perseveration subscale; β?=?0.47, p?=?0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.     

Prestroke Statins,Progression of White Matter Hyperintensities,and Cognitive Decline in Stroke Patients with Confluent White Matter Hyperintensities

Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n = 100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale–initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n = 51) had less WMH volume progression (1.54 ± 4.52 cm³vs 5.01 ± 6.00 cm³, p = 0.02) compared with the prestroke nonstatin use group (n = 30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β = –0.31, p = 0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale–initiation/perseveration subscale; β = 0.47, p = 0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-014-0270-5) contains supplementary material, which is available to authorized users.     

脑白质疏松患者“正常表现白质”的多模式影像

正脑白质疏松,又称脑白质高信号(white matter hyperintensities,WMHs),是脑小血管病的重要影像学标志,高发于老年人群。严重的脑白质高信号显著增加卒中和痴呆等疾病的发生率,但其发病机制尚不明确,也缺乏有效干预措施。本文总结了脑白质疏松患者在磁共振成像(magnetic resonance imaging,MRI)常规序列上正常表现白质(normal-appearing white     

脑白质病变患者认知功能的前瞻性研究

目的 探讨不同部位和严重程度脑白质病变（white matter lesions,WMLs）患者的认知功能损害特点。 方法 前瞻性纳入179例WMLs病例和97例磁共振成像（magnetic resonance imaging,MRI）正常对照组, 并收集人口学资料,对WMLs的严重程度进行Fazekas视觉等级评分,依据WMLs病变部位分为皮质下脑 白质病变（subcortical white matter lesions,SWML）组、脑室旁脑白质病变（periventricular lesions,PVL）组 和混合组,采用蒙特利尔认知评估量表（Montreal Cognitive Assessment Scale,MoCA）分析不同部位和 严重程度WMLs的认知功能差异。根据MoCA将WMLs组分为WMLs认知损害亚组（116例）及WMLs认知正 常亚组（63例）,分析探讨WMLs患者认知损害的危险因素。 结果 与正常组比,WMLs组在MoCA总分（P ﹤0.001）、视空间与执行能力（P ﹤0.001）、命名（P =0.019）、 语言（P =0.005）、抽象理解（P =0.003）、延迟记忆（P ﹤0.001）方面显著性减低。Fazekas分级越高, MoCA总分及各项评分显著减低（P均﹤0.05）。PVL组、SWML组和混合组与对照组相比,在MoCA总分（P 均﹤0.001）、视空间与执行能力（P 均﹤0.001）、语言（P =0.006,0.022,0.008）、抽象理解（P =0.003, 0.011,0.016）及延迟记忆（P均﹤0.001）上差异有统计学意义。WMLs亚组分析显示高教育程度是WMLs发 生认知损害的保护因素。 结论 高教育程度是WMLs患者认知损害的保护因素。WMLs患者在视空间与执行功能、延迟回忆方面 存在明显的认知损害。WMLs病变程度越严重,认知功能下降越显著。皮质下WMLs、脑室旁WMLs及混 合组均在视空间与执行能力、语言、抽象理解、延迟记忆方面损害严重。     

认知储备对不同认知阶段脑白质高信号人群脑白质纤维束完整性的影响

目的 探讨认知储备（cognitive reserve,CR）对不同认知阶段脑白质高信号（white matter hyperintensity, WMH）患者白质纤维束完整性的影响。      

Prospectively Collected Cardiovascular Biomarkers and White Matter Hyperintensity Volume in Ischemic Stroke Patients

Background: Few prospective cohort studies collect detailed information on stroke characteristics among individuals who experience ischemic stroke, including white matter hyperintensity volume, and thus cannot explore how prospectively collected biomarkers prior to the stroke influence white matter hyperintensity volume. We explored the association between a large panel of prospectively collected lipid and inflammatory biomarkers and white matter hyperintensity volume among participants in the Women's Health Study with incident ischemic stroke. Methods: Among Women's Health Study participants with first ischemic stroke who had baseline serum biomarkers and available magnetic resonance imaging, we measured white matter hyperintensity volume using a validated semi-automated method. Linear regression was used to explore the associations between biomarkers and log-transformed white matter hyperintensity volume. Results: After multivariate adjustment, a 1% increment in HbA1c% was associated with an increase in white matter hyperintensity volume (P value = .05). Evidence of a nonlinear association between high density lipoprotein cholesterol levels and ApoA1 levels with white matter hyperintensity volume was noted (P values for nonlinearity = .01 and .001, respectively). No other biomarkers were significantly associated with white matter hyperintensity volume. Conclusions: Chronic hyperglycemia as evidenced by HbA1c levels measured years prior to stroke is associated with white matter hyperintensity volume at the time of stroke. Additional research is needed to explain why low levels of high density lipoprotein cholesterol levels and ApoA1 may be associated with similar white matter hyperintensity volume as high levels.     

Fiber-Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations

Background

Patients with Parkinson's disease (PD) carrying GBA gene mutations (GBA-PD) have a more aggressive disease course than those with idiopathic PD (iPD).

Objective

The objective of this study was to investigate fiber-specific white matter (WM) differences in nonmedicated patients with early-stage GBA-PD and iPD using fixel-based analysis, a novel technique to assess tract-specific WM microstructural and macrostructural features comprehensively.

Methods

Fixel-based metrics, including microstructural fiber density (FD), macrostructural fiber-bundle cross section (FC), and a combination of FD and FC (FDC), were compared among 30 healthy control subjects, 16 patients with GBA-PD, and 35 patients with iPD. Associations between FDC and clinical evaluations were also explored using multiple linear regression analyses.

Results

Patients with GBA-PD showed significantly lower FD in the fornix and superior longitudinal fasciculus than healthy control subjects, and lower FC in the corticospinal tract (CST) and lower FDC in the CST, middle cerebellar peduncle, and striatal-thalamo-cortical pathways than patients with iPD. Contrarily, patients with iPD showed significantly higher FC and FDC in the CST and striatal-thalamo-cortical pathways than healthy control subjects. In addition, lower FDC in patients with GBA-PD was associated with reduced glucocerebrosidase enzyme activity, lower cerebrospinal fluid total α-synuclein levels, lower Montreal Cognitive Assessment scores, lower striatal binding ratio, and higher Unified Parkinson's Disease Rating Scale Part III scores.

Conclusions

We report reduced fiber-specific WM density and bundle cross-sectional size in patients with GBA-PD, suggesting neurodegeneration linked to glucocerebrosidase deficiency, α-synuclein accumulation, and poorer cognition and motor functions. Conversely, patients with iPD showed increased fiber bundle size, likely because of WM reorganization. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.