Factors affecting brain structure in smoking-related diseases: Chronic Obstructive Pulmonary Disease (COPD) and coronary artery disease.

BACKGROUND: Changes in brain structure and cognitive decline occur in Chronic Obstructive Pulmonary Disease (COPD). They also occur with smoking and coronary artery disease (CAD), but it is unclear whether a common mechanism is responsible. METHODS: Brain MRI markers of brain structure were tested for association with disease markers in other organs. Where possible, principal component analysis (PCA) was used to group markers within organ systems into composite markers. Univariate relationships between brain structure and the disease markers were explored using hierarchical regression and then entered into multivariable regression models. RESULTS: 100 participants were studied (53 COPD, 47 CAD). PCA identified two brain components: brain tissue volumes and white matter microstructure, and six components from other organ systems: respiratory function, plasma lipids, blood pressure, glucose dysregulation, retinal vessel calibre and retinal vessel tortuosity. Several markers could not be grouped into components and were analysed as single variables, these included brain white matter hyperintense lesion (WMH) volume. Multivariable regression models showed that less well organised white matter microstructure was associated with lower respiratory function (p = 0.028); WMH volume was associated with higher blood pressure (p = 0.036) and higher C-Reactive Protein (p = 0.011) and lower brain tissue volume was associated with lower cerebral blood flow (p<0.001) and higher blood pressure (p = 0.001). Smoking history was not an independent correlate of any brain marker. CONCLUSIONS: Measures of brain structure were associated with a range of markers of disease, some of which appeared to be common to both COPD and CAD. No single common pathway was identified, but the findings suggest that brain changes associated with smoking-related diseases may be due to vascular, respiratory, and inflammatory changes.

Cognitive Dysfunction in White Matter Disorders: New Perspectives in Treatment and Recovery.

White matter disorders are increasingly appreciated as capable of disrupting cognitive function, and this impairment may be sufficiently severe to produce the syndrome of white matter dementia. Although recognizing this problem is important for diagnostic accuracy, the treatment of cognitive dysfunction and dementia in the white matter disorders has received relatively little attention. Similarly, few data are available regarding the potential for cognitive recovery in these disorders. Recent clinical and laboratory advances, however, indicate that effective treatment and meaningful recovery may be achievable goals for many patients with macrostructural or microstructural white matter pathology. One recent observation is that leukoaraiosis has been observed to regress with treatment of hypertension, often with concomitant improvement in cognition. Equally novel is emerging evidence that white matter exhibits substantial plasticity related to activity-dependent myelination and that this phenomenon may produce clinical benefit. These insights suggest that noninvasive and inexpensive interventions targeting white matter are warranted for a wide range of cognitively impaired patients. Moreover, given the well-established risk that vascular white matter pathology portends for developing dementia-including both vascular dementia and Alzheimer's disease-the application of these principles before dementia onset may also be efficacious for prevention. In view of the increasingly compelling case for early white matter involvement in the etiopathogenesis of late-life dementia and the continuing lack of disease-modifying therapy, progress in treating cognitive disturbances arising from white matter disorders offers the prospect that this approach may enhance the prevention of dementia as well as the treatment of cognitive dysfunction.

The Clinical Characteristics of Patients with Pre-Existing Leukoaraiosis Compared to Those Without Leukoaraiosis in Acute Ischemic Stroke.

BACKGROUND: Leukoaraiosis (LA) is a finding in the elderly, that might be asymptomatic or can impact their motor and cognitive functions. We studied the presence of LA in the MRI of patients with AIS and its impact on functional outcome at 3 months. METHODS: 500 consecutive patients diagnosed as AIS were enrolled. Medical history included pre-medication by antiplatelets or statins, and vascular risk factors were reported by history and laboratory investigations. Severity of stroke was assessed by NIHSS and stroke outcome was evaluated on discharge and at 3 months by modified Rankin scale (mRS). LA was diagnosed by MRI-FLAIR sequence and delineated from acute infarction by diffusion-weighted image. And accordingly, patients were divided into group A (absent LA) and group B (present LA). RESULTS: 460 patients completed the study, with 53% of patients on antiplatelet therapy and 11.7% on statins prior to stroke. The percentage of patients with LA was significantly more than those without LA. Patients with LA showed a significantly higher age, more frequent and longer duration of diabetes and hypertension, ischemic heart disease, previous stroke/TIA and antiplatelet intake. Microbleeds were more and mRS was worse in LA group. CONCLUSION: The presence of LA in the background MRI of AIS patients is accompanied by the presence of more risk factors, and unfavorable outcome. Pre-medication with antiplatelets did not prevent the incidence of a new stroke especially in LA group. This might necessitate the identification of some medication for secondary prevention in patients with small vessel disease.

Brain Atrophy and Leukoaraiosis Correlate with Futile Stroke Thrombectomy.

INTRODUCTION: Although mechanical thrombectomy (MT) is a proven therapy for acute large vessel occlusion strokes, futile recanalization in the elderly is common and costly. Strategies to minimize futile recanalization may reduce unnecessary thrombectomy transfers and procedures. We evaluated whether a simple and rapid visual assessment of brain atrophy and leukoaraiosis on a plain head CT correlates with futile stroke recanalization in the elderly. METHODS: Consecutive stroke patients admitted for thrombectomy, older than 65 years of age, all with TICI 2b/3 recanalization rates were retrospectively studied from multiple comprehensive stroke centers. Brain atrophy and leukoaraiosis were visually analyzed from pre-intervention plain head CTs using a simplified scheme based on validated scales. Baseline demographics were collected and the primary outcome measure was 90-day modified Rankin score (mRS). Cochran-Armitage trend test was applied in analyzing the association of the severity of brain atrophy and leukoaraiosis with 90-day mRS. RESULTS: Between 2017 and 2019, 175 patients > 65 years who underwent thrombectomy with TICI 2b/3 recanalization from two comprehensive stroke centers were evaluated. The median age was 77 years. IV-tPA was given in 59% of patients, average initial NIHSS was 19, average baseline mRS was 0.77 and median time to recanalization was 300 minutes. Age and severity of atrophy/leukoaraiosis was categorized into three groups of increasing severity and associated with 90 day mRS 0-3 rates of 62%, 49% and 41% (p=0.037) respectively. CONCLUSIONS: A simplified, visual assessment of the degree of brain atrophy and leukoaraiosis measured on plain head CT correlates with futile recanalization in patients age >65 years. Although additional validation is needed, these findings suggest that brain atrophy and leukoaraiosis may have value as a surrogate marker of prestroke functional status. In doing so, simplified visual plain head CT grading scales may minimize elderly futile recanalization.

Painting by lesions: White matter hyperintensities disrupt functional networks and global cognition.

White matter hyperintensities (WMH) are a prominent feature of cerebral small vessel disease and are associated with cognitive impairment. These deficits in cognition may be caused by the disruption of large-scale functional networks due to the presence of WMHs. However, knowledge regarding the relevance of these lesions on functional networks remains inconclusive. These inconsistencies may derive from issues with interpreting functional imaging data from clinical populations. Lesion network mapping is a technique that allows the overlaying of lesions from a patient population to the functional connectivity of a human connectome derived from healthy adults. This allows researchers to identify functional networks that would be disrupted in a healthy population should the WMHs seen in cerebral small vessel disease be present. We hypothesized that the extent to which these functional networks are disrupted by WMHs is associated with cognitive performance in older adults with cerebral small vessel disease. This cross-sectional study combined baseline data from four studies to create a total sample of 164 older adults (aged ≥55) from metropolitan Vancouver with cerebral small vessel disease. Using lesion network mapping, we assessed the percentage overlap between voxels functionally connected with both the WMHs (lesion network) and five common functional networks: (1) visual; (2) dorsal attention; (3) ventral attention; (4) sensorimotor; and (5) frontoparietal. Cognition was assessed using: (1) Montreal Cognitive Assessment (MoCA); (2) Stroop Colour Word Test (3-2); (3) Trail Making Tests (Part B-A); and (4) Digit Symbol Substitution Test. A One-Way ANOVA and Tukey post-hoc tests were performed to identify the functional networks with greatest percentage overlap with the lesion network. Partial correlations controlling for age were used to analyse whether the extent of the overlap between the lesion and functional networks was associated with poorer cognition. The visual, ventral attention, and frontoparietal networks had significantly greater overlap with the lesion network. After controlling for multiple comparisons, level of lesion network overlap with both the sensorimotor network (p<.001) and ventral attention network (p <. 001) was significantly correlated with MoCA score. Thus, the greater the disruption to the sensorimotor and ventral attention networks, the poorer the global cognition. Our results reveal that the visual, ventral attention, and frontoparietal networks are most vulnerable to disruptions stemming from WMHs. Additionally, we identified that disruption to the sensorimotor and ventral attention networks, as a result of WMHs, may underlie deficits in global cognition in older adults with cerebral small vessel disease.

Baseline Blood-Brain Barrier Leakage and Longitudinal Microstructural Tissue Damage in the Periphery of White Matter Hyperintensities.

OBJECTIVE: To investigate the 2-year change in parenchymal diffusivity, a quantitative marker of microstructural tissue condition, and the relationship with baseline blood-brain barrier (BBB) permeability, in tissue at risk, i.e., the perilesional zone surrounding white matter hyperintensities (WMH) in patients with cerebral small vessel disease (cSVD). METHODS: Patients with sporadic cSVD (lacunar stroke or mild vascular cognitive impairment) underwent 3T MRI at baseline, including dynamic contrast-enhanced MRI to quantify BBB permeability (i.e., leakage volume and rate) and intravoxel incoherent motion imaging (IVIM), a diffusion technique that provides parenchymal diffusivity D. After 2 years, IVIM was repeated. We assessed the relation between BBB leakage measures at baseline and change in parenchymal diffusivity (∆D) over 2 years in the perilesional zones (divided in 2-mm contours) surrounding WMH. RESULTS: We analyzed 43 patients (age 68 ± 12 years, 58% male). In the perilesional zones, ∆D increased 0.10% (confidence interval [CI] 0.07-0.013%) (p < 0.01) per 2 mm closer to the WMH. Furthermore, ∆D over 2 years showed a positive correlation with both baseline BBB leakage volume (r = 0.29 [CI 0.06-0.52], p = 0.013) and leakage rate (r = 0.24 [CI 0.02-0.47], p = 0.034). CONCLUSION: BBB leakage at baseline is related to the 2-year change in parenchymal diffusivity in the perilesional zone of WMH. These results support the hypothesis that BBB impairment might play an early role in subsequent microstructural white matter degeneration as part of the pathophysiology of cSVD.

White Matter Hypoperfusion Associated with Leukoaraiosis Predicts Intracranial Hemorrhage after Intravenous Thrombolysis.

OBJECTIVES: White matter hyperintensity is common in patients receiving intravenous thrombolysis. Some studies have expressed concern about the increased risk of hemorrhagic transformation and poor prognosis for those patients with pre-existing leukoaraiosis. The purpose of this study was to evaluate hypoperfusion associated with leukoaraiosis before thrombolysis using CT perfusion and to explore whether chronic white matter hypoperfusion increases risks of intracranial hemorrhage and poor clinical prognosis. MATERIALS AND METHODS: We collected 175 patients underwent intravenous thrombolysis with complete CT perfusion data and follow-up MRI between June 2017 and January 2020. We measured cerebral blood flow, cerebral blood volume, mean transit time and transit time to the peak at both periventricular and subcortical layers in the cerebral hemisphere contralateral to the stroke. The differences of white matter perfusion were compared between groups with different leukoaraiosis severity. Univariate analysis was used to compare in incidence of hemorrhagic transformation and poor prognosis between the hypoperfusion and normal perfusion groups. Further, we examined association between white matter hypoperfusion and intracranial hemorrhage after thrombolysis using logistic regression. RESULTS: The length of periventricular transit time to the peak was independently associated with a higher risk of intracranial hemorrhage after thrombolysis (OR=4.740, 95%CI=1.624-13.837, P=0.004). The best predictive value was 4.012. But there was no significant difference in poor prognosis at 3 months between hypoperfusion (periventricular transit time to the peak≥4.012 s) and normal perfusion (periventricular transit time to the peak<4.012 s) group. CONCLUSIONS: Image presentations of white matter hypoperfusion reflected the severity of leukoaraiosis. White matter hypoperfusion was independently associated with intracranial hemorrhage after intravenous thrombolysis. However, hypoperfusion would not increase the risk of poor prognosis.

Degenerative dementia with proximal radial and lower vertical spatial neglect.

A 75 year-old man had a two-year history of progressive memory loss, trouble with finances and getting lost. On examination, he scored 16/30 in MoCA test, noticeably impaired on the attentional tasks. His screening bloodtests werenormal. Brain imaging revealed hippocampal atrophy and bilaterallarge areas of leukoaraiosis below posterior parietal lobes. On vertical line bisection he revealed a large upward bias and on radial bisection, a distal bias. Degeneration of his posterior parietal cortex may have caused both the leukoaraiosis and vertical-radial neglect. Unawareness of portions of space can be a source of disability and cause injury. Therefore, patients with degenerative dementia, especially those with similar patterns of leukoaraiosis or parietal degeneration should be tested for vertical and radial forms of spatial neglect.

High-dose atorvastatin improves vascular endothelial function in patients with leukoaraiosis.

OBJECTIVE: Leukoaraiosis (LA), as an age-related white matter degeneration, is mainly caused by chronic ischemia. Our study aims to explore the efficacy of different doses of atorvastatin (ATV) in the vascular endothelial function in patients with LA. METHODS: Our study enrolled 402 LA patients who were then randomly included as control or treated with ATV (10 mg), ATV (20 mg), or ATV (30 mg). The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected by enzyme colorimetric assay. The high-sensitivity C-reactive protein (hs-CRP) level, reactive hyperemia index (RHI), endothelin-1 (ET-1) content, and nitric oxide (NO) level were tested by latex agglutination test, peripheral arterial tonometry technology, radioimmunoassay, and nitrate reductase assay, respectively. RESULTS: After 8 weeks of ATV treatment, the levels of TC, LDL-C, and HS-CRP decreased significantly, and the trends were demonstrated in a more significant way with the increases of dose of ATV. The treatment with ATV at different doses elevated NO level and RHI and declined ET-1 content. Gastrointestinal reaction, muscular pain, and increased aminopherase were observed after treatment with the ATV at different doses with more obvious symptoms detected accompanied by the increase of the dose. The RHI was in negative correlation with the ET-1 and HS-CRP while in positive correlation with NO. CONCLUSION: Our study demonstrates that ATV can significantly improve the vascular endothelial function in LA patients with a dose-dependent effect.

Cerebral Amyloid Angiopathy: A Clinico-Radiological Study from South India.

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage (ICH) and cognitive decline in the elderly. Since it is rarely reported from the developing world, we looked into the clinical profile and neuroimaging associations of CAA. MATERIALS AND METHODS: Ours was a retrospective case series of subjects diagnosed with probable/possible CAA between January 2006 and December 2015 as per Boston criteria. Clinical profile and neuroimaging were reviewed for markers of CAA. Details of any recurrent clinical events and functional status were collected from follow-up records. RESULTS: We had 28 subjects in the series with men outnumbering women, and the mean age was 70.17 ± 8.85 years (55-87 years). At the initial presentation, ICH was most frequent-10/28 (35.7%) patients, followed by transient neurological events (TNE = 25%) and cognitive disturbances (21.4%). Less than half of the patients received a diagnosis of CAA at the initial presentation itself. In total, 68% of our patients had cognitive dysfunction at admission. In our series, 12 had seizures and 9 had a history of TNE. The majority of our patients had vascular risk factors also. Leukoaraiosis showed an association with cognitive dysfunction (P = 0.044). Superficial siderosis and subarachnoid hemorrhage (SAH) showed a positive association with seizures and TNE, respectively. However, ICH showed no association with risk factors or imaging markers of CAA. CONCLUSIONS: CAA patients, with a high prevalence of vascular risk factors mostly presented with ICH. The presence of SAH and superficial siderosis on MRI was associated with presentation as TNE and seizures, respectively.

Abnormal blood pressure circadian rhythms are relevant to cerebral infarction and Leukoaraiosis in hypertensive patients.

BACKGROUND: To investigate the relationships between blood pressure (BP) circadian rhythms and acute cerebral infarction (ACI), silent cerebral infarction (SCI) and the severity of leukoaraiosis in hypertensive patients. METHODS: A retrospective case-control study was performed among hypertensive patients with 24-h ambulatory blood pressure monitoring (ABPM) and cranial magnetic resonance imaging (MRI). RESULTS: A total of 1267 patients were enrolled. Lower nocturnal blood pressure (BP) decreases were observed in ACI patients than in controls (3.3% vs 8.2%, P<0.001). Reverse-dipper pattern (RD) and non-dipper pattern (ND) were found to be independent risk factors for ACI. In ACI patients, both RD and ND BP circadian rhythms were revealed to be independent risk factors for moderate-severe leukoaraiosis. In addition, in SCI patients, RD (OR = 1.7, 95% CI, 0.9-3.0; P = 0.047) or extreme-dipper pattern (ED) (OR = 2.9, 95% CI, 1.2-7.0; P = 0.015) were found to be independent risk factors for moderate-severe leukoaraiosis. Moreover, the greater the severity of leukoaraiosis was, the higher the ratio of abnormal BP circadian rhythms. CONCLUSION: RD and ND BP circadian rhythms might not only be relevant to the onset of ACI but also correlate with the severity of leukoaraiosis. Thus, when modulating BP with antihypertensive drugs, the BP circadian rhythms, and not merely the BP level, should warrant more attention.

Leukoaraiosis and collateral blood flow in stroke patients with anterior circulation large vessel occlusion.

BACKGROUND: Leukoaraiosis and collateral blood flow are processes that involve small vessels, the former related to flow within the deep perforating arterioles and the latter involving the small, cortical pial-pial connections, both of which are independently used to predict cerebrovascular events and treatment outcomes. The aim of this study was to investigate their relationship to each other. METHODS: We retrospectively reviewed patients who underwent mechanical thrombectomy for stroke with pre-procedural CT imaging within 24 hours of the onset of symptoms. Leukoaraiosis was graded by the total Fazekas score on non-contrast CT, periventricular white matter (PVWM) and deep white matter (DWM) scores, both ranging from 0 to 3. Collateral cerebral blood flow was measured by the American Society of Interventional and Therapeutic Radiology/Society of Interventional Radiology (ASITN/SIR) collateral scale. RESULTS: 178 patients were included with a mean age of 67.6±14.8 years. We found an inverse relationship between total Fazekas score and collateral flow (p<0.0001). Among patients with good collaterals, 75.1% had total Fazekas scores of 0-2, compared with 36.6% of patients with moderate collaterals and 32.7% of patients with poor collaterals with total Fazekas scores of 0-2. Mean Fazekas scores were 1.6±1.5, 3.1±1.5 and 3.4±1.6 for good, moderate and poor collaterals, respectively (p<0.0001). On multivariate analysis, total Fazekas score was the only variable independently associated with collateral status (p<0.0001). CONCLUSIONS: Increasing severity of leukoaraiosis is associated with poor collateral grade among ischemic stroke patients with anterior circulation large vessel occlusion. These findings suggest that leukoaraiosis may be a marker for global cerebrovascular dysfunction.

The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women.

Cerebral White Matter Hyperintensity (WMH) lesions have been identified as markers of cerebrovascular diseases and they are associated with increased risk of cognitive impairment. In this study, we investigated the relationship between midlife cardiovascular risk factors and late life WMH volumes two decades later, and examined their association with cognitive performance. 135 participants from the Women's Healthy Ageing Project had completed midlife cardiovascular risk measurement in 1992 and late life brain MRI scan and cognitive assessment in 2012. In these community-dwelling normal aging women, we found that higher midlife Framingham Cardiovascular Risk Profile (FCRP) score was associated with greater WMH volume two decades later, and was predominantly driven by the impact of HDL cholesterol level, controlling for age, education and APOE ε4 status. Structural equation modelling demonstrated that the relationship between midlife FCRP score and late life executive function was mediated by WMH volume. These findings suggest intervention strategies that target major cardiovascular risk factors at midlife might be effective in reducing the development of WMH lesions and thus late life cognitive decline.

Long-range fibre damage in small vessel brain disease affects aphasia severity.

We sought to determine the underlying pathophysiology relating white matter hyperintensities to chronic aphasia severity. We hypothesized that: (i) white matter hyperintensities are associated with damage to fibres of any length, but to a higher percentage of long-range compared to mid- and short-range intracerebral white matter fibres; and (ii) the number of long-range fibres mediates the relationship between white matter hyperintensities and chronic post-stroke aphasia severity. We measured the severity of periventricular and deep white matter hyperintensities and calculated the number and percentages of short-, mid- and long-range white matter fibres in 48 individuals with chronic post-stroke aphasia. Correlation and mediation analyses were performed to assess the relationship between white matter hyperintensities, connectome fibre-length measures and aphasia severity as measured with the aphasia quotient of the Western Aphasia Battery-Revised (WAB-AQ). We found that more severe periventricular and deep white matter hyperintensities correlated with a lower proportion of long-range fibres (r = -0.423, P = 0.003 and r = -0.315, P = 0.029, respectively), counterbalanced by a higher proportion of short-range fibres (r = 0.427, P = 0.002 and r = 0.285, P = 0.050, respectively). More severe periventricular white matter hyperintensities also correlated with a lower proportion of mid-range fibres (r = -0.334, P = 0.020), while deep white matter hyperintensities did not correlate with mid-range fibres (r = -0.169, P = 0.250). Mediation analyses revealed: (i) a significant total effect of periventricular white matter hyperintensities on WAB-AQ (standardized beta = -0.348, P = 0.008); (ii) a non-significant direct effect of periventricular white matter hyperintensities on WAB-AQ (P > 0.05); (iii) significant indirect effects of more severe periventricular white matter hyperintensities on worse aphasia severity mediated in parallel by fewer long-range fibres (effect = -6.23, bootstrapping: standard error = 2.64, 95%CI: -11.82 to -1.56) and more short-range fibres (effect = 4.50, bootstrapping: standard error = 2.59, 95%CI: 0.16 to 10.29). We conclude that small vessel brain disease seems to affect chronic aphasia severity through a change of the proportions of long- and short-range fibres. This observation provides insight into the pathophysiology of small vessel brain disease, and its relationship with brain health and chronic aphasia severity.

Abnormal Interactions of the Salience Network, Central Executive Network, and Default-Mode Network in Patients With Different Cognitive Impairment Loads Caused by Leukoaraiosis.

Leukoaraiosis (LA) is associated with cognitive impairment in the older people which can be demonstrated in functional connectivity (FC) based on resting-state functional magnetic resonance imaging (rs-fMRI). This study is to explore the FC changes in LA patients with different cognitive status by three network models. Fifty-three patients with LA were divided into three groups: the normal cognition (LA-NC; n = 14, six males), mild cognitive impairment (LA-MCI; n = 27, 13 males), and vascular dementia (LA-VD; n = 12, six males), according to the Mini Mental State Exam (MMSE) and Clinical Dementia Rating (CDR). The three groups and 30 matched healthy controls (HCs; 11 males) underwent rs-fMRI. The data of rs-fMRI were analyzed by independent components analysis (ICA) and region of interest (ROI) analysis by the REST toolbox. Then the FC was respectively analyzed by the default-mode network (DMN), salience networks (SNs) and the central executive network (CEN) with their results compared among the different groups. For inter-brain network analysis, there were negative FC between the SN and DMN in LA groups, and the FC decreased when compared with HC group. While there were enhanced inter-brain network FC between the SN and CEN as well as within the SN. The FC in patients with LA can be detected by different network models of rs-fMRI. The multi-model analysis is helpful for the further understanding of the cognitive changes in those patients.

Leukoaraiosis Predicts Short-term Cognitive But not Motor Recovery in Ischemic Stroke Patients During Rehabilitation.

BACKGROUND: Leukoaraiosis has been shown to impact functional outcomes after acute ischemic stroke. However, its association with domain specific recovery after ischemic stroke is uncertain. We sought to determine whether pre-existing leukoaraiosis is associated with short-term motor and cognitive recovery after stroke. METHODS: We retrospectively studied ischemic stroke patients admitted to acute inpatient rehabilitation (AIR) between January 2013 and September 2015. Patient baseline characteristics, infarct volume, prestroke modified Rankin Scale, stroke cause, rehabilitation length of stay, and Functional Independence Measure (FIM) scores were recorded. Leukoaraiosis severity was graded on brain magnetic resonance imaging using the Fazekas scale. Multiple linear regression was used to determine factors independently associated with the total, cognitive, and motor FIM scores at AIR discharge, respectively. RESULTS: Of 1600 ischemic stroke patients screened, 109 patients were included in the final analysis. After adjustment, the initial National Institute of Health Stroke Scale (ß -0.541, confidence interval [CI] -0.993 to -0.888; P = 0.020) and pre-existing leukoaraiosis severity (ß -1.448, CI -2.861 to -0.034; P = 0.045) independently predicted the total FIM score. Domain specific analysis showed that infarct volume (ß -0.012, CI -0.019 to -0.005; P = 0.002) and leukoaraiosis severity (ß -0.822, CI -1.223 to -0.410; P = 0.0001) independently predicted FIM cognitive scores at discharge from AIR. Leukoaraiosis did not predict FIM motor score (P = 0.17). CONCLUSIONS: Leukoaraiosis severity is an independent predictor of total and cognitive, but not motor FIM scores after AIR for acute ischemic stroke. This highlights that leukoaraiosis affects poststroke recovery in a domain specific fashion, information that may aid counseling of patients and families as well as tailor rehabilitative efforts.

Regional leukoaraiosis and cognition in non-demented older adults.

Frontal lobe-executive functions are heavily dependent on distal white matter connectivity. Even with healthy aging there is an increase in leukoaraiosis that might interrupt this connectivity. The goal of this study is to learn 1) the location, depth, and percentage of leukoaraiosis in white matter among a sample of non-demented older adults and 2) associations between these leukoarioasis metrics and composites of cognitive efficiency (processing speed, working memory, and inhibitory function), and episodic memory. Participants were 154 non-demented older adults (age range 60-85) who completed a brain MRI and neuropsychological testing on the same day. Brain MRIs were segmented via Freesurfer and white matter leukoaraiosis depth segmentations was based on published criteria. On average, leukoaraiosis occupied 1 % of total white matter. There was no difference in LA distribution in the frontal (1.12%), parietal (1.10%), and occipital (0.95%) lobes; there was less LA load within the temporal lobe (0.23%). For cortical depth, leukoaraiosis was predominantly in the periventricular region (3.39%; deep 1.46%, infracortical 0.15%). Only increasing frontal lobe and periventricular leukoaraiosis were associated with a reduction in processing speed, working memory, and inhibitory function. Despite the general presence of LA throughout the brain, only frontal and periventricular LA contributed to the speeded and mental manipulation of executive functioning. This study provides a normative description of LA for non-demented adults to use as a comparison to more disease samples.

Functional magnetic resonance imaging with encoding task in patients with mild cognitive impairment and different severity of leukoaraiosis.

Leukoaraiosis is one of the main contributors to mild cognitive impairment due to vascular damage (vascular MCI, VMCI), whose pathophysiology has not been fully elucidated yet. We aimed to shed light on such issue using functional MRI (fMRI). Sixteen patients with VMCI were enrolled and compared with twenty-five patients with MCI but without significant vascular damage (non-vascular MCI, NVMCI) and with fifteen healthy controls (HC). They all underwent fMRI with incidental verbal learning paradigm, using a 3T scanner. Differently from cases with NVMCI (versus HC), VMCI patients presented a higher BOLD activation in the right parieto-occipital cortex and a lower activation in the left superior and middle frontal gyri, anterior cingulum and in left fronto-opercular area when compared to HC. Cortical activation evaluated by fMRI may reflect specific patterns of damage and attempt of compensation in patients with MCI and different severity of leukoaraiosis.

Brain gray and white matter abnormalities in preterm-born adolescents: A meta-analysis of voxel-based morphometry studies.

INTRODUCTION: Studies using voxel-based morphometry report variable and inconsistent abnormalities of gray matter volume (GMV) and white matter volume (WMV) in brains of preterm-born adolescents (PBA). In such circumstances a meta-analysis can help identify the most prominent and consistent abnormalities. METHOD: We identified 9 eligible studies by systematic search of the literature up to October 2017. We used Seed-based d Mapping to analyze GMV and WMV alterations between PBA and healthy controls. RESULTS: In the GMV meta-analysis, PBA compared to healthy controls showed: increased GMV in left cuneus cortex, left superior frontal gyrus, and right anterior cingulate cortex; decreased GMV in bilateral inferior temporal gyrus (ITG), left superior frontal gyrus, and right caudate nucleus. In the WMV meta-analysis, PBA showed: increased WMV in right fusiform gyrus and precuneus; decreased WMV in bilateral ITG, and right inferior frontal gyrus. In meta-regression analysis, the percentage of male PBA negatively correlated with decreased GMV of bilateral ITG. INTERPRETATION: PBA show widespread GMV and WMV alterations in the default mode network, visual recognition network, and salience network. These changes may be causally relevant to socialization difficulties and cognitive impairments. The meta-regression results perhaps reveal the structural underpinning of the cognition-related sex differences in PBA.

Electrocardiographic left atrial abnormality and silent vascular brain injury: The Northern Manhattan Study.

HYPOTHESIS: We hypothesized that P wave terminal Force in the V1 lead (PTFV1) would be associated with leukoaraiosis and subclinical infarcts, especially cortical infarcts, in a population-based, multi-ethnic cohort. METHODS: PTFV1 was collected manually from baseline electrocardiograms of clinically stroke-free Northern Manhattan Study participants. Investigators read brain MRIs for superficial infarcts, deep infarcts, and white matter hyperintensity volume (WMHV). WMHV was adjusted for head size and log transformed, achieving a normal distribution. Logistic regression models investigated the association of PTFV1 with cortical and with all subclinical infarcts. Linear regression models examined logWMHV. Models were adjusted for demographics and risk factors. RESULTS: Among 1174 participants with PTFV1 measurements, the mean age at MRI was 70 ± 9 years. Participants were 14.4% white, 17.6% black, and 65.8% Hispanic. Mean PTFV1 was 3587.35 ± 2315.62 µV-ms. Of the 170 subclinical infarcts, 40 were cortical. PTFV1 ≥ 5000 µV-ms was associated with WMHV in a fully adjusted model (mean difference in logWMHV 0.15, 95% confidence interval 0.01-0.28). PTFV1 exhibited a trend toward an association with cortical infarcts (unadjusted OR per SD change logPTFV1 1.30, 95% CI 0.94-1.81), but not with all subclinical infarcts. CONCLUSION: Electrocardiographic evidence of left atrial abnormality was associated with leukoaraiosis.