Effect Of White Matter Lesions Research Articles

Effects of hippocampal atrophy and white matter lesions on cognitive function in Alzheimer’s disease

AbstractBackgroundWe investigated the effects of white matter lesions and hippocampal atrophy on head MRI on cognitive function in AD patients.MethodWe examined 47 patients who were diagnosed with Alzheimer’s disease according to the ATN classification at the geriatric department of Tokyo Medical University Hospital. We evaluated the severity of white matter damage by the sum of PVH and DWMH in the Fazekas classification on head MRI at the first visit, and hippocampal atrophy by VSRAD.ResultThere was a significant correlation between white matter impairment and cognitive changes (r = 0.292, p<0.05). And the correlation test for hippocampus atrophy and MMSE change was also performed with correlation coefficients r = 0.00926 and p = 0.951 (>0.05).ConclusionThe sum of PVH and DWMH and the amount of change in MMSE were positively correlated in AD patients. Therefore, it was concluded that the more severe the white matter disorder, the slower the progression of cognitive decline. These results suggest that advanced white matter disorders may inhibit the progression of AD in AD patients.

Mental flexibility depends on a largely distributed white matter network: Causal evidence from connectome-based lesion-symptom mapping

Mental flexibility (MF) refers to the capacity to dynamically switch from one task to another. Current neurocognitive models suggest that since this function requires interactions between multiple remote brain areas, the integrity of the anatomic tracts connecting these brain areas is necessary to maintain performance.We tested this hypothesis by assessing with a connectome-based lesion-symptom mapping approach the effects of white matter lesions on the brain’s structural connectome and their association with performance on the trail making test, a neuropsychological test of MF, in a sample of 167 first unilateral stroke patients.We found associations between MF deficits and damage of i) left lateralized fronto-temporo-parietal connections and interhemispheric connections between left temporo-parietal and right parietal areas; ii) left cortico-basal connections; and iii) left cortico-pontine connections. We further identified a relationship between MF and white matter disconnections within cortical areas composing the cognitive control, default mode and attention functional networks.These results for a central role of white matter integrity in MF extend current literature by providing causal evidence for a functional interdependence among the regional cortical and subcortical structures composing the MF network. Our results further emphasize the necessity to consider connectomics in lesion-symptom mapping analyses to establish comprehensive neurocognitive models of high-order cognitive functions.

Minimizing the effect of white matter lesions on deep learning based tissue segmentation for brain volumetry.

Automated methods for segmentation-based brain volumetry may be confounded by the presence of white matter (WM) lesions, which introduce abnormal intensities that can alter the classification of not only neighboring but also distant brain tissue. These lesions are common in pathologies where brain volumetry is also an important prognostic marker, such as in multiple sclerosis (MS), and thus reducing their effects is critical for improving volumetric accuracy and reliability. In this work, we analyze the effect of WM lesions on deep learning based brain tissue segmentation methods for brain volumetry and introduce techniques to reduce the error these lesions produce on the measured volumes. We propose a 3D patch-based deep learning framework for brain tissue segmentation which is trained on the outputs of a reference classical method. To deal more robustly with pathological cases having WM lesions, we use a combination of small patches and a percentile-based input normalization. To minimize the effect of WM lesions, we also propose a multi-task double U-Net architecture performing end-to-end inpainting and segmentation, along with a training data generation procedure. In the evaluation, we first analyze the error introduced by artificial WM lesions on our framework as well as in the reference segmentation method without the use of lesion inpainting techniques. To the best of our knowledge, this is the first analysis of WM lesion effect on a deep learning based tissue segmentation approach for brain volumetry. The proposed framework shows a significantly smaller and more localized error introduced by WM lesions than the reference segmentation method, that displays much larger global differences. We also evaluated the proposed lesion effect minimization technique by comparing the measured volumes before and after introducing artificial WM lesions to healthy images. The proposed approach performing end-to-end inpainting and segmentation effectively reduces the error introduced by small and large WM lesions in the resulting volumetry, obtaining absolute volume differences of 0.01 ± 0.03% for GM and 0.02 ± 0.04% for WM. Increasing the accuracy and reliability of automated brain volumetry methods will reduce the sample size needed to establish meaningful correlations in clinical studies and allow its use in individualized assessments as a diagnostic and prognostic marker for neurodegenerative pathologies.

Influence of white matter lesions on the prognosis of acute cardioembolic stroke without reperfusion therapy

BackgroundFew studies have investigated the influence of white matter lesions (WMLs) on the prognosis of acute cardioembolic stroke (CES). We aimed to explore the role of WMLs in predicting 3-month prognosis of CES without reperfusion therapy.MethodsA number of 251 acute CES patients without reperfusion therapy at a single center were retrospectively recruited. The severity of WMLs was evaluated by Fazekas scale and patients were divided into mild WMLs group (188 cases, Fazekas ≤ 2 points) and moderate to severe WMLs group (63 cases, Fazekas ≥ 3 points) accordingly. General data and clinical features of the two groups were compared. Functional outcomes of patients were followed up for 3 months using the modified Rankin scale (mRS) and patients were divided into poor outcome group (mRS ≥ 3) and favorable outcome group (mRS ≤ 2). The effect of WMLs on the prognosis was identified by binary logistic regression.ResultsPatients in moderate to severe WMLs group were older (P < 0.001). Also, they had higher baseline National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001) and elevated incidence of asymptomatic cerebral hemorrhage (P = 0.040) and stroke associated pneumonia (P = 0.001) than those in mild WMLs group. At 3 months, there were 100 cases in the poor outcome group. Patients in poor outcome group had higher baseline NIHSS score, increased proportion of moderate to severe WMLs, and elevated incidence of stroke associated pneumonia than those in favorable outcome group (P < 0.001). Binary logistic regression analysis showed that moderate to severe WMLs (odds ratio [OR] = 4.105, 95 % confidence interval [CI] = 1.447–11.646), baseline NIHSS score (OR = 1.368, 95 % CI = 1.240–1.511), and stroke-associated pneumonia (OR = 4.840, 95 %CI = 1.889–12.400) were independent risk factors for poor outcome.ConclusionsModerate to severe WMLs is an independent risk factor for prognosis of CES patients without reperfusion therapy.

Cochlear implantation in prelingually deaf children with white matter lesions.

White matter lesions (WMLs) are the most common central nervous system changes observed during cochlear implant evaluation. However, its clinical significance in cochlear implantation (CI) remains unclear. The purpose of this study is to explore the effects of WMLs on hearing and speech rehabilitation of prelingually deaf children after CI. The data of forty-five children with WMLs who received CI from 2011 to 2014 were retrospectively reviewed. All patients underwent magnetic resonance imaging examination preoperatively. The categories of auditory performance (CAP) and speech intelligibility rating (SIR) scales were used to evaluate changes in the auditory and speech abilities of the patients, and the Fazekas scale was adopted to assess the extent of WMLs. The degree of WMLs was divided into four grades (none, mild, moderate, severe). We assessed hearing and speech abilities at the following time points: 6, 12, 24, 36, 48 and 60-months post-operation. No significant differences in CAP scores were observed between WMLs groups and the control group at 12months post-CI (p = 0.099), but marked between-group differences were found at 6, 24, 48- and 60-months post-CI. (p < 0.05). Similarly, no significant differences in the SIR scores were observed at 6months post-CI (p = 0.087), but marked between-group differences were found at 12, 24, 48- and 60- months post-CI. (p < 0.05). Analysis of stratified group results revealed improvements in hearing and speech development for all the subgroups, including the severe WMLs subgroup following CI. However, hearing and speech ability of the severe WMLs subgroup was much slower than that of other groups. The auditory and speech abilities of prelingually deaf children with WMLs and those without WMLs can improve after CI. Therefore, WMLs should not be considered a contraindication for CI. However, the decision to perform CI in such patients needs a comprehensive evaluation because the post-surgery effects on children with severe WMLs are not ideal.

Effects of white matter lesions on brain perfusion in patients with mild cognitive impairment

ObjectiveTo evaluate the effects of white matter lesions on regional cerebral blood flow in subjects with amnestic mild cognitive impairment. Patients and MethodsSeventy-five subjects with mild cognitive impairment (36 men and 39 women; mean age, 78.1 years) were included in the study. We used the Mini-Mental State Examination to assess cognitive function. All subjects underwent brain magnetic resonance imaging and 99mTc ethylcysteinate dimer single photon emission computed tomography. Subjects were stratified based on the presence or absence of white matter lesions on magnetic resonance imaging. Statistical parametric mapping of differences in regional cerebral blood flow between the two groups were assessed by voxel-by-voxel group analysis using SPM8. ResultsOf all 75 subjects with mild cognitive impairment, 46 (61.3%) had mild to moderate white matter lesions. The prevalence of hypertension tended to be higher in subjects with white matter lesions than in those without white matter lesions. Mini-Mental State Examination scores were significantly lower in subjects with white matter lesions than in those without white matter lesions. Subjects with white matter lesions had decreased regional cerebral blood flow mainly in the frontal, parietal, and medial temporal lobes, as well as the putamen, compared to those without white matter lesions. ConclusionIn subjects with mild cognitive impairment, white matter lesions were associated with cognitive impairment and mainly frontal lobe brain function.

Conceptual elaboration versus direct lexical access in WAIS-similarities: differential effects of white-matter lesions and gray matter volumes

ABSTRACTWechsler Adult Intelligence Scale (WAIS) subscale Similarities have been classified as a test of either verbal comprehension or of inductive reasoning. The reason may be that items divide into two categories. We tested the hypothesis of heterogeneity of items in WAIS-Similarities. Consecutive patients at a memory clinic and healthy controls participated in the study. White-matter hyperintensities (WMHs) and normalized temporal lobe volumes were measured based on Magnetic resonance Imaging (MRI), and tests of verbal memory and attention were used in addition to WAIS-Similarities to collect behavioural data. Factor analysis supported the hypothesis that two factors are involved in the performance of WAIS-similarities: (1) semiautomatic lexical access and (2) conceptual elaboration. These factors were highly correlated but provided discriminative diagnostic information: In logistic regression analyses, scores of the lexical access factor and of the conceptual elaboration factor discriminated patients with mild cognitive impairment from Alzheimer’s disease patients and from healthy controls, respectively. High scores of WMH, indicating periventricular white-matter lesions, predicted factor scores of direct lexical access but not those of conceptual elaboration, which were predicted only by medial and lateral temporal lobe volumes.

Hippocampus and Basal Forebrain Volumetry for Dementia and Mild Cognitive Impairment Diagnosis: Could It Be Useful in Primary Care?

Once apatient or aknowledgeable informant has noticed decline in memory or other cognitive functions, initiation of early dementia assessment is recommended. Hippocampus and cholinergic basal forebrain (BF) volumetry supports the detection of prodromal and early stages of Alzheimer's disease (AD) dementia in highly selected patient populations. To compare effect size and diagnostic accuracy of hippocampus and BF volumetry between patients recruited in highly specialized versus primary care and to assess the effect of white matter lesions as aproxy for cerebrovascular comorbidity on diagnostic accuracy. We determined hippocampus and BF volumes and white matter lesion load from MRI scans of 71 participants included in a primary care intervention trial (clinicaltrials.gov identifier: NCT01401582) and matched 71 participants stemming from amemory clinic. Samples included healthy controls and people with mild cognitive impairment (MCI), AD dementia, mixed dementia, and non-AD related dementias. Volumetric measures reached similar effect sizes and cross-validated levels of accuracy in the primary care and the memory clinic samples for the discrimination of AD and mixed dementia cases from healthy controls. In the primary care MCI cases, volumetric measures reached only random guessing levels of accuracy. White matter lesions had only amodest effect on effect size and diagnostic accuracy. Hippocampus and BF volumetry may usefully be employed for the identification of AD and mixed dementia, but the detection of MCI does not benefit from the use of these volumetric markers in aprimary care setting.

White matter lesions reduce number of brain metastases in different cancers: a high-resolution MRI study.

Brain metastases are major complications of common cancers. Tumor type and proneness to the CNS are thought to define the number and size of brain metastases. It is not known if intrinsic vascular factors can also have an effect. Restricted perfusion due to cerebral small vessel disease is frequent in elderly patients and causes white matter lesions (WML). The aim of this analysis was to evaluate a possible negative effect of WML and patient age on the number and size of brain metastases (BM) of different tumor entities. Pre-therapeutic 3T brain magnetic resonance imaging (MRI) of 200 patients with BM were analyzed. Location, size and number of BM (NoM) were determined. T2 hyperintensive WML were scored according to Fazekas-Score (grade I-III). Patients with WML grade 1 (NoM: 5.59; p = 0.009) and grade 2 (NoM: 3.68; p = 0.002) had significantly less BM than patients without WML (NoM: 6.99). This effect was present in subgroups of different tumors: NSCLC (p = 0.05), other tumors than NSCLC (p = 0.048). Age (≤65 or >65 years) was positively correlated with the degree of WML but not with number (pNoM = 0.832) or mean diameter (pmDM = 0.662) of brain metastases. While patient age did not appear to be relevant, increasing WML were associated with lower number of brain metastases in different tumor types.

Effects of white matter lesions on trunk stability during dual-task walking among older adults with mild cognitive impairment.

The linkage between gait and cognition has been shown in cases of white matter lesion (WML) that affect gait in older adults. Dual-task walking is believed to be cognitively demanding and to alter trunk movement, and gait impairment in people with mild cognitive impairment (MCI) is highlighted under this condition. However, the association between dual-task walking and structural changes in the brain, particularly with WML, in people with MCI is still unclear. The aim of this study was to examine the association between trunk stability during dual-task walking and WML in 560 older adults with MCI. We measured magnetic resonance imaging (MRI) and gait variables. Gait variables included harmonic ratio in vertical, mediolateral, and anteroposterior directions, analyzed using a tri-axial accelerometer attached to the lower trunk. Walking conditions were normal walking and dual-task walking (counting backwards while walking) conditions. Demographical data and brain atrophy were measured as covariates. Subjects were classified into non-severe WML (n = 451, mean age = 73.2 years) and severe WML (n = 109, mean age = 75.9 years) groups. Linear mixed-effects model analysis controlled for covariates showed dual-task-related changes in all harmonic ratios associated with WML (p < 0.05). Even after adjustment for executive function, harmonic ratio in the mediolateral direction was significantly associated with WML (p < 0.05). Our findings revealed that WMLs were associated with trunk stability in dual-task walking. Further studies are required to investigate the neural basis for deficits in gait ability among MCI subjects.

Changes of ubiquitin C-terminal hydrolase-L1 levels in serum and urine of patients with white matter lesions

ObjectivesUbiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has been established as a potential biomarker of neuronal damage. There is not much information about the effects of white matter lesions (WMLs) on serum and urine UCH-L1 levels in white matter disease patients. This study was aimed to assess whether serum or urine UCH-L1 levels are a reliable marker of brain damage in patients with WMLs. Design and methodsSerum and urine levels of UCH-L1 were assessed in 125 patients with dizziness, hypertension, type 2 diabetes mellitus, or dyslipidemia. Of these 125 patient cases, 41 showed periventricular WMLs (P-WMLs), 46 showed subcortical WMLs (S-WMLs), and 38 displayed no well-defined WMLs (controls). ResultsSerum UCH-L1 levels were significantly different between the WML group and controls (p<0.05). Further subgroup analysis proved that serum UCH-L1 levels in participants with S-WMLs were significantly increased when compared with controls (p<0.001), but there was no significant differences between controls and patients with P-WMLs (p>0.05). However, urine levels of UCH-L1 were similar between these three groups (p>0.05). In addition, multivariate analysis showed that increased serum UCH-L1 levels were independently associated with the severity of WMLs using Fazekas scale (β=0.432, p<0.001). ConclusionsThese findings suggest that serum UCH-L1 levels may serve as a novel biomarker for neuronal damage from WMLs, especially S-WMLs.

Spotlight on the May 12 Issue

#### Notable in Neurology This issue features an article on the effect of white matter lesions on manual dexterity in healthy middle-aged persons and another describing that the lower the hippocampus global connectivity, the higher its local metabolism in Alzheimer disease. Another featured article focuses on perampanel efficacy and tolerability with enzyme-inducing antiepileptic drugs in patients with epilepsy. ### HIV status and the risk of ischemic stroke among men The authors analyzed data on 76,835 participants free of baseline cardiovascular disease, assessing demographics, stroke risk factors, comorbid diseases, substance use, HIV biomarkers, and incidence of ischemic stroke. HIV infection was associated with an increased ischemic stroke risk …

Effect of white matter lesions on manual dexterity in healthy middle-aged persons.

We hypothesized that integrated motor-visual functions measured by manipulative manual dexterity are affected by white matter lesion (WML) burden as measured on cranial MRI across relevant brain regions in subjects at risk of preclinical occult vascular disease. A real-time cross-sectional study of healthy subjects aged 29 to 74 years with a family history of early-onset coronary artery disease (n = 714; mean age, 51 ± 11 years; mean education, 14 ± 3 years; 42% male; 38% black) were identified from probands with coronary artery disease diagnosed before age 60 years. WMLs on 3-tesla brain MRI and Grooved Pegboard scores were measured. WMLs were observed at all ages. Mean pegboard scores were 108 ± 18, similar to normal populations. In unadjusted analysis, WMLs and pegboard scores were significantly correlated by region (total WMLs, r = 0.34, p = 0.0001; frontal [r = 0.34, p < 0.0001], insula [r = 0.31, p < 0.0001], parietal [r = 0.31, p < 0.0001], and temporal [r = 0.17, p < 0.0001]). In multivariate analysis predicting (log) pegboard score adjusted for age, sex, race, education, regional or total volumes, and familial non-independence, total WML volume (p = 5.79E - 05) and regional WML volumes (p < 0.01) retained statistical significance in all but the youngest age quartile (29-43 years). Greater WML volumes in different brain regions are associated with higher pegboard scores (worse performance) independent of age, sex, race, education, and total or regional volumes. This suggests that small vessel cerebrovascular disease may be present in healthy individuals in a preclinical state with measurable impact on complex integrative functions in individuals with excess risk of clinical vascular disease.

Evaluating the effects of white matter multiple sclerosis lesions on the volume estimation of 6 brain tissue segmentation methods.

The accuracy of automatic tissue segmentation methods can be affected by the presence of hypointense white matter lesions during the tissue segmentation process. Our aim was to evaluate the impact of MS white matter lesions on the brain tissue measurements of 6 well-known segmentation techniques. These include straightforward techniques such as Artificial Neural Network and fuzzy C-means as well as more advanced techniques such as the Fuzzy And Noise Tolerant Adaptive Segmentation Method, fMRI of the Brain Automated Segmentation Tool, SPM5, and SPM8. Thirty T1-weighted images from patients with MS from 3 different scanners were segmented twice, first including white matter lesions and then masking the lesions before segmentation and relabeling as WM afterward. The differences in total tissue volume and tissue volume outside the lesion regions were computed between the images by using the 2 methodologies. Total gray matter volume was overestimated by all methods when lesion volume increased. The tissue volume outside the lesion regions was also affected by white matter lesions with differences up to 20 cm(3) on images with a high lesion load (≈50 cm(3)). SPM8 and Fuzzy And Noise Tolerant Adaptive Segmentation Method were the methods less influenced by white matter lesions, whereas the effect of white matter lesions was more prominent on fuzzy C-means and the fMRI of the Brain Automated Segmentation Tool. Although lesions were removed after segmentation to avoid their impact on tissue segmentation, the methods still overestimated GM tissue in most cases. This finding is especially relevant because on images with high lesion load, this bias will most likely distort actual tissue atrophy measurements.

Simulated rich club lesioning in brain networks: a scaffold for communication and integration?

Brain function depends on effective neural communication and integration across different domains. This exchange of information is facilitated by the “connectome”: the complex network of all neural elements and neural connections of an organism that provides the anatomical foundation for emerging functional dynamics. How the complex wiring of the connectome relates to the demands and constraints placed upon the brain is an important question in neuroscience, receiving attention from a rapidly increasing number of researchers. One potential aspect of macroscale connectome architecture related to global communication and integration is the existence of “neural hubs,” referring to brain regions that display many connections and thus exhibit a topologically central position in the overall network. In addition to being individually rich in connectivity, hubs in neural systems tend to be also densely interconnected, together forming a central “rich club” (van den Heuvel and Sporns, 2011). Over the past years, several reports on a number of different species (including human, macaque, cat and nematode) have consistently suggested that brain hubs and their rich club connections play an important role in enabling efficient neural communication and integration, constituting a central communication backbone that boosts the functional repertoire of the system (Zamora-Lopez et al., 2010; Crossley et al., 2013; Towlson et al., 2013; de Reus and van den Heuvel, 2013a; van den Heuvel and Sporns, 2013a; Grayson et al., 2014; Misic et al., 2014; Senden et al., 2014). Since brain hubs have been shown to be implicated in both neurological (Stam et al., 2007; Buckner et al., 2009) and psychiatric (Collin et al., 2013; van den Heuvel et al., 2013) diseases, it is the general hope that a better fundamental understanding of their role in connectome organization may eventually provide insight in the pathology and effects of brain disorders. In an interesting article recently published in this journal, Andrei Irimia and John Van Horn aimed to further elucidate healthy brain network architecture by pinpointing those neural connections that are critical for the overall organization of the human connectome (Irimia and Van Horn, 2014). Simulating the effects of white matter lesions by removing individual connections from the connectome, the authors report on a scaffold of white matter connections whose disruption is suggested to have significant global-level effects on the brain. However, quite contrary to our expectations, the authors note that “connections between rich club nodes in the human brain overlap only very moderately—and even then, perhaps accidentally—with the core scaffold.” Here we discuss the apparent incongruity between Irimia and Van Horn's lesioning scaffold and the growing amount of studies suggesting that neural hubs and their connections may form a fundamental architecture for shaping global neural processes. Analyzing new data, we show that the importance of connections assessed by simulated lesioning largely depends on the measures chosen to evaluate the outcome. We further demonstrate that lesioning connections between rich club regions has pronounced effects on two specific measures of communication and integration, both in the human and animal brain.

Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter

Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDG-PET) in connected GM. WML masks from 72 cognitively normal (age 61.7±9.6years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r=0.20, p<0.05 corrected) and lower PiB uptake (r=0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (β=0.045) and FDG-PET (β=0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition.

The effect of white matter lesions on cognition after carotid revascularization

BackgroundCerebral white matter lesions (WML) are associated with cognitive impairment, and carotid revascularization with cognitive worsening or improvement. We assessed the relation between WML severity and changes in cognition after carotid endarterectomy or stenting. MethodsPatients with symptomatic carotid artery stenosis, enrolled in the International Carotid Stenting Study (ISRCTN25337470), underwent detailed neuropsychological examinations (NPEs) before and after 6months. Cognitive results were standardized into z-scores, from which a sum score was calculated. The primary outcome was the mean difference (MD) in sum score between baseline and follow-up. Changes in sum score were related to WML severity with the ‘age-related white matter changes’ score, assessed on baseline MRI-FLAIR. Three groups were formed based on this score. ResultsEighty-nine patients had both baseline MRI and NPE, of these 77 had a calculable cognitive difference score. The cognitive sum score at six months was worse than at baseline: MD, −0.21; 95% CI, −0.32 to −0.09. The change in sum score did not depend on WML load: MD for no-to-mild WML, −0.15; 95% CI, −0.39 to 0.09, for moderate WML, −0.27; 95% CI, −0.48 to −0.06; and for severe WML, −0.21; 95% CI, −0.40 to −0.04. This did not change essentially after adjustment for baseline factors. ConclusionCognitive functioning deteriorated after carotid revascularization, regardless of baseline WML burden.

Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial

SummaryBackgroundFindings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy.MethodsPatients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470.Findings1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17–6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10–8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40–3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38–5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29–6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45–27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7.InterpretationThe presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.

Effect of White Matter Lesions on Brain Perfusion in Alzheimer’s Disease

Background: This study examined the effect of white matter lesions (WMLs) on regional cerebral blood flow (rCBF) in patients with Alzheimer’s disease (AD). Methods: Ninety-eight patients with AD were included in the study (40 men and 58 women; mean age, 78.1 years). Cognitive function was assessed using the Mini-Mental State Examination. Brain magnetic resonance imaging (MRI) and ^99mTc ethyl cysteinate dimer single photon emission computed tomography were performed in all subjects. AD patients were divided into two subgroups according to the presence of WMLs on MRI. A voxel-by-voxel group analysis using Statistical Parametric Mapping 8 was used to detect the differences in rCBF between the two groups. Results: Fifty-seven of 98 AD patients (58%) showed mild to moderate WMLs on MRI. The prevalence of hypertension was significantly higher in AD patients with WMLs than in those without WMLs. AD patients with WMLs exhibited a significantly decreased rCBF in the anterior cingulate gyrus and insula, compared to AD patients without WMLs. Conclusion: We suggest that WMLs might influence brain regions associated with the limbic system in patients with AD.

The nature of episodic memory deficits in MCI with and without vascular burden

This study measured episodic memory deficits in individuals with mild cognitive impairment (MCI) as a function of their vascular burden. Vascular burden was determined clinically by computing the number of vascular risk factors and diseases and neuroradiologically by assessing the presence and severity of white matter lesions (WML). Strategic memory processes were measured with free recall and temporal contextual memory tasks requiring self-initiated retrieval. Nonstrategic memory retrieval processes were appraised with a five-choice recognition procedure. Results showed that MCI participants with high vascular burden displayed impairment of strategic memory processes, whereas MCI participants with no vascular burden showed impairment of both strategic and nonstrategic memory processes. A similar pattern was found whether vascular burden was measured using a clinical index of vascular risk profile or whether it was measured neuroradiologically by assessing the extent and severity of subcortical WML. However, the effect of WML on memory differed as function of level of education, used here as a proxy for cognitive reserve. Among participants with MCI, those who had higher education and no WML were the least memory impaired. The study also examined memory as a function of whether patients later progressed to dementia after a three-year follow-up. When examining progressors’ performance, strategic and nonstrategic processes were both impaired in progressors with no concomitant vascular conditions, whereas progressors with a high vascular burden showed less impairment of nonstrategic than strategic processes. Overall, results indicate that the presence of vascular burden in MCI is associated with selective impairment of strategic memory processes.