White Matter Hyperintensities Score Research Articles

Nighttime Blood Pressure and White Matter Hyperintensities in Patients With Parkinson Disease

Increasing evidence indicates that nocturnal blood pressure level and/or loss of nocturnal blood pressure dips are sensitive markers of cardiovascular morbidity and mortality. Several studies have suggested that blunted heart rate variability and nocturnal decline in heart rate are also associated with target organ damage. These phenomena occur relatively commonly in patients with Parkinson disease (PD); however, few studies have assessed the consequences of these abnormalities in patients with PD. We investigated the influence of circadian changes in blood pressure and heart rate on white matter hyperintensities (WMHs) in patients with PD. The presence of nocturnal hypertension was associated with increased WMH score, and nighttime systolic pressure was closely related with white matter changes. Blunted heart rate variability and nocturnal decline in heart rate were also related to increasing WMH scores. The non-dipping phenomenon did not influence WMHs. These findings suggest that white matter changes are related to circadian autonomic dysfunction, particularly nocturnal hypertension in patients with PD. Therefore, it is important to monitor nocturnal blood pressure status, because modifying these circadian regulatory disturbances can be beneficial to protect against vascular brain damage in patients with PD. (Author correspondence: neuronet@catholic.ac.kr)

FRI0212 The relationship between brain white matter changes and fatigue in granulomatosis with polyangiitis (GPA; wegener’s)

BackgroundBrain white matter (WM), and more specifically neuronal connectivity is thought to perform a crucial role in the central processing of fatigue. In diseases of the WM, such as multiple...

Fatigue-related brain white matter changes in granulomatosis with polyangiitis

To determine the association between brain white matter (WM) damage and persistent fatigue among patients with granulomatosis with polyangiitis (GPA). A case-control MRI study was conducted. Both cases, defined as GPA patients with chronic fatigue, and controls, defined as GPA patients without fatigue, underwent MRI brain scanning. Standard T1, T2 and FLAIR images were acquired and Scheltens white matter hyperintensity scores (SWMHS) reported in order to quantify macroscopic damage. In addition, diffusion tensor imaging (DTI) data were analysed using track-based spatial statistics to measure structural integrity and thus microscopic damage. No statistically significant differences in macroscopic damage were observed between cases (n = 14) and controls (n = 14) (median SWMHS 6, interquartile range 3-7 vs median SWMHS 3.5, interquartile range 3-8; P = 0.52). Compared with controls, there were no regions of WM where cases recorded reduced structural integrity; however, significantly greater structural integrity was registered in the regions of the fornix and cingulum nerve bundles of cases (P < 0.05, corrected for multiple comparisons). This study found no evidence to suggest that GPA-related fatigue is associated with either macroscopic or microscopic damage of the WM. On the contrary, regions of significantly greater structural integrity were observed among fatigued cases, which may reflect sustained activation secondary to chronic fatigue exposure.

White Matter Hyperintensities in Parkinson’s Disease: Do They Explain the Disparity between the Postural Instability Gait Difficulty and Tremor Dominant Subtypes?

BackgroundBrain white matter hyperintensities (WMHs) commonly observed on brain imaging of older adults are associated with balance and gait impairment and have also been linked to cognitive deficits. Parkinson’s disease (PD) is traditionally sub-classified into the postural instability gait difficulty (PIGD) sub-type, and the tremor dominant (TD) sub-type. Considering the known association between WMHs and axial symptoms like gait disturbances and postural instability, one can hypothesize that WMHs might contribute to the disparate clinical sub-types of patients with PD.Methods110 patients with PD underwent a clinical evaluation and a 3T MRI exam. Based on the Unified Parkinson Disease Rating Scale, the patients were classified into motor sub-types, i.e., TD or PIGD, and scores reflecting PIGD and TD symptoms were computed. We compared white matter burden using three previously validated methods: one using a semi-quantitative visual rating scale in specific brain regions and two automated methods.ResultsOverall, MRI data were obtained in 104 patients. The mean WMHs scores and the percent of subjects with lesions in specific brain regions were similar in the two subtypes, p = 0.678. The PIGD and the TD scores did not differ even when comparing patients with a relatively high burden of WMHs to patients with a relatively low burden. Across most of the brain regions, mild to moderate correlations between WMHs and age were found (r = 0.23 to 0.41; p<0.021). Conversely, no significant correlations were found between WMHs and the PIGD score or disease duration. In addition, depressive symptoms and cerebro-vascular risk factors were similar among the two subtypes.ConclusionsIn contrast to what has been reported previously among older adults, the present study could not demonstrate any association between WMHs and the PIGD or TD motor sub-types in patients with PD.

The Relationship of White Matter Hyperintensities with Depressive Symptoms and Daily Living Activities in Early-Stage Alzheimer's Disease Patients.

Cerebral white matter hyperintensities (WMHs) detected on magnetic resonance imaging scans are frequently seen in both Alzheimer's disease (AD) and depression patients and believed to play an important role in cognition and mood. Depressive symptoms and depression may accompany AD in all stages of the disease. The aim of the study was to evaluate the relationship of regional WMHs with depressive symptoms, cognitive status, medial temporal lobe atrophy, and daily living activities in early-stage AD patients. Forty-five patients with very mild or mild AD were examined. All subjects underwent MRI and were assessed by the Geriatric Depression Scale (GDS) and the Addenbrooke's Cognitive Examination-Revised (ACE-R) for the evaluation of depressive symptom severity and cognitive status, respectively. The patients were divided into two groups based on the selected cut-off point in the GDS. CDR sum of the boxes (CDR-sb) scores were calculated as a measure of activities of daily living (ADLs). MRI T2-FLAIR slices were used to rate the white-matter lesions according to the Age-Related White Matter Changes Rating Scale, assessing the WMHs in frontal, parietooccipital, temporal, infratentorial and basal ganglia areas individually. Medial temporal lobe atrophy was assessed with high-resolution T1 images using visual rating scale. In the depressive group, frontal WMH scores were found to be higher than in the non-depressive group (p=0.006). ACE-r, CDR-sb and medial temporal lobe atrophy scores did not differ among the groups. CDR-sb scores showed a significant correlation with frontal WMH scores (left frontal WMH r=0.439, p=0.003, right frontal AMH r=0.459, p=0.001). Linear regression models revealed the effect of WMHs on depressive symptoms among the other factors including age, functionality and atrophy in the medial temporal areas. Our findings underscore the potential role of regional, particularly frontal AMHs in depressive symptoms and functionality of the early AD patients.

Relationship between Orthostatic Hypotension and White Matter Hyperintensity Load in Older Patients with Mild Dementia

Background/ObjectivesWhite matter hyperintensities (WMH) in magnetic resonance imaging (MRI) scans of the brain, and orthostatic hypotension (OH) are both common in older people. We tested the hypothesis that OH is associated with WMH.DesignCross-sectional study.SettingSecondary care outpatient clinics in geriatric medicine and old age psychiatry in western Norway.Participants160 older patients with mild dementia, diagnosed according to standardised criteria.MeasurementsOH was diagnosed according to the consensus definition, measuring blood pressure (BP) in the supine position and within 3 minutes in the standing position. MRI scans were performed according to a common protocol at three centres, and the volumes of WMH were quantified using an automated method (n = 82), followed by manual editing. WMH were also quantified using the visual Scheltens scale (n = 139). Multiple logistic regression analyses were applied, with highest vs. lowest WMH quartile as response.ResultsThere were no significant correlations between WMH volumes and systolic or diastolic orthostatic BP drops, and no significant correlations between Scheltens scores of WMH and systolic or diastolic BP drops. In the multivariate analyses, only APOEε4 status remained a significant predictor for WMH using the automated method (p = 0.037, OR 0.075 (0.007–0.851)), whereas only age remained a significant predictor for WMH scores (p = 0.019, OR 1.119 (1.018–1.230)).ConclusionWe found no association between OH and WMH load in a sample of older patients with mild dementia.

Blood–Brain Barrier Permeability and Long-Term Clinical and Imaging Outcomes in Cerebral Small Vessel Disease

Increased blood-brain barrier (BBB) permeability occurs in cerebral small vessel disease. It is not known if BBB changes predate progression of small vessel disease. We followed-up patients with nondisabling lacunar or cortical stroke and BBB permeability magnetic resonance imaging after their original stroke. Approximately 3 years later, we assessed functional outcome (Oxford Handicap Score, poor outcome defined as 3-6), recurrent neurological events, and white matter hyperintensity (WMH) progression on magnetic resonance imaging. Among 70 patients with mean age of 68 (SD ± 11) years, median time to clinical follow-up was 39 months (interquartile range, 30-45) and median Oxford Handicap Score was 2 (interquartile range, 1-3); poor functional outcome was associated with higher baseline WMH score (P<0.001) and increased basal ganglia BBB permeability (P=0.046). Among 48 patients with follow-up magnetic resonance imaging, WMH progression at follow-up was associated with baseline WMH (ANCOVA P<0.0001) and age (ANCOVA P=0.032). Further long-term studies to evaluate the role of BBB dysfunction in progression of small vessel disease are required in studies that are large enough to account for key prognostic influences such as baseline WMH and age.

Association of Ultrasonographic Parameters with Subclinical White-Matter Hyperintensities in Hypertensive Patients

Background and Purpose. Cerebral white matter hyperintensities (WMHs) are regarded as typical MRI expressions of small-vessel disease (SVD) and are common in hypertensive patients. Hypertension induces pathologic changes in macrocirculation and in microcirculation. Changes in microcirculation may lead to SVD of brain and consequently to hypertensive end-organ damage. This damage is regarded the result of interactions between the macrovascular and microvascular levels. We sought to investigate the association of cerebral WMHs with ultrasonographic parameters of cerebral macrocirculation evaluated by carotid duplex ultrasound (CDU) and transcranial doppler (TCD). Subjects and Methods. The study was prospective, cross-sectional and consecutive and included hypertensive patients with brain MRI with WMHs. Patients underwent CDU and TCD. The clinical variables recorded were demographic characteristics (age, gender, race) and vascular risk factors (hypertension, diabetic mellitus, hypercholesterolemia, current smoking, and body mass index). Excluded from the study were patients with history of clinical stroke (including lacunar stroke and hemorrhagic) or transient ischemic attack (either hemispheric or ocular), hemodynamically significant (>50%) extra- or intracranial stenosis, potential sources of cardioembolism, and absent transtemporal windows. WMHs were quantified with the use of a semiquantitative visual rating method. Ultrasound parameters investigated were (1) common carotid artery (CCA) diameter and intima-media thickness, (2) blood flow velocity in the CCA and internal carotid artery (ICA), and (3) blood flow velocity and pulsatility index of middle cerebral artery (MCA). Results. A total of 52 patients fulfilled the study inclusion criteria (mean age 71.4 ± 4.5 years, 54% men, median WMH-score: 20). The only two ultrasound parameters that were independently associated with WMH score in multivariate linear regression models adjusting for demographic characteristics and vascular risk factors were increased mean common carotid artery (CCA) diameter (beta = 0.784, SE = 0.272, P = 0.006, R 2 = 23.9%) and increased middle cerebral artery pulsatility index (MCA-PI; beta = 0.262, SE = 0.110, P = 0.025, R 2 = 9.0%). Among all ultrasound parameters the highest AUC (areas under the receiver operating characteristic curve) were documented for MCA-PI (AUC = 0.82, 95% CI = 0.68−0.95, P < 0.001) and mean CCA diameter (AUC = 0.80, 95% CI = 0.67−0.92, P < 0.001). Conclusions. Our study showed that in hypertensive individuals with brain SVD the extent of structural changes in cerebral microcirculation as reflected by WMHs burden is associated with the following ultrasound parameters of cerebral macrocirculation: CCA diameter and MCA-PI.

The Effect of Ischemic Cholinergic Damage on Cognition in Patients With Subcortical Vascular Cognitive Impairment

Prior research has shown that the total amount of white matter ischemia had no significant correlation with cognitive deficits. We compared the association of white matter hyperintensities (WMHs) of total as well as cholinergic pathways with clinical dementia severity and investigated whether cholinergic ischemic burden had an independent predictive value with respect to cognitive decline in subcortical vascular cognitive impairment (SVCI). Forty-eight patients underwent detailed neuropsychological tests and brain magnetic resonance imaging. Quantification of WMH in the total white matter and in cholinergic pathways was achieved using the visual Scheltens scale and Cholinergic Pathway HyperIntensity Scale (CHIPS), respectively. We explored the association between WMH scores and clinical dementia rating scale (CDR). To assess the relation between WMH and cognitive scores, multiple linear regression analysis was used. The CHIPS score was higher in subcortical vascular dementia compared to subcortical vascular MCI, while this difference was not found with the total TMHs (TWMH) score. The TWMH score had a positive correlation with CHIPS, however only CHIPS scores positively correlated with sum of box scores of CDR scale (CDR SB; ρ = .474, P = .001). Higher CHIPS scores were associated with lower performance on the semantic word fluency test (β = -.447, P = .036), whereas the TWMH scores had no independent predictive value with respect to cognitive impairment, after controlling for CHIPS score. Our data confirmed the association of ischemic damage within cholinergic pathways with dementia severity, independent of TWMH in SVCI. In addition, this cholinergic deficit is clinically relevant to cognitive deterioration, especially with frontal dysfunction.

Cerebral White Matter Hyperintensity in African Americans and European Americans with Type 2 Diabetes

Previous studies involving inner city populations detected higher cerebral white matter hyperintensity (WMH) scores in African Americans (AAs) compared with European Americans (EAs). This finding might be attributable to the higher prevalence of cardiovascular disease (CVD) risk factors and poorer access to healthcare in AAs. Despite racial differences in CVD risk factor profiles, AAs have paradoxically lower levels of subclinical CVD. We hypothesized that AAs with diabetes and good access to healthcare would have comparable or lower levels of WMH as EAs. Racial differences in the distribution of WMH were analyzed in 46 AAs and 156 EAs with type 2 diabetes enrolled in the Diabetes Heart Study (DHS)-Mind, and replicated in a sample of 113 AAs and 61 EAs patients who had clinically indicated cerebral magnetic resonance imaging. Wilcoxon 2-sample tests and linear models were used to compare the distribution of WMH in AAs and EAs and to test for association between WMH and race. The unadjusted mean WMH score from the Diabetes Heart Study-Mind was 1.9 in AAs and 2.3 in EAs (P = .3244). Among those with clinically indicated magnetic resonance imaging, the mean WMH score was 2.9 in AAs and 3.9 in EAs (P = .0503). Adjustment for age and sex produced no statistically significant differences in WMH score between AAs and EAs. These independent datasets reveal comparable WMH scores in AAs and EAs, suggesting that disparities in access to healthcare and environmental exposures likely underlie the previously reported excess burden ofWMH in AAs.

White matter hyperintensities in patients with multiple system atrophy

Introduction Although white matter hyperintensities (WMHs) are prevalent in the elderly, the clinical significance and the underlying pathophysiological mechanisms of WMHs in neurodegenerative disorders have not been fully clarified. Objective The present study aimed to determine the degree of WMHs in patients with multiple system atrophy (MSA), and analyze the predisposing factors for WMHs. Methods Two raters blinded to clinical information assessed cerebrovascular lesions in brain MRIs from patients with MSA and age-matched controls. Patients with Parkinson’s disease (PD) were similarly studied as a disease control. The results obtained were compared with the clinical characteristics of the patients and statistically analyzed. Results WMHs in patients with MSA were statistically greater compared with PD patients or controls. There were no significant differences in either lacunar or territorial infarcts. Multiple linear regression analysis demonstrated that age, supine systolic blood pressure, and a drop in orthostatic blood pressure were significantly and independently correlated with WMH scores in MSA. Conclusions The present study suggests that white matter is differentially involved in MSA. In addition to aging, cerebral hypoperfusions caused by fluctuations of blood pressure may be a significant contributing factor to WMHs in MSA, although the possibility that degenerative processes occurring in oligodendrocytes may be associated with WMHs should not be excluded.

Childhood intelligence and brain white matter hyperintensities predict fluid intelligence age 78–81 years: a 1921 Aberdeen birth cohort study

to evaluate the role of childhood intelligence and white matter hyperintensities (WMH) in the prediction of the trajectory of fluid intelligence in healthy old people from age 78 to 81. observational follow-up study from 1999 to 2002. a university teaching hospital in Aberdeen, UK. a total of 106 volunteers born in 1921, with childhood intelligence records at 11, recruited 1997-98 to a follow-up study. participants underwent brain MRI in 1999-2000, to obtain measurements of brain WMH using Scheltens' scale and a test of fluid intelligence (Raven's Progressive Matrices) on three occasions between 1999 and 2002. in a latent growth model, we found a significant association between childhood intelligence and the intercept, but not the slope, of fluid cognitive ability in late adulthood. Similarly, baseline WMH score was associated with the intercept of late life cognitive ability, but not the slope. Age at imaging was associated with slope but not intercept. There was no significant association between sex and intercept or slope of late life cognitive ability. results suggest that brain MRI measures of WMH (attributed to cerebrovascular disease) and childhood intelligence significantly contribute to late life fluid cognitive ability but not to the trajectory of age-related change in fluid intelligence. We also show that age is associated with the cognitive trajectory from 78 to 81 years, even within our narrow age range sample. This may be a consequence of the recruitment pattern, with those having greater WMH burden, and who subsequently declined, being recruited later in the study.

Brain lesions, hypertension and cognitive ageing in the 1921 and 1936 Aberdeen birth cohorts

The objectives of this study are to model the relative effects of positive (childhood intelligence) and negative (magnetic resonance imaging (MRI)-derived white matter hyperintensities (WMH)) predictors of late-life intelligence in two well-characterised normal cohorts aged 68 and 78 and to measure the influence of hypertension on WMH and lifelong cognitive change. The Scottish Mental Surveys of 1932 and 1947 tested the intelligence of almost all school children at age 11. One hundred and one participants born in 1921 and 233 participants born in 1936 had brain MRI, with measurement of WMH using Scheltens' scale, and tests of late-life fluid intelligence. Structural equation models of the effect of childhood intelligence and brain WMH on the general intelligence factor 'g' in late life in the two samples were constructed using AMOS 18. Similar models were constructed to test the effect of hypertension on WMH and lifelong cognitive change. Fluid intelligence scores were lower and WMH scores were higher in the older samples. Hypertensive participants in both samples had more WMH than normotensive participants. The positive influence of childhood intelligence on 'g' was greater in the younger sample. The negative effect of WMH on 'g' was linear and greater in the older sample due to greater WMH burden. The negative effect of hypertension on lifelong cognitive ageing was all mediated via MRI-derived brain WMH. The positive relationship between childhood and late-life intelligence decreases with age. The negative relationship between WMH and late-life intelligence is linear and increases with age.

Relationship between interleukin‐6 and cerebral deep white matter and periventricular hyperintensity in elderly women

We evaluated the relationships between serum levels of high-sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6 with the severity of leukoaraiosis. One hundred and thirty-seven elderly women who attended the Center for Comprehensive Care on Memory Disorders at Kyorin University Hospital were enrolled in this study. Leukoaraiosis was assessed by periventricular hyperintensity (PVH) score and deep white matter hyperintensity (DWMH) score. Serum log IL-6 level correlated with PVH and DWMH scores, but hsCRP did not. By multinomial logistic analysis, IL-6 was significantly related to DWMH score, independent of age and systolic blood pressure. IL-6 is presumably an important marker of leukoaraiosis, as is the case with silent cerebral infarction.

Silent Infarction or White Matter Hyperintensity and Impaired Attention Task Scores in a Nondemented Population: The Osaki-Tajiri Project

Whether silent infarction can be completely asymptomatic remains unclear. Although the central cholinergic system affects cognition, little attention has been given to infarction. We hypothesized that specific damage to the cholinergic pathways due to infarction or white matter hyperintensity (WMH) would deteriorate cognition, especially attention. A total of 502 representative elderly participants enrolled in the Osaki-Tajiri Project in 1998 were studied. Participants with focal neurologic signs or previous history of stroke or transient ischemic attack were excluded from the analysis. MRIs were available for all participants, and the Cholinergic Pathways Hyperintensities scale (CHIPS) was used to assess vascular damage in the cholinergic pathways. The Mini-Mental State Examination (MMSE), word fluency test, Digit Symbol test, and digit span test were used to assess global cognitive function and several aspects of attention. Participants were divided into 3 groups according to the comorbidity of cerebrovascular disease (CVD) and cholinergic involvement: non-CVD, CVD with cholinergic involvement [CVD-Ch(+)], and CVD without cholinergic involvement [CVD-Ch(-)]. Cognitive scores were compared among the 3 groups. In the non-CVD group, the correlations between cognitive function and the CHIPS score were examined. The CVD-Ch(+) group exhibited significantly lower scores for the Digit Symbol test compared with the other two groups, regardless of the MMSE score. In the non-CVD group, the CHIPS score of white matter changes was irreversibly correlated (ie, biologically meaningful) with the Digit Symbol score in participants age >80 years. Our findings suggest that silent infarction or WMH may deteriorate attention regardless of global cognitive function by interrupting the central cholinergic pathway.

Impacts of Hyper-Homocysteinemia and White Matter Hyper-Intensity in Alzheimers Disease Patients with Normal Creatinine: An MRI-Based Study with Longitudinal Follow-up

White matter hyper-intensities (WMHs) on magnetic resonance imaging (MRI) are commonly found in Alzheimer's disease (AD). Cerebro-vascular risk factors including plasma total homocysteine (tHcy) may result in WMHs. This study examined the association between tHcy and WMHs, and their effects on cognitive functions in AD patients over a two-year follow-up period. One hundred and fifty-seven AD patients with a clinical dementia rating of 1 or 2 were enrolled and follow-up for two years. tHcy, biochemistry tests, and mini-mental state examination (MMSE) scores were collected. WMHs were visually rated on brain MRI and classified as deep white matter hyper-intensities (DWMHs) or peri-ventricular white matter hyper-intensities (PWMHs). MMSEs were performed every six months to survey cognitive decline. In the cross sectional study, tHcy was significantly associated with total WMHs especially in DWMHs even after adjusting for age and other cerebrovascular risk factors. Initial MMSE was inversely correlated with WMH severity but not with tHcy level. In the longitudinal analysis, no differences were found either in tHcy or WMHs score in the two AD groups defined by the cognitive decline rate. tHcy is an independent risk factor for developing moderate to severe DWMHs in AD but shows non-significant effect on cognitive performance. The close association between high WMH score and poor initial MMSE suggests an additive impact in AD. The long-term effect of elevated tHcy on cognitive decline was not conclusive in the two-year follow-up period.

White matter hyperintensities (WMH) are associated with intracranial atherosclerosis rather than extracranial atherosclerosis

There is increasing evidence for an association between WMH and large-artery atherosclerosis. We evaluated 268 patients with acute ischemic stroke to assess the relationship between intracranial (IC) atherosclerosis and WMH. The patients were classified into three groups according to the location of the stenosis; IC, extracranial (EC), and non-stenosis (NS) group. WMH were rated using the semiquantitative method of Scheltens and coworkers. The IC group had significantly more WMH score in comparison with the other groups after controlling age. The linear regression analysis showed that age was the factor most strongly associated with the total score of WMH; and the location of stenosis was positively related to WMH, especially in deep white matter. Our data show that IC stenosis is associated with WMH, indicating that IC stenosis, rather than EC stenosis, is likely to cause white matter lesions. These findings raise the possibility that occlusion of penetrating arteries, embolism to border-zone areas and a hemodynamic mechanism associated with IC stenosis leads to the formation of white matter lesions.

Proton MR spectroscopy and white matter hyperintensities in idiopathic normal pressure hydrocephalus and other dementias

The differentiation of idiopathic normal-pressure hydrocephalus (INPH) from other types of dementia is a clinical challenge. The aim of this prospective study was to evaluate the role of proton MR spectroscopy (MRS) and white matter hyperintensities (WMH) in the diagnosis of INPH, predicting response to therapy and differentiating INPH from other dementias. The study included 18 patients with INPH (Group 1), 11 patients with other types of dementia (Group 2) and 20 control patients (Group 3). The value of WMH scores and MRS findings in diagnosis, evaluation of response to therapy and in the differentiation of INPH from other dementias was statistically evaluated. The level of statistical significance was set at p<0.05 (Kruskal-Wallis and Mann-Whitney U-test). In both Groups 1 and 2, N-acetylaspartate (NAA)/choline-NAA/creatine ratios were significantly less than in the control group (p<0.05). The WMH and MRS findings of Groups 1 and 2 demonstrated no statistically significant correlation (p>0.05). No correlation was found between the outcome of shunt operations and WMH and MRS findings (p>0.05). In conclusion, neither WMH nor MRS were useful in differentiating INPH from other types of dementia. WMH and MRS showed no additional benefit in identifying INPH patients who will better respond to shunt therapy.

Clinical Features of a First-Ever Lacunar Infarction in Japanese Patients: Poor Outcome in Females

Lacunar infarction (LI) remains an important stroke subtype in Japan. The aim of this study was to investigate the characteristics of outcome determinants in LI. This study was a single center observational study and included 163 consecutive patients (108 male, 55 female; mean age 69 years). The National Institutes of Health Stroke Scale (NIHSS) score on admission and the modified Rankin scale (mRS) score at discharge were used to evaluate stroke severity. We determined the location of the infarct, the grade of white matter hyperintensity (WMH), and the prevalence of silent brain infarcts, hypertension, hypercholesterolemia, diabetes mellitus, ischemic heart disease, and smoking. We compared 2 groups, good outcome (mRS score 0-2) and poor outcome (mRS score 3-5), using multiple logistic regression analysis. We found significant differences between the 2 groups according to female sex (P = .04), WMH (P = .04), and NIHSS score (P < .001). After multivariate analysis, female sex (odds ratio [OR] = 3.4, 95% confidence interval [CI] = 1.1-11.4; P = .03), and NIHSS score (OR = 2.3, 95% CI = 1.7-3.3; P < .001) were independently associated with poor outcome. Elderly onset, poor outcome, and hypercholesterolemia were more common in female patients, whereas smoking was more prevalent in males. Our data indicate that sex differences exist in Japanese LI patients with regard to risk factors and outcome. The treatment of risk factors based on sex differences is important to the management of LI.

Diffusion-Weighted Imaging and Cognition in the Leukoariosis and Disability in the Elderly Study

The mechanisms by which leukoariosis impacts on clinical and cognitive functions are not yet fully understood. We hypothesized that ultrastructural abnormalities of the normal-appearing brain tissue (NABT) assessed by diffusion-weighted imaging played a major and independent role. In addition to a comprehensive clinical, neuropsychologic, and imaging work-up, diffusion-weighted imaging was performed in 340 participants of the multicenter leukoariosis and disability study examining the impact of white matter hyperintensities (WMH) on 65- to 85-year old individuals without previous disability. WMH severity was rated according to the Fazekas score. Multivariate regression analysis served to assess correlations of histogram metrics of the apparent diffusion coefficient (ADC) of whole-brain tissue, NABT, and of the mean ADC of WMH with cognitive functions. Increasing WMH scores were associated with a higher frequency of hypertension, a greater WMH volume, more brain atrophy, worse overall cognitive performance, and changes in ADC. We found strong associations between the peak height of the ADC histogram of whole-brain tissue and NABT with memory performance, executive dysfunction, and speed, which remained after adjustment for WMH lesion volume and brain atrophy and were consistent among centers. No such association was seen with the mean ADC of WMH. Ultrastructural abnormalities of NABT increase with WMH severity and have a strong and independent effect on cognitive functions, whereas diffusion-weighted imaging metrics within WMH have no direct impact. This should be considered when defining outcome measures for trials that attempt to ameliorate the consequences of WMH progression.