Severe Deep White Matter Hyperintensities Research Articles

Heterogeneity of White Matter Hyperintensity and Cognitive Impairment in Patients with Acute Lacunar Stroke.

The severity of white matter hyperintensity (WMH) in patients with acute lacunar stroke (ALS) may be not completely parallel to cognitive impairment. Controversies persist about the effects of WMH on cognitive dysfunction. It is vital to explore whether the association may be affected by certain factors and whether a subsequent subgroup analysis is necessary. The aim of this study was to evaluate the relationship between WMH and cognitive impairment in acute lacunar stroke patients and the possible causal factors. We continuously enrolled patients with ALS who were hospitalized at the First Affiliated Hospital of Soochow University between October 2017 and June 2022. The cognitive function of all patients was assessed by using the Montreal Cognitive Assessment (MoCA) scale 14 ± 2 days after the onset of AIS, and the results were adjusted to the education level. The MoCA scale was reevaluated at the 6-month (day 182 ± 7) follow-up by outpatient visit or video. Demographic and clinical data were collected. The manifestations of chronic cerebral small-vessel disease (CSVD), including the total Fazekas score and total CSVD burden score, were assessed with an MRI scan. A mismatch refers to an inconsistency between the severity of WMH and cognitive dysfunction. A Type 1 mismatch refers to cognitive impairment with mild WMH (total Fazekas score = 0-1), and a Type 2 mismatch refers to severe WMH (total Fazekas score = 5-6) in patients with normal cognitive function. Among 213 enrolled ALS patients, 66 patients (31.0%) had cognitive dysfunction, and 40 patients (18.8%) had mismatches. Twenty-seven cases (12.7%) were Type 1 mismatched, and seventeen cases (8.0%) were Type 2 mismatched. Age, gender, fibrinogen and cerebral infarction history were independent risk factors for cognitive impairment in ALS patients. Imaging features, including moderate to severe WMH, deep WMH and the total CSVD burden score, were also independently associated with cognitive impairment. The patients in the mismatched group were older, had more severe deep WMH and had a higher occurrence of depression (p < 0.05). The NIHSS score, depression and microbleeds were significantly different between the Type 1 mismatched group and the matched group (p = 0.018, p = 0.012 and p = 0.047). Patients in the Type 2 mismatched group were male (p = 0.04), had a lower level of fibrinogen (p = 0.005), a lower incidence of CMBs (p = 0.003), a lower total CSVD burden score (p = 0.017), more severe paraventricular WMH (p = 0.035) and milder deep WMH (p = 0.026). Our study examined a homogeneous study cohort of recruited patients with symptomatic ALS. We found heterogeneity between WMH and cognitive function in ALS patients. Despite a similar WMH severity, some baseline clinical features and other conventional CSVD imaging characteristics may account for this heterogeneity phenomenon. Our findings provide data for the early diagnosis and prevention of cognitive impairment in ALS patients and suggest that the severity of WMH is not completely parallel to cognitive impairment. The white matter microstructural injury and remote WMH effects may account for the mismatch phenomenon. More attention should be paid to understanding the underlying mechanisms and finding new imaging markers.

Asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery stenoses

Background and purposeSmall vessel diseases (SVDs) are often asymptomatic. However, SVDs significantly influence the prognosis in patients with large vessel diseases (LVDs). We investigated asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery (CA) stenoses, compared to peoples without a past history of neurological disorders, including strokes. MethodsWe retrospectively analyzed the prevalences of various asymptomatic cerebral findings which were intracerebral hemorrhages (ICHs), cortical superficial siderosis, ventricular dilatation (Evans’ index) and SVDs including cerebral microbleeds (CMBs), lacunar infarctions (LIs), deep white matter hyperintensities (WMHs), periventricular hyperintensities (PVHs). The prevalence of each finding was compared using multivariate logistic regression models with adjustment for stroke risk factors. ResultsWe evaluated the findings in 54 patients with severe CA stenosis treated by stenting (CA stenosis group) and 200 adults with health screening tests of the brain and no past history of neurological disorders (control group). Multivariate analyses adjusted for age ≥ 65 years old, female gender, hypertension, hyperlipidemia, diabetes mellitus, alcohol consumption, and smoking index revealed that the prevalences of severe PVHs, severe deep WMHs, asymptomatic deep ICHs, and asymptomatic LIs were significantly higher in the CA stenosis group than the control group. However, there were no significant differences in the prevalences of CMBs, or the remaining asymptomatic findings described above. ConclusionsWith pathological differences between SVD and LVD, asymptomatic SVDs except CMBs and deep ICHs often co-exists severe CA stenosis as a presentative LVD.

Laterality of Posterior Cerebral Artery and White Matter Hyperintensities in Patients with Severe Internal Carotid Artery Stenosis.

Collateral status of the circle of Willis was associated with white matter hyperintensities (WMHs) in patients with internal carotid artery (ICA) stenosis, but few have investigated the effect of leptomeningeal anastomoses. The aim of this study was to observe the association between WMHs and the laterality of the posterior cerebral artery (PCA) that presents leptomeningeal anastomoses in patients with severe ICA stenosis. WMHs and ipsilateral PCA laterality were evaluated in patients with unilateral ICA stenosis ≥70% (including occlusion) and contralateral ICA stenosis <50% or no stenosis. Ipsilateral PCA laterality was compared between two groups of no/mild and severe score of global, deep and periventricular WMHs, respectively. We included 115 patients with unilateral ICA stenosis ≥70%. There were 60 patients with no/mild and 55 with severe global WMHs. The patients with severe global WMHs were older (OR = 1.849, 95% CI: 1.058-3.229, P = 0.031) and had higher incidence of negative PCA laterality (OR = 3.301, 95% CI: 1.140-9.558, P = 0.028). The patients with severe deep WMHs were also older (OR = 2.031, 95% CI: 1.130-3.651, P = 0.018) and had higher incidence of negative PCA laterality (OR = 4.250, 95% CI: 1.501-12.032, P = 0.006). There was no significant difference between the patients with no/mild and severe periventricular WMHs in the incidence of negative PCA laterality. The incidence of negative PCA laterality was higher in patients with severe global and deep WMHs, but not higher in patients with severe periventricular WMHs. The leptomeningeal anastomoses may affect the deep WMHs in patients with severe ICA stenosis.

Elongated Internal Carotid Arteries in Patients with Severe Carotid Artery Stenosis.

This study aimed to investigate the risk factors and asymptomatic cerebrovascular diseases associated with elongated internal carotid arteries (ICAs) and the relationship between ICA elongation and severe carotid artery (CA) stenosis. We evaluated risk factors for stroke and magnetic resonance imaging (MRI) findings in patients with severe CA stenosis compared with people without neurological disorders who underwent brain screening (controls). On magnetic resonance angiography (MRA) images, we measured the longest distance, defined as the ICA distance, from the most distant anterior wall of the cervical ICA at the site of bending or kinking to the line between the origin of the external CA and the anterior protrusion of the ICA near the petrosal bone. We retrospectively compared various asymptomatic findings, including cerebral microbleeds, lacunar infarctions, and deep white matter hyperintensities (WMHs), between participants with an ICA distance ≥ 1.2 cm vs. < 1.2 cm. The prevalence of findings and stroke risk factors were compared using multivariate logistic regression models. We evaluated 53 patients (70.0 ± 8.1 years old, nine female) with severe CA stenosis treated by CA stenting and 400 controls (63.0 ± 9.2 years old, 227 females). Multivariate analyses showed that ICA distance ≥ 1.2 cm was associated with age ≥ 65 years (odds ratio (OR) = 1.8, p < 0.01), severe deep WMHs (OR = 2.0, p = 0.02), and severe CA stenosis (OR = 0.17, p < 0.01). ICA elongation, measured by ICA distance, was positively associated with age and deep WMHs and negatively associated with severe CA stenosis.

Lenticulostriate artery combined with neuroimaging markers of cerebral small vessel disease differentiate the pathogenesis of recent subcortical infarction

Recent subcortical infarction (RSI) in the lenticulostriate artery (LSA) territory with a non-stenotic middle cerebral artery is a heterogeneous entity. We aimed to investigate the role of LSA combined with neuroimaging markers of cerebral small vessel disease (CSVD) in differentiating the pathogenic subtypes of RSI by whole-brain vessel-wall magnetic resonance imaging (WB-VWI). Fifty-two RSI patients without relevant middle cerebral artery (MCA) stenosis on magnetic resonance angiography were prospectively enrolled. RSI was dichotomized as branch atheromatous disease (BAD; a culprit plaque located adjacent to the LSA origin) (n = 34) and CSVD-related lacunar infarction (CSVD-related LI; without plaque or plaque located distal to the LSA origin) (n = 18). Logistic regression analysis showed lacunes (odds ratio [OR] 9.68, 95% confidence interval [CI] 1.71–54.72; P = 0.010) and smaller number of LSA branches (OR 0.59, 95% CI 0.36–0.96; P = 0.034) were associated with of BAD, whereas severe deep white matter hyperintensities (DWMH) (OR 0.11, 95% CI 0.02–0.71; P = 0.021) was associated with CSVD-related LI. In conclusion, the LSA branches combined with lacunes and severe DWMH may delineate subtypes of SSI. The WB-VWI technique could be a credible tool for delineating the heterogeneous entity of SSI in the LSA territory.

Association of enlarged perivascular spaces with Aβ and tau deposition in cognitively normal older population

The relationship between magnetic resonance imaging (MRI)-visible enlarged perivascular spaces (EPVS) and Aβ and tau deposition is poorly investigated in cognitively normal older population. In our study, a total of 106 cognitively normal older subjects from the Alzheimer's Disease Neuroimaging Initiative database were included. All the subjects underwent brain MRI, florbetapir positron emission tomography (PET), and flortaucipir PET examinations. EPVS were rated on MRI using a 5-point scale in the basal ganglia (BG-EPVS) and the centrum semiovale (CSO-EPVS). Our study revealed that 43 subjects had high-degree BG-EPVS (degree >1) and 58 subjects had high-degree CSO-EPVS (degree >1). In logistic regression, high degree of BG-EPVS was associated with age (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.01–1.16) and severe deep white matter hyperintensity (OR: 2.67, 95% CI: 1.12–6.35). High degree of CSO-EPVS was associated with flortaucipir PET positivity (OR: 2.24, 95% CI: 1.02–4.93). In conclusion, high degree of CSO-EPVS was associated with tau deposition in the brain, whereas high degree of BG-EPVS was associated with age and severe deep white matter hyperintensity, a marker of small vessel disease.

White matter hyperintensities and the progression from mild parkinsonian signs to parkinsonism and Parkinson’s disease

This study investigated the impact of white matter hyperintensities (WMHs) on the progression from mild parkinsonian signs (MPS) to parkinsonism and Parkinson’s disease (PD). Participants with MPS completed 5 years of follow-up. WMHs were divided into periventricular WMHs and deep WMHs according to magnetic resonance imaging scans. The diagnosis of MPS, parkinsonism, and PD was based on the motor portion of the Unified Parkinson’s Disease Rating Scale. Cox proportional hazard models were used to identify the association between WMHs and MPS progression. Of the 636 participants, 166 (26.1%) with MPS developed parkinsonism and PD after follow-up. After adjusting for potential factors, severe WMHs were associated with an increased risk of MPS progression, moderate and severe periventricular WMHs and severe deep WMHs were associated with the risk of MPS progression, and severe WMHs were associated with the progression of gait/balance impairment, bradykinesia, and rigidity. Additionally, participants treated for vascular risk factors such as hypertension, diabetes mellitus, and hypercholesterolemia had a lower risk of MPS progression.

MRI Types of Cerebral Small Vessel Disease and Circulating Markers of Vascular Wall Damage.

The evaluation of the clustering of magnetic resonance imaging (MRI) signs into MRI types and their relationship with circulating markers of vascular wall damage were performed in 96 patients with cerebral small vessel disease (cSVD) (31 men and 65 women; mean age, 60.91 ± 6.57 years). The serum concentrations of the tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), and hypoxia-inducible factor 1-α (HIF-1α) were investigated in 70 patients with Fazekas stages 2 and 3 of white matter hyperintensities (WMH) and 21 age- and sex-matched volunteers with normal brain MRI using ELISA. The cluster analysis excluded two patients from the further analysis due to restrictions in their scanning protocol. MRI signs of 94 patients were distributed into two clusters. In the first group there were 18 patients with Fazekas 3 stage WMH. The second group consisted of 76 patients with WMH of different stages. The uneven distribution of patients between clusters limited the subsequent steps of statistical analysis; therefore, a cluster comparison was performed in patients with Fazekas stage 3 WMH, designated as MRI type 1 and type 2 of Fazekas 3 stage. There were no differences in age, sex, degree of hypertension, or other risk factors. MRI type 1 had significantly more widespread WMH, lacunes in many areas, microbleeds, atrophy, severe cognitive and gait impairments, and was associated with downregulation of VEGF-A compared with MRI type 2. MRI type 2 had more severe deep WMH, lacunes in the white matter, no microbleeds or atrophy, and less severe clinical manifestations and was associated with upregulation of TNF-α compared with MRI type 1. The established differences reflect the pathogenetic heterogeneity of cSVD and explain the variations in the clinical manifestations observed in Fazekas stage 3 of this disease.

Hyperhomocysteinemia can predict the severity of white matter hyperintensities in elderly lacunar infarction patients

Background and Purpose: Hyperhomocysteinemia (Hhcy) is a risk factor for stroke. Several studies have demonstrated that Hhcy was more closely linked to small vessel occlusive disease and white matter hyperintensities (WMH) in general and elderly population. Studies on WMH and homocysteine in elderly subjects are rare, and the results were inconsistent. Our study aimed to investigate the relationship between the serum homocysteine (HCY) and the severity of WMH in elderly lacunar stroke patients.Methods: Consecutive elderly (≥60 years old) lacunar infarction patients were recruited in this cross-sectional study. All patients were divided into two groups according to periventricular WMH (PVWMH) and deep WMH (DWMH) Fazekas scores. Patients with a Fazekas score (PVWMH or DWMH) of 0, 1, 2 were in mild-moderate group and 3 were in severe group. Vascular risk factors and clinical features were compared between these two groups. Multiple logistic regression analysis was used to determine the relationship between severity of WMH and vascular risk factors.Results: A total of 587 participants aged 60–95 years were enrolled. Patients with severe PVWMH (n = 178) had higher age (p = 0.030) and higher incidence of stroke history (p<0.001) than those in mild-moderate group. The level of serum HCY was significantly higher in patients with severe PVWMH (p ＝ 0.002). Patients with severe DWMH (n = 142) had higher age (p<0.001) and often had a history of stroke (p<0.001). The level of HCY was higher in patients with severe degree of DWMH, but had no significance (p ＝ 0.153). Multivariable logistic regression analyses showed Hhcy were independently associated with severe PVWMH after adjusted for age and vascular risk factors (p ＝ 0.014).Conclusions: Hhcy was independently associated with severe PVWMH of elderly lacunar stroke patients, but not DWMH.

Impact of periventricular hyperintensities and cystatin C on different cognitive domains in the population of non-demented elderly Chinese

ObjectivesTo investigate the impact of periventricular hyperintensities and serum cystatin C on mild cognitive impairment to provide a basis for the investigation of the pathogenesis. Method286 patients enrolled the study and underwent an examination in Shanghai Fifth People’s Hospital from June 2017 to June 2018. The participants’ cognitive function was evaluated by different cognitive domains using of mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), auditory verbal learning test, Huashan version (AVLT-H), digit span test (DST), symbol digit modalities test (SDMT), trail making test (TMT) and verbal fluency test (VFT). We measured the levels of serum cystatin C at the department of clinical laboratory in Shanghai Fifth People’s Hospital and each subject took an MRI examination in the Department of Radiology of Shanghai Fifth People’s Hospital. Multivariate linear regression analyses were used to assess the relationship of cognitive score and the level of cystatin C and periventricular hyperintensities severity. All statistical analyses were performed using the SPSS system. ResultsAmong 286 eligible participants, 203 (71.0%) were enrolled to further analysis, including 69 male and 134 female (Mean age 67.93 ± 6.19 years). Significant predictors of severe periventricular hyperintensities (PVH) were older age and hypertension. Significant predictors of severe deep white matter hyperintensities (DWMH) were older age only. PVH severity was independently associated with mild cognitive impairment and that the primary impairment was executive function and processing speed. DWMH had no significant effect on cognitive function. Cystatin C only affected the overall cognitive level, and the relationship with WMH severity was not significant. ConclusionsWe demonstrated that in the chinese non-demented elderly, the severity of PVH was independent and significant associated with mild cognitive impairment and that the primary impairment was executive capacity and processing speed, while cystatin C may be an independent risk factor for overall cognitive impairment.

Cognitive impairment, brain ischemia and shorter telomeres are predictors of mortality in the Japanese elderly: A 13-year prospective community-based study

ObjectiveTo examine whether cognitive impairment, deep white matter hyperintensity (DWMH) on brain MRI, and shorter telomere length would be predictors of mortality in community-dwelling Japanese elderly. MethodsWe followed 259 individuals (74% of all the residents at age 70) from age 70 to 83 years. The mean observation period was 133 ± 34 months. The key clinical characteristics examined included DWMH on brain MRI and cognitive function. Telomere length was also measured in 81 subjects. Both univariate and multivariate analyses were performed. ResultsOf the 259 subjects, 69 subjects (30 men, 39 women; 26.6%) died during the follow-up period. Cognitive impairment, smoking habits, diabetes mellitus, and moderate to severe DWMH were significant predictors of total mortality in univariate analysis. However, only cognitive impairment and moderate to severe DWMH remained as significant independent predictors of death in multivariate analysis. The rate of mortality increased with additional number of risk factors (cognitive impairment and DWMH). The total mortality of subjects with both cognitive impairment and DWMH was 71.4%. The median telomere length was 7.8 kb in the deceased and 8.2 kb in the living subjects. The deceased subjects had significantly shorter telomere length (P = .0025) than the living subjects. Telomere length with moderate to severe DWMH was higher than without moderate to severe DWMH on brain MRI (P = .017). ConclusionsThe present study revealed that cognitive impairment, DWMH, and shorter telomere length were significant predictors of total mortality in the community-dwelling Japanese elderly. Furthermore, the combination of cognitive impairment and DWMH increased the mortality rate, as compared with a single risk factor. It is also clarified that a significant difference was present in telomere length by severity of DWMH.

Age and recurrent stroke are related to the severity of white matter hyperintensities in lacunar infarction patients with diabetes.

Background and purposeWhite matter hyperintensities (WMH) is identified as a marker of cerebral small vessel diseases and is a major contributor to cognitive impairment, depression, gait disturbance, and urinary incontinence. However, the risk factors for WMH in patients with type 2 diabetes mellitus (T2DM) has not been well explored. Thus, in this study, we aimed to investigate the relationship between the severity of WMH and vascular risk factors in lacunar infarction patients with T2DM.MethodsConsecutive lacunar infarction patients with T2DM were recruited in this cross-sectional study. Paraventricular WMH (P-WMH) and deep WMH (D-WMH) were separately scored by the Fazekas scale, and classified into two categories by the severity. Vascular risk factors and clinical features were compared between the mild and severe WMH. Multiple logistic regression analysis was used to determine the relationship between severity of WMH and vascular risk factors.ResultsA total of 327 participants aged 34–91 years were enrolled in this study. Compared with the patients with mild P-WMH, the patients with severe P-WMH had higher age (P=0.031), higher proportion of hypertension (P=0.042) and stroke (P<0.001). Levels of TG, LDL, and HbA1c were significantly higher in patients with mild P-WMH. Compared with the patients with mild D-WMH the patients with severe D-WMH had higher age and hyperhomocysteinemia (HCY) level (P<0.001), higher proportion of hyperlipidemia (P=0.008), and stroke (P<0.001). Multivariable logistic regression analyses showed that higher age and recurrent stroke were independently related to severe P-WMH and D-WMH in lacunar infarction patients with T2DM.ConclusionsAge and recurrent stroke are related to the severity of P-WMH and D-WMH in lacunar infarction patients with T2DM.

Relationship of cardiac biomarkers with white matter hyperintensities in cardioembolic stroke due to atrial fibrillation and/or rheumatic heart disease.

White matter hyperintensities (WMHs), which are common in elderly people and contribute to age-related disability, can coexist with cardiac injury. It remains unclear whether cardiac biomarkers are associated with WMHs.To investigate this question, we prospectively recruited patients with cardioembolic stroke due to atrial fibrillation (AF) and/or rheumatic heart disease (RHD). Four cardiac biomarkers were measured: myoglobin, high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase-MB, and terminal pro-brain natriuretic peptide. WMHs in periventricular and deep white matter were assessed separately.In the entire sample of 171 patients, 120 (70.2%) presented with WMHs, of whom 18 (10.5%) presented with moderate to severe deep white matter hyperintensities (DWMH) and 55 (32.2%) presented with moderate to severe periventricular hyperintensities (PVH). Risk of moderate to severe PVH, after adjusting for confounders, was 2.460-fold higher in patients with high myoglobin levels than in those with low levels, and the risk was 2.608-fold higher in patients with high hs-cTnT levels than in those with low levels. There were no significant associations between any of the 4 cardiac biomarkers and moderate to severe DWMH.This prospective observational study provides new evidence of the potential relationship of cardiac biomarkers with WMHs in patients with cardioembolic stroke due to AF and/or RHD. We found that elevated myoglobin levels and high hs-TnT levels were independently associated with the presence of moderate to severe PVH. Further studies are required to test our findings and explore whether cardiac biomarkers contribute directly to WMHs pathogenesis.

Small Hyperintensities in the Area of the Perforating Arteries in Patients with Seizure

Background/Aim: We previously observed spotty hyperintense lesions in the region of the perforating arteries on peri-ictal diffusion-weighted imaging (DWI); however, no report has formally described these findings. The aim of this study was to investigate focal intensities on peri-ictal DWI, and to evaluate the clinical significance of these lesions. Methods: We conducted a retrospective review of 677 consecutive patients with seizure who completed peri-ictal DWI within 24 h after seizure onset. Patients were grouped according to the presence or absence of diffusion hyperintense lesions (DHLs) in the region of the perforating arteries. We compared clinical and imaging characteristics between these 2 groups. Results: Among 677 patients, 23 patients (3.4%) had DHLs. Analyses of apparent diffusion coefficient values and fluid attenuated inversion recovery images suggested that DHLs were acute or subacute ischemic lesions that had appeared prior to seizure onset. Patients with DHLs were more likely to be older in age, have atrial fibrillation, and coronary artery disease, and have more severe deep white matter hyperintensity or leukoaraiosis compared to patients without DHLs. Conclusion: DHLs detected on peri-ictal DWI may represent incidental acute cerebral microinfarcts in the aging brain, especially in patients with small vessel disease.

Post-stroke cognitive impairment - A cross-sectional comparison study between mild cognitive impairment of vascular and non-vascular etiology

PurposeTo elucidate the cognitive profiles of post-stroke vascular mild cognitive impairment (VaMCI) in comparison to MCI of non-vascular etiology and cognitively normal healthy controls at a tertiary-care hospital in southern India. ResultsLogistic regression analysis adjusted for age and sex comparing VaMCI [N=50] with controls [N=27] revealed significant impairment in visual, verbal learning-recall and executive function scores. As compared to the MCI group [N=36], VaMCI had significantly higher scores on Weschler's Memory Scale (WMS) verbal subset delayed recall scores (p=0.045, odds ratio [OR]=2.62, 95% CI=1.02–6.76) with lower scores on WMS-visual immediate learning scores (p=0.042, OR=0.35, 95% CI=0.13–0.96), Rey Auditory Verbal Learning Test (RAVLT) total learning scores (p=0.001, OR=0.17, 95% CI=0.06–0.48) and 20 minute recall (p=0.026, OR=0.33, 95% CI=0.12–0.88), Delayed Matching to Sample test (DMS-48) abstract immediate (p=0.002, OR=0.20, 95% CI=0.07–0.56), abstract delayed recognition sub-sets (p=0.014, OR=0.28, 95% CI=0.10–0.78) and made more total errors on Wisconsin Card Sorting Test (WCST; p=0.040, OR=2.70, 95% CI=1.05–7.14) while the MCI group significantly had more commission errors on RAVLT (p≤0.001, OR=0.13, 95% CI=0.05–0.38) and WCST – perseverative errors (p=0.036, OR=0.30, 95% CI=0.10–0.93). Significant differences were noted in word-list learning-recall (p=0.012) and WMS verbal delayed recall (p=0.014) between VaMCI with mild versus moderate to severe deep white matter hyperintensities on neuroimaging. ConclusionsCognitive impairment following minor stroke involves episodic verbal and visual memory over and above executive function in comparison to MCI of non-vascular etiology. Close cognitive followup is warranted with adequate risk stratification and management especially in the presence of sub-cortical leukoaraiosis which is contributory to cognitive decline in this group of patients.

Abstract WP205: C-reactive Protein Levels Are Associated With Cerebral Small Vessel-related Lesions

Introduction: Arteriosclerosis is characterized by the loss of smooth muscle cells and a hyalinized thickened wall, and concentric narrowing of the lumen in penetrating arteries causes cerebral small vessel disease, including lacunar infarcts, deep white matter lesions, and cerebral microbleeds mainly in the basal ganglia. Although infrequently fatal, lacunar infarcts and deep white matter lesions, which account for 30% of ischemic strokes in Japan, are associated with a high risk of recurrence and cognitive impairment. Basic studies have reported on the importance of inflammation in the pathogenesis of arteriosclerosis. Hypothesis: We investigated the hypothesis that serum high sensitive C-reactive protein (hs-CRP) levels have some effect on cerebral small vessel (CSV)-related lesions. Methods: From January 2008 to March 2013, a total of 1,362 Japanese subjects voluntarily participated in the health checkup system. We selected 519 neurologically normal subjects (284 males and 235 females) aged 29-90 years (mean, 63.5 ± 10.3 years) from these participants for inclusion. All the participants underwent MRI, and their CSV-related lesions (i.e., lacunar infarcts, cerebral microbleeds, deep white matter hyperintensity, and periventricular hyperintensity) were evaluated. The serum levels of hs-CRP were evaluated as common inflammatory markers. Results: Subjects with higher hs-CRP levels had more lacunar infarcts (p = 0.02). After adjusting for the traditional cardiovascular risk factors, higher hs-CRP levels were still associated with the presence of lacunar infarcts (odds ratio for the highest vs. the lowest tertile of hs-CRP, 3.57 [95% confidence interval: 1.30-9.80]). These associations did not change when the logarithmically transformed values for hs-CRP were included. Furthermore, subjects with higher CRP levels had more cerebral microbleeds (p = 0.03), more severe deep white matter hyperintensity (p = 0.04), and periventricular hyperintensity (p = 0.04); however, these associations were not observed after adjusting for the cardiovascular risk factors. Conclusions: Higher levels of hs-CRP were associated with lacunar infarcts. Thus, inflammatory processes may be involved in the pathogenesis of small vessel disease.

C-reactive protein levels are associated with cerebral small vessel-related lesions

Inflammation has received increasing attention as a cause of stroke. Although several lines of evidence suggest that inflammatory processes have a role in arteriosclerotic vascular events, their involvement remains to be determined. The purpose of this study was to examine the associations between serum high-sensitive C-reactive protein (hs-CRP) levels and cerebral small vessel (CSV)-related lesions as a manifestation of arteriosclerosis. Neurologically normal subjects without any history of neurologic or psychiatric diseases were enrolled (n = 519). All the participants underwent magnetic resonance imaging (MRI), and their CSV-related lesions (i.e., lacunar infarcts, cerebral microbleeds, deep white matter hyperintensity, and periventricular hyperintensity) were evaluated. The serum levels of hs-CRP were evaluated as common inflammatory markers. Subjects with higher C-reactive protein (CRP) levels had more lacunar infarcts (P = 0.02). After adjusting for the traditional cardiovascular risk factors, higher hs-CRP levels were still associated with the presence of lacunar infarcts [odds ratio for the highest vs the lowest tertile of hs-CRP, 3.57 (95% confidence interval: 1.30-9.80)]. These associations did not change when the logarithmically transformed values for hs-CRP were included. Furthermore, subjects with higher CRP levels had more cerebral microbleeds (P = 0.03), more severe deep white matter hyperintensity (P = 0.04), and periventricular hyperintensity (P = 0.04); however, these associations were not observed after adjusting for the cardiovascular risk factors. Higher levels of hs-CRP were associated with lacunar infarcts. Thus, inflammatory processes may be involved in the pathogenesis of small-vessel disease.

Association of cerebral white matter lesions with cognitive function and mood in Japanese elderly people: a population-based study.

BackgroundTo determine the relationships between regional white matter lesions (WMLs), lifestyle factors, and cognitive, motor function and mood.MethodsA comprehensive evaluation, including brain MRI, blood tests, the Unified Parkinson's Disease Rating Scale, the Mini Mental State Examination, and the Geriatric Depression Scale, was performed for people aged 65 years or older living in Ama-cho on October 1, 2009. Participants were classified by severity of periventricular hyperintensities (PVH) and deep white matter hyperintensities (DWMH) using the Fazekas score.ResultsOf 900 eligible participants, 688 (76.4%) were enrolled, including 303 men. Significant predictors of severe PVH were older age, lower low-density lipoprotein cholesterol (LDL-C) levels, elevated blood pressure (BP), cerebral infarction, and no current alcohol use. Significant predictors of severe DWMH were older age, lower 1,5-anhydroglucitol (1,5-AG) levels, elevated BP, cerebral infarction, and no current alcohol use. Higher cognitive function was associated with younger age, female sex, mild DWMH, more years of education, and higher high-density lipoprotein cholesterol levels. Depressive symptoms were associated with lower 1,5-AG levels, lower LDL-C levels, moderate to severe PVH, and no current alcohol use.ConclusionsWhite matter lesions in elderly people were related to hypertension and impaired glucose tolerance. The severity of WMLs was associated with cognitive function and mood.

White matter hyperintensities and self-reported depression in a sample of patients with chronic headache

White matter hyperintensities (WMH) have been associated with mood disorders in psychiatric patients. In the present study, we aimed to assess whether WMHs are associated with depressive symptoms and different sensitivity of the behavioral inhibition (BIS), and activation (BAS) systems in patients with chronic headache. Participants were 85 adult outpatients (16 men and 69 women) with a diagnosis of chronic headache. All of the patients underwent brain magnetic resonance imaging (MRI) and were administered the BIS/BAS scales and the Center for Epidemiologic Studies Depression Scale. Above 40 % of patients had periventricular WMHs (PWMHs) and almost 98 % had deep WMHs (DWMHs). Patients with PWMHs reported fewer depressive symptoms than patients without PWMHs. Patients with more severe DWMHs (compared with patients with mild or without DWMH lesions) were older and reported lower scores on the drive dimension of the BIS/BAS scales. In multivariate analyses, patients with PWMHs were 1.06 times more likely to report fewer depressive symptoms than patients without PWMHs. WMH lesions in patients with chronic headache were associated with less depression severity.

Contribution of Cystatin C Gene Polymorphisms to Cerebral White Matter Lesions

Background: Vascular remodeling plays an important role in the development of arteriosclerosis and any of the resulting white matter lesions in the brain. An imbalance between cysteine proteases and the cysteine protease inhibitor cystatin C (CST3) may exacerbate vascular remodeling through degradation of extracellular matrix proteins. Therefore, we evaluated the association between functional polymorphisms in the CST3 gene and the development of cerebral white matter lesions. Methods: In a total of 2,676 participants, 3 CST3 genepolymorphisms were genotyped in 92 cases with severe deep white matter hyperintensity (DWMH), and 184 subjects were randomly selected age- and sex-matched controls without any signs of DWMH. The genetic effects of these polymorphisms on DWMH and plasma CST3 levels were examined. CST3 expression vectors were transfected into an astrocytoma cell line and the expression level of CST3 mRNA was analyzed by quantitative RT-PCR. Intracellular and secreted levels of CST3 in the cell culture were quantified by Western blot and ELISA, respectively. Results: A significant association was found between one CST3 gene haplotype and DWMH (p = 0.002). This haplotype was also associated with lower plasma CST3 levels (p = 0.01). An in vitro transfection study revealed that the +148A allele, which is included in the risk haplotype, significantly reduced the secretion and increased the intracellular accumulation of CST3; however, it had no effect on the mRNA expression. Conclusions: Our study shows that polymorphisms in the CST3 gene are significantly associated with the likelihood of DWMH. Substitution of A for G at +148 of the CST3 gene decreased the extracellular availability of CST3 in vitro, which might result in the activation of protease activity.