Number Of Lacunes Research Articles

Effects of APOE ɛ4 on brain amyloid, lacunar infarcts, and white matter lesions: a study among patients with subcortical vascular cognitive impairment

The relationship between the apolipoprotein E ɛ4 allele (APOE4) and factors associated with vascular cognitive impairment (VCI) is unclear. We aimed to examine the effects of APOE4 on brain amyloid beta using Pittsburg compound B (PiB) and subcortical cerebrovascular disease, as assessed by lacunes and white matter hyperintensities (WMH) in subcortical VCI (SVCI) patients. We recruited 230 subjects with normal cognition, 111 subjects with cognitive impairment due to clinically defined Alzheimer’s disease (ADCI), and 134 subjects with clinically defined SVCI. A PiB retention ratio greater than 1.5 was considered to be PiB positive. Logistic regression analysis was performed to investigate whether APOE4 increased the risk for each cognitive impairment group. Multiple linear regression analysis was performed to investigate whether APOE4 was associated with brain amyloid beta, lacunes, and WMH. APOE4 did not increase the risk of PiB(−) SVCI (odds ratio [OR], 1.50; 95% confidence interval [CI], 0.79–2.84), whereas APOE4 increased the risk of PiB(+) SVCI (OR, 4.52; 95% CI, 1.70–11.97) and PiB(+) ADCI (odds ratio, 4.84; 95% CI, 2.54–7.91). In SVCI patients, APOE4 was positively associated with PiB retention ratio, whereas APOE4 was not associated with the number of lacunes or with WMH volume. Our results suggest that amyloid beta burden can occur in patients with and without subcortical cerebrovascular disease, and that it is associated with APOE4. However APOE4 might be independent of subcortical cerebrovascular disease.

Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment

Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment. We included 226 patients: 89 with Alzheimer disease-related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [(11) C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes. Parietal and occipital lobar CMBs counts were higher in PiB(+) ADCI with moderate WMH than PiB(+) ADCI with minimal WMH, whereas PiB(-) patients with SVCI (ie, "pure" SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001). Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs.

Cavitation of Deep Lacunar Infarcts in Patients With First-Ever Lacunar Stroke

Studies in patients with lacunar stroke often assess the number of lacunes. However, data on how many symptomatic lacunar infarcts cavitate into a lacune are limited. We assessed the evolution of symptomatic lacunar infarcts over 2-year follow-up. In 82 patients with first-ever lacunar stroke with a lacunar infarct in the deep brain regions (excluding the centrum semiovale), we performed a brain MR at presentation and 2 years later. We classified cavitation of lacunar infarcts at baseline and on follow-up MR as absent, incomplete, or complete. We recorded time to imaging, infarct size, and vascular risk factors. On baseline MR, 38 (46%) index infarcts showed complete or incomplete cavitation. Median time to imaging was 8 (0-73) days in noncavitated and 63 (1-184) days in cavitated lesions (P<0.05). On follow-up imaging, 94% of the lacunar infarcts were completely or incompletely cavitated, most had reduced in diameter, and 5 (6%) had disappeared. Vascular risk factors were not associated with cavitation. Cavitation and lesion shrinkage were seen in almost all symptomatic lacunar infarcts in the deep brain regions over 2-year follow-up. Counting lacunes in these specific regions at a random moment might slightly, however not substantially, underestimate the burden of deep lacunar infarction.

Measurements of lenticulostriate arteries using 7T MRI: new imaging markers for subcortical vascular dementia

Recent studies have demonstrated that ultra-high resolution MRA imaging using 7 Tessla (T) MRI can be employed to noninvasively visualize the lenticulostriate arteries (LSA) that supply the basal ganglia and internal capsule. Subcortical vascular dementia (SVaD) is believed to involve these regions from an early stage. We investigated whether LSA abnormalities measured by 7T MRA correlate with MRI ischemia markers and neuropsychological/motor deficits. A total of 24 subjects (12 with SVaD, 12 normal controls (NC)) were imaged with 3T and 7T MRIs. We assessed the severity of white matter hyperintensities (WMH) and the number of lacunes and microbleeds (MB) by visually inspecting images obtained from conventional 3T MRI. We also analyzed three-dimensional models of the measured LSAs obtained from 7T MRI. Compared to the NC, the SVaD subjects had fewer branches of LSAs and greater radii of LSAs. The number of branches was correlated with the number of lacunes. The number of branches was correlated with the delayed recall scores on Rey's Complex Figure Test (RCFT). While not quite reaching statistical significance, the immediate recall, recognition scores on the RCFT, recognition scores on the Seoul Verbal Learning Test, and the word and color readings of Stroop trended in the direction of correlation with the number of branches, as well as with the extrapyramidal scores. Our findings suggest that LSA imaging using 7T MRI might be a potent candidate for the detection of SVaD.

Cerebellar Atrophy in Patients with Subcortical-Type Vascular Cognitive Impairment

Recent studies suggest that the role of the cerebellum extends into cognitive regulation and that subcortical vascular dementia (SVaD) can result in cerebellar atrophy. However, there has been no evaluation of the cerebellar volume in the preclinical stage of SVaD. We aimed to compare cerebellar volume among patients with amnestic mild cognitive impairment (aMCI) and subcortical vascular mild cognitive impairment (svMCI) and evaluate which factors could have contributed to the cerebellar volume. Participants were composed of 355 patients with aMCI, svMCI, Alzheimer's disease (AD), and SVaD. Cerebellar volumes were measured using automated methods. A direct comparison of the cerebellar volume in SVaD and AD groups showed that the SVaD group had a statistically smaller cerebellar volume than the AD group. Additionally, the svMCI group had a smaller cerebellar volume than the aMCI group, with the number of lacunes (especially in the supratentorial regions) being associated with cerebellar volume. Cerebellar volumes were associated with some neuropsychological tests, digit span backward and ideomotor apraxia. These findings suggest that cerebellar atrophy may be useful in differentiating subtypes of dementia and the cerebellum plays a potential role in cognition.

Association of cerebral small vessel disease with delusions in patients with Alzheimer's disease

Cerebral small vessel disease (SVD) is frequently observed in patients with Alzheimer's disease (AD). However, the association between SVD and clinical symptoms exhibited by patients with AD remains unclear. This study examined the association of SVD as observed on magnetic resonance imaging (MRI) with behavioural and psychological symptoms of dementia and cognitive function of patients with probable AD. A total of 163 consecutive patients (55 men, 108 women) with probable AD were included in this cross-sectional study of a prospective cohort. Patients were divided into two groups based on the presence or absence of cerebral SVD [white matter hyperintensities (WMH) grade 0/1 (Fazekas scale) and no lacunes: SVD absent, WMH grade 2/3 (Fazekas scale) or the number of lacunes ≥1: SVD present]. Cognitive functions were assessed using the Mini mental state examination, word recall and recognition subtests in the Alzheimer's Disease Assessment Scale-Cognitive Subscale, as well as the letter fluency task and the category fluency task. Psychiatric symptoms were rated according to Neuropsychiatric Inventory. Patients with probable AD with cerebral SVD had significantly more delusions and depression than those without SVD. No significant differences were observed in other neuropsychiatric symptoms, MMSE or word recall and recognition tests between both groups. Our results suggest that cerebral SVD observed on MRI of patients with AD is associated with delusions and depression.

Multi-stage segmentation of white matter hyperintensity, cortical and lacunar infarcts

Cerebral abnormalities such as white matter hyperintensity (WMH), cortical infarct (CI), and lacunar infarct (LI) are of clinical importance and frequently present in patients with stroke and dementia. Up to date, there are limited algorithms available to automatically delineate these cerebral abnormalities partially due to their complex appearance in MR images. In this paper, we describe an automated multi-stage segmentation approach for labeling the WMH, CI, and LI using multi-modal MR images. We first automatically segment brain tissues (white matter, gray matter, and CSF) based on the T1-weighted image and then identify hyperintense voxels based on the fluid attenuated inversion recovery (FLAIR) image. We finally label the WMH, CI, and LI based on the T1-weighted, T2-weighted, and FLAIR images. The segmentation accuracy is evaluated using a community-based sample of 272 old adults. Our results show that the automated segmentation of the WMH, CI, and LI is comparable with manual labeling in terms of spatial location, volume, and the number of lacunes. Additionally, the WMH volume is highly correlated with the visual grading score based on the Age-Related White Matter Changes (ARWMC) protocol. The evaluations against the manual labeling and ARWMC visual grading suggest that our algorithm provides reasonable segmentation accuracy for the WMH, CI, and LI.

Post-stroke dementia: the contribution of thalamus and basal ganglia changes

The neurobiological basis of increased risk of dementia in stroke patients is unclear, though there are several related pathological changes, including white matter hyperintensities (WMH), and medial temporal atrophy. Subcortical gray matter structures have also been implicated in dementia resulting from vascular pathology, particularly vascular dementia. This study aimed to investigate the contribution of changes in subcortical gray matter structures to post-stroke dementia (PSD). T1- and T2-weighted images and T2-weighted fluid-attenuated inversion recovery (FLAIR) images were obtained on a 3-Tesla magnetic resonance (MR) system, in four groups aged over 75 years: post-stroke with dementia (PSD; 8), post-stroke no dementia (PSnoD; 33), Alzheimer's disease (AD; 26) and controls (30). Automated software was used to measure the volume of thalamus, putamen, caudate nucleus, and hippocampus as well as total WMH volume. The number of subcortical lacunes was also counted. The number of caudate lacunes was higher in the PSnoD group, compared with AD (p = 0.029) and controls (p = 0.019). The putamen volume was smaller in the stroke and AD groups, when compared with controls. In the whole stroke group, putamen lacunes were correlated with impairment in memory (Rey test; ρ = -0.365; p = 0.031), while WMH and hippocampal volume both correlated with global dysfunction. Our findings implicate a variety of neurobiological substrates of dementia, such as small vessel disease and Alzheimer pathology, which develop after stroke in an old older population, with a contribution from subcortical brain structures.

Identification of pure subcortical vascular dementia using 11 C-Pittsburgh compound B

Subcortical vascular dementia (SVaD) is considered the most common type of vascular dementia and often follows a slowly progressive course, simulating Alzheimer disease (AD). Whether the progressive cognitive decline is associated with pure SVaD or concomitant AD remains unknown. The purpose of this study was to determine what proportion of patients with SVaD lack abnormal amyloid imaging, and to examine differences in the clinical or MRI features between subjects with SVaD with cortical amyloid deposition and those without. We measured brain amyloid deposition using (11)C-Pittsburgh compound B (PiB) PET in 45 patients (men: women = 19:26; mean age 74.2 ± 7.6 years) with SVaD. They all met DSM-IV criteria for vascular dementia and had severe white matter high signal intensities without territorial infarction or macrohemorrhage on MRI. Thirty-one (68.9%) of 45 patients with SVaD were negative for cortical PiB binding. There was significant difference between (11)C-PiB-positive and (11)C-PiB-negative groups in terms of age (79.5 vs 71.9 years), Mini-Mental State Examination score (18.6 vs 22.6), the number of lacunes (3.9 vs 9.0), and the visual rating scale of hippocampal atrophy (3.1 vs 2.3). The neuropsychological assessments revealed that patients with (11)C-PiB-negative SVaD performed better on the delayed recall of both the verbal and visual memory test than did those with (11)C-PiB-positive scan. SVaD without abnormal amyloid imaging was more common than expected. Patients with SVaD with and without abnormal amyloid imaging differed in clinical and MRI features, although there was considerable overlap.

Incident lacunes influence cognitive decline

In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML. Within the Leukoaraiosis and Disability Study (LADIS), 387 subjects were evaluated with repeated MRI and neuropsychological assessment at baseline and after 3 years. Predictors of change in global cognitive function and specific cognitive domains over time were analyzed with multivariate linear regression. After controlling for demographic factors, baseline cognitive performance, baseline lacunar and WML lesion load, and WML progression, the number of new lacunes was related to subtle decrease in compound scores for executive functions (p = 0.021) and speed and motor control (p = 0.045), but not for memory or global cognitive function. Irrespective of lacunes, WML progression was associated with decrease in executive functions score (p = 0.016). Incident lacunes on MRI parallel a steeper rate of decline in executive functions and psychomotor speed. Accordingly, in addition to WML, lacunes determine longitudinal cognitive impairment in small vessel disease. Although the individual contribution of lacunes on cognition was modest, they cannot be considered benign findings, but indicate a risk of progressive cognitive impairment.

Effects of Lacunar Infarctions on Cognitive Impairment in Patients with Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Background and PurposeCerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. Although previous studies have shown an association between lacunar infarction and cognitive impairment, the relationship between MRI parameters and cognition remains unclear. In this study we investigated the influence of MRI parameters on cognitive impairment in CADASIL.MethodsWe applied a prospective protocol to 40 patients. MRI analysis included the normalized volume of white-matter hyperintensities (nWMHs), number of lacunes, and number of cerebral microbleeds. Cognition was assessed with the aid of psychometric tests [Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognition (ADAS-cog), Trail-Making Test, and Stroop interference (Stroop IF)].ResultsA multivariate regression analysis revealed that the total number of lacunes influenced the performance in the MMSE, ADAS-cog, and Stroop IF, while nWMHs had a strong univariate association with ADAS-cog and Stroop IF scores. However, this association disappeared in the multivariate analysis.ConclusionsThese findings demonstrate that the number of lacunes is the main predictive factor of cognitive impairment in CADASIL.

Diffusion Tensor Imaging Changes Correlate with Cognition Better than Conventional MRI Findings in Patients with Subcortical Ischemic Vascular Disease

Background/Aims: To investigate whether diffusion tensor imaging (DTI) is more sensitive than conventional MRI at detecting cognitive deterioration in patients with subcortical ischemic vascular disease (SIVD). Methods: Forty-two SIVD patients had a diagnosis of no cognitive impairment (NCI), vascular cognitive impairment/no dementia or vascular dementia (VaD). Whole-brain DTI histography and routine MRI were performed on these participants. Results: There were significant differences between cognitively impaired patients and NCI subjects in mean diffusivity and fractional anisotropy in either whole-brain white matter (WBWM) or in normal-appearing white matter (NAWM). All DTI indices within either WBWM or NAWM were found to be significantly correlated with both the attention-executive and memory measures in SIVD subjects. Lacune numbers and T₂-weighted lesions correlated only with attention-executive measures, whereas hippocampal volumes correlated only weakly with memory measures. Whole-brain gray matter volumes correlated with Z scores for all cognitive domains but language. After VaD patients had been excluded from the analysis, cognitive measures remained significantly correlated with some of the DTI indices, but not with conventional MRI findings. Conclusions: Compared with conventional MRI, whole-brain DTI is a more reliable and sensitive technique for the early detection of cognitive impairment in SIVD patients.

Vascular Care in Patients With Alzheimer Disease With Cerebrovascular Lesions Slows Progression of White Matter Lesions on MRI

White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

Brachial-Ankle Pulse Wave Velocity Predicts Silent Cerebrovascular Diseases in Patients with End-Stage Renal Diseases

Cerebrovascular disease (CVD) is a major determinant of the prognosis in end-stage renal diseases (ESRD). The purpose of this study was to examine whether factors associated with arterial stiffness contributed to the development of CVD in patients with ESRD. CVD (lacunes and carotid/intracranial artery stenosis) was evaluated with brain magnetic resonance imaging (MRI), and carotid/intracranial artery magnetic resonance angiography (MRA) in 44 pre-dialytic patients. The severity of CVD was evaluated by the number of lacunes and the degree of stenosis, respectively. The association between CVD and atherosclerotic parameters was evaluated. Patients with severe lacunes (n=18) manifested older age, lower diastolic blood pressure, serum creatinine and albumin, and higher CRP and serum calcium than those with absent-moderate lacunes (n=26). When assessed by multivariate analysis, only baPWV was adopted as an independent risk factor for severe lacunes. Furthermore, baPWV and i-PTH were associated with the severity of carotid/intracranial artery stenosis, both of which were independent of other risk factors, including age and diabetes. Arterial stiffness may constitute a novel determinant predicting the severity of CVD in pre-dialytic patients besides classical risk factors.

Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study

Objectives: In cerebral small vessel disease, white-matter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study...

IC-P2-140: Progression of MCI to dementia: The contribution of atrophy and vascular disease

Mild cognitive impairment (MCI) is generally considered as the transition phase between normal ageing and dementia. In various types of dementia, including Alzheimer's disease (AD), atrophy as well as vascular disease (white matter hyperintensities (WMH), lacunes, microbleeds and infarcts) are a frequent finding on brain MRI. The aim of this study was to determine the contribution of atrophy and vascular disease to progression of MCI to dementia. One hundred fifty three consecutive patients, diagnosed with MCI based on the Petersen criteria, were included in the study. Baseline MRI was used to determine the presence of medial temporal lobe atrophy (Scheltens score [0–4]) and vascular disease (the number of lacunes and microbleeds were counted, presence of infarcts was determined, and WMH was rated using the 4-point Fazekas scale [0–3]). MRI measures were dichotomised as follows: presence of lacunes, microbleeds, infarcts: yes/no; MTA: absent 0/1, present 2–4; WMH absent 0/1, present 2/3. Patients were followed for almost 2 years (1.9 SD 1.3). All patients were re-examined for possible progression to AD or another type of dementia. Of the total of 153 MCI patients, 82 (54%) patients progressed to dementia during follow-up. Sixty-six patients (43%) were diagnosed with a diagnosis of AD, and sixteen patients (11%) were diagnosed with another type of dementia (including vascular dementia, frontotemporal lobar degeneration or Parkinson dementia). Converters were older, and had lower MMSE at baseline. Cox regression analysis showed that adjusted for age, sex and MMSE, baseline medial temporal lobe atrophy (HR 1.7 95%CI 1.0–2.9), but not vascular disease, was associated with progression to AD. By contrast, presence of WMH (HR 2.9 95%CI 1.1–7.8) and microbleeds (HR 3.4 95%CI 1.1–10.2) were associated with progression to another type of dementia. In addition, MTA was associated with a twofold – though nonsignificant – increased risk of another type of dementia (HR 2.0 95%CI 0.7–5.9). In a clinical cohort of MCI patients, MTA, but not cerebrovascular disease predicted progression to AD, while conversely, WMH and microbleeds predicted progression to other types of dementia.

Neuropathological basis of magnetic resonance images in aging and dementia

Magnetic resonance (MR) imaging is used widely for assessment of patients with cognitive impairment, but the pathological correlates are unclear, especially when multiple pathologies are present. This report includes 93 subjects from a longitudinally followed cohort recruited for the study of Alzheimer's disease (AD) and subcortical cerebrovascular disease (CVD). MR images were analyzed to quantify cortical gray matter volume, hippocampal volume, white matter hyperintensities, and lacunes. Neuropathological examination quantified CVD parenchymal pathology, AD pathology (defined as Consortium to Establish a Registry for Alzheimer's Disease scores and Braak and Braak stage), and hippocampal sclerosis. Subjects were pathologically classified as 12 healthy control subjects, 46 AD, 14 CVD, 9 mixed AD/CVD, and 12 cognitively impaired patients without significant AD/CVD pathology. Multivariate models tested associations between magnetic resonance and pathological findings across the entire sample. Pathological correlates of cortical gray matter volume were AD, subcortical vascular pathology, and arteriosclerosis. Hippocampal volume was related to AD pathology and hippocampal sclerosis, and the effects of hippocampal sclerosis were greater for subjects with low levels of AD pathology. White matter hyperintensities were related to age and to white matter pathology. Number of MRI lacunes was related to subcortical vascular pathology. In this clinical setting, the presence of lacunes and white matter changes provide a good signal for vascular disease. The neuropathological basis of MR defined cerebral cortical and hippocampal atrophy in aging and dementia is complex, with several pathological processes converging on similar brain structures that mediate cognitive decline.

Subcortical Lacunes Are Associated With Executive Dysfunction in Cognitively Normal Elderly

The relationship between subcortical ischemic vascular disease (SIVD) and cognition in normal elderly is unclear, in part because of methodological inconsistencies across studies. To clarify this relationship, the current study investigated a well characterized cognitively normal elderly sample (>or=55 years) with quantitative MRI and psychometrically robust neuropsychological measures within a multivariate model. Converging evidence suggests that SIVD selectively impairs frontal-executive tasks by disrupting frontal-subcortical circuits. We therefore hypothesized that MRI markers of SIVD would be selectively associated with worse executive functioning. We studied 94 participants who were cognitively and functionally normal. Volumetric measures of white matter signal hyperintensity (WMH), subcortical lacunes, hippocampal volume, and cortical gray matter were obtained to predict performance on composite measures of executive functioning and episodic memory. Hierarchical regression demonstrated that after controlling for demographic variables, MMSE, and total intracranial volume, the total number of subcortical lacunes was the only significant predictor, with a greater number of lacunes associated with poorer executive performance. Hippocampal volume best predicted episodic memory performance. Results suggest that SIVD in the form of silent lacunes corresponds to poorer executive functioning even in otherwise normal elderly, which is consistent with the hypothesis that SIVD preferentially disrupts frontal-subcortical circuits. The clinical importance of these findings is highlighted by the fact that 33% of the normal elderly participants in this study had lacunar infarcts.

Cerebral small vessel disease and C-reactive protein: Results of a cross-sectional study in community-based Japanese elderly

Inflammatory processes are involved in the pathogenesis of atherosclerosis. Inflammation has been known as a risk factor for coronary heart disease, whereas inflammation as a risk for cerebrovascular disease is less well established. Whether inflammatory processes, excluded from their involvement in large-vessel disease, are implicated in the pathogenesis of cerebral small vessel disease remains unclear. We assessed whether higher C-reactive protein (CRP) levels were associated with an increased number of lacunar infarcts or severity of white matter lesions. In a community-based group of Japanese elderly (n=689), CRP concentrations were measured using a highly sensitive assay. All participants underwent magnetic resonance imaging (MRI), and cerebral small vessel disease-related lesions (lacunar infarcts and white matter hyperintensity) were subsequently evaluated. Furthermore, carotid atherosclerosis was also assessed with ultrasonography. As the grades of white matter hyperintensity and the numbers of lacunes were considered small vessel disease-related lesions, we evaluated the relationships between CRP levels and small vessel disease-related brain lesions. Interestingly, the median CRP concentration of our participants was remarkably lower, being approximately one third or one quarter of the value of Western populations. Subjects with higher CRP levels tended to have more small vessel disease-related lesions; however, these associations were not seen after adjustment for cardiovascular risk factors and carotid atherosclerosis. The relationship between CRP levels and small vessel disease-related lesions was not apparent in the community-based Japanese elderly. The impact of inflammation in the pathogenesis of small vessel disease-related brain lesions seems to be weak among the Japanese elderly.

Clinical Significance of Microbleeds in Subcortical Vascular Dementia

Despite many studies investigating the association between the ischemic changes and cognitive impairment in subcortical vascular dementia (SVaD), few studies correlated cognitive impairment with microbleeds (MBs) frequently seen in SVaD. Participants consisted of 86 patients with SVaD who fulfilled the criteria proposed by Erkinjuntti et al. MBs occurred in 73 of 86 (84.9%) patients with SVaD. MBs were most commonly distributed in the cortex, and the cortical MBs were most pronounced in the temporoparietal area. A multiple regression showed that the number of cerebral MB was an independent predictor of cognitive impairment in multiple domains and the severity of dementia even after controlling confounding factors such as age, education, ischemic severity, and number of lacunes. These results indicate that cerebral MB is one of the important factors that cause cognitive impairments in SVaD.