Prevalence Of White Matter Lesions Research Articles

Neural Dysconnectivity in the Hippocampus Correlates With White Matter Lesions and Cognitive Measures in Patients With Coronary Artery Disease.

PurposeRecent neuroimaging reports have shown the microstructural changes in coronary artery disease (CAD) and its correlation with cognitive dysfunction while little is known about the functional characteristics of CAD. We hypothesize that functional characteristics may give clues to underlying pathology in CAD and its link with cognitive dysfunction. Degree centrality (DC), a graph-based assessment of network organization was performed to explore the neural connectivity changes in CAD patients compared with healthy controls and their correlation with cognitive measures.MethodsThirty CAD patients and 36 healthy controls were included in our study. All participants underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were done. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA and Mini-Mental State Examination, MMSE).ResultsOur data analysis included 30 CAD patients (59.90 ± 7.53 years) and 36 HCs (61.61 ± 6.19 years). CAD patients showed a greater prevalence of white matter lesions using the Fazekas score than healthy controls (P < 0.001). Importantly, CAD patients showed significantly lower (P < 0.001) MoCA and MMSE scores compared with healthy controls. CAD patients showed significantly decreased DC value (P < 0.001) in the right hippocampus (hippocampus_R), right lingual gyrus (lingual_R), and significantly increased DC value (P < 0.001) in the left middle frontal gyrus (Frontal_Mid_L) when compared with healthy controls respectively. DC value in the hippocampus_R significantly correlated (P < 0.00) with MMSE and MoCA scores in CAD patients. Fazekas scores in CAD patients showed a significant correlation (P < 0.001) with the DC value in the hippocampus_R.ConclusionThese findings suggest that reduced cerebral neural connectivity in CAD may contribute to their cognitive impairment and white matter microstructural damage.

Clinical Significance of White Matter Lesions in Idiopathic Sudden Sensorineural Hearing Loss.

Background : We aimed to analyze the patient characteristics in accordance with white matter lesions and confirm whether white matter lesions affect final treatment outcomes in idiopathic sudden sensorineural hearing loss.Methods: Medical records of 126 patients treated for unilateral idiopathic sudden sensorineural hearing loss and who underwent magnetic resonance imaging of the brain at an otology clinic in a university hospital from 2013 to June 2019 were reviewed. The Fazekas scale was used to evaluate the severity of white matter lesions. Complete recovery was defined if final hearing at 3 months did not exceed 25 dB.Results: Overall, 107 patients were enrolled in this study. A score of 0 on the Fazekas scale was most frequent (n = 78, 72.9%), followed by 1 (n = 17, 15.9%), and 2 (n = 12, 11.2%). Prevalence of diabetes (P = .032) and/or hypertension (P = .006) and distribution of age (P < .001) were different according to Fazekas scale scores. Hearing level in the affected side was significantly different between those with scores of 1 and 2 (P = .009). Contralateral hearing thresholds were not different according to Fazekas scale scores, but hearing on the contralateral side was significantly poorer in patients with hypertension than those without hypertension (P < .001). Regression analysis revealed that Fazekas scale score and initial hearing thresholds of the affected side were significant prognostic factors for complete recovery.Conclusion: Although the prevalence of white matter lesions in idiopathic sudden sensorineural hearing loss was not high, severe white matter lesions and accompanying cardiovascular risk factors may increase the possibility of initially worse hearing and decrease response to treatment in idiopathic sudden sensorineural hearing loss. Therefore, it might be important to control cardiovascular abnormalities in idiopathic sudden sensorineural hearing loss to achieve a better prognosis.

Association of Left Ventricular Hypertrophy and Atrial Fibrillation with Hemorrhagic Evolution of Small Vessel Disease

ObjectivesCerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood. Materials and MethodsThis retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography. ResultsIn multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18–0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated. ConclusionsMost SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions).

Cognitive, Brain and Intracranial Artery Involvement in Beta Thalassemia

Background: Brain involvement in beta thalassemia is scarcely known so far, and available data show different degrees of abnormalities in terms of neuroradiologic findings and cognitive impairment, mainly showing asymptomatic white matter lesions in transfusion dependent thalassemia (TDT; Karimi et al, Ann Hematol 2016) or in non transfusion dependent thalassemia (NTDT; Karimi et al, Ann Hematol 2012 ; Pazgal et al, Thrombosis Research 2016), arterial stenosis in NTDT (Musallam et al, EJH 2011) and a general impairment in cognitive function in TDT (Elalfy et al, Hematology 2017). To our knowledge there are no studies investigating neuroimaging and cognitive function in both groups of patients, comparing results to healthy subjects.Methods: In our observational study thalassemic patients from 4 major Centers in the South of Italy, aged more than 16 years, both Transfusion Dependent (TDT) and Not Transfusion Dependent (NTDT), and healthy volunteers underwent 3T brain MRI including a FLAIR sequence and intracranial time-of-flight MR-angiography. Three neuroradiologists blinded of clinical data evaluated the MR-exams reporting the presence of artery stenosis and aneuryms and the presence of white matter signal abnormalities graded according to the Fazekas score; the number and the size of parenchymal lesions (<0.5cm, 0.5-1.5cm, >1.5cm) were recorded. Both patients and controls were administered the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) to detect cognitive ability, and results were analyzed by a team of blinded psychologists and psychiatrists. Clinical and laboratory data were collected to correlate neurologic and psychometric findings with disease history and severity.Results: Seventy-four thalassemic patients (46/74 females, mean-age 35.2±11.4 years, range 16-66; 51 TDT and 23 NTDT; mean hemoglobin 9.3±1.4 g/dl, range 7.5-12; 41 splenectomized; 34 on prophylactic aspirin) and 56 healthy controls (36/56 females, mean-age 34.2±11.7 years, range 17-66) were enrolled. No intracranial artery stenosis was detected. Patients and controls did not differ regarding the incidence rate of aneurysms (9.46% vs 9.67%). White matter lesions (WML) were found both in patients and controls, but the prevalence (35/74; 47.30% vs 28/56; 50.0%), the number (4.1 vs 4.6), the size and the Fazekas score did not differ between the groups. Compared to controls, patients presenting WML tend to be younger (35.32y compared to 39.89y, p= 0.033). No differences in WML were found between TDT and NTDT, nor between patients on aspirin and others, and splenectomy was associated with an increased lesion burden only in TDT (mean 5.56 versus 1.53, p= 0.048); in splenectomized patients on aspirin the number and prevalence of WML was lower compared to those splenectomized not on prophylaxis, but the difference did not reach the statistical significance. Patients with WML did not differ from others in terms of comorbidities, hemoglobin, platelets, erythroblasts, ferritin, hemolysis markers and chelation therapies. The presence of WML did not correlate with cognitive impairment as measured by the Intelligence Quotient (IQ) derived from the WAIS-IV test, both in patients and in controls. IQ in patients was significantly lower than controls, and this finding remained significant after correction for education (IQ: 82.75±11.11 in patients, 93.96±SD13.22 in controls, p=0.032), regardless of the presence of WML, that was again comparable.Conclusions: Beta-thalassemia and chronic blood transfusion treatment do not seem to imply significant brain and intracranial artery changes, although cognitive function seems to be affected. Further analysis are required to clarify if the general cognitive impairment derives from functional changes in cerebral connectivity, or if it is one of the effect of the chronic course of the disease. DisclosuresNo relevant conflicts of interest to declare.

No association between migraine frequency, white matter lesions and silent brain infarctions: a study in a series of women with chronic migraine.

It has been suggested that silent infarctions (SIs) and hyperintense white matter lesions (WMLs) are related to migraine frequency. We studied their prevalence and anatomical distribution in patients with chronic migraine (CM). A total of 96 women with CM [mean age 43 (range 16-65)years] and 29 women with episodic migraine (EM) [mean age 36 (range 16-58)years] underwent 1.5-T magnetic resonance imaging following the CAMERA protocol. The number, size and location of SIs and deep WMLs were recorded and a modified Fazekas scale was applied to assess periventricular WMLs. White matter lesions were found in 59 (61.5%) women with CM and 17 (58.6%) women with EM (odds ratio, 1.13; 95% confidence intervals, 0.48-2.62; P=0.784). The majority (63% CM and 71% EM) were small deep WMLs. Exclusive periventricular WMLs were exceptional. Of the 739 WMLs seen in patients with CM, 734 (99.3%) were hemispheric and mostly frontal (81%). Posterior fossa WMLs were seen in only five (5.2%) women with CM (always in the pons) and two (6.9%) women with EM. Age >45years was the only vascular risk factor associated with a higher WML number (median: 0<45years and 3>45years; P=0.004). We found seven SIs in six women with CM (6.3%). As compared with the expected prevalence at this age, this study confirms that the prevalence of WMLs, in most cases small, deep and frontal, was increased in CM and EM. However, our results do not support an association of WMLs or SIs with a higher frequency of attacks, but with the presence of vascular risk factors and mainly age >45years.

White matter lesions in magnetic resonance imaging of the brain in 56 patients with visual vertigo.

Visual vertigo is defined as a condition in which there is worsening or triggering of vestibular symptoms in certain visual environments. Previous studies have associated visual vertigo with an increased prevalence of underlying white matter lesions on brain imaging. This study evaluated the magnetic resonance imaging scans of the brain from a cohort of patients with visual vertigo, and compared the outcomes to an age- and gender-matched group of healthy volunteers.Results and conclusionWhite matter lesions were observed in 17.9 per cent of the patient group and in 16.3 per cent of the control group. The prevalence of white matter lesions in the patient group was not too different to that expected based on age.

Ischemic cerebrovascular burden evaluated by magnetic resonance imaging in an elderly Brazilian community: The Pietà study.

In developing countries, cardiovascular risk factors are poorly controlled, leading to high prevalence of cerebrovascular diseases. The aim of the study was to evaluate the burden of white matter lesions in magnetic resonance through the Fazekas scale in a population aged 75 + years living in the community, and to investigate possible associations between vascular lesions, cardiovascular risk factors and cognitive status. Subjects were selected from a community-based study on brain aging conducted in Caeté (Minas Gerais state), Brazil. Overall, 177 participants (112 cognitively healthy, 36 with cognitive impairment-no dementia and 29 with dementia), being 108 women, aged 79.3 ± 3.8 years, with 3.1 ± 2.9 years of educational level, underwent a 3 Tesla magnetic resonance scanner with fluid attenuated image recovery acquisition. Severity of white matter lesions was assessed through the Fazekas scale. Severe white matter lesions were present in 31.1% of the whole sample and in 25.0% of the cognitively healthy individuals. A significant association was found between severe white matter lesions and cognitive impairment (OR = 2.20, 95% CI 1.17–6.53; p = 0.021), as well as with hypertension (OR = 1.92, 95% CI 1.03–7.39; p = 0.043). In conclusion, a high prevalence of severe white matter lesions was observed in this elderly Brazilian population sample, and white matter lesions were associated with hypertension and cognitive status. Importantly, the prevalence of white matter lesions was also high in cognitively healthy subjects.

Cerebral white matter lesions and silent cerebral infarcts in postmenopausal women with polycystic ovary syndrome

Objectives: The association between polycystic ovary syndrome (PCOS) and cardiovascular disease remains unclear. Our objective was to examine the relation of PCOS with cerebrovascular disease measured by brain magnetic resonance imaging (MRI) as white matter lesions (WMLs) and silent cerebral infarcts (SCIs).Methods: Seventy postmenopausal women with PCOS and 140 controls participated in the case–control, cross-sectional study. Clinical, anthropometric, hormonal and metabolic parameters were measured. WMLs and SCIs were evaluated by brain MRI.Results: Compared with controls, postmenopausal women with PCOS had higher mean body mass index, larger waist hip ratio, higher level of low-density lipoprotein cholesterol, free androgen index and lower sex hormone-binding globulin level. The PCOS group had a significantly higher prevalence of WMLs (40% versus 22%, p = 0.009), and SCIs (17% versus 7%, p = 0.032) compared to the control group.Conclusions: Postmenopausal women with PCOS are associated with WMLs and SCIs.

Lack of Association of CNS Lesion Number with Cognitive Performance and Cerebral Blood Flow in Sickle Cell Disease

Background: Neurocognitive studies demonstrate a deficit in performance for sickle cell anemia (SCA) patients as compared to age-matched peers. The underlying mechanism for this deficit is not yet understood, but possible contributors include CNS lesion load, perfusion deficits, oxygen deprivation and cerebrovascular autoregulatory impairment. We hypothesized that the number of white matter hyperintensities and the cerebral blood flow (CBF) might contribute to cerebral dysfunction in SCA patients. We sought to examine the relationship between cognition, laboratory parameters and brain perfusion in sickle cell patients as compared to non-sickle cell (AA) controls.Methods: SCA (HbSS/HbSβ0) and AA subjects, ages 18-55 years old, with no evidence of TIA/Stroke, no clotting/bleeding disorders, and not on anticoagulation were recruited. Hydroxyurea use was noted but was neither an inclusion nor exclusion criterion. Evaluation included a routine questionnaire for basic social, educational and health information. Steady state laboratory evaluation was obtained within one week of imaging. Neurocognitive performance was evaluated by the Cogstate battery at the time of the MRI. Cogstate analysis included tests of executive function, recall, social and emotional cognition and learning. Lesion number and CBF were determined using 3T MRI, which included T1w 3D, T2 FLAIR, pseudo-continuous arterial spin labeling, diffusion tensor imaging, and blood oxygen level depending imaging before and during a brief period of hyperoxia. Oxygen saturation and blood pressure were monitored throughout the procedure at 5-minute intervals.Results: To date, we have recruited 15 SCA and 7 AA subjects who answered a tailored questionnaire and underwent 3T MRI, routine laboratory testing and neurocognitive testing. Of the 15 SCA subjects, 6 had no lesions on 3T MRI and 9 had multiple lesions with 8 persons having more than 5. Lesion number correlated only with age (p=0.02). Of the 7 AA patients, 3 had no lesions, 2 had 1, 1 had 4 and 1 patient had >20 lesions. SCA patients fared worse on only one of the cognitive tests, the Groton Maze Learning Test for executive function (GMLT), in which a higher GMLT demonstrates decreased ability (p=0.02). Amongst the SCA subjects, a worse score on GMLT correlated positively with age (p=0.03), ferritin (p=0.02), mean arterial pressure (p=.02) and %HbF (p=0.03) while GMLT correlated negatively with %S (p=0.007), indirect bilirubin (p=0.02) and absolute reticulocyte count (p=0.005). There did not appear to be a relationship of GMLT with LDH, Hb, MCV, MCHC, platelet count, white cell parameters, number of crisis, oxygen saturation, CBF or lesion load. Gray matter CBF in SCA patients was significantly greater than that in AA subjects (164 ml/100g/min vs 113 ml/100g/min in AA, p < 0.007) as was white matter CBF (93 ml/100g/min vs 71 ml/100g/min, p=0.03). Both gray matter and white matter CBF correlated negatively with Hb/Hct levels in SCA patients (p=0.004). SCA patients also had a significantly lower average DP and MAP than the AA patients (p-0.004 and 0.015 respectively).Discussion: This study was undertaken to assess the role of a variety of clinical parameters against neurocognitive performance in SCA patients who had not been diagnosed with prior CVA or stroke. None-the-less, with the use of more powerful 3T MRI technology, there is an increase in the measurement and prevalence of white matter lesions in both SCA and AA subjects and a significant proportion of subjects were found to have evidence of white matter lesions. While white matter hyperintensities have been associated with cognitive outcomes, better detection of these lesions questions these assumptions and the prevailing theory that white matter hyperintensities are a marker of cerebral health and predict cognitive performance. Lesion number did not demonstrate an association with CBF or the GMLT; CBF correlated only with Hb levels and did not correlate with GMLT. There was an association of age with both cognition, as measured by the GMLT, and with lesion number.Conclusion: We suggest that diffuse cerebral dysfunction, rather than discrete infarct quantity, may be the more important mechanism of decreased cognition. We are currently assessing the functional assessments by fMRI to better delineate the nature of this cerebral dysfunction. DisclosuresNo relevant conflicts of interest to declare.

Increased number of white matter lesions in patients with familial cerebral cavernous malformations.

Familial cerebral cavernous malformations, an autosomal dominant disorder, result in excess morbidity and mortality in affected patients. The disorder is most prevalent in the Southwest United States, where the affected families are most often carriers of the CCM1-KRIT1 Common Hispanic Mutation. The brain and spinal cord parenchyma in these individuals is usually affected by multiple cavernous malformations. Previous studies have shown abnormalities of endothelial cell junctions and the blood-brain barrier in cerebral cavernous malformations. Endothelial cell abnormalities have also been described in pathologic studies of white matter hyperintensities. We compared the prevalence of white matter hyperintensities in a population with known familial cerebral cavernous malformations. We examined 191 subjects with familial cerebral cavernous malformations who were enrolled into an institutional review board-approved study. All carry the same Common Hispanic Mutation in the CCM1 gene. Each subject underwent 3T MR imaging, including gradient recalled-echo, SWI, and FLAIR sequences. The number of cavernous malformations and the number of nonhemorrhagic white matter hyperintensities were counted. Subjects older than 60 years of age were excluded due to the high prevalence of white matter lesions in this population, and children younger than 6 were excluded due to potential sedation requirements. Logistic regression analysis was performed to determine the prevalence of abnormal white matter hyperintensities in those with familial cerebral cavernous malformations compared with healthy controls or those with sporadic cerebral cavernous malformation within the familial cerebral cavernous malformations group; it was also performed to evaluate the associations between abnormal white matter hyperintensities and age, sex, headaches, thyroid disease, diabetes, hypertension, hyperlipidemia, seizure history, or modified Rankin Scale score. Familial CCM1 carriers have a higher prevalence of abnormal white matter hyperintensities (15.4%) compared with both control populations (2.1% and 2.5%, respectively) (P < .05). Logistic regression showed no statistical association with sex, headaches, hyperlipidemia, hypertension, thyroid disease, seizure history, number of cerebral cavernous malformations, or modified Rankin Scale score among those with familial cerebral cavernous malformation. An expected correlation with age was shown. Familial CCM1 carriers have not only an increased number of cerebral cavernous malformations but also an increased number of white matter T2 hyperintensities, spatially distinct from cerebral cavernous malformations, which exceeded that of a healthy population. Clinical findings did not explain the association with abnormal white matter hyperintensities in the familial cerebral cavernous malformation population. To our knowledge, these relationships have not been previously reported. This finding suggests an additional manifestation of endothelial abnormalities in this population.

WHITE MATTER LESIONS AFTER CEREBRAL ANEURYSM COILING

White matter lesions (WML) on T2-weighted magnetic resonance imaging (MRI), particularly when extensive, are a marker of cerebral small-vessel disease (SVD). Anecdotally, WMLs were noted in follow-up imaging of patients with symptomatic cerebral aneurysms, but the underlying reason for this is unknown. In this study we investigated WMLs in patients with cerebral aneurysms. Consecutive patients were identified who underwent endovascular coiling of cerebral aneurysms at the Royal Preston Hospital between 2008 and 2010, for whom follow-up MRI scans were available. Scans from patients showing WMLs were anonymised and the lesion burden was estimated using the Fazekas visual rating score and by software-aided volumetric analysis. Comparison was made with an age-stratified outpatient control group who underwent brain MRI for headache. 157 patients had follow-up MRI scans. WMLs were reported in 38.2%, and 48% were scored Fazekas grade 2 or higher. The prevalence of WMLs in cases was significantly greater than that in age-stratified controls in patients aged 60–69y (p

Association between metabolic syndrome and white matter lesions in middle‐aged and elderly patients

Metabolic syndrome (MetS) has been reported to be associated with silent lacunar infarction, which is highly related to white matter lesions (WMLs). However, little is known about the relationship between MetS and the prevalence of WMLs. The association between MetS, its components and WMLs in middle-aged and elderly patients was investigated. Consecutive patients aged 50years and older were prospectively enrolled in this study. All participants underwent magnetic resonance imaging scans to assess the presence and severity of WMLs. The MetS was defined according to the updated National Cholesterol Education Program's Adult Treatment Panel III criteria. Multivariate logistic regression analyses were performed to examine the relationship between MetS, its components and WMLs. A total of 852 patients were enrolled in the study. MetS was present in 38.4%. MetS was associated with an increased risk of periventricular WMLs (PVWMLs) and deep WMLs (DWMLs) after multivariable adjustment (odds ratio 3.21, 95% confidence interval 2.26-4.55 for PVWMLs; odds ratio 2.93, 95% confidence interval 2.09-4.09 for DWMLs). Amongst MetS components, elevated blood pressure, elevated fasting blood glucose and low high density lipoprotein cholesterol were associated with PVWMLs, whilst elevated blood pressure and low high density lipoprotein cholesterol were related to DWMLs. Our findings demonstrate that MetS is associated with the prevalence of PVWMLs and DWMLs independent of other risk factors in middle-aged and elderly patients. The association between MetS as a cluster and WMLs was not driven by MetS components.

Spotlight on the October 15 Issue

The authors performed genetic analyses and Sanger sequencing, identifying a homozygous deletion of GRID2 exon 4 in the index family and compound heterozygous deletions involving GRID2 exon 2 in a second family. Biallelic deletions of GRID2 may lead to a syndrome of cerebellar ataxia and tonic upgaze in affected individuals. See p. 1378 Of 926 patients diagnosed with migraine, 375 had MRIs and 115 had abnormalities, with 39 having white matter lesions. The prevalence of white matter lesions is more common in pediatric migraine with aura, but they appear to be …

Prevalence of white matter lesions and stroke in children with migraine

To determine the prevalence of white matter lesions (WMLs) and infarcts in children with migraine and whether pediatric migraine could be a risk factor for silent ischemic lesions or stroke. Prospectively collected data from 1,008 pediatric patients with headache were reviewed. The MRI data were collected and retrospectively reviewed. Of the 926 patients diagnosed with migraine, 375 patients had MRIs and 115 had abnormalities, of which 39 had WMLs. Among them, 24 (6% of migraine) patients had incidental white matter findings without known neurovascular disease, risk factors, or etiologies for WMLs. The prevalence of WMLs is more common in migraine with aura (10%) than without aura (4%) (p = 0.038), but it is not statistically significant compared with controls (4%) (p = 0.119). Deep WMLs are more prevalent than periventricular lesions; these are detected mainly in the frontal and parietal lobes. No lesions appeared to be infarct-like lesions. There was no association between the total lesion load and chronicity or the frequency of migraine. WMLs are nonprogressive. Pediatric migraineurs with aura do not develop stroke, based on the available follow-up data. WMLs in pediatric patients with migraine and aura are no more prevalent than in controls. They appear to be benign and are not associated with stroke.

Abstract TP183: Cerebral Small Vessel Disease - A Population-based Cross-Ethnic Comparison between Chinese and White Elderly Individuals

Background and Purpose: Ethnic differences have been reported between Asians and Whites in the prevalence of certain stroke subtypes. However, it is unknown if such differences exist with respect to manifestations of cerebral small vessel disease. We compared the prevalence of white matter lesions [WML], lacunes, and microbleeds between Han Chinese and White Australian individuals randomly selected from their respective populations. Methods: Magnetic resonance imaging (1.5 Tesla) was performed on participants of the Shanghai Aging Study (n=321, mean age 69±6 years) and Tasmanian Study of Cognition and Gait (n=397, mean age 72±7 years). A single expert rater recorded measures of WML, lacunes, and microbleeds. We compared lesion prevalence between age- and gender-matched subgroups from the two study population. Among all subjects (n=718), we used multivariable logistic regression to examine if ethnicity was associated with the presence of these lesions. Results: The prevalence rates of confluent WML, lacunes, and microbleeds among Chinese and Whites were 37% vs. 34% (p=0.09), 29% vs. 34% (p=0.24), and 9% vs. 11% (p=0.59), respectively. Subgroup analysis among age- and gender- matched subjects confirmed that confluent WML was more common among Chinese (38.5%) than Whites (28.4%, p=0.01). In multivariable regression, Chinese had a higher risk of confluent WML (odds ratio 1.53, 95% confidence interval 1.04-2.24, p=0.03) independent of other risk factors, but no differences were seen for lacunes and micro bleeds. Conclusion: In this population-based cross-national comparison, Chinese had a greater risk of moderate-to-severe WML than white Australians, but had a similar risk of lacunes and microbleeds.

Lower Susceptibility to Cerebral Small Vessel Disease in Human Familial Longevity

On MRI, cerebral white matter lesions, lacunar infarcts, and cerebral microbleeds are common imaging correlates of cerebral small vessel damage in apparently healthy elderly individuals. We investigated whether middle-aged to elderly offspring of nonagenarian siblings, who are predisposed to become long-lived as well, have a lower prevalence of white matter lesions, lacunar infarcts, and cerebral microbleeds than control subjects. All subjects were from the Leiden Longevity Study. In this study, middle-aged to elderly offspring of nonagenarian siblings, who are predisposed to become long-lived as well, were contrasted to their spouses. Cerebral small vessel disease was assessed using 3-T MRI. Offspring were less likely to have severe periventricular frontal caps (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-1.1; P trend=0.01) and severe periventricular bands (OR, 0.4; 95% CI, 0.2-0.8; P trend=0.02). Moreover, offspring were less likely to have frontal (OR, 0.4; 95% CI, 0.2-0.9; P trend=0.05), parietal (OR, 0.4; 95% CI, 0.1-0.9; P trend=0.001), temporal (OR, 0.3; 95% CI, 0.1-0.8]; P trend=0.004), and occipital subcortical white matter lesions (OR, 0.3; 95% CI, 0.1-0.6; P trend=0.001). Prevalence of lacunar infarcts also was lower in offspring (OR, 0.3; 95% CI, 0.1-1.1; P=0.07). Prevalence of microbleeds was not significantly different in offspring and control subjects. Exceptional familial longevity is associated with a lower susceptibility to white matter lesions and lacunar infarcts, but not cerebral microbleeds.

Microvascular pathology in late-life depression

Since the era of Gaupp who introduced the concept of atheroscletic depressive disorder, the concept of late-life depression has been correlated with cerebrovascular comorbidities, microvascular lesions, frontal cortical and subcortical gray and white matter hyperintensities. The predominant neuropsychological deficits concern the domains of planning, organization and abstraction, with executive dysfunction being the predominant finding. MRI studies reveal a higher prevalence of white matter lesions in elderly patients with depression. Molecular mechanisms underlying the disease still remain unclear. Hyperhomocysteinemia has been associated with depression through its toxicity to neurons and blood vessels. Endothelial dysfunction is another possible mechanism referring to the loss of vasodilatation capacity. Inflammatory phenomena, such as increased peripheral leucocytes, elevated CRP and cytokine levels, could play a role in endothelial dysfunction. In this review we will briefly combine findings from neurobiological, epidemiological, structural and post-mortem data. A more complex model in late-life depression combining different modalities could be an elucidating approach to the disease's etiopathogeny in the future.

Abstract 2513: Intraventricular Administration of Cystatin C Attenuates White Matter Injury In Rat Chronic Ischemia

Background and Purpose Cerebral white matter lesions (WMLs) contribute to elderly cognitive deterioration and are usually caused by chronic ischemic insult. Experimental studies have shown that proteases are highly expressed in activated astrocyte and microglia, which are thought to be crucial in the development of WMLs. Cystatin C (CSTC) functions as a major extracellular cysteine protease inhibitor in mammals. Since the concentration of CSTC is 5 times higher in CSF than in plasma, CSTC is thought to be a major inhibitor of cysteine proteases in the central nervous system. We have shown that polymorphisms in the CSTC gene, which results in a decrease of plasma CSTC level, are significantly associated with prevalence of WMLs. However, direct impact of CSTC on the development of WMLs has not been elucidated yet. Here we studied whether direct administration of CSTC into brain has a protective effect on the pathophysiology of WMLs produced by chronic cerebral hypoperfusion in a rat model of permanent bilateral common carotid artery occlusion. Methods Adult Wister rats underwent ligation of bilateral common carotid arteries (LBCCA) and were divided into three groups; the CSTC group in which CSTC was injected continuously into the ventricle 14 consecutive days after LBCCA (n=10), the PBS group in which PBS was injected continuously into the ventricle 14 consecutive days after LBCCA (n=10), and the sham group (n=10). All rats were perfused on 14 days after LBCCA. The severity of WMLs and accumulation of microglia and astrocytes in the corpus callosum (CC) and optic nerve (ON) were evaluated. Furthermore, the activity of cathepsin B, one of the major proteases, was measured in the tissue lysates of CC and ON using the assay kit. Results Continuous intraventricular infusion of CSTC significantly reduced the severity of WMLs (CC; p&lt;0.001 vs. PBS, ON; p&lt;0.001 vs. PBS) and inhibited the accumulation and activation of microglia (CC; p=0.03 vs. PBS, ON; p&lt;0.001 vs. PBS) and astrocytes (CC; p=0.003 vs. PBS, ON; p=0.04 vs. PBS) both in CC and ON. There were no alterations in cathepsin B activity in these regions. Conclusions The present study indicates that CSTC could suppress chronic ischemia-induced WMLs and the inhibition of proteases other than cathepsin B may be implicated in this beneficial effect.

Age-Related Changes in White Matter Lesions, Hippocampal Atrophy, and Cerebral Microbleeds in Healthy Subjects Without Major Cerebrovascular Risk Factors

Although cumulative evidence indicates that risk factors for arteriosclerosis have an impact on age-related changes in brain pathology, the influence of aging without major risk factors on changes in brain structures has not yet been fully elucidated. We used magnetic resonance imaging (MRI) to study how aging affects structural changes in the brain (eg, white matter lesions, hippocampal atrophy [HA], microbleeds) in normal subjects without major risk factors for cerebrovascular diseases. We studied 1108 subjects who underwent voluntary brain screening and had no cerebrovascular risk factors, such as hypertension, diabetes mellitus, or hyperlipidemia. We examined the conventional and T2-weighted MRI to define white matter hyperintensities, HA, and cerebral microbleeds in addition to all physical parameters, blood biochemical data, and neuropsychiatric symptoms. We found that the prevalence of white matter lesions and HA increased significantly with age (P < .001). Logistic analysis showed that periventricular hyperintensity was significantly related to age (P < .0001) and depressive state (P < .01). A linear relation was found between white matter lesions and HA (P < .05). Cerebral microbleeds also increased with age, and their presence was associated with HA (P < .001). White matter lesions, HA, and cortical microbleeds were associated with one another in healthy elderly subjects, and these changes were affected by the aging process independent of any cerebrovascular risk factors. Cerebral amyloid angiopathy may underlie these age-related brain changes.

White Matter Lesions in Migraine and Right-to-Left Shunt: A Conventional and Diffusion MRI Study

Subjects with migraine with aura (MA) have a high prevalence of white matter lesions (WMLs) on magnetic resonance imaging (MRI). Moreover, right-to-left shunt (RILES), mainly due to patent foramen ovale, is frequently associated with MA. The aim of this study was to clarify the relationship between RILES and WML in MA. We enrolled 87 consecutive subjects affected by MA. Patients were screened for migraine characteristics and cerebrovascular risk factors. Transcranial Doppler was used to diagnose RILES and MRI with T2-weighted and diffusion-weighted imaging (DWI) to evaluate presence, number and volume of WMLs. RILES was present in 45% of patients. We did not detect any DWI hyperintense lesion; WMLs were present in 61% of patients on T2-weighted images. Presence of WMLs did not correlate with any migraine clinical feature, whereas the presence, number and volume of WMLs increased with subjects' age. There was no significant difference in the total volume and number of WMLs in the group with and without RILES. In conclusion, RILES does not increase the likelihood of finding WMLs in migraineurs.