Silent Lacunar Infarcts Research Articles

Reduced muscle strength of knee extensors is a risk factor for silent lacunar infarcts among Japanese elderly people: the Bunkyo Health Study

AbstractBackgroundSilent lacunar infarcts (SLIs) are often incidentally diagnosed by brain magnetic resonance imaging in elderly people and are associated with the future onset of stroke, dementia, and frailty. While decreased muscle strength was reported as a risk factor for stroke, it is still unclear whether it also predisposes to SLI. In this study, we investigated the association between muscle strength and SLI in elderly subjects.MethodsThe subjects were 1536 elderly people aged 65–84 years without previous stroke events, living in an urban area of Tokyo, Japan, and recruited in the Bunkyo Health Study. Lacunar infarcts were defined by brain magnetic resonance imaging. Muscle strength of the knee extensors was measured using a dynamometer. After categorizing subjects by age and sex, we divided them into three groups based on muscle strength tertiles (High, Medium, and Low) and investigated the association between muscle strength and SLI.ResultsThe mean subject age was 73.0 ± 5.4 years, and 58.9% were female. The prevalence of SLI was 16.4% and was inversely associated with muscle strength (High, 12.3%; Medium, 17.7%; and Low, 19.3%; P for trend 0.003). After multivariate adjustment, the odds ratio for SLI was increased in the Medium and Low groups compared with the High group (High, 1.00 [reference]; Medium, 1.42 [95% confidence interval: 0.98–2.04]; and Low: 1.48 [1.02–2.14]), and the linear trend across the three groups was significant (P for trend 0.043).ConclusionsReduced knee extensor muscle strength is associated with SLI among Japanese elderly, independently of other established risk factors.

1585-P: Reduced Insulin Sensitivity and Muscle Strength Are Independent Risk Factors for Silent Lacunar Infarcts and Synergistically Increase the Risk among Japanese Elderly People: The Bunkyo Health Study

Silent lacunar infarcts (SLI) are often incidentally found on brain MRI scans in asymptomatic elderly people, and are associated with the future onset of stroke and dementia. However, the risk factors for SLI have not been fully elucidated yet. We recently found that reduced muscle strength is a risk factor for SLI. Systemic insulin sensitivity (IS) that reflects the metabolic function of muscles could also be a risk factor for SLI; however, interactive effect of IS and muscle strength on SLI is totally unknown. Here, we evaluated SLI, recently established index of IS (PREDIM) and knee extensor muscle strength by MRI, oral glucose tolerance test, and dynamometer, respectively on 1,531 elderly people aged 65-84 years living in an urban area of Tokyo. The subjects were categorized into 3 groups based on the standard deviation of PREDIM and the tertiles of muscle strength, respectively, then categorized into 9 groups by their combination, then we estimated odd ratios for SLI by logistic regression analysis. Among the study subjects, we found 251 (16.4%) subjects had silent lacunar infarcts. IS was weakly correlated to muscle strength (r=0.185, p=0.001). Impaired IS [High; 1.00 (reference), Medium; 1.53 (95%CI: 0.94-2.48), Low; 1.85 (95%CI: 1.02-3.38), p for trend 0.047] and reduced muscle strength [High; 1.00 (reference), Medium; 1.42 (95%CI: 0.99-2.04), Low; 1.51 (95%CI: 1.05-2.16), p for trend 0.034] were independently associated with increased risk for SLI in the fully adjusted model. In terms of interactive association, subjects categorized in the lowest IS and muscle strength had 4.4 fold (95%CI: 1.67-11.64) higher risk for SLI compared with those categorized in both are the highest. In summary, reduced muscle strength and IS were independently associated with higher risk for SLI in elderly subjects, and combination of both was synergistically elevated the risk for SLI. Disclosure Y. Someya: None. Y. Tamura: Advisory Panel; Self; Astellas Pharma Inc. Research Support; Self; Kowa Company, Ltd. Speaker’s Bureau; Self; Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd. H. Kaga: None. D. Sugimoto: None. S. Kadowaki: None. R. Suzuki: None. R. Kawamori: None. H. Watada: Advisory Panel; Self; Abbott, Ajinomoto, Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Fuji Film, Janssen Pharmaceuticals, Inc., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Research Support; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Yakult. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Strategic Research Foundation at Private Universities (S1411006); Japan Society for the Promotion of Science (18H03184); Mizuno Sports Promotion Foundation; Mitsui Life Social Welfare Foundation

0805 Lack of Association Between Periodic Limb Movements of Sleep and Neuroimaging Signatures of Cerebral Small Vessel Disease in Stroke-Free Community-Dwelling Older Adults

Abstract Introduction Evidence of the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease (cSVD) is limited and inconsistent. Here, we aimed to assess the independent association between PLMS and the different neuroimaging signatures of cSVD. Methods Community dwelling adults aged ≥60 years enrolled in the Atahualpa Project undergoing PSG and MRI with time intervals ≤6 months were included. MRI readings focused on white matter hyperintensities (WMH) of presumed vascular origin, deep cerebral microbleeds (CMB), silent lacunar infarcts (LI), and >10 enlarged basal ganglia-perivascular spaces (BG-PVS). Data from single-night polysomnograms were interpreted according to recommendations of the American Academy of Sleep Medicine. Associations between the PLMS index and neuroimaging signatures of cSVD (as dependent variables) were assessed by means of logistic regression models, adjusted for relevant confounders. Results A total of 146 individuals (mean age: 71.4 ± 7.5 years; 64% women) were included. A PLMS index ≥15/hour were noted in 48 (33%) participants. Moderate-to-severe WMH were present in 33 individuals (23%), deep CMB in 9 (6%), silent LI in 16 (11%), and >10 BG-PVS in 44 (30%). In univariate analyses, silent LI (p=0.035) and the presence of >10 enlarged BG-PVS (p=0.034) were significantly higher among participants with a PLMS index ≥15/hour. However, fully-adjusted multivariate models showed no significant association between PLMS index ≥15/hour and any of the neuroimaging signatures of cSVD. Conclusion This study shows no independent association between the PLMS index and neuroimaging signatures of cSVD in stroke-free community-dwelling older adults. Support This study was supported by Universidad Espíritu Santo - Ecuador.

Lack of Association between Periodic Limb Movements during Sleep and Neuroimaging Signatures of Cerebral Small Vessel Disease in Stroke-Free Community-Dwelling Older Adults. The Atahualpa Project

Evidence of the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease (cSVD) is limited and inconsistent. Here, we aimed to assess the independent association between PLMS and the different neuroimaging signatures of cSVD. Atahualpa residents aged more than or equal to 60 years enrolled in the Atahualpa Project undergoing polysomnography and MRI with time intervals less than or equal to 6 months were included. MRI readings focused on white matter hyperintensities (WMH) of presumed vascular origin, deep cerebral microbleeds (CMB), silent lacunar infarcts (LI), and more than 10 enlarged basal ganglia-perivascular spaces (BG-PVS). Data from single-night polysomnograms were interpreted according to recommendations of the American Academy of Sleep Medicine. Associations between the PLMS index and neuroimaging signatures of cSVD (as dependent variables) were assessed by means of logistic regression models, adjusted for relevant confounders. A total of 146 individuals (mean age: 71.4 ± 7.5 years; 64% women) were included. A PLMS index more than or equal to 15 per hour were noted in 48 (33%) participants. Moderate-to-severe WMH were present in 33 individuals (23%), deep CMB in 9 (6%), silent LI in 16 (11%), and more than 10 BG-PVS in 44 (30%). In univariate analyses, silent LI (P = .035) and the presence of more than 10 enlarged BG-PVS (P = .034) were significantly higher among participants with a PLMS index more than or equal to 15 per hour. However, fully-adjusted multivariate models showed no significant association between PLMS index more than or equal to 15 per hour and any of the neuroimaging signatures of cSVD. This study shows no independent association between the PLMS index and neuroimaging signatures of cSVD in stroke-free community-dwelling older adults.

Basal Ganglia-Cortical Circuit Disruption in Subcortical Silent Lacunar Infarcts.

To investigate the alterations of basal ganglia (BG)-cortical structural and functional connectivity induced by subcortical silent lacunar infarct (SLI), and their associations with cognitive impairment in SLI subjects. All participants were recruited from communities, including 30 subcortical SLIs and 30 age-, gender-, and education-matched healthy controls. The structural and functional connectivity of BG-cortical circuits using diffusion and resting-state functional magnetic resonance imaging data were obtained. Diffusion abnormalities of the white matter tracts connecting the BG and cortical areas were observed in SLI subjects, including the BG-lateral frontal, BG-orbital frontal, and BG-insula tracts. Multiple regions showed a reduced BG-cortical functional connectivity in SLI patients, including direct connectivities with the BG, such as the BG-limbic, BG-insula, and BG-frontal connectivities, and others that showed no direct causation with the BG, such as the insula-limbic, insula-parietal, and frontal-parietal connectivities. Coupling of structural and functional BG-cortical connectivity was observed in healthy controls but not in SLI patients. Significant correlations between structural and functional BG-cortical connectivity and cognitive performance were demonstrated in SLI patients, indicating the potential use of BG-cortical connectivities as MRI biomarkers to assess cognitive impairment. These findings suggest that subcortical SLIs can impair BG-cortical circuits, and these changes may be the pathological basis of cognitive impairment in SLI patients.

Neuroimaging signatures of cerebral small vessel disease and risk of falls in stroke-free older adults living in rural Ecuador. The Atahualpa Project

PurposeThis study aimed to assess the association between neuroimaging signatures of cerebral small vessel disease (cSVD) and the risk of falls in stroke-free older adults living in rural Ecuador. MethodsRisk of falls was evaluated by the Downton Fall Risk Index (DFRI). MRI readings focused on white matter hyperintensities (WMH) of presumed vascular origin, deep cerebral microbleeds (CMB), silent lacunar infarcts (LI), and > 10 enlarged basal ganglia-perivascular spaces (BG-PVS). Logistic regression models were fitted to evaluate whether these neuroimaging signatures were associated with the DFRI, after adjusting for relevant confounders. ResultsWe included 288 participants. The DFRI was positive in 69 (24%). Moderate-to-severe WMH were noticed in 55 individuals (19%), deep CMB in 18 (6%), LI in 23 (8%), and > 10 BG-PVS in 65 (23%). Multivariate models showed a significant association between moderate-to-severe WMH and the DFRI (p = .016). There were no associations between other neuroimaging signatures of cSVD and the DFRI. Age was the single covariable remaining significant in all models. ConclusionsWMH is associated with the DFRI in stroke-free older adults living in a remote rural setting. A target for fall prevention should include the control of factors favoring the development of diffuse subcortical damage of vascular origin.

Serum alkaline phosphatase level is correlated with the incidence of cerebral small vessel disease.

Vascular calcification is one of the mechanisms underlying the pathogenesis of cerebral small vessel disease (CSVD). Whether higher levels of serum alkaline phosphatase (ALP), a predictor of vascular calcification, are independently associated with CSVD remains inconclusive. The present study explored the link between levels of circulating ALP and CSVD in a Chinese population. A total of 568 participants were recruited from the healthcare center at the affiliated Zhongshan Hospital of Dalian University and the Fifth People Hospital of Dalian between January 2010 and December 2016. The subjects were divided into three groups based on the infarct and severity of white matter hyper-intensities (WMH) as categorized by brain magnetic resonance imaging (MRI) analysis and Fazekas rating scales: no/mild cerebral WMH (nm-WMH); moderate-to-severe WMH (MS-WMH); and silent lacunar infarct (SLI). The subjects were also divided into three tertiles based on circulating levels of ALP: ≤64, 65-105 and ≥106 (IU/L). Information regarding the risk factors, such as coronary artery disease, diabetes mellitus, hypertension and serum ALP level, C-reactive protein, homocysteine (HCY), and other laboratory results, were collected. The associations of ALP with WMH and SLI were evaluated using logistic regression analysis. After adjustment for vascular risk factors, subjects with MS-WMH and SLI were more likely to have ALP levels ≥106 IU/L than ≤64 IU/L. The mean circulating level of ALP was substantially increased in patients with MS-WMH or SLI compared with patients with nm-WMH. The multivariate model revealed that this significant difference remained when MS-WMH or SLI was added to the model, after adjustment for confounding factors. The circulating level of ALP was positively correlated with a high risk of silent lacunar infarct and white matter hyperintensity; important indicators of small vessel disease.

Abstract WP569: Gut Microbiota and Dementia: A Cross-Sectional Study

Background: The gut microbiota is associated with several life-threatening conditions andthus might represent a useful strategy for the prevention of dementia. However, the association between gut microbiota and dementia has not yet been fully clarified. Hypothesis: There are differences in the components of gut microbiota between demented and non-demented patients. Methods: We recruited outpatients who visited our memory clinic to participate in this study. Information on patients’ demographics, risk factors, activities of daily living was collectedand cognitive function was assessed using neuropsychological tests and brain MRI scans. Faecal samples were obtained and the gut microbiota was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, one of the most well-established and reliable 16S ribosomal RNA-based methods for classifying gut microbiota. Patients were divided into two groups, demented and non-demented. Multivariable logistic regression models were used to identify the variables independently associated with dementia. Results: We analyzed 128 eligible patients (female: 59%, mean age: 74.2 years). Silent lacunar infarcts and cerebral microbleeds were more frequently observed on MRI scans of patients with dementia. The T-RFLP analysis revealed differences in the components of gut microbiota: levels of Bacteroides (enterotype I) were decreased and other bacteria (enterotype III) were increased in demented compared with non-demented patients. Multivariable analyses showed that enterotype I (OR 0.1, 95%CI 0.02-0.4, P<0.001) and enterotype III (OR 12.7, 95%CI 3.3-65.8, P<0.001) were strongly associated with dementia, independent of the traditional dementia biomarkers. Faecal concentrations of ammonia, indole, skatole, and phenol were higher in demented compared with non-demented patients. Conclusion: Gut microbiota is an independent and strong risk factor for dementia.

Atypical phenotype of an old disease or typical phenotype of a new disease: deficiency of adenosine deaminase 2

Çakan M, Aktay-Ayaz N, Karadağ ŞG, Tahir-Turanlı E, Stafstrom K, Bainter W, Geha RS, Chou J. Atypical phenotype of an old disease or typical phenotype of a new disease: deficiency of adenosine deaminase 2. Turk J Pediatr 2019; 61: 413-417. Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder caused by mutations in CECR1 (cat eye syndrome chromosome region, canditate 1) gene, which encodes the enzyme adenosine deaminase 2 necessary for endothelial cell survival and function. The diversity of the clinical phenotypes associated with DADA2 include polyarteritis nodosa-like vasculitic features, early-onset stroke, mild to severe immunodeficiency and cytopenias. The diagnosis of the disease may be difficult due to complex clinical phenotype. Herein, we present a case of DADA2 presenting with vasculitis, amarousis fugax, gastrointestinal bleeding and silent lacunar infarct successfully treated with etanercept.

25-Hydroxy vitamin D level is associated with total MRI burden of cerebral small vessel disease in ischemic stroke patients

Background: Decreased 25-hydroxyvitamin D [25(OH)D] has been reported to be related to increased risk of cerebrovascular disease. We aimed to investigate whether an association exists between 25(OH)D levels and cerebral small vessel disease (cSVD).Method: Patients with first-ever minor ischemic stroke or transient ischemic attack were recruited prospectively during Jan 2017 to December 2017. Serum 25(OH)D levels were measured at admission in all patients. Magnetic resonance imaging (MRI) was performed to determine the presence of cSVD, including silent lacunar infarcts (SLIs), white matter lesions (WMLs), cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVs). The severity of cSVD was evaluated by total MRI cSVD burden, an ordinal score from 0 to 4. The association between the baseline 25(OH)D level and cSVD was analyzed by multiple logistic regression models.Results: Of 234 patients included, the median 25(OH)D level was 39.2 nmol/L. The proportions of patients with 0 to 4 cSVD features were 8.5%, 29.1%, 42.3%, 16.2%, and 3.8%, respectively. After adjusting for potential confounders, multiple logistic regression analysis demonstrated that patients with 25(OH)D level in its first quartile, compared with those in its fourth quartile, were more likely to have severe WMLs [odds ratio (OR), 3.31; 95% confidence interval (CI) 1.74–9.67; p = .004], severe EPVs (OR, 2.35; 95% CI 1.11–6.02, p = .046] and increasing total MRI cSVD burden (OR, 3.00; 95% CI 1.36–6.53, p = .006).Conclusions: Lower levels of 25(OH)D are associated with greater total MRI cSVD burden in ischemic stroke patients.

Hemispheric Asymmetry of White Matter Hyperintensity in Association With Lacunar Infarction.

BackgroundWhite matter hyperintensities (WMHs) are commonly asymmetric between hemispheres but for unknown reasons. We investigated asymmetric WMHs associated with lacunar infarcts.Methods and ResultsA total of 267 consecutive patients with small first‐ever supratentorial infarcts (≤20 mm) were included. None had a relevant vascular stenosis. WMH asymmetry was measured based on the hemispheric difference of a modified Scheltens scale score (≥3 defined as asymmetric). We analyzed the association of the hemispheric WMH asymmetry with old silent lacunar infarcts or acute lacunar infarcts. We compared lesion frequency maps between groups and generated t‐statistics maps. The mean age of patients was 64 years, and 63% were men. Asymmetric WMH was more than 3‐fold as frequent (P<0.001) in the group with old silent lacunar infarcts (42%, 43/102) than in the group without old silent lacunar infarcts (15%, 24/165). In patients with left hemispheric dominance of WMHs, an acute lacunar infarct was more likely to be located in the left (versus right) hemisphere (74% versus 26%, P<0.001). In patients with right hemispheric dominance of WMHs, an acute lacunar infarct was more likely to be located on the right (versus left) hemisphere (81% versus 19%, P<0.001). Mapping studies showed that the side of hemispheric dominance of WMHs was associated with acute and silent lacunes on the same side.ConclusionsThese are the first data to show that asymmetric WMHs are associated with both old silent lacunar infarcts and acute lacunar infarcts ipsilateral to the greatest WMH burden. This suggests that the hemisphere with relatively large WMHs is more vulnerable to ischemia.

Is hyperhomocysteinemia associated with the structural changes of the substantia nigra in Parkinson's disease? A two-year follow-up study

ObjectiveIt was recently found that structural changes in the substantia nigra (SN) and motor symptoms become more prominent in Parkinson's disease (PD) patients with striatal silent lacunar infarction (SSLI) than in those without SSLI. Hyperhomocysteinemia (HHCY) was an independent risk factor for SSLI in PD patients. In this follow-up study, we investigated the relationship between HHCY and structural changes of the SN in PD patients. MethodsA total of 72 untreated early PD patients without SSLI, divided into control and HHCY groups, were enrolled in this study. All participants underwent conventional MRI and diffusion kurtosis imaging (DKI) twice; at baseline and at the 2-year visit. The differences of the following variables between the two groups were analyzed: mean kurtosis (MK) values of the SN, the severity of disease, daily dosage of levodopa, and the variation of these indexes from baseline to 2-year visit. Logistic regression analysis was used to identify the relationship between HHCY and structural changes of the SN in PD patients. Results1.All variables mentioned above showed significant differences between the two groups. 2. The variation in MK values of the SN were positively correlated with the variation in the severity of disease. 3. HHCY was an independent risk factor for the variation in MK values of the SN in PD patients. ConclusionHHCY is associated with the structural changes of the SN in PD patients. As PD progresses, motor symptoms become aggravated with increased structural changes to the SN, especially in patients with HHCY.

Association Between the Serum Uric Acid Levels and Lacunar Infarcts in the Elderly.

Increasing evidence suggests that uric acid (UA) is a relevant risk factor for arteriolosclerosis and recent studies have demonstrated the positive relationship between UA concentrations and the severity of leukoaraiosis. However, the association between lacunar infarcts (LI) and UA levels has seldom been reported in the literature. The aim of our study was to assess whether serum UA levels may be related to the presence of LI. We recruited 242 patients (113 males and 129 females, aged 82.83 ± 6.49years) from our Geriatric Department for whom CAT scans (CT) were available. Clinical and laboratory data was collected. Patients CT images were examined to identify the presence, the size, the number, and the location of LI. LI without neurological symptoms were considered silent LI. Serum UA levels were found to be positively associated with the presence (p = 0.0001), the number (p = 0.001), the size (p = 0.001), and the location of LI in the basal ganglia (p = 0.0038), the deep white matter (DWM) (p < 0.0001), and the pons (p = 0.0156). A significant association was also found between UA and silent LI (p = 0.0002). The prevalence of LI increased starting from UA levels of 5.7mg/dl. Stepwise multiple regression analysis confirmed that UA was independently related with the presence, the number, the size, LI in the basal ganglia, the DWM, the pons, and with silent LI. Our study suggests a positive association between UA levels and LI, which is independent of traditional cardiovascular risk factors. This data suggests that UA plays an influential role on the physiopathology of LI and could represent a potential target to prevent cerebral microinfarcts.

Cerebral Microbleeds Are Associated With Mild Cognitive Impairment in Patients With Hypertension.

BackgroundCerebral microbleeds (CMBs) are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. The aim of this study was to determine whether CMB count and location are associated with an increased risk for mild cognitive impairment (MCI) in patients with essential hypertension without a history of transient ischemic attack or stroke.Methods and ResultsIn this cross‐sectional study, patients were prospectively enrolled from consecutive outpatients with essential hypertension 50 years and older at 3 centers in northern China. Generalized linear Poisson models were used to determine the association between the number and location of CMBs and MCI in patients with hypertension. The association of microbleeds with different cognitive domains was estimated using linear mixed models. The presence, number, and distribution of CMBs were greater in patients with hypertension who had MCI (P<0.001). The presence of any CMBs, strictly lobar CMBs, and deep or infratentorial CMBs were all related to MCI after adjusting for age, sex, education, cardiovascular risk factors, body mass index, intima‐media thickness, the presence of silent lacunar infarctions, white matter lesion grade, and brain atrophy. Furthermore, the presence of multiple microbleeds (≥5) was associated with lower Montreal Cognitive Assessment total scores and worse performance on specific domains of cognitive tests, such as global cognitive function, information processing speed, and motor speed.ConclusionsThis study suggests that the presence of and a greater number of cerebral CMBs independently correlate with MCI in patients with essential hypertension without a history of transient ischemic attack or stroke.

Association between Homocysteine and Cerebral Small Vessel Disease: A Meta-Analysis

This study aimed to evaluate whether elevated homocysteine levels is associated with risk of different subtypes of cerebral small vessel disease (CSVD) by using meta-analysis. Electronic databases were systematically searched up to April 2018 for collecting the studies reporting homocysteine levels in CSVD or CSVD subtypes. After an inclusion and exclusion criteria, the data was extracted. All data was analyzed using Stata software v.12.0 (Stata Corp LP, College Station, TX). The standardized mean difference (SMD) and 95% confidence interval (CI) were used to compare continuous variables. Eighteen studies met eligibility criteria with 5088 participants (1987 patients with CSVD and 3101 controls) included in the meta-analysis. Meta-analysis revealed that, compared with the controls group, the CSVD group had significantly higher homocysteine levels, with the SMD of .50 and 95% CI (.36-.64). Subgroup analyses suggested white matter lesion had significantly higher levels of homocysteine compared with controls (SMD = .56, 95% CI .39-.73), followed by silent brain infarction (SMD = .33, 95% CI .24-.42) and lacunar infarction (SMD = .17, 95% CI -.06 to .40). This meta-analysis found that CSVD or CSVD subtypes have a significantly higher homocysteine levels than in controls. Further prospective population-based studies are needed to longitudinally evaluate the association between homocysteine levels and progression of different CSVD subtypes.

Increased level of procalcitonin is associated with total MRI burden of cerebral small vessel disease in patients with ischemic stroke.

Procalcitonin (PCT) has been found to be associated with subclinical cerebrovascular damage. The relationship between PCT levels and cerebral small vessel disease (cSVD), especially cSVD burden, has not been fully understood. This study aimed to investigate the association between PCT levels and cSVD in patients with first-ever acute ischemic stroke or transient ischemic attack (TIA). Two hundred and seventy-eight consecutive patients were prospectively recruited during Jan 2016 to Jun 2017. Serum PCT concentrations measurement was performed after admission. The presence and burden of cSVD was determined by magnetic resonance imaging (MRI). Multivariable logistic regression was used to assess whether serum PCT levels were associated with cSVD. The median PCT level was 0.042μg/L (interquartile range, 0.025-0.065μg/L). Univariable logistic regression analysis indicated that patients with PCT level in the top quartile, compared with the lowest quartile, were more likely to have silent lacunar infarctions [odds ratio (OR), 2.266; 95% confidence interval (CI) 1.131-4.538, P=0.021], white matter lesions (OR, 1.793; 95% CI 1.029-3.574, P=0.047), high-grade enlarged perivascular spaces (OR, 8.061; 95% CI 3.599-14.055, P=0.001) and increased total MRI cSVD burden (OR, 3.743; 95% CI 1.998-7.008, P=0.002). These results persisted even after adjusting for potential confounders. This study demonstrated that elevated PCT levels might be associated with total MRI cSVD burden in patients with ischemic stroke or TIA.

P.4.a.006 - Different effects of anxiolytics phenazepam and fabomotizole on dipeptidylpeptidase-IV plasma activity in patients with anxiety disorders

Procalcitonin (PCT) has been found to be associated with subclinical cerebrovascular damage. The relationship between PCT levels and cerebral small vessel disease (cSVD), especially cSVD burden, has not been fully understood. This study aimed to investigate the association between PCT levels and cSVD in patients with first-ever acute ischemic stroke or transient ischemic attack (TIA).Two hundred and seventy-eight consecutive patients were prospectively recruited during Jan 2016 to Jun 2017. Serum PCT concentrations measurement was performed after admission. The presence and burden of cSVD was determined by magnetic resonance imaging (MRI). Multivariable logistic regression was used to assess whether serum PCT levels were associated with cSVD.The median PCT level was 0.042 μg/L (interquartile range, 0.025–0.065 μg/L). Univariable logistic regression analysis indicated that patients with PCT level in the top quartile, compared with the lowest quartile, were more likely to have silent lacunar infarctions [odds ratio (OR), 2.266; 95% confidence interval (CI) 1.131–4.538, P = 0.021], white matter lesions (OR, 1.793; 95% CI 1.029–3.574, P = 0.047), high-grade enlarged perivascular spaces (OR, 8.061; 95% CI 3.599–14.055, P = 0.001) and increased total MRI cSVD burden (OR, 3.743; 95% CI 1.998–7.008, P = 0.002). These results persisted even after adjusting for potential confounders.This study demonstrated that elevated PCT levels might be associated with total MRI cSVD burden in patients with ischemic stroke or TIA.

041Enlarged Perivascular Spaces of Subjects with Silent Lacunar Infarction from A National Longitudinal Study on Ageing

041Enlarged Perivascular Spaces of Subjects with Silent Lacunar Infarction from A National Longitudinal Study on Ageing

Subclinical hypothyroidism and risk of cerebral small vessel disease: A hospital‐based observational study

Subclinical hypothyroidism (SCH) has been associated with atherosclerosis and increased risk of ischaemic stroke. However, whether SCH is associated with cerebral small vessel disease (cSVD) remains largely unexplored. This study aimed to investigate the relationship between SCH and total cSVD burden, a composite measurement detected with magnetic resonance imaging (MRI), in patients with minor ischaemic stroke or transient ischaemic attack (TIA). This was a prospective observational cohort study conducted in a tertiary referral hospital. Subclinical hypothyroidism (SCH) was defined as with mildly or moderately increased thyroid-stimulating hormone levels (TSH, 4.5-10.0mIU/L), but with normal free thyroxine levels. Brain MRI presence of silent lacunar infarcts (LIs), white matter lesions (WMLs), cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVs) were summed to a validated scales ranging from 0 to 4 to represent the load of cSVD. The associations between SCH and cSVD were analysed by logistic regression analyses. Subclinical hypothyroidism (SCH) was identified in 43 of 229 (18.8%) patients with minor stroke or TIA. Compared with patients without SCH, those with SCH had higher risks of WMLs, CMBs and total cSVD burden. Adjustment of potential confounders did not change these associations. These findings showed that SCH might be associated with the presence of WMLs, CMBs, as well as cSVD burden in patients with minor stroke or TIA.

Relationship between obstructive sleep apnea and neuroimaging signatures of cerebral small vessel disease in community-dwelling older adults. The Atahualpa Project

Background/ObjectivesEvidence of a relationship between obstructive sleep apnea (OSA) and neuroimaging signatures of cerebral small vessel disease (SVD) is limited. The present study aimed to evaluate this association in older adults living in rural Ecuador, where small vessel disease is a major pathogenetic mechanism underlying stroke. MethodsA representative random sample of Atahualpa residents aged ≥60 years enrolled in the Atahualpa Project neuroimaging substudy underwent a single-night diagnostic polysomnography. We evaluated whether OSA associates with severity of white matter hyperintensities (WMH), silent lacunar infarctions and deep cerebral microbleeds, using multivariate models adjusted for relevant confounders. ResultsOf 351 candidates, 104 (30%) were randomly selected. Of these, 97 individuals (mean age 72.3 ± 7 years, 65% women) had adequate recordings and were included. Mean apnea/hypopnea index was 13.8 ± 14.1 episodes per hour; 27 persons (28%) had ≥15 episodes per hour and were considered to have moderate-to-severe OSA. Moderate-to-severe WMH were noticed in 25 individuals (25.8%), silent lacunar infarctions in 22 (22.7%) and deep cerebral microbleeds in 12 (12.4%). In multivariate models, OSA was associated with moderate-to-severe WMH (OR: 3.94; 95% C.I.: 1.09–14.97; p = 0.037), but not with silent lacunar infarctions (p = 0.195) or deep cerebral microbleeds (p = 0.405). A linear regression model confirmed the independent association between the apnea/hypopnea index and moderate-to-severe WMH (β: −7.14; 95% C.I.: −13.6 to −0.69; p = 0.031). ConclusionsIndividuals with moderate-to-severe OSA are almost four times more likely to have diffuse subcortical damage of vascular origin than those with none-to-mild OSA, independently of demographics and cardiovascular risk factors.