scholarly journals Aging, inflammation and depressive behavior: a review

2015 ◽  
Vol 6 (2) ◽  
pp. 67-80 ◽  
Author(s):  
Adriana Uzoni ◽  
Ciobanu Ovidiu ◽  
Elena Raluca Sandu ◽  
Ana Maria Buga ◽  
Aurel Popa-Wagner
Keyword(s):  
Risk Factors ◽  
Molecular Mechanisms ◽  
Small Vessel Disease ◽  
Cerebrovascular Disorders ◽  
Cerebral Small Vessel Disease ◽  
Pathophysiological Mechanism ◽  
Vessel Disease ◽  
Cerebrovascular Events ◽  
Cerebral Insult ◽  
Cns Lesions

One of the most common co-morbidities of cerebrovascular disorders is neuroinflammation, a hallmark and decisive contributor to many central nervous system (CNS) diseases. Although neuropathological conditions differ in etiology and in the way in which the inflammatory response is mounted, cellular and molecular mechanisms of neuroinflammation are probably similar in aging, hypertension, depression and cognitive impairment or after cerebral insult such as stroke. Moreover, a number of highly prevalent risk factors such as hypertension, diabetes and atherosclerosis are increasingly understood to act as “silent contributors” to neuroinflammation – not only establishing the condition as a central pathophysiological mechanism, but also constantly fuelling it. Mild, but continuous neuroinflammation can provide the ground for disorders such as cerebral small vessel disease (cSVD) and subsequent dementia. Acute neuroinflammation, often in the context of traumatic or ischemic CNS lesions, aggravates the acute damage and can lead to depression, post-stroke dementia and neurodegeneration. All of these sequelae impair recovery and provide the ground for further cerebrovascular events.

Abstract TP407: Effects of Remote Ischemic Conditioning on Cerebral Small Vessel Disease Outcomes

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yuan Wang ◽  
Haiqing Song ◽  
Kai Dong ◽  
Ran Meng ◽  
Shuying Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Flow Velocity ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Vascular Risk Factors ◽  
Control Group ◽  
Vascular Risk ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Vessel Disease

Objective: To evaluate the preliminary efficacy of remote ischemic conditioning (RIC) on patients with cerebral small vessel disease (SVD). Methods: Thirty patients diagnosed with symptomatic SVD within 30 days of onset were enrolled in this prospectively randomized controlled study for 1 year. All patients received routine medical treatment including treating vascular risk factors according to the guideline. Patients in the experimental group (n=14) were administered 5 cycles consisting of ischemia followed by reperfusion for 5 minutes on bilateral upper limbs twice daily for 1 year. Those in the control group (n=16) underwent sham ischemia-reperfusion cycles. Primary outcome was the change of cognitive function measured by mini-mental state examination (MMSE) and montreal cognitive assessment scale (MoCA), and secondary outcomes were changes of plasma biomarkers, cerebral hemodynamic parameters measured by vascular ultrasound and brain lesions measured by MRI FLAIR both at baseline and at the end of 1 year visit. Results: Compared with patients in the control group, patients in the RIC group had higher flow velocity (FV), and lower pulsatility index (PI), but without statistical difference. Patients in the RIC group had improvement in visuospatial and executive abilities (3.86±1.03 vs. 4.43±0.85, p=0.026), reduced plasma triglyceride (1.60±0.74 vs. 1.25±0.38, p=0.019), low density lipoprotein (2.89±0.81 vs. 2.26±0.67, p=0.003) and homocysteine (15.66±10.11 vs. 13.66±9.80 p=0.017). Similarly in the RIC group, the diastolic flow velocity (DFV) of middle cerebral artery (MCA) (right: 33.93±7.67 vs. 36.93±6.12, p=0.032; left: 33.93±7.67 vs. 36.93± 6.12, p=0.032) and the mean flow velocity (MFV) of left MCA (35.00±5.04 vs. 39.50±5.59, p=0.003) increased, and the PI of MCA (right: 1.11±0.19 vs. 1.02±0.14 p=0.030; left: 1.10±0.22 vs. 0.99±0.14, p=0.037) decreased. Conclusion: RIC appears to be potentially effective for improving cognition, enhancing cerebral perfusion, and modifying vascular risk factors in SVD patients. Further studies focusing on long-term neurological outcomes and potential mechanisms underlying RIC on SVD patients are needed.

Abstract 224: Increased Total Homocysteine Levels Are Associated With the Risk of Dementia Independently of Cerebral Small-vessel Disease

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Kaori Miwa ◽  
Shuhei Okazaki ◽  
Yoshiki Yagita ◽  
Manabu Sakaguchi ◽  
Hideki Mochizuki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Small Vessel Disease ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Mri Findings ◽  
Vessel Disease ◽  
Cerebrovascular Events ◽  
Multivariable Analyses ◽  
Total Homocysteine

Objectives: Increased serum total homocysteine (tHcy) levels have been associated with not only vascular injury but also dementia. However, given an association between Hcy and vascular injury, such as cerebral small-vessel disease (SVD) or renal impairment, to what extent Hcy would impact future dementia beyond these confouders is unknown. We assessed the predictive value of tHcy levels with the risk of dementia in patients with vascular risk factors, when controlling for the MRI-findings and renal imapirment. Methods: Within a Japanese cohort of partients with vascular risk factors in an observational study from 2001, we evaluated the association between tHcy levels at baseline, defined as a continuous variable (per 1 μmol/L) and as a categorical variable (the tertile of tHcy), the prevalence of MRI-findings, and incident all-cause dementia during follow-up. Baseline brain MRI was used to determine SVD (lacuna, white matter hyperintensities and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy). Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOEε4 allele, educational level, cerebrovascular events, estimated glomerular filtration rate (eGFR), vascular risk factors, and MRI-findings. Results: Of the 643 subjects (mean:67.2±8.4years, male:59%, 12.9±2.6years of schooling), in multivariable analyses adjusted for age, sex, hypertension, cerebrovascular events, eGFR, and intima-media thickness, the highest tHcy tertile (vs lowest) were associated with lacuna, CMBs and strictly deep CMBs, respectively. During the mean 7.3-year follow-up (range:3-13), 47 incident dementia patients (Alzheimer’s disease:24; vascular dementia:18; mixed-type:3; other:2) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, eGFR, and MRI-findings, tHcy level or the highest tertile of tHcy for all-cause dementia remained significant, respectively (relative risk [RR]1.09: p=0.02, RR;2.59: p=0.021). Conclusions: Our results provide additional evidence of Hcy that leads to increased susceptibility to the risk of dementia, suggesting that this association may be mediated by independent mechanisms.

scholarly journals A population neuroscience approach to the study of cerebral small vessel disease in midlife and late life: an invited review

2018 ◽  
Vol 314 (6) ◽  
pp. H1117-H1136 ◽  
Author(s):  
Dana R. Jorgensen ◽  
C. Elizabeth Shaaban ◽  
Clayton A. Wiley ◽  
Peter J. Gianaros ◽  
Joseph Mettenburg ◽  
...  
Keyword(s):  
Risk Factors ◽  
Small Vessel Disease ◽  
Later Life ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cross Sectional ◽  
Vessel Disease ◽  
Age Related ◽  
Cerebral Microvasculature ◽  
Study Designs

Aging in later life engenders numerous changes to the cerebral microvasculature. Such changes can remain clinically silent but are associated with greater risk for negative health outcomes over time. Knowledge is limited about the pathogenesis, prevention, and treatment of potentially detrimental changes in the cerebral microvasculature that occur with advancing age. In this review, we summarize literature on aging of the cerebral microvasculature, and we propose a conceptual framework to fill existing research gaps and advance future work on this heterogeneous phenomenon. We propose that the major gaps in this area are attributable to an incomplete characterization of cerebrovascular pathology, the populations being studied, and the temporality of exposure to risk factors. Specifically, currently available measures of age-related cerebral microvasculature changes are indirect, primarily related to parenchymal damage rather than direct quantification of small vessel damage, limiting the understanding of cerebral small vessel disease (cSVD) itself. Moreover, studies seldom account for variability in the health-related conditions or interactions with risk factors, which are likely determinants of cSVD pathogenesis. Finally, study designs are predominantly cross-sectional and/or have relied on single time point measures, leaving no clear evidence of time trajectories of risk factors or of change in cerebral microvasculature. We argue that more resources should be invested in 1) developing methodological approaches and basic science models to better understand the pathogenic and etiological nature of age-related brain microvascular diseases and 2) implementing state-of-the-science population study designs that account for the temporal evolution of cerebral microvascular changes in diverse populations across the lifespan.

scholarly journals Cerebral small vessel disease, cardiovascular risk factors, and future walking speed in old age: a population-based cohort study

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Emerald G. Heiland ◽  
Anna-Karin Welmer ◽  
Grégoria Kalpouzos ◽  
Anna Laveskog ◽  
Rui Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Cardiovascular Risk ◽  
Cognitive Function ◽  
Walking Speed ◽  
Small Vessel Disease ◽  
Population Based ◽  
Cerebral Small Vessel Disease ◽  
Vessel Disease

Abstract Background The purpose of this study was to examine the associations between combined and individual cerebral small vessel disease (cSVD) markers on future walking speed over 9 years; and to explore whether these associations varied by the presence of cardiovascular risk factors (CRFs). Methods This population-based cohort study included 331 adults, aged ≥60 years, without limitation in walking speed (≥0.8 m/s). At baseline, cSVD markers, including white matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS), were assessed on magnetic resonance imaging. The modifiable CRFs (physical inactivity, heavy alcohol consumption, smoking, hypertension, high total cholesterol, diabetes, and overweight/obese) were combined into a score. The association between baseline cSVD markers and the decline in walking speed was examined using linear mixed-effects models, whereas Cox proportional hazards models were used to estimate the association with walking speed limitation (defined as < 0.8 m/s) over the follow-up. Results Over the follow-up period, 76 (23.0%) persons developed walking speed limitation. Participants in the highest tertile of the combined cSVD marker score had a hazard ratio (HR) of 3.78 (95% confidence interval [CI] 1.70-8.45) for walking speed limitation compared with people in the lowest score tertile, even after adjusting for socio-demographics, CRFs, cognitive function, and chronic conditions. When investigating the cSVD markers individually, having the highest burden of WMH was associated with a significantly faster decline in walking speed (β coefficient − 0.020; 95% CI -0.035-0.004) and a greater HR of walking speed limitation (HR 2.78; 95% CI 1.31-5.89) compared with having the lowest WMH burden. Similar results were obtained for the highest tertile of PVS (HR 2.13; 95% CI 1.04-4.36). Lacunes were associated with walking speed limitation, but only in men. Having ≥4 CRFs and high WMH volume simultaneously, showed a greater risk of walking speed limitation compared with having ≥4 CRFs and low WMH burden. CRFs did not modify the associations between lacunes or PVS and walking speed. Conclusions Combined cSVD markers strongly predict walking speed limitation in healthy older adults, independent of cognitive function, with WMH and PVS being the strongest contributors. Improving cardiovascular health may help to mitigate the negative effects of WMH on future walking speed.

scholarly journals Endothelial CXCL5 negatively regulates myelination and repair after white matter stroke

2019 ◽  
Author(s):  
Guanxi Xiao ◽  
Rosie Kumar ◽  
Yutaro Komuro ◽  
Jasmine Burguet ◽  
Visesha Kakarla ◽  
...  
Keyword(s):  
Risk Factors ◽  
Endothelial Cells ◽  
White Matter ◽  
Signaling Pathway ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Oligodendrocyte Progenitor ◽  
Vessel Disease ◽  
Cerebral Endothelial Cells

AbstractCerebral small vessel disease and resulting white matter pathologies are worsened by cardiovascular risk factors including obesity. The molecular changes in cerebral endothelial cells caused by chronic cerebrovascular risk factors remain unknown. We developed a novel approach for molecular profiling of chronically injured cerebral endothelial cells using cell-specific translating ribosome affinity purification (RiboTag) with RNA-seq in Tie2-Cre:RiboTag mice. We used this approach to identify the transcriptome of white matter endothelial cells after the onset of diet-induced obesity (DIO). DIO induces an IL-17B signaling pathway that acts on the cerebral endothelia through IL-17Rb to increase levels of both circulating CXCL5 and local endothelial expression of CXCL5 in both the DIO mouse model and in humans with imaging or pathologic evidence of cerebral small vessel disease. In the white matter, endothelial CXCL5 acts as a chemoattractant and promotes the association of oligodendrocyte progenitor cells (OPCs) with cerebral endothelia increasing vessel-associated OPC cell number and triggers OPC gene expression programs regulating migration and chemokine receptor activation. Targeted blockade of IL-17B with peripheral antibody administration reduced the population of vessel-associated OPCs by reducing endothelial CXCL5 expression. CXCL5-mediated sequestration of OPCs to white matter vasculature impairs OPC differentiation after a focal white matter ischemic lesion. DIO promotes a unique white matter endothelial-to-oligodendrocyte progenitor cell signaling pathway that compromises brain repair after stroke.

scholarly journals Risk factor profile of different clinical manifestations of cerebral small vessel disease - data from SHEF-CSVD Study

2017 ◽  
Author(s):  
J. Staszewski ◽  
E. Skrobowska ◽  
R. Piusińska-Macoch ◽  
B. Brodacki ◽  
A. Stępień
Keyword(s):  
Risk Factors ◽  
Uric Acid ◽  
Risk Factor ◽  
Cerebrovascular Disease ◽  
Fasting Glucose ◽  
Small Vessel Disease ◽  
Clinical Manifestations ◽  
Cerebral Small Vessel Disease ◽  
Vascular Risk ◽  
Vessel Disease

AbstractBACKGROUNDLittle is known of the mechanisms of cerebral small vessel disease (CSVD). Both atherosclerosis or non-atherosclerotic diffuse arteriopathy are involved.METHODSA single-center, prospective, case-control study was performed in consecutive patients with different CSVD manifestations. The study group consisted of 205 patients: 52 with lacunar stroke (LS), 20 with subcortical hemorrhagic stroke (HS), 50 with vascular dementia (VaD), 28 with vascular parkinsonism (VaP) and 55 controls (CG) free of cerebrovascular disease but with high vascular risk.RESULTSPatients with CSVD had significantly higher prevalence of vascular risk factors including hypertension, diabetes mellitus, polymetabolic syndrome and chronic kidney disease. Patients with CSVD had also significantly higher fasting blood glucose, homocysteine, fibrinogen, systolic blood pressure, IMT values and lower eGFR, albumin and HDL levels. After adjustment for age and sex, low eGFR, albumin and high levels of uric acid and fibrinogen were associated with all CSVD groups, elevated fasting glucose was related to LS and HS. In the multivariate analysiss, the independent predictors for CSVD were female sex, low albumin, high fibrinogen, fasting glucose and uric acid. Patients with LS had significantly higher IMT values comparing to other CSVD groups, patients with VaP had a trend towards higher homocysteine levels.CONCLUSIONRisk factor profile for CSVD as a whole differs from subjects with proatherogenic profile without history of cerebrovascular disease. Our results support the concept that CSVD is not homogeneous, and that unique risk factors profiles exist for different clinical manifestations of the disease.

Risk Factors for and Clinical Relevance of Incident and Progression of Cerebral Small Vessel Disease Markers in an Asian Memory Clinic Population

2019 ◽  
Vol 67 (4) ◽  
pp. 1209-1219 ◽  
Author(s):  
Bibek Gyanwali ◽  
Muhammad Amin Shaik ◽  
Boon Yeow Tan ◽  
Narayanaswamy Venketasubramanian ◽  
Christopher Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Relevance ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Memory Clinic ◽  
Vessel Disease ◽  
Disease Markers ◽  
Clinic Population

scholarly journals Cerebral Small Vessel Disease, Risk Factors, and Cognition in Tenants of Precarious Housing

Stroke ◽  
2020 ◽  
Vol 51 (11) ◽  
pp. 3271-3278
Author(s):  
Lily W. Zhou ◽  
William J. Panenka ◽  
Ghadeer Al-Momen ◽  
Kristina M. Gicas ◽  
Allen E. Thornton ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Risk Factors ◽  
White Matter ◽  
Odds Ratio ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Resonance Imaging ◽  
Vessel Disease

Background and Purpose: We aim to describe the burden, characteristics, and cognitive associations of cerebral small vessel disease in a Canadian sample living with multimorbidity in precarious housing. Methods: Participants received T1, T2-fluid-attenuated inversion recovery, and susceptibility-weighted imaging 3T magnetic resonance imaging sequences and comprehensive clinical, laboratory, and cognitive assessments. Cerebral small vessel disease burden was characterized using a modified Small Vessel Disease (mSVD) score. One point each was given for moderate-severe white matter hyperintensities, ≥1 cerebral microbleeds, and ≥1 lacune. Multivariable regression explored associations between mSVD score, risk factors, and cognitive performance. Results: Median age of the 228 participants (77% male) was 44.7 years (range, 23.3–63.2). In n=188 participants with consistent good quality magnetic resonance imaging sequences, mSVD scores were 0 (n=127, 68%), 1 (n=50, 27%), and 2 (n=11, 6%). Overall, one-third had an mSVD ≥1 n=61 (32%); this proportion was unchanged when adding participants with missing sequences n=72/228 (32%). The most prevalent feature was white matter hyperintensities 53/218 (24%) then cerebral microbleed 16/191 (8%) and lacunes 16/228 (7%). Older age (odds ratio, 1.10 [95% CI, 1.05–1.15], P <0.001), higher diastolic blood pressure (odds ratio, 1.05 [95% CI, 1.01–1.09], P =0.008), and a history of injection drug use (odds ratio, 3.13 [95% CI, 1.07–9.16], P =0.037) had significant independent associations with a mSVD score of ≥1 in multivariable analysis. mSVD ≥1 was associated with lower performance on tests of verbal memory, sustained attention, and decision-making, contributing 4% to 5% of the variance in each cognitive domain. Conclusions: The 32% prevalence of cerebral small vessel disease in this young, socially marginalized cohort was higher than expected for age and was associated with poorer cognitive performance.

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