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

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.

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Low carotid endothelial shear stress associated with cerebral small vessel disease in an older population: A subgroup analysis of a population-based prospective cohort study

Atherosclerosis ◽

10.1016/j.atherosclerosis.2019.07.006 ◽

2019 ◽

Vol 288 ◽

pp. 42-50 ◽

Cited By ~ 2

Author(s):

Yali Chen ◽

Huapeng Yu ◽

Jizheng Zhu ◽

Hua Zhang ◽

Yingxin Zhao ◽

...

Keyword(s):

Shear Stress ◽

Cohort Study ◽

Prospective Cohort Study ◽

Subgroup Analysis ◽

Prospective Cohort ◽

Small Vessel Disease ◽

Population Based ◽

Cerebral Small Vessel Disease ◽

Vessel Disease ◽

Endothelial Shear Stress

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Prevalence and Risk Factors of Cerebral Small Vessel Disease in a Chinese Population-Based Sample

Journal of Stroke ◽

10.5853/jos.2017.02110 ◽

2018 ◽

Vol 20 (2) ◽

pp. 239-246 ◽

Cited By ~ 22

Author(s):

Fei Han ◽

Fei-Fei Zhai ◽

Quan Wang ◽

Li-Xin Zhou ◽

Jun Ni ◽

...

Keyword(s):

Risk Factors ◽

Chinese Population ◽

Small Vessel Disease ◽

Population Based ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease

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Increased Risk for Cerebral Small Vessel Disease is Associated with Quantitative Susceptibility Mapping in HIV Infected and Uninfected Individuals

10.1101/2021.03.13.435243 ◽

2021 ◽

Author(s):

Kyle Douglass Murray ◽

Md. Nasir Uddin ◽

Madalina E Tivarus ◽

Bogachan Sahin ◽

Henry Z Wang ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Brain Tissue ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Susceptibility Mapping ◽

Risk Scores ◽

Quantitative Susceptibility Mapping ◽

Vessel Disease

The aim of this study was to assess in the context of cerebral small vessel disease (CSVD), cardiovascular risk factors and white matter hyperintensities (WMHs) were associated with brain tissue susceptibility as measured by quantitative susceptibility mapping (QSM). Given that CSVD is diagnosed by the presence of lacunar strokes, periventricular and deep WMHs, increased perivascular spaces, and microbleeds, we expected that QSM could capture changes in brain tissue due to underlying CSVD pathology. We compared a cohort of 101 HIV-infected individuals (mean age (SD) = 53.2 (10.9) years) with mild to moderate cardiovascular risk scores, as measured by the Reynold's risk score, to 102 age-matched controls (mean age (SD) = 50.3 (15.7) years) with similar Reynold scores. We performed brain MRI to assess CSVD burden by acquiring 3D T1-MPRAGE, 3D FLAIR, 2D T2-TSE, and mGRE for QSM. We found that signs of CSVD are significantly higher in individuals with HIV-infection compared to controls and that WMH volumes are significantly correlated with age and cardiovascular risk scores. Regional QSM was associated with cardiovascular risk factors, age, sex, and WMH volumes but not HIV status. These results suggest that QSM may be an early imaging marker reflective of alterations in brain microcirculation.

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Predictors for intra cranial haemorrhage in frail elderly patients with frequent falls using antithrombotic medication

European Heart Journal ◽

10.1093/eurheartj/ehab724.0549 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

L.A.R Zwart ◽

J.J Walgers ◽

R.L.C Vogels ◽

T Germans ◽

S Simsek ◽

...

Keyword(s):

Risk Factors ◽

Elderly Patients ◽

Major Bleeding ◽

Small Vessel Disease ◽

Vitamin K Antagonists ◽

Cerebral Small Vessel Disease ◽

Bleeding Events ◽

Vessel Disease ◽

Major Bleeding Events

Abstract Background Physicians can be reluctant to prescribe antithrombotic agents in frail elderly patients with frequent falls due to the fear for severe bleeding, mainly for intracranial haemorrhage (ICH). Presently, there is only a limited amount of inconclusive data available on the topic. Purpose Identification of risk factors for ICH within a cohort of geriatric patients with repeated falls. Methods All patients of 65 years of age and older with repeated falls at our day clinic were eligible. If an MRI of the brain was performed as part of the assessment, patients were included in this analysis. Baseline characteristics including medical, functional, and cognitive state were collected, a Frailty Index (FI) was calculated [1,2]. Cerebral small vessel disease was described and evaluated as proposed in a position paper in 2013 [3]. Follow-up data concerning major bleeding events were retrieved from the electronic medical files. Odds ratios (OR) with confidence intervals (CI) were calculated. Results 670 patients were eligible; an MRI was performed in 486 patients. The average age was 80 years, 50% was severely frail at the time of inclusion. 83 patients (17%) used OAC (mainly Vitamin K antagonists prescribed for atrial fibrillation), 165 patients (34%) used anti platelet agents (APA), 1 patient used both OAC and APA. In total, 29 major bleeding events (MB) occurred, of which 13 were ICH. Among patients using OAC, 8 MB occurred, of which 2 were ICH. The patient with both OAC and APA did not experience a bleeding event. Well known risk factors for ICH such as hypertension, diabetes mellitus and cognitive impairment were not predictive for ICH in this cohort, nor were the use APA (OR 0.86, 95% CI 0.26–2.84), or vitamin K antagonists (OR 0.88, 95% CI 0.19–4.05). However, a composite factor of using either APA or OAC, heightened the risk for MB (OR 3.24, 95% CI 1.35–7.74), but not for ICH (OR 0.83, 95% 0.27–2.49). Of cerebral small vessel disease, predictive factors for ICH were the presence of lacunes (OR 3.81, 95% CI 1.25–11.56), and relevant white matter hyperintensities (WMH) (defined as a Fazekas score of 2 or more) (OR 11.3, 95% CI 1.45–87.3). Furthermore, cognitive decline defined as an MMSE score of ≤26 heightened the risk of MB (OR 2.28, 95% CI 1.05–4.96). The low number of ICH did not allow for a multivariate analysis. Conclusion This analysis has several important findings. First, despite the long follow up of a cohort of severely frail patients that frequently fall, a low number of MB and ICH was observed. Second, well known risk factors for MB do not seem predictive of ICH in this cohort of very elderly patients. Finally, cognitive decline was predictive for MB, and WMH and lacunes were predictive for ICH. Adding cognitive screening and brain imaging to the diagnostic work up of patients with an indication for OAC could be of value when assessing the future risk for major bleeding events. FUNDunding Acknowledgement Type of funding sources: None.

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Total Cerebral Small Vessel Disease Score and Anthropometric Indices: A Population-Based Study in Older Adults of Amerindian Ancestry

European Neurology ◽

10.1159/000517915 ◽

2021 ◽

pp. 1-4

Author(s):

Oscar H. Del Brutto ◽

Robertino M. Mera

Keyword(s):

Older Adults ◽

Small Vessel Disease ◽

Brain Magnetic Resonance Imaging ◽

Population Based ◽

Cerebral Small Vessel Disease ◽

The Body ◽

Small Vessel ◽

Population Based Study ◽

Vessel Disease ◽

Ordinal Logistic Regression Model

A total of 590 older adults of Amerindian ancestry living in rural Ecuador received anthropometric measurements and a brain magnetic resonance imaging to estimate the total cerebral small vessel disease (cSVD) score. A fully adjusted ordinal logistic regression model, with categories of the total cSVD score as the dependent variable, disclosed significant associations between the waist circumference, the waist-to-hip, and the waist-to-height ratios – but not the body mass index (BMI) – and the cSVD burden. Indices of abdominal obesity may better correlate with severity of cSVD than the BMI in Amerindians. Phenotypic characteristics of this population may account for these results.

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Cerebral small vessel disease is related to disturbed 24-h activity rhythms: a population-based study

European Journal of Neurology ◽

10.1111/ene.12775 ◽

2015 ◽

Vol 22 (11) ◽

pp. 1482-1487 ◽

Cited By ~ 16

Author(s):

L. A. Zuurbier ◽

M. A. Ikram ◽

A. I. Luik ◽

A. Hofman ◽

E. J. W. Van Someren ◽

...

Keyword(s):

Small Vessel Disease ◽

Population Based ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Population Based Study ◽

Activity Rhythms ◽

Vessel Disease

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Gender Inequalities in Diagnostic Inertia around the Three Most Prevalent Cardiovascular Risk Studies: Protocol for a Population-Based Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18084054 ◽

2021 ◽

Vol 18 (8) ◽

pp. 4054

Author(s):

Concepción Carratala-Munuera ◽

Adriana Lopez-Pineda ◽

Domingo Orozco-Beltran ◽

Jose A. Quesada ◽

Jose L. Alfonso-Sanchez ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Health Care ◽

Cohort Study ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Disease Incidence ◽

Population Based ◽

Gender Inequalities ◽

Primary Health Care Centers

Evidence shows that objectives for detecting and controlling cardiovascular risk factors are not being effectively met, and moreover, outcomes differ between men and women. This study will assess the gender-related differences in diagnostic inertia around the three most prevalent cardiovascular risk factors: dyslipidemia, arterial hypertension, and diabetes mellitus, and to evaluate the consequences on cardiovascular disease incidence. This is an epidemiological and cohort study. Eligible patients will be adults who presented to public primary health care centers in a Spanish region from 2008 to 2011, with hypertension, dyslipidemia, or/and diabetes and without cardiovascular disease. Participants’ electronic health records will be used to collect the study variables in a window of six months from inclusion. Diagnostic inertia of hypertension, dyslipidemia, and/or diabetes is defined as the registry of abnormal diagnostic parameters—but no diagnosis—on the person’s health record. The cohort will be followed from the date of inclusion until the end of 2019. Outcomes will be cardiovascular events, defined as hospital admission due to ischemic cardiopathy, stroke, and death from any cause. The results of this study could inform actions to rectify the structure, organization and training of health care teams in order to correct the inequality.

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

Stroke ◽

10.1161/str.48.suppl_1.tp407 ◽

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.

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