Yi-Cheng Zhu

Headache, migraine, and structural brain lesions and function: population based Epidemiology of Vascular Ageing-MRI study

Objective To evaluate the association of overall and specific headaches with volume of white matter hyperintensities, brain infarcts, and cognition. Design Population based, cross sectional study. Setting Epidemiology of Vascular Ageing study, Nantes, France. Participants 780 participants (mean age 69, 58.5% women) with detailed headache assessment. Main outcome measures Brain scans were evaluated for volume of white matter hyperintensities (by fully automated imaging processing) and for classification of infarcts (by visual reading with a standardised assessment grid). Cognitive function was assessed by a battery of tests including the mini-mental state examination. Results 163 (20.9%) participants reported a history of severe headache and 116 had migraine, of whom 17 (14.7%) reported aura symptoms. An association was found between any history of severe headache and increasing volume of white matter hyperintensities. The adjusted odds ratio of being in the highest third for total volume of white matter hyperintensities was 2.0 (95% confidence interval 1.3 to 3.1, P for trend 0.002) for participants with any history of severe headache when compared with participants without severe headache being in the lowest third. The association pattern was similar for all headache types. Migraine with aura was the only headache type strongly associated with volume of deep white matter hyperintensities (highest third odds ratio 12.4, 1.6 to 99.4, P for trend 0.005) and with brain infarcts (3.4, 1.2 to 9.3). The location of infarcts was predominantly outside the cerebellum and brain stem. Evidence was lacking for cognitive impairment for any headache type with or without brain lesions. Conclusions In this population based study, any history of severe headache was associated with an increased volume of white matter hyperintensities. Migraine with aura was the only headache type associated with brain infarcts. Evidence that headache of any type by itself or in combination with brain lesions was associated with cognitive impairment was lacking.

Severity of Dilated Virchow-Robin Spaces Is Associated With Age, Blood Pressure, and MRI Markers of Small Vessel Disease A Population-Based Study

Background and Purpose— Little is known about the risk factors of dilated Virchow-Robin spaces (dVRS) and their relation with other markers of brain small vessel disease. We investigated both issues in a large population-based sample of elderly individuals. Methods— Severity of dVRS was semiquantitatively graded in both white matter and basal ganglia using high-resolution 3-dimensional MRI images taken from 1818 stroke- and dementia-free subjects enrolled in the Three-City Dijon MRI study. Multinomial logistic regression models were used to model the association of cardiovascular risk factors, APOE genotype, brain atrophy, and MRI markers of small vessel disease with the degree of dVRS. Results— Severity of dVRS was found to be strongly associated with age in both basal ganglia (degree 4 versus 1: OR, 2.1; 95% CI, 1.4 to 3.2) and white matter (OR, 1.5; 95% CI, 1.2 to 1.9). The proportion of hypertensive subjects increased with the degrees of dVRS in both basal ganglia (P=0.02) and white matter (P=0.048). Men presented a higher risk of severe dVRS in basal ganglia than women, particularly degree 4 (OR, 6.0; 95% CI, 1.8 to 19.8). The degree of dVRS was associated with the volume of white matter hyperintensities and the prevalence of lacunes, but not with brain atrophy. Conclusion— In this large cohort study of elderly subjects, the degree of dVRS appears independently associated with age, hypertension, volume of white matter hyperintensities, and lacunar infarctions. dVRS should be considered as another MRI marker of cerebral small vessel disease in the elderly with regional variations in their severity.

White matter lesions volume and motor performances in the elderly

To investigate the cross‐sectional and longitudinal associations between performance‐based measures of motor function and volume of white matter lesions (WMLs), and to examine the influence of the localization of these lesions.

Silent Brain Infarcts A Review of MRI Diagnostic Criteria

Background and Purpose— Silent brain infarcts (SBIs) have been recognized as common lesions in elderly subjects and their diagnosis relies on brain imaging. In this study, we aimed to evaluate the different MRI parameters and criteria used for their evaluation in the literature to better understand the variation across studies and related limitations. Method— Original MRI studies of SBI performed in human populations and reported in the English literature were reviewed. Analyses were restricted to population-based studies or studies in which at least 50 subjects with SBI were detected. The MRI parameters as well as the MRI criteria of SBI (size, signal characteristics, and criteria for differentiation of dilated Virchow-Robin spaces) were described and analyzed. Result— Magnetic field strength, slice thickness, and gap between slices greatly varied among the 45 articles included in this review. The MRI definition of SBI was inconsistent across studies. In half of them, SBI was defined as hypointense on T1 and hyperintense on T2-weighted images. Exclusion criteria for dilated Virchow-Robin spaces were used only in 7 studies. Conclusions— The variation in MRI characteristics and diagnostic criteria for SBI represent a major limitation for interpretation and comparison of data between studies. Efforts are needed to reach unified imaging criteria for SBI.

Large-vessel correlates of cerebral small-vessel disease

Objective: Our aim was to investigate the relationship of carotid structure and function with MRI markers of cerebral ischemic small-vessel disease. Methods: The study comprised 1,800 participants (aged 72.5 ± 4.1 years, 59.4% women) from the 3C-Dijon Study, a population-based, prospective cohort study, who had undergone quantitative brain MRI and carotid ultrasound. We used multivariable logistic and linear regression adjusted for age, sex, and vascular risk factors. Results: Presence of carotid plaque and increasing carotid lumen diameter (but not common carotid artery intima-media thickness) were associated with higher prevalence of lacunar infarcts: odds ratio (OR) = 1.60 (95% confidence interval [CI]: 1.09–2.35), p = 0.02 and OR = 1.24 (95% CI: 1.02–1.50), p = 0.03 (by SD increase). Carotid plaque was also associated with large white matter hyperintensity volume (WMHV) (age-specific top quartile of WMHV distribution): OR = 1.32 (95% CI: 1.04–1.67), p = 0.02, independently of vascular risk factors. Increasing Young elastic modulus and higher circumferential wall stress, reflecting augmented carotid stiffness, were associated with increasing WMHV (effect estimate [β] ± standard error: 0.0003 ± 0.0001, p = 0.024; β ± standard error: 0.005 ± 0.002, p = 0.008). Large WMHV was also associated with increasing Young elastic modulus (OR = 1.22 [95% CI: 1.04–1.42], p = 0.01) and with decreasing distensibility coefficient (OR = 0.83 [95% CI: 0.69–0.99], p = 0.04), independently of vascular risk factors. Associations of carotid lumen diameter with lacunar infarcts and of carotid stiffness markers with WMHV were independent of carotid plaque. Conclusions: In addition to and independently of carotid plaque, increasing carotid lumen diameter and markers of carotid stiffness were associated with increasing prevalence of lacunar infarcts and increasing WMHV, respectively.

Distribution of white matter hyperintensity in cerebral hemorrhage and healthy aging

We compared the severity of white matter T2-hyperintensities (WMH) in the frontal lobe and occipital lobe using a visual MRI score in 102 patients with lobar intracerebral hemorrhage (ICH) diagnosed with possible or probable cerebral amyloid angiopathy (CAA), 99 patients with hypertension-related deep ICH, and 159 normal elderly subjects from a population-based cohort. The frontal-occipital (FO) gradient was used to describe the difference in the severity of WMH between the frontal lobe and occipital lobe. A higher proportion of subjects with obvious occipital dominant WMH (FO gradient ≤−2) was found among patients with lobar ICH than among healthy elderly subjects (FO gradientxa0≤−2: 13.7 vs. 5.7%, pxa0=xa00.03). Subjects with obvious occipital dominant WMH were more likely to have more WMH (pxa0=xa00.0006) and a significantly higher prevalence of the apolipoprotein E ε4 allele (45.8% vs. 19.4%, pxa0=xa00.04) than those who had obvious frontal dominant WMH. This finding is consistent with the relative predilection of CAA for posterior brain regions, and suggests that white matter lesions may preferentially occur in areas of greatest vascular pathology.

Joint effect of white matter lesions and hippocampal volumes on severity of cognitive decline: the 3C-Dijon MRI study.

Several brain magnetic resonance imaging (MRI) changes are observed in older individuals including white matter lesions (WML), silent brain infarcts (SBI), and cerebral atrophy. Few studies, however, have assessed the combined association of these changes on the severity of future cognitive decline. In the prospective population-based 3C-Dijon MRI study, 1701 non-demented participants aged 65 to 80 years at entry had a brain MRI. Information on WML, hippocampal volumes, SBI presence, and brain parenchymal fraction were obtained. At 4-year follow-up, participants were screened for cognitive decline and dementia. Severity of cognitive decline was defined as none, moderate, or severe calculated from neuropsychological test performance change. The relation between brain MRI markers and longitudinal change in cognition was studied using polytomous logistic regression and multiple linear regression models controlling for potential confounders. Two-by-two interactions were tested including with the apolipoprotein E genotype. At follow-up, 46 participants showed severe cognitive deterioration and 224 participants showed moderate cognitive deterioration. In multivariable analyses, risk of severe cognitive deterioration as well as the cognitive decline rate were significantly increased in participants with higher WML volume (p< 0.01) and smaller hippocampal volume (p< 0.01). The results suggested that WML and hippocampal volumes had a cumulative effect on the future level of cognitive decline. The APOE genotype was found to be an effect modifier of this association. Vascular brain changes and degenerative processes coexist in normal older individuals. The co-occurrence of degenerative and non-degenerative pathologies could strongly affect the course of dementia expression.

Implementation of a Structured Guideline–Based Program for the Secondary Prevention of Ischemic Stroke in China

Background and Purpose— High rates of ischemic stroke and poor adherence to secondary prevention measures are observed in the Chinese population. Methods— We used a national, multicenter, cluster-randomized controlled trial in which 47 hospitals were randomized to either a structured care program group (n=23) or a usual care group (n=24). The structured care program consisted of a specialist-administered, guideline-recommended pharmaceutical treatment and a lifestyle modification algorithm associated with written and Internet-accessed educational material for patients for the secondary prevention of ischemic stroke. The primary efficacy outcome was the proportion of patients who adhered to the recommended measures at 12-month postdischarge. This trial is registered with ClinicalTrial.gov (NCT00664846). Results— At 12 months, 1287 (72.1%) patients in the Standard Medical Management in Secondary Prevention of Ischemic Stroke in China (SMART) group and 1430 (72%) patients in the usual care group had completed the 12-month follow-up (P=0.342). Compared with the usual care group, those in the SMART group showed higher adherence to statins (56% versus 33%; P=0.006) but no difference in adherence to antiplatelet (81% versus 75%; P=0.088), antihypertensive (67% versus 69%; P=0.661), or diabetes mellitus drugs (73% versus 67%; P=0.297). No significant difference in the composite end point (new-onset ischemic stroke, hemorrhagic stroke, acute coronary syndrome, and all-cause death) was observed (3.56% versus 3.59%; P=0.921). Conclusions— The implementation of a program to improve adherence to secondary ischemic stroke prevention efforts in China is feasible, but these programs had only a limited impact on adherence and no impact on 1-year outcomes. Further development of a structured program to reduce vascular events after stroke is needed. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00664846.

Plasma lipids and cerebral small vessel disease

Objectives: We examined the cross-sectional association between lipid fractions and 2 MRI markers of cerebral small vessel disease, white matter hyperintensity volume (WMHV) and lacunes, representing powerful predictors of stroke and dementia. Methods: The study sample comprised 2,608 participants from the 3C-Dijon Study (n = 1,842) and the Epidemiology of Vascular Aging Study (EVA) (n = 766), 2 large French population-based cohorts (72.8 ± 4.1 and 68.9 ± 3.0 years; 60.1% and 58.4% women, respectively). Analyses were performed separately in each study and combined using inverse variance meta-analysis. Lipid fractions (triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol) were studied as continuous variables. WMHV was studied both in a continuous and dichotomous manner, the latter reflecting the age-specific top quartile of WMHV (EXT-WMHV). Analyses were adjusted for age and sex. Results: Increasing triglycerides were associated with larger WMHV in the 3C-Dijon Study (β ± SE = 0.0882 ± 0.0302, p = 0.0035), in the EVA Study (β ± SE = 0.1062 ± 0.0461, p = 0.021), and in the combined analysis (β ± SE = 0.0936 ± 0.0252, p = 0.0002) and with higher frequency of lacunes in the 3C-Dijon Study (odds ratio [OR] = 1.65 [95% confidence interval 1.10–2.48], p = 0.015), in the EVA Study (OR = 1.58 [95% confidence interval 0.93–2.70], p = 0.09), and in the combined analysis (OR = 1.63 [95% confidence interval 1.18–2.25], p = 0.003). Associations were attenuated but maintained after adjusting for other vascular risk factors or for inflammatory markers. Associations were present and in the same direction both in participants taking and those not taking lipid-lowering drugs but tended to be stronger in the former for EXT-WMHV. Increasing low-density lipoprotein cholesterol tended to be associated with a decreased frequency and severity of all MRI markers of cerebral small vessel disease in both studies. Conclusions: Increasing triglycerides but not other lipid fractions were associated with MRI markers of cerebral small vessel disease in older community persons.

Abdominal obesity and lower gray matter volume: a Mendelian randomization study

We investigated the relationship of anthropometric markers of obesity with quantitative magnetic resonance imaging markers of brain aging, including measures of total brain volume (TBV), gray matter volume (GMV), hippocampal volume, white matter hyperintensity volume (WMHV), and brain infarcts, and examined causality using Mendelian randomization (MR). Analyses were performed in 1779 individuals (60.4% women, 72.8 ± 4.1 years of age) from the 3C-Dijon population-based cohort study (N = 1555 for the MR). Larger waist-to-hip-ratio (WHR) and waist circumference (WC) were associated with lower TBV (p = 0.0001 and p = 0.005), and lower GMV (p = 0.0008 and p = 0.003), independently of age, gender, body mass index (BMI), and vascular risk factors. Higher BMI, WC, and WHR were associated with larger WMHV and WC with brain infarcts, before adjusting for vascular risk factors only. We used MR to investigate the inverse relationship between WHR and GMV. One valid instrumental variable was available in women only (rs6905288), which was associated with GMV (p = 0.015). Age and BMI-adjusted effect estimates from the MR analysis confirmed the inverse association between GMV and WHR and are in favor of a causal association.