Incident Cerebral Microbleeds Research Articles

De novo appearance of cerebral microbleeds in community-dwelling older adults. Neuroimaging and clinical correlates.

Prospective studies on cerebral microbleeds (CMB) have departed from individuals who already have CMB at baseline. Therefore, main outcomes have usually been the composite of new lesions appearing on the follow-up among patients who already had CMB together with those who de novo developed CMB. Using the Atahualpa Project Cohort, we aimed to assess correlates of incident CMB in community-dwelling older adults free of CMB at baseline. Atahualpa residents aged ≥ 60years received baseline clinical interviews and a brain MRI. Those who were free of CMB at baseline and received follow-up brain MRI at the end of the study were included. Multivariate logistic and Poisson regression models were fitted to assess the association and the incidence rate ratio (IRR) of incident CMB according to clinical and neuroimaging variables. The mean age of 241 study participants was 65.6 ± 6.1years (57% women). After 6.5years of follow-up, 25 subjects (10.4%) developed incident CMB. A total of 37 CMB were noticed in these 25 patients. A parsimonious logistic regression model demonstrated an association between the Edmonton Frail Scale (EFS) and incident CMB (p = .043). Multivariate logistic regression models showed an association between WMH progression and incident CMB (p = .011). Using Poisson regression models, the IRR for WMH progression at follow-up was increased in subjects with incident CMB (p = .029). Study results show a significant relationship between the EFS, WMH progression, and incident CMB. This knowledge will allow the implementation of preventive policies to reduce incident CMB and its consequences.

Association of Arterial Spin Labeling Parameters With Cognitive Decline, Vascular Events, and Mortality in a Memory-Clinic Sample

BackgroundCognitive decline in older adults has been attributed to reduced cerebral blood flow (CBF). Recently, the spatial coefficient of variation (sCoV) of ASL has been proposed as a proxy marker of cerebrovascular insufficiency. We investigated the association between baseline ASL parameters with cognitive decline, incident cerebrovascular disease, and risk of vascular events and mortality. Design, Setting, and ParticipantsAbout 368 memory-clinic patients underwent three-annual neuropsychological assessments and brain MRI scans at baseline and follow-up. MRIs were graded for white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), cortical infarcts, and intracranial stenosis. Baseline gray (GM) and white matter (WM) CBF and GM-sCoV were obtained with ExploreASL from 2D-EPI pseudo-continuous ASL images. Cognitive assessment was done using a validated neuropsychological battery. Data on incident vascular events (heart disease, stroke, transient ischemic attack) and mortality were obtained. ResultsHigher baseline GM-sCoV was associated with decline in the memory domain over 3 years of follow-up. Furthermore, higher GM-sCoV was associated with a decline in the memory domain only in participants without dementia. Higher baseline GM-sCoV was associated with progression of WMH and incident CMBs. During a mean follow-up of 3 years, 29 (7.8%) participants developed vascular events and 18 (4.8%) died. Participants with higher baseline mean GM-sCoV were at increased risk of vascular events. ConclusionsHigher baseline GM-sCoV of ASL was associated with a decline in memory and risk of cerebrovascular disease and vascular events, suggesting that cerebrovascular insufficiency may contribute to accelerated cognitive decline and worse clinical outcomes in memory clinic participants.

The Effects of Mean of Visit-to-Visit Blood Pressure on Incident Brain Vascular Lesions and Functional-Cognitive Decline.

Cerebrovascular disease (CeVD) is an underlying cause of cognitive impairment and dementia. Hypertension is a known risk factor of CeVD, but the effects of mean of visit-to-visit blood pressure (BP) on incident CeVD and functional-cognitive decline remains unclear. To determine the association between mean of visit-to-visit BP with the incidence and progression of CeVD [white matter hyperintensities (WMH), infarcts (cortical infarcts and lacunes), cerebral microbleeds (CMBs), intracranial stenosis, and hippocampal volume] as well as functional-cognitive decline over 2 years of follow-up. 373 patients from a memory-clinic underwent BP measurements at baseline, year 1, and year 2. The mean of visit-to-visit systolic BP, diastolic BP, pulse pressure, and mean arterial pressure were calculated. Baseline and year 2 MRI scans were graded for WMH, infarcts, CMBs, intracranial stenosis, and hippocampal volume. Functional-cognitive decline was assessed using locally validated protocol. Logistic and linear regression models with odds ratios, mean difference, and 95%confidence interval were constructed to analyze associations of visit-to-visit BP on CeVD incidence and progression as well as functional-cognitive decline. Higher mean of visit-to-visit diastolic BP was associated with WMH progression. Higher tertiles of diastolic BP was associated with WMH progression and incident CMBs. There was no association between mean of visit-to-visit BP measures with incident cerebral infarcts, intracranial stenosis, change in hippocampal volume, and functional-cognitive decline. These findings suggest the possibility of hypertension-related vascular brain damage. Careful monitoring and management of BP in elderly patients is essential to reduce the incidence and progression of CeVD.

Blood-Based Cardiac Biomarkers and the Risk of Cognitive Decline, Cerebrovascular Disease, and Clinical Events.

Cardiac biomarkers, NT-proBNP (N-terminal probrain natriuretic peptide), hs-cTnT (high-sensitivity-cardiac troponin T), and GDF-15 (growth differentiation factor-15) have been proposed as important biomarkers of early vascular pathology. However, little is known of the longitudinal associations of these cardiac biomarkers with cerebrovascular disease and clinical events. We examine the association of blood-based cardiac biomarkers (NT-proBNP, hs-cTnT, and GDF-15) with cognitive decline, incident cerebrovascular disease, vascular events, and mortality. Four hundred thirty-four memory-clinic patients provided blood samples at baseline, underwent 3 annual neuropsychological assessments and brain magnetic resonance imaging scans at baseline and follow-up. NT-proBNP and hs-cTnT concentrations were measured by electrochemiluminescence immunoassay and GDF-15 by quantitative sandwich immunoassay. Baseline and follow-up magnetic resonance imagings were graded for white matter hyperintensities, lacunes, cerebral microbleeds, cortical infarcts, and intracranial stenosis. Data on incident vascular events and mortality were obtained. Patients with higher levels of NT-proBNP, hs-cTnT, and GDF-15 showed greater decline in memory domain. Additionally, hs-cTnT was associated with decline in global cognition, executive function, and visuomotor speed. Higher levels of NT-proBNP were associated with incident cerebral microbleeds and hs-cTnT with incident cortical infarcts. During a mean follow-up of 3 years, 26 (5.9%) patients died and 35 (8.1%) developed vascular events. Patients with higher levels of NTpro-BNP and hs-cTnT were at increased risk of vascular events whereas those with higher levels of NT-proBNP and GDF-15 were at risk of mortality. Higher levels of blood-based cardiac biomarkers were associated with decline in memory and risk of vascular events and mortality. Moreover, NT-proBNP and hs-cTnT were associated with incident cerebral microbleeds and cortical infarcts. Thus, these biomarkers are potentially useful in identifying patients at risk of adverse vascular events and death.

Incident cerebral microbleeds and hypertension defined by the 2017 ACC/AHA Guidelines.

BackgroundThe cut-off for hypertension was lowered to blood pressure (BP) over 130/80 mmHg in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline. Whether the new definition of hypertension remains a potent risk factor of cerebral microbleeds (CMBs) is uncertain. We aimed to analyze the relationship between the new definition of hypertension and incident CMBs in a 7-year longitudinal community study.MethodsThis study is a sub-study of the Shanghai Aging Study (SAS). A total of 317 participants without stroke or dementia were included at baseline (2009–2011), and were invited to repeated clinical examinations and cerebral magnetic resonance imaging (MRI) at follow-up (2016–2018). CMBs at baseline and follow-up were evaluated on T2*-weighted gradient recalled echo (GRE) and susceptibility-weighted angiography (SWAN) sequence of MRI. We classified baseline BP into four categories: normal BP, elevated systolic BP, stage 1 hypertension and stage 2 hypertension according to the ACC/AHA guideline. We assessed the associations between BP categories and incident CMBs by generalized linear models.ResultsA total of 159 participants (median age, 67 years) completed follow–up examinations with a mean interval of 6.9 years. Both stage 1 and stage 2 hypertension at baseline were significantly related with a higher risk of incident CMBs (IRR 2.77, 95% CI, 1.11–6.91, P=0.028; IRR 3.04, 95% CI, 1.29–7.16, P=0.011, respectively), indicating dose-response effects across BP categories. Participants with ≥5 incident CMBs or incident CMBs in the deep locations all had baseline stage 1 and 2 hypertension.ConclusionsParticipants with baseline stage 1 and stage 2 hypertension had a significantly higher risk of incident CMBs in this 7-year longitudinal community cohort.

White matter hyperintensities associated with progression of cerebral small vessel disease: a 7-year Chinese urban community study.

We aimed to explore the role of white matter hyperintensities (WMH) in progression of cerebral small vessel disease (CSVD) in an urban community in China over a period of 7 years, and to investigate associations between WMH volume (baseline and progression) and cognitive impairment. CSVD markers and neuropsychological tests at baseline and follow-up of 191 participants of the Shanghai Aging Study (SAS) were assessed. WMH volume were assessed by automatic segmentation based on U-net model. Lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (ePVS) were rated manually. Small vessel disease (SVD) score was rated as the total burden of CSVD markers. Global cognitive function and 5 main cognitive domains (memory, language, spatial construction, attention and executive function) were evaluated by neuropsychological tests. We performed multivariable linear regression and binominal logistic regression. Participants with higher baseline WMH volume developed more progression of WMH volume, increased risk of incident lacunes, incident CMBs, and ePVS progression. WMH (baseline and progression) were associated with decline of executive function. WMH were associated with progression of cerebral small vessel disease and decline of executive function in a Chinese urban community study over a period of 7 years.

Abstract WP245: New Definition of Hypertension and Incident Cerebral Microbleeds: A 7-Year Chinese Urban Community Study

Background and Purpose: Cerebral microbleeds (CMBs) are associated with recurrent stroke, dementia and mortality in the general population. Hypertension (blood pressure over 140/90 mmHg) was thought as a crucial risk factor of CMBs in the general population. However, the cutoff for diagnosis of hypertension was lowered to blood pressure over 130/80 mmHg in the 2017 American College of Cardiology / American Heart Association (ACC/AHA) guidelines. Whether the new definition of hypertension remains a potent risk factor of CMBs is questionable. We aimed to analyze the relationship between the new definition of hypertension and incident CMBs in a 7-year longitudinal community study. Methods: This study is part of the Shanghai Aging Study (SAS). 159 participants without stroke or dementia (mean age, 67.7 years) underwent repeated clinical examinations and cerebral MRI at baseline (2009-2011) and follow-up (2016-2018) with a median interval of 6.9 years. CMBs at baseline and follow-up were evaluated on T2*-GRE and SWAN sequence of MRI. We classified baseline blood pressure into four categories: normal BP, elevated systolic blood pressure, stage 1 hypertension and stage 2 hypertension according to the new criteria. We assessed the association of blood pressure categories with incident CMBs by generalized linear models. Results: Participants with incident CMBs had higher baseline systolic blood pressure (SBP) and pulse pressure (PP) than those without incident CMBs. The difference was significant in SBP (P=0.024), and marginally significant in PP (P=0.057). Both stage 1 and stage 2 hypertension were associated with a higher risk of incident CMBs (IRR=2.77, P=0.028; IRR=3.04, P=0.011, respectively). Conclusions: In this 7-year longitudinal study, participants with incident CMBs had higher SBP and PP at baseline. Stage 1 and stage 2 hypertension defined by this new criterion were associated with incident CMBs.

Abstract WMP59: White Matter Hyperintensities Play a Pivotal Role in Progression of Cerebral Small Vessel Disease: A 7-Year Chinese Urban Community Study

Objective: To explore the role of WMH in progression of CSVD in an urban community in China over a period of 7 years, and to investigate associations between WMH volume (baseline & progression) and cognitive impairment. Methods: CSVD markers and neuropsychological tests at baseline and follow-up of 191 participants of the Shanghai Aging Study (SAS) were assessed. WMH volume were assessed by automatic segmentation based on U-net model. Lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (ePVS) were rated manually. SVD score was rated as the total burden of CSVD markers. We performed multivariate linear regression and binominal logistic regression. We plotted progression of markers by baseline WMH volume in tertile. Results: Participants with higher baseline WMH volume developed more progression of WMH volume, increased risk of incident lacunes, incident CMBs, and ePVS progression. Mean change of WMH volume over 7 years was 4.27mL (0.62mL/y) for all participants, 3.21mL for participants with 1st tertile WMH volume at baseline, 4.19mL for those with 2nd tertile WMH, and 5.43mL for those with 3rd tertile WMH. Incident lacunes and incident CMBs were predominantly seen in participants with 2nd and 3rd tertile WMH. WMH (baseline & progression) were associated with decline of executive function. Conclusions: WMH play a pivotal role in progression of cerebral small vessel disease and are associated with decline of executive function in a Chinese urban community study over a period of 7 years.

Incident Cerebral Microbleeds After Intracerebral Hemorrhage.

Background and Purpose- The frequency and prognostic implications of incident cerebral microbleeds (CMB), defined as development of one or more new CMB, after intracerebral hemorrhage (ICH) is unclear. Therefore, we performed a systematic review and meta-analysis to investigate the frequency and prognostic implications of incident CMB after ICH. Methods- We searched Ovid Medline and Embase in May 2018 for longitudinal studies of adults who underwent brain magnetic resonance imaging at 2 or more times after ICH. We calculated the pooled proportion of adults with incident CMB and sought associations between incident CMB and clinical outcomes (death, recurrent ICH, or new ischemic stroke). We planned subgroup analyses to investigate clinical variables associated with incident CMB. Results- We identified 2354 publications, of which we included 4 cohort studies involving 349 patients. The pooled proportion of adults with at least one new CMB during a mean 27 months follow-up (SD 20 months) was ≈40% (95% CI, 30%-50%). In one study, as the number of incident CMB increased (0 versus 1-3 new CMB versus ≥4 new CMB) the risk of recurrent symptomatic lobar ICH increased (hazard ratio 3.0; 95% CI, 1.2-7.3). No study reported on outcomes of incident ischemic stroke or death. Conclusions- Incident CMB occurs in ≈40% of adults after ICH. The association of incident CMB with recurrent lobar ICH needs confirmation and their association with death and ischemic stroke investigation.

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

Cerebral small vessel disease (SVD) is one of the major contributors to cognitive impairment and dementia. However, data on the incidence and progression of SVD in an Asian population are lacking. The present study aims to investigate the incidence, progression, associated risk factors, and clinical relevance of SVD in a memory clinic setting. A prospective case-control study, where 346 patients underwent repeated brain MRI with a mean interval of 24.5 months, accessing white matter hyperintensities (WMH), lacunes and cerebral microbleeds (CMBs). Severity of cognitive impairment was assessed using Clinical Dementia Rating scale and change in clinical diagnosis. Data on demographics, vascular risk factors, and clinical history were collected at baseline. The prevalence of significant WMH (Fazekas ≥2) was 56.6% at baseline which progressed to 59.0% at follow-up. Overall prevalence of CMBs increased from 42.2% to 47.4% (9% new cases) and lacunes increased from 31.8% to 33.2% (2.1% new cases). Hypertension was associated with WMH progression (OR: 1.78, 95% CI: 1.01, 2.99) and increasing age was associated with incident CMBs (OR: 1.04, 95% CI: 1.01, 1.08). Moreover, the use of lipid-lowering medications decreased the incidence of lacunes (OR: 0.15, 95% CI: 0.04, 0.61). The major risk factor for incident SVD was baseline SVD lesion load. WMH progression was associated with increased severity of cognitive impairment (OR: 1.95, 95% CI: 1.16, 3.23). Vascular risk factors and baseline severity of SVD lesion load were associated with progression of SVD. Furthermore, WMH progression was linked with increased severity of cognitive impairment. Future studies should be aimed to slow cognitive deterioration by preventing SVD related brain damage by targeting vascular risk factors.

Cognitive Impact of Cerebral Small Vessel Disease Changes in Patients With Hypertension.

Hypertension is one of the principal risk factors for cerebral small vessel disease progression and cognitive impairment. We aimed to investigate how changes in cerebral small vessel disease lesions relate to cognitive decline and incident mild cognitive impairment in hypertensive patients. Data were obtained from the ISSYS cohort (Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study)-a longitudinal population-based study on hypertensive patients aged 50 to 70 years without dementia and stroke at baseline. Patients underwent a brain magnetic resonance imaging, a cognitive screening test, and cognitive diagnosis (normal aging or mild cognitive impairment) at baseline and follow-up. We evaluated incident lacunar infarcts and cerebral microbleeds. Changes in the periventricular and deep white matter hyperintensities (WMH) were qualitatively defined as none, minor, or marked. We followed up 345 patients (median age, 65 [61-68]; 55.4% men) for 3.95 (3.83-4.34) years. Incident mild cognitive impairment was diagnosed in 9.1% of the sample. Considering the progression of cerebral small vessel disease, the prevalence of incident infarcts was 6.1% and that of incident cerebral microbleeds was 5.5%; progression of periventricular WMH was 22% and that of deep WMH was 48%. Patients with marked progression of periventricular WMH showed a significant decrease in global cognition compared with patients without progression (adjusted mean [SE], -0.519 [0.176] versus 0.057 [0.044], respectively; P value=0.004) and a higher risk of incident mild cognitive impairment (OR, 6.184; 95% CI, 1.506-25.370; P value=0.011). Therefore, our results indicate that hypertensive patients with progression of periventricular WMH have higher odds of cognitive impairment, even in the early stages of cognitive decline.

Incident Cerebral Microbleeds Detected by Susceptibility Weight-Imaging Help to Identify Patients with Mild Cognitive Impairment Progressing to Alzheimer's Disease.

The relationship between cerebral microbleeds (CMB) and Alzheimer's disease (AD) has not yet been clearly determined, particularly with susceptibility weight-imaging (SWI). To evaluate the SWI sequence using 3T MRI for the detection of CMB, and its ability to differentiate elderly control subjects (CS), stable mild cognitive impairment patients (MCI-s), MCI patients progressing to AD (MCI-p), and AD patients. It was a prospective, monocentric, observational study that took place in Toulouse, France. Participants were 65 years and older, enrolled in three groups: CS, MCI, and AD. Based on the longitudinal analysis of cognitive decline, MCI subjects were retrospectively classified as MCI-s or MCI-p. Each patient had a 4-year follow-up with MRI at baseline (MRI#1) and during the fourth year (MRI#3). CMB were counted on native SWI images juxtaposed to minIP reformatted images. 150 patients were enrolled: 48 CS, 25 MCI-s, 18 MCI-p, 59 AD. At MRI#1 and at MRI#3, there was no significant difference in the prevalence of CMB between groups (p = 0.75 and p = 0.87). In the MCI-p + AD group, significantly more subjects had≥4 incident CMB compared to the CS + MCI-s group (p = 0.016). In the MCI-p + AD group, the prevalence of patients with >4 CMB was significantly higher at MRI#3 than at MRI#1 (p = 0.008). Using SWI, AD and MCI-p patients had developed significantly more new CMB than CS and MCI-s patients during the follow-up. Incident CMB might be suggested as a potential imaging marker of AD progression.

Synergistic effects of longitudinal amyloid and vascular changes on lobar microbleeds

To determine whether amyloid and hypertensive cerebral small vessel disease (hCSVD) changes synergistically affect the progression of lobar microbleeds in patients with subcortical vascular mild cognitive impairment (svMCI). Among 72 patients with svMCI who underwent brain MRI and [11C] Pittsburgh compound B (PiB)-PET, 52 (72.2%) completed the third year of follow-up. These patients were evaluated by annual neuropsychological testing, brain MRI, and follow-up PiB-PET. Over 3 years, 31 of 52 patients (59.6%) had incident cerebral microbleeds (CMBs) in the lobar and deep regions. Both baseline and longitudinal changes in lacune numbers were associated with increased numbers of lobar and deep microbleeds, while baseline and longitudinal changes in PiB uptake ratio were associated only with the progression of lobar microbleeds, especially in the temporal, parietal, and occipital areas. Regional white matter hyperintensity severity was also associated with regional lobar CMBs in the parietal and occipital regions. There were interactive effects between baseline and longitudinal lacune number and PiB retention on lobar microbleed progression. Increased lobar, but not deep, CMBs were associated with decreased scores in the digit span backward task and Rey-Osterrieth Complex Figure Test. Our findings suggest that amyloid-related pathology and hCSVD have synergistic effects on the progression of lobar microbleeds, providing new clinical insight into the interaction between amyloid burden and hCSVD on CMB progression and cognitive decline with implications for developing effective prevention strategies.

Incident Cerebral Microbleeds in a Cohort of Intracerebral Hemorrhage.

We aimed to identify prognostic and associated factors of incident cerebral microbleeds (CMBs) in intracerebral hemorrhage (ICH) survivors. Observational prospective cohort of 168 ICH survivors who underwent 1.5T magnetic resonance imaging at ICH onset and during follow-up (median scan interval, 3.4; interquartile range, 1.4-4.7) years. We used logistic regression adjusted for age, sex, and scan interval. Analyses were stratified according to the index ICH location (58 lobar ICH, 103 nonlobar ICH, excluding patients with multiple or unclassifiable ICH). Eighty-nine (53%) patients had CMBs at ICH onset, and 80 (48%) exhibited incident CMBs during follow-up. Predictors of incident CMBs at ICH onset were ≥1 CMBs (adjusted odds ratio [aOR], 2.27; 95% confidence interval [CI], 1.18-4.35), old radiological macrohemorrhage (aOR, 6.78; 95% CI, 2.76-16.68), and CMBs in mixed location (aOR, 3.73; 95% CI, 1.67-8.31). When stratifying by ICH location, incident CMBs were associated in nonlobar ICH with incident lacunes (aOR, 2.86; 95% CI, 1.04-7.85) and with the use of antiplatelet agents (aOR, 2.89; 95% CI, 1.14-7.32). In lobar ICH, incident CMBs were associated with incident radiological macrohemorrhage (aOR, 9.76; 95% CI, 1.07-88.77). Prognostic and associated factors of incident CMBs differed according to the index ICH location. Whereas in lobar ICH, incident CMBs were associated with hemorrhagic biomarkers, in nonlobar ICH, ischemic burden also increased. CMBs may be interesting biomarkers to monitor in randomized trials on restarting antithrombotic drugs after ICH.

Oily fish consumption is inversely correlated with cerebral microbleeds in community-dwelling older adults: results from the Atahualpa Project.

Oily fish is a major dietary source of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). These nutrients improve endothelial dysfunction, reduce β-amyloid induced damage of neurovascular units, and might prevent the occurrence of cerebral microbleeds. However, this relationship has not been investigated so far. To evaluate the association between oily fish intake and cerebral microbleeds in a population of frequent fish consumers living in coastal Ecuador. Cerebral microbleeds were identified by gradient-echo MRI and oily fish consumption was calculated in community-dwellers aged ≥60years enrolled in the Atahualpa Project. The association between cerebral microbleeds and fish servings was examined in regression models adjusted for relevant confounders. A predictive model was constructed using quintiles of fish servings to take into account the non-linearity in the relationship. Out of 311 eligible individuals, 293 (94%) were enrolled. Cerebral microbleeds were recognized in 37 (13%) individuals. Mean fish consumption was 8.8±5.4 servings per week (ω-3 PUFAs estimates: 10.2±7.1g). Multivariate analysis showed an inverse relationship between cerebral microbleeds and fish consumption (p<0.001). Predictive margins of CMB were higher for individuals in the lowest (≤4.3) than for those in the highest (≥13.1) quintile of fish servings (17.4 vs 2.3%, p<0.001). This study shows a lower cerebral microbleed presence among older adults eating large amounts of oily fish (13 servings per week, equivalent to about 15g of ω-3 PUFAs). These high requirements can be more readily accomplished in other populations by taking fish oil preparations. Longitudinal studies are warranted to assess whether these interventions reduce incident cerebral microbleeds in high-risk individuals.

Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study.

Age and high blood pressure are major risk factors for cerebral microbleeds (CMBs). However, the underlying mechanisms remain unclear and arterial stiffness may be important. We investigated whether carotid arterial stiffness is associated with incidence and location of CMBs. In the prospective, population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik study, 2512 participants aged 66 to 93 years underwent a baseline brain MRI examination and carotid ultrasound in 2002 to 2006 and returned for a repeat brain MRI in 2007 to 2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain, distensibility coefficient, and Young elastic modulus. Modified Poisson regression was applied to relate carotid arterial stiffness parameters to CMB incidence. During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex, and follow-up interval, arterial stiffness measures were associated with incident CMBs (risk ratio per SD decrease in carotid arterial strain, 1.11 [95% confidence interval, 1.01-1.21]; per SD decrease in natural log-transformed distensibility coefficient, 1.14 [1.05-1.24]; and per SD increase in natural log-transformed Young elastic modulus, 1.13 [1.04-1.23]). These measures were also significantly associated with incident deep CMBs (1.18 [1.02-1.37]; 1.24 [1.08-1.42]; and 1.23 [1.07-1.42]) but not with lobar CMBs. When further adjusted for blood pressure and other baseline vascular risk factors, carotid plaque, prevalent CMBs, subcortical infarcts, and white matter hyperintensities, the associations persisted. Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially in a deep location attributable to hypertension.

Risk Factors Associated With Incident Cerebral Microbleeds According to Location in Older People: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.

The spatial distribution of cerebral microbleeds (CMBs), which are asymptomatic precursors of intracerebral hemorrhage, reflects specific underlying microvascular abnormalities of cerebral amyloid angiopathy (lobar structures) and hypertensive vasculopathy (deep brain structures). Relatively little is known about the occurrence of and modifiable risk factors for developing CMBs, especially in a lobar location, in the general population of older people. To investigate whether lifestyle and lipid factors predict new CMBs in relation to their anatomic location. We enrolled 2635 individuals aged 66 to 93 years from the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study in a brain imaging study. Participants underwent a baseline magnetic resonance imaging (MRI) examination of the brain from September 1, 2002, through February 28, 2006, and returned for a second MRI examination from April 1, 2007, through September 30, 2011. Lifestyle and lipid factors assessed at baseline included smoking, alcohol consumption, body mass index, and serum levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides. Incident CMBs detected on MRIs, which were further categorized as exclusively lobar or as deep. During a mean follow-up of 5.2 years, 486 people (18.4%) developed new CMBs, of whom 308 had lobar CMBs only and 178 had deep CMBs. In the multivariate logarithm-binomial regression model adjusted for baseline cardiovascular risk factors, including blood pressure, antihypertensive use, prevalent CMBs, and markers of cerebral ischemic small-vessel disease, heavy alcohol consumption (vs light to moderate consumption; relative risk [RR], 2.94 [95% CI, 1.23-7.01]) was associated with incident CMBs in a deep location. Baseline underweight (vs normal weight; RR, 2.41 [95% CI, 1.21-4.80]), current smoking (RR, 1.47 [95% CI, 1.11-1.94]), an elevated serum level of high-density lipoprotein cholesterol (RR per 1-SD increase, 1.13 [95% CI, 1.02-1.25]), and a decreased triglyceride level (RR per 1-SD decrease in natural logarithm-transformed triglyceride level, 1.17 [95% CI, 1.03-1.33]) were significantly associated with an increased risk for lobar CMBs exclusively but not for deep CMBs. Lifestyle and lipid risk profiles for CMBs were similar to those for symptomatic intracerebral hemorrhage and differed for lobar and deep CMBs. Modification of these risk factors could have the potential to prevent new-onset CMBs, particularly those occurring in a lobar location.

Retinal Microvascular Signs and Age-related Macular Degeneration are Associated with Incident Cerebral Microbleeds according to Location in Older People: the AGES-Reykjavik Study (I1-1A)

Retinal Microvascular Signs and Age-related Macular Degeneration are Associated with Incident Cerebral Microbleeds according to Location in Older People: the AGES-Reykjavik Study (I1-1A)

Retinal Microvascular Signs and Age-related Macular Degeneration are Associated with Incident Cerebral Microbleeds according to Location in Older People: the AGES-Reykjavik Study (S45.005)

Retinal Microvascular Signs and Age-related Macular Degeneration are Associated with Incident Cerebral Microbleeds according to Location in Older People: the AGES-Reykjavik Study (S45.005)

Abstract MP90: Carotid Arterial Stiffness is Associated with An Increased Risk of Incident Cerebral Microbleeds in Older People: the Age, Gene/Environment Susceptibility-Reykjavik Study

Introduction: Cerebral microbleeds (CMBs) resulting from cerebral amyloid angiopathy are predominantly located in lobar regions, whereas those from hypertension are in deep and infratentorial regions. Although age and high blood pressure are major risk factors for CMBs, the underlying mechanisms remain unclear; arterial stiffness may be important. Hypothesis: We hypothesized that carotid arterial stiffness, would be associated with incident CMBs. Given the spatial distributions of the underlying arteriopathies in which hypertensive arteriopathy typically affects the small perforating end-arteries of the deep structures, we further hypothesized that the associations would be more robust for deep CMBs attributed to hypertensive arteriopathy. Methods: In the prospective, population-based Age, Gene/Environment Susceptibility-Reykjavik Study, 2,512 participants aged 66-97 years underwent a baseline brain MRI examination and carotid ultrasound in 2002-2006, and returned for a repeat brain MRI in 2007-2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain (CAS), distensibility coefficient (DC) and Young’s elastic modulus (YEM). Log-binomial regression was applied to relate carotid arterial stiffness parameters to CMBs incidence. Results: During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex and brain MRI interval, all arterial stiffness parameters were each significantly associated with incident CMBs (Risk ratio [RR] per SD decrease in CAS, 1.11 [95%CI, 1.02-1.21]; RR per SD decrease in natural log-transformed DC, 1.14[1.05-1.23]; RR per SD decrease in natural log-transformed YEM, 1.13[1.04-1.22]) and deep CMBs (RR, 1.17[1.00-1.36]; 1.24[1.07-1.43]; 1.22[1.06-1.41] respectively) but not with lobar CMBs. When further adjusted for baseline vascular risk factors including blood pressure and use of blood pressure lowering drugs, the presence of carotid plaque, prevalent CMBs, subcortical infarcts and white matter hyperintensities, the associations persisted. Conclusion: Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially those occuring in a deep location.