scholarly journals Quantitative Measurements of Enlarged Perivascular Spaces in the Brain are Associated with Retinal Microvascular Parameters in Older Community-Dwelling Subjects

2019 ◽  
Author(s):  
Lucia Ballerini ◽  
Sarah McGrory ◽  
Maria del C. Valdés Hernández ◽  
Ruggiero Lovreglio ◽  
Enrico Pellegrini ◽  
...  

ABSTRACTBackgroundPerivascular Spaces (PVS) become increasingly visible with advancing age on brain MRI, yet their relationship to morphological changes in the underlying microvessels remains poorly understood. Retinal and cerebral microvessels share morphological and physiological properties. We compared computationally-derived PVS morphologies with retinal vessel morphologies in older people.MethodsWe analysed data from community-dwelling individuals who underwent multimodal brain MRI and retinal fundus camera imaging at mean age 72.55 years (SD=0.71). We assessed centrum semiovale PVS computationally to determine PVS total volume and count, and mean per-subject individual PVS length, width and size. We analysed retinal images using the VAMPIRE software suite, obtaining the Central Retinal Artery and Vein Equivalents (CRVE and CRAE), Arteriole-to-Venule ratio (AVR), and fractal dimension (FD) of both eyes. We investigated associations using general linear models, adjusted for age, gender, and major vascular risk factors.ResultsIn 381 subjects with all measures, increasing total PVS volume and count were associated with decreased CRAE in the left eye (volume β=-0.170, count β=-0.184, p<0.001). No associations of PVS with CRVE were found. The PVS total volume, individual width and size increased with decreasing FD of the arterioles (a) and venules (v) of the left eye (total volume: FDa β=-0.137, FDv β=-0.139, p<0.01; width: FDa β=-0.144, FDv β=-0.158, p<0.01; size: FDa β=-0.157, FDv β=-0.162, p<0.01).ConclusionsIncrease in PVS number and size visible on MRI reflect arteriolar narrowing and lower retinal arteriole and venule branching complexity, both markers of impaired microvascular health. Computationally-derived PVS metrics may be an early indicator of failing vascular health and should be tested in longitudinal studies.

2019 ◽  
Vol 14 (5) ◽  
pp. 1865-1875 ◽  
Author(s):  
Maria del C. Valdés Hernández ◽  
Lucia Ballerini ◽  
Andreas Glatz ◽  
Susana Muñoz Maniega ◽  
Alan J. Gow ◽  
...  

Abstract Brain iron deposits (IDs) are indicative of microvessel dysfunction which may predispose to small vessel disease (SVD) brain damage and worsen cognition later in life. Visible perivascular spaces in the centrum semiovale (CSO-PVS) are SVD features linked with microvessel dysfunction. We examined possible associations of CSO-PVS volume and count with brain IDs and cognitive abilities in 700 community-dwelling individuals from the Lothian Birth Cohort 1936 who underwent detailed cognitive testing and multimodal brain MRI at mean age 72.7 years. Brain IDs were assessed automatically followed by manual editing. PVS were automatically assessed in the centrum semiovale and deep corona radiata supraventricular. General factors of overall cognitive function (g), processing speed (g-speed) and memory (g-memory) were used in the analyses. Median (IQR) volumes of IDs and CSO-PVS expressed as a percentage of intracranial volume were 0.0021 (0.011) and 0.22 (0.13)% respectively. Median count of CSO-PVS was 410 (IQR = 201). Total volumes of CSO-PVS and ID, adjusted for head size, were correlated (Spearman ρ = 0.13, p < 0.001). CSO-PVS volume, despite being correlated with all three cognitive measures, was only associated with g-memory (B = -114.5, SE = 48.35, p = 0.018) in general linear models, adjusting for age, sex, vascular risk factors, childhood intelligence and white matter hyperintensity volume. The interaction of CSO-PVS count with diabetes (B = -0.0019, SE = 0.00093, p = 0.041) and volume with age (B = 1.57, SE = 0.67, p = 0.019) were also associated with g-memory. Linear regression models did not replicate these associations. Therefore, it does not seem that CSO-PVS burden is directly associated with general cognitive ability in older age.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jose Gutierrez ◽  
Chuanhui Dong ◽  
Mitchell Elkind ◽  
Noam Alperin ◽  
Ahmet Bagci ◽  
...  

Introduction: Brain perivascular spaces (PVS) are associated with higher pulse pressures and may be imaging biomarkers of systemic arterial stiffness. We hypothesized that larger proximal arterial diameters act as effect modifiers between downstream PVS and surrogate measures of arterial stiffness. Methods: Stroke-free Northern Manhattan Study participants with brain MRI and carotid ultrasound were analyzed. Perivascular spaces were rated semi-quantitatively as ≤ 3 mm voids on axial T1 images without associated FLAIR hyperintensities. Intracranial brain arterial diameters were measured on MRA. The right common carotid artery (CCA) was assessed by high resolution B-mode ultrasound to obtain systolic and diastolic diameters. CCA stiffness was calculated as a ratio between log n transformed systolic-diastolic blood pressure and (systolic - diastolic diameter)/diastolic diameter. We created generalized linear models using and pulse pressure (PP) and CCA stiffness as predictors as independent variables and right anterior PVS score as the outcome, adjusting for demographics, risk factors, head size. Results: Among 941 participants (N=941, mean age 71 ± 9 year, 60% women, 66% Hispanic), PP was associated with PVS score (B=0.003, P=0.04) in an adjusted model. There was a statistical interaction between PP, right CCA diastolic diameter, and right intracranial arterial diameters as predictors of right anterior PVS score (P=0.03), but this interaction was not significant for posterior fossa PVS score (B=0.015, P=0.191), or when substituting right intracranial arterial diameters with the basilar artery diameter (B=-0.004, P=0.191). The association between PP (P=0.003) or carotid stiffness (P=0.002) with right anterior PVS score was greater among participants with larger right intracranial arterial and larger CCA diameters. Conclusions: Arterial stiffness is related to downstream PVS in those with larger proximal arterial diameters. These results suggest a mechanical effect of pulsatility on brain parenchyma and further studies are needed to enhance our understanding of the link between systemic hemodynamics and brain diseases such as dementia and stroke.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anette Johansson ◽  
Marie Ernsth Bravell ◽  
Eleonor I. Fransson ◽  
Sofi Fristedt

Abstract Background Home rehabilitation is a growing rehabilitation service in many countries, but scientific knowledge of its components and outcomes is still limited. The aim of this study was to investigate; 1) which changes in functioning and self-rated health could be identified in relation to a home rehabilitation program in a population of community-dwelling citizens, and 2) how socio-demographic factors, health conditions and home rehabilitation interventions were associated to change in functioning and self-rated health after the home rehabilitation program. Method The sample consisted of participants in a municipal home rehabilitation project in Sweden and consisted of 165 community-dwelling citizens. General Linear Models (ANOVA repeated measures) was used for identifying changes in rehabilitation outcomes. Logistic regressions analysis was used to investigate associations between rehabilitation outcomes and potential factors associated to outcome. Result Overall improvements in functioning and self-rated health were found after the home rehabilitation program. Higher frequencies of training sessions with occupational therapists, length of home rehabilitation, and orthopaedic conditions of upper extremities and spine as the main health condition, were associated with rehabilitation outcomes. Conclusion The result indicates that the duration of home rehabilitation interventions and intensity of occupational therapy, as well as the main medical condition may have an impact on the outcomes of home rehabilitation and needs to be considered when planning such programs. However, more research is needed to guide practice and policymaking.


2020 ◽  
pp. 1-14
Author(s):  
Jessica Mozersky ◽  
Sarah Hartz ◽  
Erin Linnenbringer ◽  
Lillie Levin ◽  
Marissa Streitz ◽  
...  

Background: Cognitively normal (CN) older adults participating in Alzheimer’s disease (AD) research increasingly ask for their research results—including genetic and neuroimaging findings—to understand their risk of developing AD dementia. AD research results are typically not returned for multiple reasons, including possible psychosocial harms of knowing one is at risk of a highly feared and untreatable disease. Objective: We developed materials that convey information about 5-year absolute risk of developing AD dementia based on research results. Methods: 20 CN older adults who received a research brain MRI result were interviewed regarding their wishes for research results to inform material development (Pilot 1). Following material development, 17 CN older adults evaluated the materials for clarity and acceptability (Pilot 2). All participants were community-dwelling older adults participating in longitudinal studies of aging at a single site. Results: Participants want information on their risk of developing AD dementia to better understand their own health, satisfy curiosity, inform family, and future planning. Some articulated concerns, but the majority wanted to know their risk despite the limitations of information. Participants found the educational materials and results report clear and acceptable, and the majority would want to know their research results after reviewing them. Conclusion: These materials will be used in a clinical study examining the psychosocial and cognitive effects of offering research results to a cohort of CN older adults. Future AD research may incorporate the return of complex risk information to CN older adults, and materials are needed to communicate this information.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012916
Author(s):  
Aline Thomas ◽  
Fabrice Crivello ◽  
Bernard Mazoyer ◽  
Stephanie Debette ◽  
Christophe Tzourio ◽  
...  

Background and Objective:Fish intake may prevent cerebrovascular disease (CVD), yet the mechanisms are unclear, especially regarding its impact on subclinical damage. Assuming that fish may have pleiotropic effect on cerebrovascular health, we investigated the association of fish intake with global CVD burden based on brain MRI markers.Methods:This cross-sectional analysis included participants from the Three-City Dijon population-based cohort (aged ≥65 years) without dementia, stroke, or history of hospitalized cardiovascular disease, who underwent brain MRI with automated assessment of white matter hyperintensities, visual detection of covert infarcts, and grading of dilated perivascular spaces. Fish intake was assessed through a frequency questionnaire and the primary outcome measure was defined as the first component of a factor analysis of mixed data applied to MRI markers. The association of fish intake with the CVD burden indicator was studied using linear regressions.Results:In total, 1,623 participants (mean age, 72.3 years; 63% women) were included. The first component of factor analysis (32.4% of explained variance) was associated with higher levels of all three MRI markers. Higher fish intake was associated with lower CVD burden. In a model adjusted for total intracranial volume, compared to participants consuming fish <1 per week, those consuming fish 2-3 and ≥4 times per week had a β = -0.19 (95% CI, -0.37; -0.01) and β = -0.30 (-0.57; -0.03) lower indicator of CVD burden, respectively (P trend <0.001). We found evidence of effect modification by age, so that the association of fish to CVD was stronger in younger participants (65-69 years) and not significant in participants aged ≥75 years. For comparison, in the younger age group, consuming fish 2-3 times a week was roughly equivalent (in opposite direction) to the effect of hypertension.Discussion:In this large population-based study, higher frequency of fish intake was associated with lower CVD burden, especially among participants younger than 75 years, suggesting a beneficial effect on brain vascular health before manifestation of overt brain disease.Classification of Evidence:This study provides Class II evidence that in individuals without stroke or dementia, higher fish intake is associated with lower subclinical CVD at MRI.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gabriel Haddad ◽  
Anthony Fontanini ◽  
Sara Bellali ◽  
Tatsuki Takakura ◽  
Yusuke Ominami ◽  
...  

Background: Enabling faster Antimicrobial Susceptibility Testing (AST) is critical, especially to detect antibiotic resistance, to provide rapid and appropriate therapy and to improve clinical outcomes. Although several standard and automated culture-based methods are available and widely used, these techniques take between 18 and 24 h to provide robust results. Faster techniques are needed to reduce the delay between test and results.Methods: Here we present a high throughput AST method using a new generation of tabletop scanning electron microscope, to evaluate bacterial ultra-structural modifications associated with susceptibilities to imipenem as a proof of concept. A total of 71 reference and clinical strains of Gram-negative bacteria were used to evaluate susceptibility toward imipenem after 30, 60, and 90 min of incubation. The length, width and electron density of bacteria were measured and compared between imipenem susceptible and resistant strains.Results: We correlated the presence of these morphological changes to the bacterial susceptibility and their absence to the bacterial resistance (e.g., Pseudomonas aeruginosa length without [2.24 ± 0.61 μm] and with [2.50 ± 0.68 μm] imipenem after 30 min [p = 3.032E-15]; Escherichia coli width without [0.92 ± 0.07 μm] and with [1.28 ± 0.19 μm] imipenem after 60 min [p = 1.242E-103]). We validated our method by a blind test on a series of 58 clinical isolates where all strains were correctly classified as susceptible or resistant toward imipenem.Conclusion: This method could be a potential tool for rapidly identifying carbapenem-resistance in Enterobacterales in clinical microbiology laboratories in &lt;2 h, allowing the empirical treatment of patients to be rapidly adjusted.


Neurology ◽  
2018 ◽  
Vol 91 (13) ◽  
pp. e1237-e1244 ◽  
Author(s):  
Shadi Yaghi ◽  
Traci M. Bartz ◽  
Richard Kronmal ◽  
Hooman Kamel ◽  
John Gottdiener ◽  
...  

ObjectiveTo determine the association left atrial diameter (LAD) and vascular brain injury on brain MRI.MethodsWe analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort of community-dwelling adults ≥65 years old. LAD was measured from 2-dimensional transthoracic echocardiograms. Among CHS participants who underwent brain MRI, we examined associations of LAD with brain infarcts and leukoaraiosis. Primary outcomes (number for analysis) were prevalent infarcts (2,327) and degree of leukoaraiosis on initial MRI (2,315). Secondary outcomes were prevalent nonlacunar infarcts (2,327), incident infarcts (939), incident nonlacunar infarcts (1,185), and degree of leukoaraiosis on follow-up MRI adjusted for initial MRI (1,158). Relative risk (RR) and linear regression models were adjusted for demographics, vascular risk factors, and potential confounders.ResultsMean age of the 2,335 participants with initial brain MRI was 72.0 ± 4.8 years; 38.7% were men; and 29.0% participants had prevalent infarcts. In multivariable, fully adjusted models, LAD was associated with prevalent infarcts (RR 1.20, 95% confidence interval [CI] 1.08–1.34) and prevalent nonlacunar infarcts (RR 1.28, 95% CI 1.06–1.54) but not with leukoaraiosis (−0.08, 95% CI −0.17 to 0.07), incident infarcts (RR 1.00, 95% CI 0.78–1.29), nonlacunar infarcts (RR 0.98, 95% CI 0.67–1.42), or worsening leukoaraiosis (−0.04, 95% CI −0.10 to 0.02).ConclusionLAD is independently associated with prevalent brain infarcts, particularly nonlacunar infarcts, but not leukoaraiosis. Larger studies are needed to determine associations with incident infarct risk and whether this risk in patients with left atrial enlargement can be reduced with anticoagulant agents.


2018 ◽  
Vol 8 (3) ◽  
pp. 207-213 ◽  
Author(s):  
Radhika Dhamija ◽  
Steven M. Weindling ◽  
Alyx B. Porter ◽  
Leland S. Hu ◽  
Christopher P. Wood ◽  
...  

BackgroundWe retrospectively reviewed the neuroimaging findings of patients with Cowden syndrome and determined their frequency in a single cohort.MethodsElectronic medical records were queried from January 1999 to January 2017 to identify patients who fit the clinical criteria for diagnosis of Cowden syndrome with or without a documentedPTENmutation. Patients with brain MRI examinations were then identified.ResultsWe retrospectively identified 44 patients with Cowden syndrome, 22 of whom had neuroimaging for review. Eleven (50%) had Lhermitte-Duclos disease, 4 (18.1%) had meningiomas, 13 (59.1%) had at least one developmental venous anomaly, 3 had cavernous malformations, 2 had evidence of dural arteriovenous fistula, 7 had increased white matter signal abnormalities relative to age (31.8%), 4 had prominent perivascular spaces, cerebellar tonsillar ectopia was present in 7 of 21 (33.3%), and 1 had cortical malformation.ConclusionsIt is important to recognize that in addition to Lhermitte-Duclos disease, other intracranial findings such as multiple venous anomalies, meningiomas, greater than expected white matter signal abnormality, prominent perivascular spaces, and cortical malformations may warrant a thorough evaluation for Cowden syndrome in the appropriate clinical setting. We further recommend that this broader spectrum of intracranial abnormalities be considered for addition to the Cowden syndrome diagnostic criteria at the time of next revision.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Andreas Charidimou ◽  
Gregoire Boulouis ◽  
Matthew Frosch ◽  
Jean-Claude Baron ◽  
Marco Pasi ◽  
...  

Introduction: The Boston criteria are used worldwide for in vivo diagnosis of cerebral amyloid angiopathy (CAA). Given substantial advances in CAA research, we aimed to update the Boston criteria and externally validate their diagnostic accuracy across the spectrum of CAA-related presentations and across international sites. Methods: As part of an International CAA Association multicenter study, we identified patients age 50 or older with potential CAA-related clinical presentations (spontaneous intracerebral hemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathologic assessment for the diagnosis of CAA. We derived Boston criteria v2.0 by selecting MRI features to optimize diagnostic specificity and sensitivity in a pre-specified derivation sample (Boston cases 1994 to 2012, n=159), then externally validated in pre-specified temporal (Boston cases 2012-2018, n=59) and geographical (non-Boston cases 2004-2018; n=123) validation samples and compared their diagnostic accuracy to the currently used modified Boston criteria. Results: Based on exploratory analyses in the derivation sample, we derived provisional criteria for probable CAA requiring presence of at least 2 strictly lobar hemorrhagic lesions (intracerebral hemorrhage, cerebral microbleed, or cortical superficial siderosis focus) or at least 1 strictly lobar hemorrhagic lesion and 1 white matter characteristic (severe degree of visible perivascular spaces in centrum semiovale or white matter hyperintensities multispot pattern). Sensitivity/specificity of the criteria were 74.8/84.6% in the derivation sample, 92.5/89.5% in the temporal validation sample, 80.2/81.5% in the geographic validation sample, and 74.5/95.0% in cases across all samples with autopsy as the diagnostic gold standard. The v2.0 criteria for probable CAA had superior accuracy to the currently modified Boston criteria (p<0.005) in the autopsied cases. Conclusion: The Boston criteria v.2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their high specificity. Validation of the criteria across independent patient settings firmly supports their adoption into clinical practice and research.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
YANPENG LIU ◽  
YIWEI XIA ◽  
XIAOXIAO WANG ◽  
YI WANG ◽  
LUMENG YANG ◽  
...  

Background and purpose: White matter hyperintensities (WMH) are common in elderly individuals and contribute to age-related cognitive dysfunction. Converging evidence indicates that WMH affect white matter (WM) microstructural integrity in WMH and their penumbra. We aimed to investigate whether this effect extends to the distal WM tracts, and to examine the association between distal WM microstructural integrity and cognitive dysfunction in community-dwelling elderly people. Methods: Brain MRI data including FLAIR and DTI sequences of 174 participants (74 ± 5 years) of the Shanghai Aging Study (SAS) were collected and analyzed. For each participant, WMH lesions were segmented automatically. Eighteen major WM tracts were reconstructed using automated quantitative tractography, and the mean diffusivity (MD) of distal WM tracts (excluding an area of 12 mm around the WMH) was calculated. Multivariable linear regression was performed. Results: A high burden of tract-specific WMH was related to a high MD of distal WM tracts in the forceps major (FMA), anterior thalamic radiations (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a high MD of distal tracts was linked to worse attention and executive function in the forceps minor (FMI), right CCG, left inferior longitudinal fasciculus (ILF), SLFP, SLFT and UNC. Conclusions: The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions farther than the penumbra and eventually might affect attention and executive function.


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