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Background: Lacunes, a characteristic feature of cerebral small vessel disease (CSVD), are critical public health concerns, especially in the aging population. Traditional neuroimaging techniques often fall short in early lacune detection, prompting the need for more precise predictive models. Methods: In this retrospective study, 587 patients from the Neurology Department of the Affiliated Hospital of Hebei University who underwent cranial MRI were assessed. A nomogram for predicting lacune incidence was developed using LASSO regression and binary logistic regression analysis for variable selection. The nomogram's performance was quantitatively assessed using AUC-ROC, calibration plots, and decision curve analysis (DCA) in both training (n = 412) and testing (n = 175) cohorts. Results: Independent predictors identified included age, gender, history of stroke, carotid atherosclerosis, hypertension, creatinine, and homocysteine levels. The nomogram showed an AUC-ROC of 0.814 (95% CI: 0.791-0.870) for the training set and 0.805 (95% CI: 0.782-0.843) for the testing set. Calibration and DCA corroborated the model's clinical value. Conclusion: This study introduces a clinically useful nomogram, derived from binary logistic regression, that significantly enhances the prediction of lacunes in patients undergoing brain MRI for various indications, potentially advancing early diagnosis and intervention. While promising, its retrospective design and single-center context are limitations that warrant further research, including multi-center validation.

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Cerebral small vessel disease (CSVD) is a spectrum of disorders that affect small arterioles, venules, cortical and leptomeningeal vessels, perivascular spaces, and the integrity of neurovascular unit, blood brain barrier, and surrounding glia and neurons. CSVD is an important cause of lacunar ischemic stroke and sporadic hemorrhagic stroke, as well as dementia-which will constitute some of the most substantive population and public health challenges over the next century. This article provides an overview of updated pathophysiologic frameworks of CSVD; discusses common and underappreciated clinical and neuroimaging manifestations of CSVD; and reviews emerging genetic risk factors linked to sporadic CSVD.

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BACKGROUND: Cerebral small vessel disease (SVD) has previously been associated with worse stroke outcome, vascular dementia, and specific post-stroke cognitive deficits. The underlying causal mechanisms of these associations are not yet fully understood. We investigated whether a relationship between SVD and certain stroke aetiologies or a specific stroke lesion anatomy provides a potential explanation. METHODS: In a retrospective observational study, we examined 859 patients with first-ever, non-SVD anterior circulation ischemic stroke (age = 69.0±15.2). We evaluated MRI imaging markers to assess an SVD burden score and mapped stroke lesions on diffusion-weighted MRI. We investigated the association of SVD burden with i) stroke aetiology, and ii) lesion anatomy using topographical statistical mapping. RESULTS: With increasing SVD burden, stroke of cardioembolic aetiology was more frequent (ρ = 0.175; 95 %-CI = 0.103;0.244), whereas cervical artery dissection (ρ = -0.143; 95 %-CI = -0.198;-0.087) and a patent foramen ovale (ρ = -0.165; 95 %-CI = -0.220;-0.104) were less frequent stroke etiologies. However, no significant associations between SVD burden and stroke aetiology remained after additionally controlling for age (all p>0.125). Lesion-symptom-mapping and Bayesian statistics showed that SVD burden was not associated with a specific stroke lesion anatomy or size. CONCLUSIONS: In patients with a high burden of SVD, non-SVD stroke is more likely to be caused by cardioembolic aetiology. The common risk factor of advanced age may link both pathologies and explain some of the existing associations between SVD and stroke. The SVD burden is not related to a specific stroke lesion location.

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INTRODUCTION: Arterial stiffness may have a significant impact on the development of cerebral small vessel disease (cSVD). PATIENTS AND METHODS: We obtained pulse wave velocity (24-h PWV) by means of ambulatory blood pressure monitoring (ABPM) in patients with a recent small subcortical infarct (RSSI). Patients with known cardiac or arterial embolic sources were excluded. Lacunes, microbleeds, white matter hyperintensities and enlarged perivascular spaces at baseline were assessed in a brain MRI and included in a cSVD score. A follow-up MRI was obtained 2 years later and assessed for the appearance of new lacunes or microbleeds. We constructed both unadjusted and adjusted models, and subsequently selected the optimal models based on the area under the curve (AUC) of the predicted probabilities. RESULTS: Ninety-two patients (mean age 67.04 years, 69.6% men) were evaluated and 25 had new lacunes or microbleeds during follow-up. There was a strong correlation between 24-h PWV and age (r = 0.942, p < 0.001). cSVD was associated with new lacunes or microbleeds when adjusted by age, 24-h PWV, NT-proBNP and hypercholesterolemia (OR 2.453, CI95% 1.381-4.358). The models exhibiting the highest discrimination, as indicated by their area under the curve (AUC) values, were as follows: 1 (AUC 0.854) - Age, cSVD score, 24-h PWV, Hypercholesterolemia; 2 (AUC 0.852) - cSVD score, 24-h PWV, Hypercholesterolemia; and 3 (AUC 0.843) - Age, cSVD score, Hypercholesterolemia. CONCLUSIONS: cSVD score is a stronger predictor for cSVD progression than age or hemodynamic parameters in patients with a RSSI.

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Imaging markers of cerebral small vessel disease provide valuable information on brain health, but their manual assessment is time-consuming and hampered by substantial intra- and interrater variability. Automated rating may benefit biomedical research, as well as clinical assessment, but diagnostic reliability of existing algorithms is unknown. Here, we present the results of the VAscular Lesions DetectiOn and Segmentation (Where is VALDO?) challenge that was run as a satellite event at the international conference on Medical Image Computing and Computer Aided Intervention (MICCAI) 2021. This challenge aimed to promote the development of methods for automated detection and segmentation of small and sparse imaging markers of cerebral small vessel disease, namely enlarged perivascular spaces (EPVS) (Task 1), cerebral microbleeds (Task 2) and lacunes of presumed vascular origin (Task 3) while leveraging weak and noisy labels. Overall, 12 teams participated in the challenge proposing solutions for one or more tasks (4 for Task 1-EPVS, 9 for Task 2-Microbleeds and 6 for Task 3-Lacunes). Multi-cohort data was used in both training and evaluation. Results showed a large variability in performance both across teams and across tasks, with promising results notably for Task 1-EPVS and Task 2-Microbleeds and not practically useful results yet for Task 3-Lacunes. It also highlighted the performance inconsistency across cases that may deter use at an individual level, while still proving useful at a population level.

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BACKGROUND: Growing interest surrounds perivascular spaces (PVS) as a clinical biomarker of brain dysfunction given their association with cerebrovascular risk factors and disease. Neuroimaging techniques allowing quick and reliable quantification are being developed, but, in practice, they require optimisation as their limits of validity are usually unspecified. NEW METHOD: We evaluate modifications and alternatives to a state-of-the-art (SOTA) PVS segmentation method that uses a vesselness filter to enhance PVS discrimination, followed by thresholding of its response, applied to brain magnetic resonance images (MRI) from patients with sporadic small vessel disease acquired at 3 T. RESULTS: The method is robust against inter-observer differences in threshold selection, but separate thresholds for each region of interest (i.e., basal ganglia, centrum semiovale, and midbrain) are required. Noise needs to be assessed prior to selecting these thresholds, as effect of noise and imaging artefacts can be mitigated with a careful optimisation of these thresholds. PVS segmentation from T1-weighted images alone, misses small PVS, therefore, underestimates PVS count, may overestimate individual PVS volume especially in the basal ganglia, and is susceptible to the inclusion of calcified vessels and mineral deposits. Visual analyses indicated the incomplete and fragmented detection of long and thin PVS as the primary cause of errors, with the Frangi filter coping better than the Jerman filter. COMPARISON WITH EXISTING METHODS: Limits of validity to a SOTA PVS segmentation method applied to 3 T MRI with confounding pathology are given. CONCLUSIONS: Evidence presented reinforces the STRIVE-2 recommendation of using T2-weighted images for PVS assessment wherever possible. The Frangi filter is recommended for PVS segmentation from MRI, offering robust output against variations in threshold selection and pathology presentation.

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BACKGROUND: This study explored the risk factors, neuroimaging features, and prognostic implications of nonhypertensive white matter hyperintensity (WMH) in patients with acute ischemic stroke and transient ischemic attack. METHODS AND RESULTS: We included 2283 patients with hypertension and 1003 without from a pool of 10 602. Associations of moderate-to-severe WMH with known risk factors, functional outcome, and a composite of recurrent stroke, myocardial infarction, and all-cause mortality were evaluated. A subset of 351 patients without hypertension and age- and sex-matched pairs with hypertension and moderate-to-severe WMH was created for a detailed topographic examination of WMH, lacunes, and microbleeds. Approximately 35% of patients without hypertension and 65% of patients with hypertensive stroke exhibited moderate-to-severe WMH. WMH was associated with age, female sex, and previous stroke, irrespective of hypertension. In patients without hypertension, WMH was associated with initial systolic blood pressure and was more common in the anterior temporal region. In patients with hypertension, WMH was associated with small vessel occlusion as a stroke mechanism and was more frequent in the periventricular region near the posterior horn of the lateral ventricle. The higher prevalence of occipital microbleeds in patients without hypertension and deep subcortical lacunes in patients with hypertension were also observed. Associations of moderate-to-severe WMH with 3-month functional outcome and 1-year cumulative incidence of the composite outcome were significant (both P<0.01), although the latter lost significance after adjustments. The associations between WMH and outcomes were consistent across hypertensive status. CONCLUSIONS: One-third of patients without hypertension with stroke have moderate-to-severe WMH. The pathogenesis of WMH may differ between patients without and with hypertension, but its impact on outcome appears similar.

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Perivascular spaces (PVS) and their enlargement (EPVS) have been gaining interest as EPVS can be visualized non-invasively by magnetic resonance imaging (MRI) when viewing T-2-weighted images. EPVS are most commonly observed in the regions of the basal ganglia and the centrum semiovale; however, they have also been identified in the frontal cortex and hippocampal regions. EPVS are known to be increased in aging and hypertension, and are considered to be a biomarker of cerebral small vessel disease (SVD). Interest in EPVS has been significantly increased because these PVS are now considered to be an essential conduit necessary for the glymphatic pathway to provide the necessary efflux of metabolic waste. Metabolic waste includes misfolded proteins of amyloid beta and tau that are known to accumulate in late-onset Alzheimer's disease (LOAD) within the interstitial fluid that is delivered to the subarachnoid space and eventually the cerebral spinal fluid (CSF). The CSF acts as a sink for accumulating neurotoxicities and allows clinical screening to potentially detect if LOAD may be developing early on in its clinical progression via spinal fluid examination. EPVS are thought to occur by obstruction of the PVS that associates with excessive neuroinflammation, oxidative stress, and vascular stiffening that impairs flow due to a dampening of the arterial and arteriolar pulsatility that aids in the convective flow of the metabolic debris within the glymphatic effluxing system. Additionally, increased EPVS has also been associated with Parkinson's disease and non-age-related multiple sclerosis (MS).

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Background: Lacunes represent key imaging markers of cerebral small vessel diseases (cSVDs). During their progression, incident lacunes are related to stroke manifestations and contribute to progressive cognitive and/or motor decline. Assessing new lesions has become crucial but remains time-consuming and error-prone, even for an expert. We, thus, sought to develop and validate an automatic segmentation method of incident lacunes in CADASIL caused by cysteine mutation in the EGFr domains of the NOTCH3 gene, a severe and progressive monogenic form of cSVD. Methods: Incident lacunes were identified based on difference maps of 3D T1-weighted MRIs obtained at the baseline and 2 years later. These maps were thresholded using clustering analysis and compared with results obtained by expert visual analysis, which is considered the gold standard approach. Results: The median number of lacunes at the baseline in 30 randomly selected patients was 7 (IQR = [2, 11]). The median number of incident lacunes was 2 (IQR = [0, 3]) using the automatic method (mean time-processing: 25 s/patient) and 0.5 (IQR = [0, 2]) using the standard visual approach (mean time-processing: 8 min/patient). The complementary analysis of segmentation results is enabled to quickly remove false positives detected in specific locations and to identify true incident lesions not previously detected by the standard analysis (2 min/case). A combined approach based on automatic segmentation of incident lacunes followed by quick corrections of false positives allowed to reach high individual sensitivity (median at 0.66, IQR = [0.21, 1.00]) and global specificity scores (0.80). Conclusion: The automatic segmentation of incident lacunes followed by quick corrections of false positives appears promising for properly and rapidly quantifying incident lacunes in large cohorts of cSVDs.

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BACKGROUND: Lacunes are the manifestations of lacunar infarction which can lead many patients to the clinical outcome of disability or dementia. However, the relationship between lacune burden, cognitive function and blood glucose fluctuation in patients with type 2 diabetes mellitus (T2DM) complicated with lacunes is not very clear. AIM: To explore the correlation between glucose variability, lacune burden and cognitive function in patients with lacunes complicated with T2DM. METHODS: The clinical and imaging data of 144 patients with lacunes combined with T2DM were reviewed retrospectively. 72 h continuous glucose monitoring was performed. The Montreal Cognitive Assessment was used to assess cognitive function. The burden of lacunes was evaluated using magnetic resonance imaging performance. Multifactorial logistic regression analysis was used to study the affecting the lacune load and cognitive impairment in patients. To predict the value of patients' cognitive impairment with lacunes complicated with T2DM, a receiver operating characteristic (ROC) curve and a nomogram prediction model were constructed. RESULTS: The standard deviation (SD) of the average blood glucose concentration, percentage coefficient of variation (%CV) and time of range (TIR) were significantly different between the low and the high load groups (P < 0.05). The SD, %CV and TIR of the cognitive impairment group and non-cognitive impairment group were significantly different (P < 0.05). SD (odds ratio (OR): 3.558, 95% confidence interval (CI): 1.268-9.978, P = 0.006), and %CV (OR: 1.192, 95%CI: 1.081-1.315, P < 0.05) were the risk factors for an increased infarct burden in lacunes patients complicated with T2DM. TIR (OR: 0.874, 95%CI: 0.833-0.928, P < 0.05) is a protective factor. In addition, an increased SD (OR: 2.506, 95%CI: 1.008-6.23, P = 0.003), %CV (OR: 1.163, 95%CI: 1.065-1.270, P < 0.05) were the risk factors for cognitive impairment in patients with lacunes complicated with T2DM, TIR (OR: 0.957, 95%CI: 0.922-0.994, P < 0.05) is a protective factor. A nomogram prediction model of the risk of cognitive impairment was established based on SD, %CV and TIR. Decision curve analysis and the internal calibration analysis were used for internal verification and showed that the model was clinical benefit. The area under the ROC curves for predicting cognitive impairment in patients with lacunes complicated with T2DM was drawn were %CV: 0.757 (95%CI :0.669-0.845, P < 0.05), TIR: 0.711 (95%CI: 0.623-0.799, P < 0.05). CONCLUSION: Blood glucose variability is closely associated with the level of lacune burden and cognitive dysfunction in lacune patients combined with T2DM. %CV, TIR have a certain predictive effect in cognitive impairment in lacune patients.

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BACKGROUND: Perihematomal edema (PHE) is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to cerebral small vessel disease (CSVD). However, it is not known to date whether the severity of CSVD is associated with the extent of PHE progression in the acute phase. PURPOSE: To investigate the association between the magnetic resonance imaging (MRI) marker of severe chronic-ischemia cerebral small vessel changes (sciSVC) and PHE growth or hematoma absorption among ICH patients with hypertension. STUDY TYPE: Retrospective. POPULATION: Three hundred and sixty-eight consecutive hypertensive ICH patients without surgical treatment. FIELD STRENGTH/SEQUENCE: 3 T; spin-echo echo-planar imaging-diffusion-weighted imaging (DWI); T2-weighted, fluid-attenuated inversion recovery (FLAIR), T2*-weighted gradient-recalled echo and T1-weighted. ASSESSMENT: The hematoma and PHE volumes at 24 hours and 5 days after symptom onset were measured in 121 patients with spontaneous ICH who had been administered standard medical treatment. Patients were grouped into two categories: those with sciSVC and those without. The imaging marker of sciSVC was defined as white matter hyperintensities (WMHs) Fazekas 2-3 combined cavitating lacunes. STATISTICAL TESTS: Univariable analyses, χ2 test, Mann-Whitney U test, and multiple linear regression. RESULTS: The presence of sciSVC (multiple lacunes and confluent WMH) had a significant negative influence on PHE progress (Beta = -5.3 mL, 95% CI = -10.3 mL to -0.3 mL), and hematoma absorption (Beta = -3.2 mL, 95% CI = -5.9 mL to -0.4 mL) compared to that observed in the absence of sciSVC, as determined by multivariate linear regression analysis. DATA CONCLUSIONS: The presence of sciSVC (multiple lacunes and confluent WMH) negatively influenced hematoma absorption and PHE progress in ICH patients. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

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BACKGROUND: Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. AIM: This study aims to systematically review the prevalence of cSVD in LMICs. RESULTS: Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3-80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high (>95%). Male participants were overrepresented. CONCLUSIONS: This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.

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BACKGROUND AND PURPOSE: The circle of Willis (COW) is a circulatory anastomosis located at the base of the brain. Little is known about the association between covert vascular brain injury and COW configurations in the general population. We explored this relationship in a community-based Chinese sample. METHODS: A total of 1,055 patients (mean age, 54.8 ± 8.9 years; 36.0% men) without intracranial arterial stenosis were included in the analysis. Magnetic resonance imaging was performed to evaluate the presence of imaging markers of covert vascular brain injury, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy. Magnetic resonance angiography was used to classify the COW configurations according to the completeness, symmetry, and presence of the fetal posterior cerebral artery (FTP). The association between vascular lesions and variations in COW was analyzed. RESULTS: Among the 1,055 patients, 104 (9.9%) had a complete COW. Completeness correlated with age (p = 0.001). Incomplete COW was positively associated with WMH severity (OR = 2.071; 95% CI, 1.004-4.270) and CMB presence (OR = 1.542; 95% CI, 1.012-2.348), independent of age and sex. The presence of FTP was associated with lacunes (OR = 1.878; 95% CI, 1.069-3.298), more severe WMHs (OR = 1.739; 95% CI, 1.064-2.842), and less severe enlarged perivascular spaces (OR = 0.562; 95% CI, 0.346-0.915). CONCLUSIONS: COW configuration was significantly related to various covert vascular brain injuries.

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BACKGROUND: As one of the imaging markers of cerebral small vessel disease, lacunes has received little attention. The objective of this study was to investigate the associations of lacunes, cognition and motor function in patients with Parkinson's disease (PD) and whether these associations are independent of other imaging markers. METHODS: Patients were consecutively included from April 2019 to July 2022 in Beijing Rehabilitation Hospital. All patients underwent brain magnetic resonance imaging scans, clinical scale evaluations, and neuropsychological tests, as well as quantitative evaluation of postural control. To eliminate the possible factors contributing to cognition and motor dysfunction in patients with PD, in particular white matter hyperintensities and enlarged perivascular space in the basal ganglia, multivariate linear regression models were constructed to sort out the effect of lacunes. RESULTS: Ninety-four patients were included in this study, 56 without lacunes and 38 with lacunes. Patients with lacunes showed shorter disease duration, slower gait speed and spent more time on Trail-Making Test part A (TMT-A) than those without lacunes. The number of lacunes were positively correlated with the time to complete the TMT-A and negatively related to gait speed. Multivariate linear regression models showed that the presence of lacunes was associated with longer TMT-A time after adjusting for potential confounders. CONCLUSIONS: Lacunes were independently associated with worse visual scanning, attention, and processing speed in patients with PD. In addition, lacunes may accelerate the course of PD. Early treatment of vascular disease provides an alternate way to mitigate some motor and cognitive dysfunction in patients with PD.

Lacunes were independently associated with worse visual scanning, attention, and processing speed in patients with Parkinson's disease (PD). Lacunes may accelerate the course of PD. Early treatment of vascular disease provides an alternate way to mitigate some motor and cognitive dysfunction in patients with PD.

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BACKGROUND: The underlying mechanisms of incident lacunes regarding their spatial distribution remain largely unknown. We investigated the spatial distribution pattern and MRI predictors of incident lacunes in relation to white matter hyperintensity (WMH) over 14 years follow-up in sporadic small vessel disease. METHODS: Five hundred three participants from the ongoing prospective single-center Radboud University Nijmegen Diffusion Tensor and Magnetic resonance Cohort (RUN DMC) were recruited with baseline assessment in 2006 and follow ups in 2011, 2015, and 2020. Three hundred eighty-two participants who underwent at least 2 available brain MRI scans were included. Incident lacunes were systematically identified, and the spatial relationship between incident lacunes located in subcortical white matter and WMH were determined using a visual rating scale. Adjusted multiple logistic regression and linear mixed-effect regression models were used to assess the association between baseline small vessel disease markers, WMH progression, and incident lacunes. Participants with atrial fibrillation were excluded in multivariable analysis. RESULTS: Eighty incident lacunes were identified in 43 patients (mean age 66.5±8.2 years, 37.2% women) during a mean follow-up time of 11.2±3.3 years (incidence rate 10.0/1000 person-year). Sixty percent of incident lacunes were in the white matter, of which 48.9% showed no contact with preexisting WMH. Baseline WMH volume (odds ratio=2.5 [95% CI, 1.6-4.2]) predicted incident lacunes after adjustment for age, sex, and vascular risk factors. WMH progression was associated with incident lacunes independent of age, sex, baseline WMH volume, and vascular risk factors (odds ratio, 3.2 [95% CI, 1.5-6.9]). Baseline WMH volume and progression rate were higher in participants with incident lacunes in contact with preexisting WMH. No difference in vascular risk factors was observed regarding location or relation with preexisting WMH. CONCLUSIONS: The 2 different distribution patterns of lacunes regarding their relation to WMH may suggest distinct underlying mechanisms, one of which may be more closely linked to a similar pathophysiology as that of WMH. The longitudinal relation between WMH and lacunes further supports plausible shared mechanisms between the 2 key markers.

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OBJECTIVES: One-third of adults in Canada are overweight and 26.8% experience obesity. Bariatric surgery confers effective weight loss and reduces obesity-related complications, including type 2 diabetes, but remains an underutilized treatment. Our objective in this study was to determine whether a gap exists in bariatric program referrals for patients with type 2 diabetes seen in endocrinology clinics at an ambulatory tertiary care hospital in Toronto, Canada. METHODS: A retrospective chart review was conducted of 843 consecutive patients with type 2 diabetes in endocrinology clinics between January 1, 2015 and December 31, 2020. Inclusion criteria were age ≥18 years, type 2 diabetes and body mass index (BMI)>35 kg/m2. Exclusion criteria were recent active cancer, uncontrolled psychiatric disease or active substance use disorder within 6 months of the initial visit. Referrals to bariatric surgery were assessed within a 5-year follow-up period and compared with baseline referral rates from the Ontario Bariatric Network (OBN). An online survey of 48 endocrinologists in Toronto, Ontario, was also conducted to assess physician-level barriers to referral. RESULTS: The proportion of patients with class II obesity (BMI>35 kg/m2) and type 2 diabetes meeting the eligibility criteria for bariatric referral was 4.6% (n=38). A documented discussion about bariatric surgery occurred with 7 (18.0%) of these eligible patients, and 1 patient (2.6%) was referred for surgery. Aside from surgical referrals, only 2.6% of eligible patients were referred to cognitive-behavioural therapy, 36.8% were initiated on obesity pharmacotherapy and 42.1% were referred to a dietitian. Baseline OBN data demonstrated that most surgical referrals (n=6,360) were from family physicians (65.0%) and only 8.8% were from a medical specialist. Eight percent of surveyed endocrinologists reported that they discussed bariatric surgery with at least half of their eligible patients. The most frequent barrier to discussing bariatric surgery during visits was time constraints. Physicians identified that simplifying the referral process and providing bariatric surgery handouts would be helpful interventions to improve referral rates. CONCLUSIONS: Our gap analysis demonstrated a low bariatric surgery referral rate by tertiary care endocrinologists. Our study also identified a large gap in the appropriate treatment of obesity with poor utilization of behavioural, lifestyle and pharmacotherapy practices. As obesity and diabetes rates increase, better education, training and knowledge translation will be necessary to overcome weight bias and prioritize obesity management.

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BACKGROUND: This study aims to explore the features of gait disorders with cerebral small vessel disease (CSVD), and results from magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) were analyzed. METHODS: The 139 patients with CSVD were divided into two groups by the Tinetti scale scores: the gait disorder (GD) group with a score <24 (63 patients) and the normal gait (GN) group with a score ≥24 (76 patients). A series of scales and 3.0T MRI with DTI were used to analyze the correlation between the abnormal gaits and imaging findings. RESULTS: The differences in the Barthel Index, Unified Parkinson's Disease Rating Scale part III, and Montreal Cognitive Assessment (MoCA) scores between the two groups were significant (p < 0.05), and there were significant correlations between MoCA and total gait scores (r = 0.201, p = 0.002). The GD group had a more degraded gait score, widened gait base, and degraded gait length than the GN group (p < 0.05). There were significant differences between the two groups (p < 0.05) in white matter (WM) hyperintensities (WMH) of the Fazekas scale grade 2-3 and lacunes. The GD group had a greater total MRI burden than the GN group (p < 0.05). In DTI parameters, the GD group had lower fractional anisotropy (FA) and higher mean diffusion (MD) values in WM tracts in many areas around the ventricles (family-wise error corrected, p < 0.05). Significant correlations were observed between FA and the total gait score (r = 0.467, p < 0.01), and also between MD and total gait score (r  = -0.422, p < 0.01). CONCLUSIONS: Patients with CSVD with gait disorders had more WMH of Fazekas scale grade 2-3, lacunes, and total MRI burden than the GN patients, and those with gait disorders may suffer from demyelination of nerve fibers and damage to the fibers' microstructures.

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BACKGROUND: Both cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA) are related to cognitive impairment and dementia. This study aimed to clarify CAA- and HA-related small vessel disease (SVD) imaging marker associations with cognitive dysfunction and Alzheimer disease (AD) subtypes. METHODS: A sample of 137 subjects with clinically diagnosed late-onset AD identified from the dementia registry of a single center from January 2017 to October 2021 were enrolled. Semi-quantitative imaging changes (visual rating scale grading) suggestive of SVD were analyzed singularly and compositely, and their correlations with cognitive domains and AD subtypes were examined. RESULTS: Patients with typical and limbic-predominant AD subtypes had worse cognitive performance and higher dementia severity than minimal-atrophy subtype patients. Deep white matter hyperintensity (WMH) presence correlated inversely with short-term memory (STM) performance. The three composite SVD scores correlated with different cognitive domains and had distinct associations with AD subtypes. After adjusting for relevant demographic factors, multivariate logistic regression (using minimal-atrophy subtype as the reference condition) revealed the following: associations of the typical subtype with periventricular WMH [odds ratio (OR) 2.62; 95% confidence interval (CI), 1.23-5.57, p = 0.012], global SVD score (OR 1.67; 95%CI, 1.11-2.52, p = 0.009), and HA-SVD score (OR 1.93; 95%CI, 1.10-3.52, p = 0.034); associations of limbic-predominant subtype with HA-SVD score (OR 2.57; 95%CI, 1.23-5.37, p = 0.012) and most global and domain-specific cognitive scores; and an association of hippocampal-sparing subtype with HA-SVD score (OR 3.30; 95%CI, 1.58-6.85, p = 0.001). CONCLUSION: Composite SVD imaging markers reflect overall CAA and/or HA severity and may have differential associations with cognitive domains and AD subtypes. Our finding supports the possibility that the clinical AD subtypes may reflect differing burdens of underlying CAA and HA microangiopathologies.

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Cerebral small-vessel disease (CSVD) has been found to have a strong association with vascular cognitive impairment (VCI) and functional loss in elderly patients. At present, the diagnosis of CSVD mainly relies on brain neuroimaging markers, but they cannot fully reflect the overall picture of the disease. Currently, some biomarkers were found to be related to CSVD, but the underlying mechanisms remain unclear. We aimed to systematically review and summarize studies on the progress of biomarkers related to the pathogenesis of CSVD, which is mainly the relationship between these indicators and neuroimaging markers of CSVD. Concerning the pathophysiological mechanism of CSVD, the biomarkers of CSVD have been described as several categories related to sporadic and genetic factors. Monitoring of biomarkers might contribute to the early diagnosis and progression prediction of CSVD, thus providing ideas for better diagnosis and treatment of CSVD.

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Background: Twenty-four-hour and nighttime blood pressure (BP) levels are more strongly associated with cardiovascular risk than office or daytime BP measurements. However, it remains undocumented which of the office and ambulatory BP measurements have the strongest association and predictive information in relation to the presence of type I, or arteriolosclerosis type, cerebral small vessel diseases (CSVD). Methods: A subset of 429 participants from the Maracaibo Aging Study [aged ≥40 years (women, 73.7%; mean age, 59.3 years)] underwent baseline brain magnetic resonance imaging (MRI) to visualize CSVD, which included log-transformed white matter hyperintensities (log-WMH) volume and the presence (yes/no) of lacunes, cerebral microbleeds (CMB), or enlarged perivascular spaces (EPVS). Linear and logistic regression models were applied to examine the association between CSVD and each +10-mmHg increment in the office and ambulatory systolic BP measurements. Improvement in the fit of nested logistic models was assessed by the log-likelihood ratio and the generalized R 2 statistic. Results: Office and ambulatory systolic BP measurements were related to log-WMH (ß-correlation coefficients ≥0.08; P < 0.001). Lacunes and CMB were only associated with ambulatory systolic BP measurements (odds ratios [OR] ranged from 1.31 [95% confidence interval, 1.10-1.55] to 1.46 [1.17-1.84], P ≤ 0.003). Accounted for daytime systolic BP, both the 24-h (ß-correlation, 0.170) and nighttime (ß-correlation, 0.038) systolic BP measurements remained related to log-WMH. When accounted for 24-h or daytime systolic BP levels, the nighttime systolic BP retained the significant association with lacunes (ORs, 1.05-1.06; 95% CIs, ≥1.01 to ≤ 1.13), whereas the 24-h and daytime systolic BP levels were not associated with lacunes after adjustments for nighttime systolic BP (ORs, ≤ 0.88; 95% CI, ≥0.77 to ≤ 1.14). On top of covariables and office systolic BP, ambulatory systolic BP measurements significantly improved model performance (1.05% ≥ R 2 ≤ 3.82%). Compared to 24-h and daytime systolic BP, nighttime systolic BP had the strongest improvement in the model performance; for WMH (1.46 vs. 1.05%) and lacunes (3.06 vs. ≤ 2.05%). Conclusions: Twenty-four-hour and nighttime systolic BP were the more robust BP measurements associated with CSVD, but the nighttime systolic BP level had the strongest association. Controlling ambulatory BP levels might provide additional improvement in the prevention of CSVD.