Cerebral Small Vessel Disease Burden Research Articles

Association of pulsatility index with total burden of cerebral small vessel disease and cognitive impairment.

This study investigated the correlation between the pulsatility index (PI) of the middle cerebral artery with the total burden of cerebral small vessel disease and cognitive impairment. Information on patients hospitalized in the Department of Neurology was collected retrospectively. These patients had complete clinical and laboratory data. The middle cerebral artery PI was measured using transcranial Doppler, a Mini-Mental State Examination (MMSE) was used to assess cognitive function, and the total cerebral small vessel disease burden was assessed using magnetic resonance imaging. Patients were grouped according to their scores for total imaging burden of cerebral small vessel disease and cognitive function. Logistic regression analysis assessed the association between the PI, total imaging burden, and cognitive impairment. Spearman analysis was used to evaluate the correlation between the PI and total imaging burden and cognitive impairment, and receiver operating characteristic (ROC) curves were used to determine the predictive value of the PI for cognitive function. The PI was higher in the cognitive impairment (CI) group than in the no-CI group. Binary logistic regression analysis showed that increased PI was an independent risk factor for CI (OR=1.582; 95% CI: 1.043-2.401; p=.031) and total imaging burden (OR=1.842; 95% CI: 1.274-2.663; p=.001). Spearman analysis found that the PI correlated negatively with the MMSE score (r=-.627, p<.001). ROC curve analysis showed the PI predicted CI with an area under the curve of 0.784. The PI combined with the total imaging burden predicted CI in cerebral small vessel disease with an area under the curve of 0.832. An increased PI was associated with CI and a high imaging burden in cerebral small vessel disease patients. The PI combined with the total burden score shows a high predictive value for CI.

The clinical characteristics of cerebral small vessel disease patients with motoric cognitive risk syndrome during single- and dual-task walking

ObjectiveWe aimed to (1) identify neuroimaging biomarkers of distinguishing motoric cognitive risk syndrome (MCRS) risk among older Chinese adults with cerebral small vessel disease (CSVD) and (2) detect differences in gait parameters and neuroimaging biomarkers between CSVD individual with and without MCRS, especially during dual-task walking (DTW). MethodsWe enrolled 126 inpatients with CSVD who were divided into two groups according to MCRS status. Data on basic parameters, variability, asymmetry, and coordination were collected during single-task walking (STW) and DTW. Neuroimaging features (white matter hyperintensities, lacunes, and microbleeds) and total disease burden were calculated. Analysis of variance and logistic regression analyses were applied to assess the role of STW, DTW, and neuroimaging biomarkers in MCRS. ResultsIn total, 126 consecutive inpatients with CSVD were included (84 and 42 patients were classified as MCRS-negative and MCRS-positive, respectively). The MCRS-positive group showed poorer performance for nearly all gait parameters compared with the MCRS-negative group during cognitive DTW. Meanwhile, all gait parameters except asymmetry were assessed in participants with MCRS for significant deterioration during cognitive DTW compared with that during STW. However, only basic parameters differed between STW and cognitive DTW in participants without MCRS. A significant independent association between total CSVD scores and MCRS was also detected. ConclusionsFor CSVD patients, with higher total CSVD burden rather than any single neuroimaging marker, was linked to a greater risk of MCRS. In addition, CSVD individuals with MCRS had higher variability and phase coordination index (PCI), especially in cognitive DTW. Thus, they should concentrate more on their gait variability or coordination and reduce secondary task loads while walking in daily life, especially in cognitive secondary tasks.

Correlation between Carotid Blood Flow Velocity and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease in Patients with Recent Small Subcortical Infarcts

Background: The common and internal carotid arteries are the upstream vessels of the small cerebral vessels. The relationship between hemodynamic changes in the significant cervical vessels and cerebral small vessel disease (CSVD) remains uncertain. This research sought to analyze the correlation between carotid blood flow velocity and the total magnetic resonance imaging (MRI) burden of CSVD in patients with recent small subcortical infarcts (RSSIs). Methods: Data were gathered from individuals diagnosed with RSSIs admitted to Changzhou Second People's Hospital between January 2022 and June 2023. Brain MRI was performed on every patient to determine the overall MRI burden of CSVD, along with carotid duplex ultrasound to evaluate carotid blood flow velocity and pulsatility index (PI) of the common carotid (CCA) and internal carotid (ICA) arteries. The association between carotid blood flow velocity and the total MRI load of CSVD was examined using univariate and multivariate analyses. Results: For our investigation, 272 individuals with RSSIs were screened. 82 individuals had a moderate to severe load of CSVD, while 190 participants showed a mild burden. Patients with moderate to severe burden of CSVD had lower end-diastolic velocity (EDV) and higher PI in CCA and ICA than those with mild load (P &lt; 0.001). After adjusting for variables like age, hypertension, systolic blood pressure, and blood homocysteine levels, multivariate logistic regression analysis showed that EDV in CCA (OR, 0.894; P = 0.011), PI in CCA (OR, 5.869; P = 0.017), EDV in ICA (OR, 0.909; P = 0.008), and PI in ICA (OR, 5.324; P = 0.041) were independently related to moderate to severe CSVD burden. Spearman correlation analysis showed that EDV in CCA and ICA was negatively related to the total MRI load of CSVD in patients with RSSIs (P &lt; 0.001). PI in CCA and ICA was positively associated with the whole MRI load of CSVD (P &lt; 0.001). Conclusion: Low carotid blood flow velocity and high carotid pulsatility index are independently associated with moderate to severe burden of CSVD.

Analysis of gait pattern related to high cerebral small vessel disease burden using quantitative gait data from wearable sensors

Background and ObjectivesSensor-based wearable devices help to obtain a wide range of quantitative gait parameters, which provides sufficient data to investigate disease-specific gait patterns. Although cerebral small vessel disease (CSVD) plays a significant role in gait impairment, the specific gait pattern associated with a high burden of CSVD remains to be explored. MethodsWe analyzed the gait pattern related to high CSVD burden from 720 participants (aged 55–65 years, 42.5 % male) free of neurological disease in the Taizhou Imaging Study. All participants underwent detailed quantitative gait assessments (obtained from an insole-like wearable gait tracking device) and brain magnetic resonance imaging examinations. Thirty-three gait parameters were summarized into five gait domains. Sparse sliced inverse regression was developed to extract the gait pattern related to high CSVD burden. ResultsThe specific gait pattern derived from several gait domains (i.e., angles, phases, variability, and spatio-temporal) was significantly associated with the CSVD burden (OR=1.250, 95 % CI: 1.011–1.546). The gait pattern indicates that people with a high CSVD burden were prone to have smaller gait angles, more stance time, more double support time, larger gait variability, and slower gait velocity. Furthermore, people with this gait pattern had a 25 % higher risk of a high CSVD burden. ConclusionsWe established a more stable and disease-specific quantitative gait pattern related to high CSVD burden, which is prone to facilitate the identification of individuals with high CSVD burden among the community residents or the general population.

Total cerebral small vessel disease burden and stroke outcomes in large vessel occlusion stroke receiving endovascular treatment: A systematic review and meta-analysis

BackgroundCerebral small vessel disease (CSVD) is prevalent in the population, especially among the elderly. Various types of CSVD markers commonly coexist, and the neurological function outcome is affected by their combined effect. Studies investigating the association between total CSVD burden and stroke outcomes in large vessel occlusion (LVO) stroke receiving endovascular treatment (EVT) are expanding but have not been systematically assessed. MethodsWe systematically searched the PubMed, Embase, and Cochrane databases for relevant clinical studies. The total CSVD burden score summarized the markers of CSVD, including lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVSs), which was a comprehensive index of overall CSVD burden. The pooled odds ratios (ORs) were used to calculate the association between high total CSVD burden score and outcomes of EVT in patients with LVO stroke. The primary outcome was poor functional outcome, which was defined as a modified Rankin Scale score (mRS) ≥ 3 at 90 days after EVT. The secondary outcomes were symptomatic intracranial hemorrhage (sICH) and poor collateral flow. ResultsOverall, 6 eligible studies with 1,774 patients with LVO stroke undergoing EVT were pooled in meta-analysis. High overall CSVD burden score was significantly associated with increased risks of poor functional outcome at 90 days (pooled OR 2.86, 95 % CI 1.31–6.25, p = 0.008). Besides, high overall CSVD burden score was associated with sICH (pooled OR 2.07, 95 % CI 0.38–5.17; p = 0.118) and poor collateral flow (pooled OR 1.57, 95 % CI 0.75–3.27; p = 0.232), but were not statistically significant. ConclusionsHigh overall CSVD burden was associated with increased risks of unfavorable outcomes in patients with LVO stroke undergoing EVT.

A Nomogram Including Total Cerebral Small Vessel Disease Burden Score for Predicting Mild Vascular Cognitive Impairment in Patients with Type 2 Diabetes Mellitus.

Total cerebral small vessel disease (CSVD) burden score is an important predictor of vascular cognitive impairment (VCI). However, few predictive models of VCI in type 2 diabetes mellitus (T2DM) patients have included the total CSVD burden score, especially in the early stage of VCI. To develop and validate a nomogram that includes the total CSVD burden score to predict mild VCI in patients with T2DM. A total of 322 eligible participants with T2DM who were divided into mild and normal cognitive groups were enrolled in this retrospective study. Demographic data, laboratory data and imaging markers of CSVD were collected. The total CSVD burden score was calculated by combining the different CSVD markers. Step-backward multivariable logistic regression analysis with the Akaike information criterion was applied to select significant predictors and develop a best-fit predictive nomogram. The performance of the nomogram was assessed in terms of discriminative ability, calibrated ability, and clinical usefulness. The nomogram model consisted of five variables: age, education, hemoglobin A1c level, serum homocysteine level, and total CSVD burden score. A nomogram with these variables showed good discriminative ability (area under the receiver operating characteristic curve was 0.801 in internal verification). In addition, the Hosmer-Lemeshow test (χ2 =9.226, P=0.417) and bootstrap-corrected calibration plot indicated that the nomogram had good calibration. The Brier score of the predictive model was 0.178. Decision curve analysis demonstrated that when the threshold probability ranged between 16% and 98%, the use of the nomogram to predict mild VCI in patients with T2DM provide a greater net benefit. The nomogram, composed of age, education, stroke, HbA1c level, Hcy level, and total CSVD burden score, had good predictive accuracy and may provide clinicians with a practical tool for predicting the risk of mild VCI in T2DM patients.

The factors influencing the occurrence of post-ischemic stroke depression and its relationship with the burden score of cerebral small vessel disease.

This study explored the determinants of post-stroke depression (PSD) in ischemic stroke (AIS) patients and its association with the burden score of cerebral small vessel disease (CSVD). We analyzed 374 AIS patients treated between January 2020 and January 2022. Patients were categorized into 90 with PSD and 284 without PSD, enabling an investigation into PSD risk factors and the CSVD-PSD relationship. There was no significant difference in health factors between PSD and non-PSD patients (p>0.05). However, significant disparities were noted in age, gender, initial Barthel Index (BI), Mini-Mental State Examination (MMSE) score, plasma fibrinogen, homocysteine, red cell distribution width, National Institutes of Health Stroke Scale (NIHSS) score, and CSVD burden score (p<0.05). Regression analysis indicated that these variables were pivotal PSD predictors (OR>1, p<0.05). Surprisingly, a positive correlation with PSD occurrence was found for age, NIHSS score, plasma fibrinogen, homocysteine levels, red cell distribution width, CSVD burden score (r=0.565, 0.615, 0.482, 0.514, 0.572, 0.608, respectively; p<0.05). Meanwhile, the MMSE score and BI index were inversely related to PSD onset (r=-0.604, -0.590; p<0.05). The ROC curve analysis of the combination model based on MMSE, NIHSS and CSVD score revealed an AUC of 0.926 and Youden's index of 0.744. Age, MMSE score, BI index, NIHSS score, plasma fibrinogen concentration, homocysteine level, red blood cell distribution width, and CSVD burden score are all major influencing factors in the occurrence of PSD. The combination model based on MMSE, NIHSS, and CSVD scores presented a valuable approach to predicting PSD.

Modified Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease and Related Risk Factors in Patients With Thalassemia.

This study aimed to explore the burden of magnetic resonance imaging (MRI) of cerebral small vessel disease (CSVD) in patients with thalassemia and related risk factors. The clinical data and MRI of patients with thalassemia were retrospectively analyzed, and non-thalassemia controls with matched sex and age were selected. The modified MRI burden of CSVD included recent small subcortical infarct, presumed vasogenic white matter hyperintensity, presumed vasogenic lacunae, perivascular space (PVS), and brain atrophy. This study included 110 patients in each of the thalassemia and control groups. There was no significant difference in sex, age, and common cerebrovascular disease risk factors between the 2 groups. The patients with thalassemia had a higher red blood cell count and lower content of hemoglobin. The PVS and modified MRI burden scores in the thalassemia group were higher than in the control group. With the increase in age, patients with thalassemia have a more severe CSVD burden. Patients with thalassemia have a heavier modified MRI burden of CSVD than non-thalassemia patients, particularly PVS, and aging is an important risk factor for CSVD changes.

The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer’s disease continuum participants

BackgroundGlymphatic dysfunction is a crucial pathway for dementia. Alzheimer’s disease (AD) pathologies co-existing with cerebral small vessel disease (CSVD) is the most common pathogenesis for dementia. We hypothesize that AD pathologies and CSVD could be associated with glymphatic dysfunction, contributing to cognitive impairment.MethodParticipants completed with amyloid PET, diffusion tensor imaging (DTI), and T2 fluid-attenuated inversion-recovery (FLAIR) sequences were included from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). White matter hyperintensities (WMH), the most common CSVD marker, was evaluated from T2FLAIR images and represented the burden of CSVD. Amyloid PET was used to assess Aβ aggregation in the brain. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, the burden of enlarged perivascular spaces (PVS), and choroid plexus volume to reflect glymphatic function. The relationships between WMH burden/Aβ aggregation and these glymphatic markers as well as the correlations between glymphatic markers and cognitive function were investigated. Furthermore, we conducted mediation analyses to explore the potential mediating effects of glymphatic markers in the relationship between WMH burden/Aβ aggregation and cognition.ResultsOne hundred and thirty-three participants along the AD continuum were included, consisting of 40 CN − , 48 CN + , 26 MCI + , and 19 AD + participants. Our findings revealed that there were negative associations between whole-brain Aβ aggregation (r = − 0.249, p = 0.022) and WMH burden (r = − 0.458, p < 0.001) with DTI-ALPS. Additionally, Aβ aggregation (r = 0.223, p = 0.041) and WMH burden (r = 0.294, p = 0.006) were both positively associated with choroid plexus volume. However, we did not observe significant correlations with PVS enlargement severity. DTI-ALPS was positively associated with memory (r = 0.470, FDR-p < 0.001), executive function (r = 0.358, FDR-p = 0.001), visual-spatial (r = 0.223, FDR-p < 0.040), and language (r = 0.419, FDR-p < 0.001). Conversely, choroid plexus volume showed negative correlations with memory (r = − 0.315, FDR-p = 0.007), executive function (r = − 0.321, FDR-p = 0.007), visual-spatial (r = − 0.233, FDR-p = 0.031), and language (r = − 0.261, FDR-p = 0.021). There were no significant correlations between PVS enlargement severity and cognitive performance. In the mediation analysis, we found that DTI-ALPS acted as a mediator in the relationship between WMH burden/Aβ accumulation and memory and language performances.ConclusionOur study provided evidence that both AD pathology (Aβ) and CSVD were associated with glymphatic dysfunction, which is further related to cognitive impairment. These results may provide a theoretical basis for new targets for treating AD.

Handwriting Movement Abnormalities in Older Adults with Silent Cerebral Small Vessel Disease-A Preliminary Study.

The features of cerebral small vessel disease (CSVD) range from occurrence of asymptomatic radiological markers to symptomatic characteristics that include cognitive deficits and gait decline. The aim of the present study was to examine whether handwriting movement is abnormal in older people with CSVD through handwriting and drawing tasks using digitized handwriting kinematic assessment technology. Older subjects (n = 60) were grouped according to Fazekas score, with 16 in the Severe CSVD group, 12 in the Non-severe group and 32 in the Healthy group. Kinematic data were recorded and analyzed during handwriting and drawing tasks: signature; writing of Chinese characters ("" and ""); and Archimedes' spiral drawing. The Severe CSVD group showed lower velocity and higher tortuosity during signature writing, lower velocity of stroke #4 of "" and vertical size of "" than did the Non-severe and Healthy groups. Both Severe CSVD and Non-severe CSVD subjects displayed higher average normalized jerk than did the Healthy group. Partial correlation analysis adjusting for age, gender, education, and mini-mental state evaluation (MMSE) showed that CSVD burden was positively associated with tortuosity of signature and average normalized jerk of Archimedes' spiral, and was negatively associated with velocity of strokes #3 and #4 of "", as well as vertical size of "". Older adults with CSVD showed abnormal handwriting movement. And the handwriting abnormalities captured by digitized handwriting analysis were correlated with CSVD severity in users of simplified Chinese characters.

Prevalence of small vessel disease and incidental DWI-positive lesions in patients with aneurysmal subarachnoid hemorrhage versus intracerebral hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) and intracerebral hemorrhage (ICH) are main forms of hemorrhagic stroke. Data regarding cerebral small vessel disease (SVD) burden and incidental small lesions on diffusion-weighted imaging (DWI) following aSAH are sparse. We retrospectively analyzed a prospective cohort of aSAH and ICH patients with brain MRI within 30 days after onset from March 2015 to January 2023. White matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed (CMB), total SVD score, and incidental DWI lesions were assessed and compared between aSAH and ICH. Clinical and radiological characteristics associated with small DWI lesions in aSAH were investigated. We included 180 patients with aSAH (median age [IQR] 53 [47-61] years) and 299 with ICH (63 [53-73] years). DWI lesions were more common in aSAH than ICH (47.8% vs 14.4%, p < 0.001). Higher total SVD score was associated with ICH versus aSAH irrespective of hematoma location, whereas DWI lesions and strictly lobar CMBs were correlated with aSAH. Multivariable analysis showed that shorter time from onset to MRI, anterior circulation aneurysm rupture, CMB ⩾ 5, and total SVD score were associated with DWI lesions in aSAH. Incidental DWI lesions and strictly lobar CMBs were more frequent in aSAH versus ICH whereas ICH had higher SVD burden. Incidental DWI lesions in aSAH were associated with multiple clinical and imaging factors. Longitudinal studies to investigate the dynamic change and prognostic value of the covert hemorrhagic and ischemic lesions in aSAH seem justified.

Abstract WMP22: Higher Burden of Cerebral Small Vessel Disease is Associated With Risk of Incident Stroke in Community-Dwelling Individuals

Background: Mild manifestations of individual cerebral small vessel disease (CSVD) markers are common and may not denote increased risk, but high CSVD burden identifies individuals at increased risk of stroke and dementia. Scores incorporating multiple CSVD markers may better identify a person’s risk, but it remains unclear if they offer benefit beyond tools based on clinical factors alone such as the revised Framingham Stroke Risk Profile (FSRP). Therefore, we related a multi-marker CSVD score to risk of incident stroke and compared the findings with the FSRP in community-dwelling individuals. Methods: Framingham Heart Study (FHS) participants aged ≥55 years, free of stroke and dementia and with brain magnetic resonance imaging (MRI) ratings of CSVD markers were included. A multi-marker CSVD score reflecting increasing CSVD burden was used (one point each for presence of cerebral microbleeds, severe perivascular spaces, extensive white matter hyperintensities, covert brain infarcts, and cortical superficial siderosis, ranging 0-5). Multivariable Cox proportional hazards regression analyses were used to relate CSVD score to incident stroke. Results: Among 1,154 participants (46% male, mean age 70.9±8.7), 590 (51%) had score 0, 352 (31%) had score 1, 164 (14%) had score 2, and 48 (4%) had score ≥ 3. Over a median follow-up of 8.2 years (Q1-Q3: 5.1-12.5) from the time of MRI, 92 (8%) developed stroke. In models adjusting for time interval between clinic exam and MRI, FHS cohort, and FSRP score, number of CSVD manifestations was associated with increased risk of stroke in a dose-dependent manner: score 1 (HR: 1.73; 95% CI 1.05-2.84), score 2 (HR 1.83; 95% CI: 1.01-3.30), and score ≥ 3 (HR: 3.31; 95% CI: 1.50-7.28) in relation to participants with no CSVD markers. In comparison, a 5-percent increase in FSRP alone was associated with increased risk of stroke (HR: 1.25; 95% CI 1.15-1.36). Interpretation: Higher CSVD burden is associated with increased risk of stroke, beyond the effect explained by risk factors in the FSRP. These findings support consideration of CSVD burden to identify risk of stroke in community-dwelling individuals.

Abstract TP166: White Matter Hyperintensity Burden Associated With Stroke Severity, Aphasia, and Motor Deficits During Intracerebral Hemorrhage Hospitalization

Introduction: Cerebral Small Vessel Disease (CSVD) is associated with cognitive disruptions after intracerebral hemorrhage (ICH), however evidence connecting CSVD to specific neurological deficits after ICH is limited. Methods: Electronic medical record data were retrieved for adult patients (&gt;18 years) with admission for primary non-traumatic ICH, available admission NIHSS scores, and CSVD assessment. CSVD burden was graded from 0-4, with 1 point assessed for: 1) deep Fazekas white matter hyperintensity (WMH) score of 2-3 or periventricular (PV) Fazekas score of 3; 2) cerebral microbleed presence; 3) lacune presence; 4) &gt; 20 basal ganglia perivascular spaces. Severe CSVD was assessed scores ≥ 3, and individual marker severity was assessed using the same criteria. The primary outcome was moderate-severe stroke (total NIHSS score ≥5). Secondary outcomes were severe motor deficit (motor score &gt;12), complete aphasia (language score = 3), and cortical deficit (any impairment in language, extinction, and gaze). Associations between CSVD and NIHSS were determined using multivariable logistic regression, adjusting for major clinical and demographic factors. Adjusted odds ratios (aOR) and 95% confidence interval (CI) are reported. Results: The cohort included 1024 patients (median age [interquartile range]: 71 [61-79], 53% male). Patients were 22% Hispanic and had a racial distribution of 61% White, 24% Black, 8% Asian, 7% other. The median NIHSS score was 4 [1-11]; 477 (47%) showed moderate-severe NIHSS scores and 262 (26%) showed severe CSVD. Severe PV WMH burden was independently associated with moderate-severe NIHSS score (vs non-severe; aOR, 95% CI: 1.55, [1.02-2.36]). Severe deep WMH burden (vs non-severe) was independently associated with aphasia (1.97, [1.02-3.81]), and motor deficit (3.95, [1.22-12.73]) (Figure 1). Conclusion: Severe WMH burdens increase odds of neurological deficit among patients with primary ICH.

Abstract TP39: Multi-Marker Cerebral Small Vessel Disease Score and Risk of Incident Depression: The Framingham Heart Study

Introduction: The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) contributes to the development of depression. A multi-marker CSVD score based on brain magnetic resonance imaging (MRI) could serve as a valuable tool for predicting the risk of developing vascular depression. This is important as depression can mimic cognitive impairment, dementia and is treatable. This study aimed to determine the relation of a MRI multi-marker CSVD score with incident depression in community-dwelling individuals. Methods: Framingham Heart Study participants from the Original and Offspring cohorts free of stroke, dementia and depression with available data on depression and CSVD ratings on MRI were included. Depression was defined as Center for Epidemiological Studies Depression scale score ≥16 or use of antidepressant medication. The multi-marker CSVD score was calculated by summing 1 point for individual CSVD markers present (covert brain infarcts, cerebral microbleeds, extensive white matter hyperintensities, high burden perivascular spaces, cortical superficial siderosis), ranging 0-5. Multivariable logistic regression models were used to relate the MRI-multi-marker CSVD score and incident depression in a primary analysis and individual CSVD biomarkers and depression in an exploratory analysis. Models were adjusted for age, sex, FHS cohort, time interval between MRI and clinic exam, body mass index, smoking, prevalent hypertension and diabetes. Results: In 1768 participants included (mean age 54.4±12.4 years, 54% male), the incidence of depression was 11% (median follow-up 6.0 years, IQR: 5.3-6.7). No CSVD score group had a statistically significant association with incident depression, however a CSVD score 3+ showed a trend towards increased odds of developing incident depression (OR 2.65 [0.87, 8.06], p =0.09). Among the individual CSVD markers, visible perivascular spaces had the highest odds for incident depression (OR 1.55 [0.96, 2.51] p =0.07). Conclusion: A higher multi-marker CSVD score might be associated with increased odds of incident depression. Further studies with a larger sample may help elucidate a potential association between this CSVD burden and onset of depression.

Abstract WMP16: Multi-Marker Cerebral Small Vessel Disease Score and Risk of Incident Dementia in the Framingham Heart Study

Background: Individual magnetic resonance imaging (MRI) markers of cerebral small vessel disease (CSVD) are associated with impaired cognition and dementia but may not reflect the overall burden of CSVD. It is unclear whether these markers provide additional value in evaluating the risk of dementia beyond assessments based solely on clinical risk factors. Thus, we aimed to determine whether the association of additive burden of multiple CSVD markers was independent of vascular risk factors and the Framingham Stroke Risk Profile (FSRP) and to also compare results with the FSRP. Methods: We included 1,152 Framingham Heart Study (FHS) participants over the age of 55, free of stroke and dementia, from the Original and Offspring cohorts with available MRI and FSRP data. CSVD score was calculated by summing the number of CSVD features detected in the MRI: cerebral microbleeds, cerebral brain infarcts, extensive white matter hyperintensities, severe perivascular spaces, and cortical superficial siderosis. Two Cox proportional hazards regression models were used to relate the multi-marker CSVD score to incident all-cause dementia and Alzheimer’s dementia. The first model adjusted for education, cohort, and clinical risk factors while the second adjusted for education, cohort, and FSRP. Results: Mean age was 70.9 years (SD: 8.7), 527 (46%) were male, and 211 (18%) had score ≥ 2. Over a median follow-up time of 6.4 years (Q1-Q3: 4.6-11.3), participants with score ≥ 2 had elevated risk of all-cause dementia compared to those with no CSVD markers after adjustment for FSRP (HR: 2.32; 95% CI: 1.46-3.69; p&lt;0.001) and vascular risk factors (HR: 1.76; 95% CI: 1.10-2.81; p=0.02). Score ≥ 2 was also significantly associated with AD after adjustment for FSRP (HR: 2.05; 95% CI: 1.19-3.62; p&lt;0.01), but not vascular risk factors (HR: 1.50; 95% CI: 0.87-2.60; p=0.15). In addition, a 5-percent increase in FSRP was independently associated with incident dementia after adjustment for education and FHS cohort (HR: 1.21; 95% CI: 1.13-1.30; p&lt;0.001). Conclusions: Our results support the use of CSVD score as an indicator for dementia risk and it may be as robust as the FSRP. Further studies are necessary to validate the use of CSVD score in quantifying dementia risk.

Abstract TP152: Systolic Blood Pressure Variability Characteristics Increase With Severity Among Intracerebral Hemorrhage Patients

Introduction: Selected studies link high systolic blood pressure variability (SBPV) to poor patient outcome after intracerebral hemorrhage (ICH). SBPV levels during real-world ICH admission remain unknown, however. We profile SBPV across ICH patient characteristics. Methods: Clinical data for adult patients (≥18) with primary non-traumatic ICH were retrieved from the electronic medical records. Patient SBPV was calculated as the Coefficient of Variation (CV; CV = (Standard Deviation/Mean)*100) during the first 24 hours of admission and across whole hospitalization. Hemorrhage characteristics and cerebral small vessel disease burden (CSVD; STRIVE 2.0 criteria) were assessed from neuroimaging during admission. Severe CSVD was assessed at summary scores ≥3. Cerebral Amyloid Angiopathy (CAA) was graded via Modified Boston Criteria. Descriptive statistics are provided for SBPV during first 24 hours of admission and whole-stay. Population differences are assessed using Mann Whitney Rank Sum and Kruskal Wallis tests of hypothesis. Results: Patient cohort included 2,020 primary ICH patients (median age: 67, IQR: [55-77]; 45.2% female), with an ethno-racial distribution of 43.6% White, 23.3% Black, 22.5% Hispanic, 8.2% Asian, and 2.5% Other. Median hemorrhage volume was 12.1 [1.9-36.3] cm 3 ; SBPVs over the first 24-hours and whole-stay were 12.6 [9.9-16.2] (Mean: 13.7; Skewness: 1.9; Kurtosis; 11.3) and 12.5 [10.7-15.0] (Mean: 13.4; Skewness: 3.05; Kurtosis; 21.3), respectively. SBPV significantly increased with female sex, worsening discharge disposition, increasing Glasgow Coma Scale severity, hemorrhage volume, intraventricular hemorrhage presence, and severe CSVD. Increasing CAA tiers showed reductions in SBPV. (Figure 1) Discussion: Levels of SBPV during ICH vary across patient characteristics and are elevated in those with more severe hemorrhage characteristics and worse hospital outcomes.

Abstract TP15: Association Between Prevalent Cardiovascular Disease Plus Atrial Fibrillation and Global Cerebral Small Vessel Disease- The Framingham Heart Study

Background: Cardiovascular diseases (CVD) contribute to stroke and dementia, which can be due to cerebral small vessel disease (CSVD) detectable on brain MRI. Aim: To determine the association between prevalent CVD and atrial fibrillation (AF) with CSVD. Methods: We assessed a composite of CVD including coronary heart disease, intermittent claudication, congestive heart failure (CHF) and AF, as well as the individual components. A multi-marker CSVD score was used to reflect increasing CSVD burden (cerebral microbleeds, high burden perivascular spaces, extensive white matter hyperintensity, or covert brain infarcts were assigned 1 point each, range 0-4). We related prevalent CVD or the individual components to the CSVD score using logistic regression analyses adjusted for age, sex, FHS cohort, time between MRI-clinic exam (model-1), and vascular risk factors (model-2). Results: In 3413 participants (mean age 59±14 years, 46.6% males), 8.4% had prevalent CVD, 4.1% had AF and 10.9% had both. One CSVD marker was seen in 22.7% participants, two in 7.1% and ≥3 in 1.82%. In multivariable-adjusted analyses prevalent CVD was associated with presence of one CSVD marker (OR 1.40, 95% confidence interval [CI] 1.07-1.84). The association with 2 or ≥3 markers did not reach statistical significance. The strongest association with subtype of CVD was between CHF and ≥3 CSVD markers (OR 5.67, 95% CI 1.90-16.9). Stratified analyses in subgroups by hypertension status, APOE- ε4 presence, and age &lt; 65 years were limited by smaller number of events, with no significant differences. Interpretation: Prevalent CVD (including AF) is associated with presence of CSVD in community dwelling middle-aged adults free of stroke and dementia, with stronger associations with CHF.

The association between alpha diversity of gut microbiota, neuroimaging markers and cognitive function in cerebral small vessel disease

There is increasing recognition of gut microbial dysbiosis in cerebral small vessel disease (CSVD). The altered diversity in a single ecosystem - alpha diversity index of gut microbiota has attracted wide attention. Our study aims to determine whether the alpha diversity index differs among healthy control (HC), CSVD with and without cognitive impairment. Moreover, we investigate the correlation between the alpha diversity index, neuroimaging markers, and cognitive function. We recruited 40 HC, 43 CSVD patients without cognitive impairment (CSVD-NCI), and 35 CSVD patients with mild cognitive impairment (CSVD-MCI). Clinical and neuropsychological assessments, MRI scanning, and gut microbiota analysis were performed on all participants. The alpha diversity indexes Chao1 and Shannon were calculated to evaluate community richness and diversity in a sample, respectively. Individual neuroimaging markers of CSVD and the CSVD burden score were also evaluated. A significantly lower level of Chao 1 rather than the Shannon index was observed in the CSVD subgroups than in the HC group. The level of the Chao 1 index was negatively correlated with both CMB counts, a neuroimaging characteristic of CSVD, and CSVD burden score in patients with CSVD. Additionally, the Chao 1 index has been associated with general cognitive function, information processing speed, and language function in patients with CSVD. Remarkably, the increased CSVD burden score mediated the effects of decreased levels of Chao 1 on information processing speed and language function. Hence, the alterations in species richness may be associated with CSVD-related cognitive impairment and mediated by CSVD neuroimaging markers.

White matter microstructure alterations in type 2 diabetes mellitus and its correlation with cerebral small vessel disease and cognitive performance

Microstructural abnormalities of white matter fiber tracts are considered as one of the etiology of diabetes-induced neurological disorders. We explored the cerebral white matter microstructure alteration accurately, and to analyze its correlation between cerebral small vessel disease (CSVD) burden and cognitive performance in type 2 diabetes mellitus (T2DM). The clinical-laboratory data, cognitive scores [including mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), California verbal learning test (CVLT), and symbol digit modalities test (SDMT)], CSVD burden scores of the T2DM group (n = 34) and healthy control (HC) group (n = 21) were collected prospectively. Automatic fiber quantification (AFQ) was applied to generate bundle profiles along primary white matter fiber tracts. Diffusion tensor images (DTI) metrics and 100 nodes of white matter fiber tracts between groups were compared. Multiple regression analysis was used to analyze the relationship between DTI metrics and cognitive scores and CSVD burden scores. For fiber-wise and node-wise, DTI metrics in some commissural and association fibers were increased in T2DM. Some white matter fiber tracts DTI metrics were independent predictors of cognitive scores and CSVD burden scores. White matter fiber tracts damage in patients with T2DM may be characterized in specific location, especially commissural and association fibers. Aberrational specific white matter fiber tracts are associated with visuospatial function and CSVD burden.

The association of global vessel width with cognitive decline and cerebral small vessel disease burden in the KaiLuan study.

As the retinal microvasculature shares similarities with the cerebral microvasculature, numerous studies have shown that retinal vascular is associated with cognitive decline. In addition, several population-based studies have confirmed the association between retinal vascular and cerebral small vessel disease (CSVD) burden. However, the association of retinal vascular with CSVD burden as well as cognitive function has not been explored simultaneously. This study investigated the relations of retinal microvascular parameters (RMPs) with CSVD burden and cognitive function. We conducted a cross-sectional study of participants in the KaiLuan study. Data were collected from subjects aged ≥18 years old who could complete retinal photography and brain magnetic resonance imaging (MRI) between December 2020 to October 2021 in the Kailuan community of Tangshan. RMPs were evaluated using a deep learning system. The cognitive function was measured using the Montreal Cognitive Assessment (MoCA). We conducted logistic regression models, and mediation analysis to evaluate the associations of RMPs with CSVD burden and cognitive decline. Of the 905 subjects (mean age: 55.42±12.02 years, 54.5% female), 488 (53.9%) were classified with cognitive decline. The fractal dimension (FD) [odds ratio (OR), 0.098, 95% confidence interval (CI): 0.015-0.639, P=0.015] and global vein width (OR: 1.010, 95% CI: 1.005-1.015, P<0.001) were independent risk factors for cognitive decline after adjustment for potential confounding factors. The global artery width was significantly associated with severe CSVD burden (OR: 0.985, 95% CI: 0.974-0.997, P=0.013). The global vein width was sightly associated with severe CSVD burden (OR: 1.005, 95% CI: 1.000-1.010, P=0.050) after adjusting for potential confounders. The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of global vein width were 1.290 (0.901-1.847) for cognitive decline and 1.546 (1.004-2.290) for severe CSVD burden, respectively. Moreover, CSVD burden played a partial mediating role in the association between global vein width and cognitive function (mediating effect 6.59%). RMPs are associated with cognitive decline and the development of CSVD. A proportion of the association between global vein width and cognitive decline may be attributed to the presence of CSVD burden.