Periventricular White Matter Hyperintensities Volume Research Articles

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen’s criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

Serum albumin and white matter hyperintensities

People living with HIV and those diagnosed with alcohol use disorders (AUD) relative to healthy individuals commonly have low levels of serum albumin, substantiated as an independent predictor of cardiovascular events. White matter hyperintensities (WMH)—a neuroimaging feature of cerebral small vessel disease—are also related to cardiovascular disease. Despite consensus regarding associations between high levels of urine albumin and WMH prevalence, and low serum albumin levels and impaired cognitive functioning, relations between serum albumin and WMH burdens have rarely been evaluated. Here, a sample including 160 individuals with AUD, 142 living with HIV, and 102 healthy controls was used to test the hypothesis that serum albumin would be inversely related to WMH volumes and directly related to cognitive performance in the two diagnostic groups. Although serum albumin and periventricular WMH volumes showed an inverse relationship in both AUD and HIV groups, this relationship persisted only in the HIV group after consideration of traditional cardiovascular (i.e., age, sex, body mass index (BMI), nicotine use, hypertension, diabetes), study-relevant (i.e., race, socioeconomic status, hepatitis C virus status), and disease-specific (i.e., CD4 nadir, HIV viral load, HIV duration) factors. Further, serum albumin contributed more significantly than periventricular WMH volume to variance in performance on a verbal learning and memory composite score in the HIV group only. Relations in both HIV and AUD groups between albumin and hematological red blood cell markers (e.g., hemoglobin, hematocrit) suggest that in this sample, serum albumin reflects hematological abnormalities. Albumin, a simple serum biomarker available in most clinical settings, may therefore help identify periventricular WMH burden and performance levels in specific cognitive domains in people living with HIV. Whether serum albumin contributes mechanistically to periventricular WMH in HIV will require additional investigation.

Association between white matter hyperintensity and anxiety/depression.

Although previous studies have explored the associations of white matter hyperintensity with psychiatric disorders, the sample size is small and the conclusions are inconsistent. The present study aimed to further systematically explore the association in a larger sample. All data were extracted from the UK Biobank. First, general linear regression models and logistic regression models were used to assess the association between white matter hyperintensity volume and anxiety/depression. White matter hyperintensity has been classified into periventricular white matter hyperintensity and deep white matter hyperintensity. Anxiety was determined by General Anxiety Disorder-7 score (n = 17,221) and self-reported anxiety (n = 15,333), depression was determined by Patient Health Questionnaire-9 score (n = 17,175), and self-reported depression (n = 14,519). Moreover, we employed Cox proportional hazard models to explore the association between white matter hyperintensity volume and anxiety/depression. The covariates included in fully adjusted model are age, gender, body mass index, Townsend deprivation index, healthy physical activity, cigarette consumption, alcohol consumption, educational attainment, diabetes, hypertension, and coronary heart disease. The results of the fully adjusted model showed that white matter hyperintensity volume was significantly associated with General Anxiety Disorder-7 score (periventricular white matter hyperintensity: β = 0.152, deep white matter hyperintensity: β = 0.094) and Patient Health Questionnaire-9 score (periventricular white matter hyperintensity: β = 0.168). Logistic regression analysis results indicated that periventricular white matter hyperintensity volume (odds ratio = 1.153) was significantly associated with self-reported anxiety. After applying the Cox proportional hazard models, we found that larger white matter hyperintensity volume was associated with increased risk of depression (periventricular white matter hyperintensity: hazard ratio = 1.589, deep white matter hyperintensity: hazard ratio = 1.200), but not anxiety. In summary, our findings support a positive association between white matter hyperintensity volume and depression.

Correlation between white matter hyperintensity and delusional symptoms in Alzheimer’s disease

BackgroundPatients with Alzheimer’s disease (AD) often exhibit neuropsychiatric symptoms (NPS), particularly delusions. Previous studies have shown an association between white matter hyperintensities (WMH) and specific NPS. This study aims to explore the relationship between WMH volume and delusions in AD patients by comparing the WMH volumes of delusional and non-delusional subgroups.Methods80 AD patients were divided into a delusion group (n = 36) and a non-delusion group (n = 44) based on the Neuropsychiatric Inventory (NPI). The brain cortical volume and WMH volume were quantitatively calculated for all 80 patients, including total WMH volume, periventricular WMH (PVWMH) volume, deep WMH volume, as well as bilateral frontal lobe, temporal lobe, parietal lobe, and occipital lobe WMH volumes. Firstly, we compared the differences in WMH volumes between the delusion group and non-delusion group. Then, within the delusion group, we further categorized patients based on severity scores of their delusional symptoms into mild (1 point), moderate (2 points), or severe groups (3 points). We compared the WMH volumes among these three groups to investigate the role of WMH volume in delusional symptoms.ResultsThere was a significant difference in left occipital lobe WMH volume between the delusion group and non-delusion group(P < 0.05). Within the delusion group itself, there were significant differences in overall WMH volume as well as PVWMH volume among patients with mild or severe levels of delusions(P < 0.05).ConclusionLeft occipital lobe WMH volume may be associated with the occurrence of delusional AD patients, and the total volume of whole-brain WMH and PVWMH volume may affect the degree of severity of delusional symptoms.

Regional differences in the link between water exchange rate across the blood–brain barrier and cognitive performance in normal aging

The blood–brain barrier (BBB) undergoes functional changes with aging which may contribute to cognitive decline. A novel, diffusion prepared arterial spin labeling-based MRI technique can measure the rate of water exchange across the BBB (kw) and may thus be sensitive to age-related alterations in water exchange at the BBB. However, studies investigating relationships between kw and cognition have reported different directions of association. Here, we begin to investigate the direction of associations between kw and cognition in different brain regions, and their possible underpinnings, by evaluating links between kw, cognitive performance, and MRI markers of cerebrovascular dysfunction and/or damage. Forty-seven healthy older adults (age range 61–84) underwent neuroimaging to obtain whole-brain measures of kw, cerebrovascular reactivity (CVR), and white matter hyperintensity (WMH) volumes. Additionally, participants completed uniform data set (Version 3) neuropsychological tests of executive function (EF) and episodic memory (MEM). Voxel-wise linear regressions were conducted to test associations between kw and cognitive performance, CVR, and WMH volumes. We found that kw in the frontoparietal brain regions was positively associated with cognitive performance but not with CVR or WMH volumes. Conversely, kw in the basal ganglia was negatively associated with cognitive performance and CVR and positively associated with regional, periventricular WMH volume. These regionally dependent associations may relate to different physiological underpinnings in the relationships between kw and cognition in neocortical versus subcortical brain regions in older adults.

Correlation between enlarged perivascular space and brain white matter hyperintensities in patients with recent small subcortical infarct.

This study aimed to investigate the correlation between enlarged perivascular space (EPVS) and white matter hyperintensities (WMH) at different locations in patients with recent small subcortical infarct (RSSI). Data were collected from patients with RSSI who were hospitalized at Changzhou Second People's Hospital between October 2020 and December 2021. All patients underwent cranial magnetic resonance imaging, and the grades of EPVS and WMH were assessed, including basal ganglia EPVS (BG-EPVS), centrum semiovale EPVS (CSO-EPVS), deep WMH (DWMH), and periventricular WMH (PWMH). The volumes of EPVS and WMH at different locations were quantified using 3D Slicer software. Patients were grouped according to the severity of BG-EPVS and CSO-EPVS. Univariate and multivariate analyses were used to analyze the relationship between EPVS and WMH. A total of 215 patients with RSSI were included in the analysis. Patients with moderate-to-severe BG-EPVS had higher DWMH and PWMH severity than those with mild BG-EPVS, both in terms of volume and grade. There was no significant difference in WMH severity between patients with mild CSO-EPVS and those with moderate-to-severe CSO-EPVS. Multivariate analysis indicated that after adjustments were made for confounding factors, DWMH volume (β=0.311; 95% CI, 0.089-0.400; p=.002) and PWMH volume (β=0.296; 95% CI, 0.083-0.424; p=.004) were independently associated with BG-EPVS. Pearson correlation showed that PWMH volume (r=.589; p<.001) and DWMH volume (r=.596; p<.001) were positively related to BG-EPVS volume. DWMH and PWMH are closely related to BG-EPVS in patients with RSSI.

Association of blood pressure with brain perfusion and structure: A population-based prospective study

PurposeTo explore the association of blood pressure (BP) measurements with cerebral blood flow (CBF) and brain structure in general population. MethodThis prospective study included 902 participants from Kailuan community. All participants underwent brain MRI and BP measurements. The association of BP indicators with CBF, brain tissue volume and white matter hyperintensity (WMH) volume were investigated. In addition, mediation analysis was used to determine whether significantly changed brain tissue volume explained associations between BP and CBF. ResultsElevated diastolic BP (DBP), but not systolic BP (SBP), was associated with lower CBF in the total brain (β [95 % CI]: −0.62 [−1.14, −0.10]), total gray matter (β [95 % CI]: −0.71 [−1.27, −0.14]), hippocampus (β [95 % CI]: −0.59 [−1.13, −0.05]), frontal (β [95 % CI]: −0.72 [−1.31, −0.13]), parietal (β [95 % CI]: −0.92 [−1.54, −0.3]), temporal (β [95 % CI]: −0.63 [−1.18, −0.08]), and occipital lobe (β [95 % CI]: −0.69 [−1.37, −0.01]). Higher SBP and DBP were associated with reduced total and regional brain tissue volume (all p < 0.05). Increased SBP and PP were associated with higher total and periventricular WMH volume (all p < 0.05). In addition, mediation analysis identified that significantly decreased brain volume did not mediate the associations of BP measurements and lower CBF in corresponding region (all p > 0.05). ConclusionsElevated BP level was associated with decreased total and regional CBF and brain tissue volume and increased WMH burden.

Characteristics and Clinical Implication of White Matter Lesions in Patients With Adult Moyamoya Disease.

White matter hyperintensities (WMHs) are reportedly increased in moyamoya disease (MMD); however, their clinical importance is not well-established owing to their pathophysiologic heterogeneity by distribution. This study aimed to evaluate the burden and pattern of WMHs and its clinical implications in the MMD trajectory. Adult patients with MMD without significant structural lesions were 1:1 propensity score-matched with healthy controls for sex and vascular risk factors. The total, periventricular, and subcortical WMH volumes were segmented and quantified fully automatically. WMH volumes were detrended by age and compared between the 2 groups. MMD severity based on Suzuki stage and future ischemic events were assessed for their association with WMH volumes. A total of 161 pairs of patients with MMD and controls were analyzed. MMD significantly correlated with increased total WMH volume (B [standard error], 0.126 [0.030]; p < 0.001), periventricular WMH volume (0.114 [0.027]; p < 0.001), and periventricular-to-subcortical ratio (0.090 [0.034]; p = 0.009). In the MMD subgroup (n = 187), advanced MMD had an independent association with the total WMH volume (0.120 [0.035]; p < 0.001), periventricular WMH volume (0.110 [0.031]; p < 0.001), and periventricular-to-subcortical ratio (0.139 [0.038]; p < 0.001). Periventricular WMH volume (adjusted hazard ratio [95% confidence interval], 5.12 [1.26-20.79]) and periventricular-to-subcortical ratio (3.80 [1.51-9.56]) were associated with future ischemic events in patients with medically followed up MMD. However, no demonstrable association was found between subcortical WMH volume and MMD, MMD severity, or future ischemic events. Periventricular WMHs, but not subcortical WMHs, may represent the main pathophysiology of MMD. Periventricular WMHs may be used as a marker for ischemic vulnerability in patients with MMD.

Clonal hematopoiesis with DNMT3A mutation is associated with lower white matter hyperintensity volume.

Clonal hematopoiesis of indeterminate potential (CHIP) increases the risk of cerebrovascular events, while its association with cerebral white matter hyperintensity (WMH) is undemonstrated. We evaluated the effect of CHIP and its major driving mutations on cerebral WMH severity. From an institutional cohort of a routine health check-up program with a DNA repository database, subjects who were ≥50 years of age, with one or more cardiovascular risk factors but no central nervous system disorder, and performed brain MRI were included. Along with the presence of CHIP and its major driving mutations, clinical and laboratory data were obtained. WMH volume was measured in total, periventricular, and subcortical regions. Among the total 964 subjects, 160 subjects were classified as CHIP positive group. CHIP was most frequently associated with DNMT3A mutation (48.8%), followed by TET2 (11.9%) and ASXL1 (8.1%) mutations. Linear regression analysis adjusting for age, sex, and conventional cerebrovascular risk factors suggested that CHIP with DNMT3A mutation was associated with the lower log-transformed total WMH volume, unlike other CHIP mutations. When classified according to variant allele fraction (VAF) value of DNMT3A mutation, higher VAF classes were associated with the lower log-transformed total WMH and the lower log-transformed periventricular WMH volume, but not with the log-transformed subcortical WMH volumes. Clonal hematopoiesis with DNMT3A mutation is quantitatively associated with a lower volume of cerebral WMH, especially in the periventricular region. CHIP with DNMT3A mutation might have a protective role in the endothelial pathomechanism of WMH.

Abstract 115: Periventricular But Not Subcortical White Matter Lesions Are Associated With Adult Moyamoya Disease

Introduction: White matter hyperintensities (WMH) are reportedly increased in moyamoya disease (MMD); however, their clinical importance is not well-established owing to their pathophysiological heterogeneity by distribution. This study aimed to evaluate the burden and pattern of WMH and its clinical implications in the MMD trajectory. Methods: Adult MMD patients without significant structural lesions were 1:1 propensity score-matched with healthy controls for sex and vascular risk factors. The total, periventricular, and subcortical WMH volumes were segmented and quantified fully automatically. WMH volumes were detrended by age and compared between the two groups. MMD severity based on Suzuki stage and future ischemic events were assessed for their association with WMH volumes. Results: A total of 190 pairs of patients with MMD and controls were analyzed. MMD significantly correlated with increased total (B, 0.086; standard error [SE], 0.027; p=0.002) and periventricular WMH volumes (B, 0.079; SE, 0.025; p=0.002). In the MMD subgroup, advanced MMD had an independent positive association with the total (B, 0.124; SE, 0.034; p&lt;0.001) and periventricular WMH volumes (B, 0.116; SE, 0.030; p&lt;0.001). Periventricular WMH volume was associated with future ischemic events (adjusted hazard ratio [aHR], 4.96; 95% confidence intervals [CIs], 1.21-20.25) in medically followed-up MMD patients. However, no demonstrable association was found between subcortical WMH volume and MMD (B, 0.007; SE, 0.007; p=0.35), MMD severity (B, 0.010; SE, 0.011; p=0.37), or future ischemic events (aHR, 14.15; 95% CIs, 0.20-1022.96). Conclusions: Periventricular WMH, but not subcortical WMH, may represent the main pathophysiology of MMD. Periventricular WMH may be used as a marker for ischemic vulnerability in patients with MMD.

Association between sub‐classified white matter hyperintensities (WMH) volume and and cognitive function in patients with Alzheimer`s disease

AbstractBackgroundWMH in MRI are common among the elderly. WMH are associated with increased cognitive impairment and risk of Alzheimer`s disease (AD). Although WMH contribute to AD pathology, their clinical implications are not fully understood. This study aimed to assess whether WMH predict AD and investigate the association between WMH (including subclassified WMH volume) and cognitive function in AD.MethodThis study enrolled 171 patients with AD. All participants underwent clinical evaluations including brain MRI study and neuropsychological tests using the CERAD‐K neuropsychological assessment battery. In addition, Charlson comorbidity index, the Korean version of the Geriatric Depression Scale short from were administered. WMH volume was calculated using automated quantification method with SPM and MATLAB image processing software. WMH were classified according to the distance from the ventricular surface. WMH located in juxtaventricular areas, within 3 mm from the ventricular surface, were classified as juxtaventricular with matter hyperintensities (JVWMH). WMH located within 3–13 mm or farther than 13 mm from the ventricular surface were classified as periventricular white matter hyperintensities (PVWMH) or deep white matter hyperintensities (DWMH), respectively. WMH volume data were right‐skewed. Consequently, WMH volume data were logarithmic transformed.ResultThe AD group had a higher mean WMH volume(20.7 ± 18.2 ml). Multivariate linear regression analysis showed that total WMH volume in AD was associated with poor performance in categorical verbal fluency test (p = 0.008) and word list memory test (p = 0.023). JVWMH volume in AD was associated with poor performance on categorical verbal fluency test (p = 0.013) and digit span test forward (p = 0.037). PVWMH volume in AD was associated with poor performance on categorical verbal fluency test (p = 0.011) and word list memory test (p = 0.021), whereas DWMH volume showed no association with cognitive dysfunction in AD.ConclusionTotal WMH, JVWMH and PVWMH were associated specifically with executive function, immediate memory, and working memory, independently of hippocampal atrophy in AD. WMH were associated with AD risk and cognitive dysfunction differentially according to the distance from the ventricular surface.

Association between Serum Amyloid A Level and White Matter Hyperintensity Burden: a Cross-Sectional Analysis in Patients with Acute Ischemic Stroke.

This work aimed to determine the potential link between white matter hyperintensity (WMH) burden and serum amyloid A (SAA) level in patients with acute ischemic stroke. Consecutive patients with acute large artery atherosclerosis (LAA) stroke between April 2021 and May 2022 were included. WMH volumes (periventricular, deep, and total) were measured using the Fazekas score and a semiautomated volumetric analysis on fluid-attenuated inversion recovery-magnetic resonance imaging. The burdens of WMH were scored to assess the dose-dependent association between SAA and WMH volume. Multivariate regression and a two-piecewise linear regression model were used to evaluate whether SAA levels are an independent predictor of WMH, and to discover the threshold effect or saturation effect of SAA levels with respect to WMH volume. The mean age of patients was 63.2 ± 11.5years, with 65.9% men. The median SAA level was 3.93mg/L and the total WMH volume of 6.86cm3. In the multivariable analysis, SAA remained an independent predictor of total WMH volume [β = 0.82, 95% confidence interval (CI) = 0.49-1.07, p < 0.001], periventricular WMH volume (adjusted β = 0.76, 95% CI = 0.46-1.07, p < 0.001), and deep WMH volume (adjusted β = 0.26, 95% CI = 0.06-0.45, p = 0.011) after controlling for confounders. Furthermore, SAA levels were associated with periventricular Fazekas score, deep Fazekas score, and Fazekas grades. Threshold effect and saturation effect analyses demonstrated a nonlinear relationship between SAA levels and periventricular white matter hyperintensity (PVWMH) volumes, with SAA levels (2.12-19.89mg/L) having significant dose-dependent relationships with periventricular WMH volumes (adjusted β = 1.98, 95% CI = 1.12-2.84, p < 0.001). SAA level ranging from 2.12 to 19.89mg/L is dose-dependently associated with periventricular WMH development. These findings point the way forward for future research into the pathophysiology of WMH.

Menopausal Vasomotor Symptoms and White Matter Hyperintensities in Midlife Women.

The menopause transition is increasingly recognized as a time of importance for women's brain health. A growing body of work indicates that the classic menopausal symptom, vasomotor symptom (VMS), may be associated with poorer cardiovascular health. Other work links VMS to poorer cognition. We investigate whether VMS, when rigorously assessed using physiologic measures, are associated with greater white matter hyperintensity volume (WMHV) among midlife women. We consider a range of potential explanatory factors in these associations and explore whether VMS are associated with the spatial distribution of WMHV. Women aged 45-67 years and free of hormone therapy underwent 24 hours of physiologic VMS monitoring (sternal skin conductance), actigraphy assessment of sleep, physical measures, phlebotomy, and 3 Tesla neuroimaging. Associations between VMS (24-hour, wake, and sleep VMS, with wake and sleep intervals defined by actigraphy) and whole brain WMHV were considered in linear regression models adjusted for age, race, education, smoking, body mass index, blood pressure, insulin resistance, and lipids. Secondary models considered WMHV in specific brain regions (deep, periventricular, frontal, temporal, parietal, and occipital) and additional covariates including sleep. The study sample included 226 women. Physiologically assessed VMS were associated with greater whole brain WMHV in multivariable models, with the strongest associations observed for sleep VMS (24-hour VMS, B[SE] = 0.095 [0.045], p = 0.032; Wake VMS, B[SE] = 0.078 [0.046], p = 0.089, Sleep VMS, B[SE] = 0.173 [0.060], p = 0.004). Associations were not accounted for by additional covariates including actigraphy-assessed sleep (wake after sleep onset). When considering the spatial distribution of WMHV, sleep VMS were associated with both deep WMHV, periventricular WMHV, and frontal lobe WMHV. VMS, particularly VMS occurring during sleep, were associated with greater WMHV. Identification of female-specific midlife markers of poor brain health later in life is critical to identify women who warrant early intervention and prevention. VMS have the potential to serve as female-specific midlife markers of brain health in women.

Different mechanisms in periventricular and deep white matter hyperintensities in old subjects.

ObjectiveAlthough multiple pieces of evidence have suggested that there are different mechanisms in periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs), the exact mechanism remains uncertain.MethodsWe reviewed clinical and imaging data of old participants from a local She Ethnic group. We assessed the cerebral blood flow of white matter (WM-CBF) on arterial spin-labeling, deep medullary veins (DMVs) visual score on susceptibility-weighted imaging, and index for diffusion tensor image analysis along the perivascular space (ALPS index), indicating glymphatic function on diffusion tensor imaging. Furthermore, we investigated their relationships with volumes of PWMHs and DWMHs.ResultsA total of 152 subjects were included, with an average age of 63 ± 8 years old. We found that higher age and history of hypertension were independently related to higher volumes of both PWMHs and DWMHs (all p < 0.05). Lower ALPS index was independently associated with higher PWMHs volumes (β = 0.305, p < 0.001), and this relationship was accounted for by the indirect pathway via DMVs score (β = 0.176, p = 0.017). Both lower ALPS index and WM-CBF were independent risk factors for higher DWMHs volumes (β = −0.146, p = 0.041; β = −0.147, p = 0.036).ConclusionsOur study indicated that there were different mechanisms in PWMHs and DWMHs. PWMHs were mainly attributed to the damage of veins due to the dysfunction of the glymphatic pathway, while DWMHs could be affected by both ischemia-hypoperfusion and dysfunction of the glymphatic pathway.Advances in knowledgeThe relationship between glymphatic dysfunction and PWMHs might be accounted for by the indirect pathway via venous abnormalities, a glymphatic dysfunction, and lower CBF in white matter were independent risk factors for DWMHs.

Association of Vascular Properties With the Brain White Matter Hyperintensity in Middle-Aged Population.

BackgroundThe periventricular white matter is more sensitive to the systemic hemodynamic alterations than the deep white matter because of differences in its vascular structure and systemic circulation relationship. We hypothesize that periventricular white matter hyperintensity (PVWMH) volume shows greater association than deep white matter hyperintensity (DWMH) volume with vascular properties (VPs) reflecting arterial stiffness and cardiovascular remodeling, indicators of the systemic circulation.Methods and ResultsA total of 426 participants (age, 59.0±6.1 years; 57.5% women; and 39.7% Black race) in the Genetic Study of Atherosclerosis Risk who were aged ≥50 years and had brain magnetic resonance imaging were studied. VPs included pulse pressure, hypertensive response to exercise, diastolic brachial artery diameter, diastolic common carotid artery diameter, common carotid artery distensibility coefficient, and left ventricular function. The relative associations of VPs with PVWMH and DWMH as multiple measures within the same individual were determined using multilevel linear models. We also determined if age modified the differences in VPs associations with PVWMH and DWMH. Our findings indicated that, within the same subject, PVWMH volume had greater association than DWMH volume with pulse pressure (P=0.002), hypertensive response to exercise (P=0.04), diastolic brachial artery diameter (P=0.012), and diastolic common carotid artery diameter (P=0.04), independent of age and cardiovascular risk factors. The differences of PVWMH versus DWMH associations with VPs did not differ at any age threshold.ConclusionsWe show, for the first time, that PVWMH has greater association than DWMH, independent of age, with vascular measurements of arterial stiffness and cardiovascular remodeling suggesting that changes in the systemic circulation affect the PVWMH and DWMH differently.

Abstract WP14: Association Of Vascular Properties With The Periventricular And Deep White Matter Hyperintensity In Middle-age Population

Introduction: The periventricular white matter is more sensitive to alterations in the hemodynamics of the systemic circulation than the deep white matter due to differences in its vascular supply and relationship to systemic circulation. We hypothesize that periventricular white matter hyperintensity volume (PVWMH) shows greater association than deep white matter hyperintensity (DWMH) volume with vascular property measures of arterial stiffness (AS) and cardiovascular remodeling, important indicators of the systemic circulation. Methods: Participants in the Genetic Study of Atherosclerosis Risk ≥ 50 years of age with brain MRI were selected. Vascular property measures included pulse pressure (PP), hypertension response to exercise (HRE), diastolic brachial artery (BA) diameter, diastolic common carotid artery (CCA) diameter, CCA distensibility coefficient, and left ventricular function. PVWMH and DWMH were measured using semi-automated segmentation approach. The relative associations of these parameters with PVWMH and DWMH volumes as multiple measures within the same individual further nested within families were determined using multilevel linear models. We also determined if differences between PVWMH and DWMH associations were modified by age. Results: 426 participants (age 59.0±6.1 years, 57.5% females, and 39.7% African American) were included. Within the same subject, PVWMH volume showed greater association than DWMH volume with PP (P=0.002), HRE (p=0.04), diastolic BA diameter (p=0.012), and diastolic CCA diameter (p=0.04) independent of age and cardiovascular risk factors. This difference in PVWMH versus DWMH association with vascular properties did not differ at any age threshold. Conclusions: We show for the first time that PVWMH volume has greater association than DWMH volume, independent of age, with vascular property measurements of AS and cardiovascular remodeling. Our findings suggest that changes in the systemic circulation may affect PVWMH and DWMH differently adding to a growing body of literature that PVWMH and DWMH may represent different phenotypes of cerebral small vessel disease.

Abstract WMP20: Association Of Periventricular And Deep White Matter Hyperintensity With Cognitive Performance In A Middle-aged Population

Introduction: White matter hyperintensity (WMH) has been associated with manual dexterity performance in apparently healthy middle-aged population. However, the relative effect of WMH topographic distribution on cognition remains unknown. We hypothesized that periventricular WMH (PVWMH) is more strongly associated with manual dexterity and cognitive measures compared to deep WMH (DWMH) given its proximity to the white matter tracts involved in motor and executive functions. Methods: Apparently healthy middle-aged participants in the Genetic Study of Atherosclerosis Risk with brain MRI and cognitive measurements were selected. Cognitive measures included delayed word recall short (DWRS) and long (DWRL), digit symbol substitution (DSS), word fluency (WF), digit span forward test (DSFT), backward (DSBT) and total (DSTS), and grooved peg board test (GPBT) including the dominant and non-dominant hand (GPBTD, GPBTnD). PVWMH and DWMH volumes were measured using semi-automated segmentation paradigm. The relative associations of these measurements with PVWMH and DWMH volumes as multiple measurements within the same individual further nested within families were determined using multilevel linear models adjusting for intracranial volume, age, sex and cardiovascular risk factors. Results: 782 subjects were included (age 51.1±10.6, 58.4% female and 39% African American, PVWMH volume 437.4 [0-1646] mm 3 , DWMH volume 273.5 [76-665] mm 3 ). Within the same subject, PVWMH showed greater association than DWMH with worse performance on GPBT, GPBTD, GPBTnD, DWRS, and DWRL (P=0.006, 0.01, 0.01, 0.01 and 0.03, respectively) after adjusting for age and other cardiovascular risk factors. There was no difference in the association of PVWMH versus DWMH volumes with DSS, WF, DSFT, DSBT, DSTS (P=0.19, 0.52, 0.13, 0.6, and 0.6, respectively). Conclusions: PVWMH shows greater association than DWMH with cognitive measures of manipulative manual dexterity and recall suggesting that PVWMH and DWMH may have different cognitive phenotypes in middle-aged population with cerebral small vessel disease.

Beyond WMH volume: Coalescence score as a new measure of cerebral small‐vessel disease pattern

AbstractBackgroundTotal white matter hyperintensity (WMH) volume is a hallmark of cerebral small vessel disease that is associated with accelerated cognitive decline and dementia onset. The shape of lesions is a key component of existing visual rating scales. While automated methods have been developed to assess WMH volume, evaluation of the lesion shape is still limited. We describe an automatic method to derive an overall coalescence score and investigate its association with Framingham cardiovascular risk score (FRS) and blood pressure (BP) in elderly individuals.Method750 individuals from the Southall And Brent Revisited cohort (age 71.1(6.9) years; 54.7% male) underwent brain MRI including 3D T1‐weighted and FLAIR images. WMH volumes were automatically segmented. Each non‐periventricular lesion (&lt;25% of the border touching the ventricles) was automatically classified into a coalescence category ranging from 0 to 4 describing its level of confluency (0 punctuate – 4 fully confluent) using derived shape features. An overall coalescence score (CS) was generated based on the proportion of lesions residing in each of the five categories with respect to the global WMH volume. Biological relevance of the coalescence score (log‐transformed due to its skewness) was evaluated by assessing its association with FRS and BP using linear regression adjusting for global WMH volume and proportion of excluded periventricular lesions as well as age and sex (BP).ResultFigure 1 presents the CS frequency distribution (a), its relationship with global WMH volume (b) and an example of how CS captures differences in WMH pattern independent of classical volumetric measurements (c) (same load but different CS). After correction for global and periventricular WMH volume and other confounders, there was a positive association between CS and FRS (mean[95% confidence interval] +6.9[3.7;10.2] %CS per 10% increase FRS; p&lt;0.0001), and with diastolic BP (+0.5[0;0.90] % per mmHg; p=0.04). There was no evidence of an association with systolic BP [+0.05[‐0.19;0.30]% per mmHg; p=0.63).ConclusionThe coalescence score provides an automated tool to quantify varying degrees of WMH confluency, which may lead to better understanding of the pathophysiology of WMH in the context of ageing, risk factors and dementia.

Effect of obstructive sleep apnea on cerebrovascular compliance and cerebral small vessel disease.

Reduced cerebrovascular compliance is the major mechanism of cerebral small vessel disease (SVD). Obstructive sleep apnea (OSA) also promotes SVD development, but the underlying mechanism was not elucidated. We investigated the association among OSA, cerebrovascular compliance, and SVD parameters. This study retrospectively included individuals ≥ 50 years of age, underwent overnight polysomnographic (PSG) for the evaluation of OSA, and performed MRI and transcranial Doppler (TCD) within 12 months of interval without a neurological event between the evaluations. TCD parameters for the cerebrovascular compliance included middle cerebral artery pulsatility index (MCA PI) and mean MCA resistance index ratio (MRIR). SVD parameters included white matter hyperintensity (WMH) volume, number of lacunes, enlarged perivascular space (ePVS) score, and the presence of microbleeds or lacunes. Ninety-seven individuals (60.8% male, mean age 70.0±10.5 years) were included. MRIR was associated with higher respiratory distress index (B = 0.003; 95% confidence interval [CI] 0.001-0.005; P = 0.021), while MCA PI was not associated with any of the PSG markers for OSA severity. Apnea-hypopnea index was associated with the log-transformed total WMH volume (B = 0.008; 95% confidence interval [CI] 0.001-0.016; P = 0.020), subcortical WMH volume (B = 0.015; 95% CI 0.007-0.022; P<0.001), total ePVS score (B = 0.024; 95% CI 0.003-0.045; P = 0.026), and centrum semiovale ePVS score (B = 0.026; 95% CI 0.004-0.048; P = 0.019), and oxygen-desaturation index with periventricular WMH volume, independently from age, MCA PI, and MRIR. This study concluded that OSA is associated with reduced cerebrovascular compliance and also with SVD independently from cerebrovascular compliance. Underlying pathomechanistic link might be region specific.

Editors' Note: White Matter Hyperintensities Mediate the Association of Nocturnal Blood Pressure With Cognition

In “White Matter Hyperintensities Mediate the Association of Nocturnal Blood Pressure With Cognition,” Chesebro et al. reported that patients with hypertension who have reverse dipping of blood pressure (night/day blood pressure ratio >1) have elevated periventricular white matter hyperintensity volume on MRI and lower memory scores on neuropsychological testing. Fisher et al. noted that they had similar findings in a prior cohort, although their reverse dippers had higher white matter hyperintensity volume in all locations. Chesebro responded that they may have only seen a regional, rather than global, relationship between white matter hyperintensities and blood pressure because their participants were younger than those included in the study by Fisher et al. Chesebro et al. and Fisher et al. agree that (1) these findings support nighttime administration of antihypertensives and (2) additional studies on tract-specific analysis of white matter changes in this patient population are needed. Chesebro et al. further noted that more research on the optimal timing and frequency of blood pressure assessment is warranted. Cimolai reiterated the importance of these findings in demonstrating the intimate connection between hypertension and cerebrovascular disease. In “White Matter Hyperintensities Mediate the Association of Nocturnal Blood Pressure With Cognition,” Chesebro et al. reported that patients with hypertension who have reverse dipping of blood pressure (night/day blood pressure ratio >1) have elevated periventricular white matter hyperintensity volume on MRI and lower memory scores on neuropsychological testing. Fisher et al. noted that they had similar findings in a prior cohort, although their reverse dippers had higher white matter hyperintensity volume in all locations. Chesebro responded that they may have only seen a regional, rather than global, relationship between white matter hyperintensities and blood pressure because their participants were younger than those included in the study by Fisher et al. Chesebro et al. and Fisher et al. agree that (1) these findings support nighttime administration of antihypertensives and (2) additional studies on tract-specific analysis of white matter changes in this patient population are needed. Chesebro et al. further noted that more research on the optimal timing and frequency of blood pressure assessment is warranted. Cimolai reiterated the importance of these findings in demonstrating the intimate connection between hypertension and cerebrovascular disease.