Deep White Matter Hyperintensities Research Articles

Inferior Frontal Sulcal Hyperintensity on Fluid-Attenuated Inversion Recovery Is Related to Cerebrospinal Fluid Clearance via Putative Meningeal Lymphatics.

Inferior frontal sulcal hyperintensity (IFSH) on FLAIR sequence may indicate elevated cerebrospinal fluid (CSF) wastes. The objective of this study was to investigate its association with the clearance function of putative meningeal lymphatic vessels (mLVs). We included patients who underwent FLAIR sequence and dynamic contrast MRI with intrathecal administration of contrast agent. The visibility of IFSH was quantitatively assessed by measuring the mean signal intensity of inferior frontal sulci on 2D FLAIR. The clearance function of putative mLVs was defined as the percentage change of signal unite ratio in the parasagittal dura from baseline to 4.5, 15 and 39 hours after intrathecal injection on dynamic contrast MRI. Additionally, imaging markers of cerebral small vessel disease, including white matter hyperintensities and enlarged perivascular spaces, were measured. Correlation analysis and linear regression were employed to verify the association of IFSH with the clearance function of mLVs. A total of 76 patients were included in the study. The visibility of IFSH was found to be associated with the percentage change of signal unite ratio in parasagittal dura from baseline to 15 and 39 hours in adjusted analyses. Furthermore, the visibility of IFSH was positively related to the age, scores of both periventricular and deep white matter hyperintensities, and the grade of enlarged perivascular spaces in centrum semiovale. These findings suggest that the visibility of IFSH on 2D FLAIR may serve as an indicator of clearance dysfunction of mLVs and may be implicated in the development of cerebral small vessel disease.

SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study

BackgroundSodium-glucose cotransporter 2 (SGLT2) and SGLT1 inhibitors may have additional beneficial metabolic effects on circulating metabolites beyond glucose regulation, which could contribute to a reduction in the burden of cerebral small vessel disease (CSVD). Accordingly, we used Mendelian Randomization (MR) to examine the role of circulating metabolites in mediating SGLT2 and SGLT1 inhibition in CSVD.MethodsGenetic instruments for SGLT1/2 inhibition were identified as genetic variants, which were both associated with the expression of encoding genes of SGLT1/2 inhibitors and glycated hemoglobin A1c (HbA1c) level. A two-sample two-step MR was used to determine the causal effects of SGLT1/2 inhibition on CSVD manifestations and the mediating effects of 1400 circulating metabolites linking SGLT1/2 inhibition with CSVD manifestations.ResultsA lower risk of deep cerebral microbleeds (CMBs) and small vessel stroke (SVS) was linked to genetically predicted SGLT2 inhibition. Better white matter structure integrity was also achieved, as evidenced by decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), as well as lower deep (DWMH) and periventrivular white matter hyperintensity (PWMH) volume. Inhibiting SGLT2 could also lessen the incidence of severe enlarged perivascular spaces (EPVS) located at white matter, basal ganglia (BG) and hippocampus (HIP). SGLT1 inhibition could preserve white matter integrity, shown as decreased MD of white matter and DWMH volume. The effect of SGLT2 inhibition on SVS and MD of white matter through the concentration of 4-acetamidobutanoate and the cholesterol to oleoyl-linoleoyl-glycerol (18:1 to 18:2) ratio, with a mediated proportion of 30.3% and 35.5% of the total effect, respectively.ConclusionsSGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism. Further mechanistic and clinical studies research are needed to validate our findings.

Relationship between prognostic nutritional index and post-stroke cognitive impairment

ABSTRACT Background The Prognostic Nutritional Index (PNI) has been described as a useful screening tool for patient prognosis in several diseases. As a potential diagnostic index, it has attracted the interest of many physicians. However, the correlation between the PNI and post-stroke cognitive impairment (PSCI) remains unclear. Methods A total of 285 patients with acute ischemic stroke were included. PNI was assessed as serum albumin (g/L) + 5× lymphocyte count (109/L) and was dichotomized according to the prespecified cut-off points 48.43 for the high and low groups. PSCI was defined as Mini-Mental State Examination (MMSE) < 27 at the 6–10 months follow-up. Multiple logistic regression and linear regression analyses were performed to examine the association between PNI and cognitive outcomes. Results A low PNI was independently associated with PSCI after adjusting for age, sex, education, National Institutes of Health Stroke Scale (NIHSS), deep white matter hyperintensity (DWMH), and stroke history (odds ratio [OR]: 2.158; 95% confidence interval [CI]: 1.205–3.863). The PNI scores were significantly associated with MMSE and attention domain (β = 0.113, p = 0.006; β = 0.109, p = 0.041, respectively). The PNI improved the model’s discrimination when added to the model with other clinical risk factors. Conclusions A low PNI was independently associated with the occurrence of PSCI and the PNI scores were specifically associated with the scores of global cognition and attention domain. It can be a promising and straightforward screening indicator to identify the person with impaired immune-nutritional status at higher risk of PSCI.

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.

Retinal vascular density as a potential biomarker of diabetic cerebral small vessel disease.

The retina and brain share similar anatomical and physiological features. Thus, retinal imaging by optical coherence tomography angiography (OCTA) might be a potential tool for the early diagnosis of diabetic cerebral small vessel disease (CSVD). In this study, we aimed to evaluate retinal vascular density (VD) in diabetic CSVD by OCTA imaging and explore the associations between retinal VD and cerebral magnetic resonance imaging (MRI) markers and cognitive function. In total, 131 patients were enrolled, including CSVD (n = 43) and non-CSVD groups (n = 88). The VD and foveal avascular zone of the retinal capillary plexus were measured with OCTA. A brain MRI was performed. MRI imaging showed that in the diabetic CSVD group, white matter hyperintensities (WMHs), particularly deep WMHs (58.82%), are the most common MRI marker, followed by cerebral microbleeds in the subtentorial and cortical areas (34.78%). The CSVD group showed increases in the prevalence of cognitive dysfunction (p = .034) and depression (p = .033) and decreases in visuospatial/executive ability and delayed recall ability. In the CSVD group, VDs of the macular superficial vascular plexus (32.93 ± 7.15% vs. 36.97 ± 6.59%, p = .002), intermediate capillary plexus (20.87 ± 4.30% vs. 23.08 ± 4.30%, p = .005) and deep capillary plexus (23.54 ± 5.00% vs. 26.05 ± 4.20%, p = .003) were lower than those of the non-CSVD group. Multiple linear regression analysis showed that VD of the macular superficial vascular plexus was independently associated with cerebral microbleeds. Meanwhile, VD of the macular intermediate capillary plexus was associated with white matter lacunar infarcts after adjustment. Diabetic CSVDs are characterized by MRI markers, including deep WMHs and cerebral microbleeds, and showed impaired cognition with decreased visuospatial/executive ability and delayed recall ability. OCTA imaging revealed a significant decrease in retinal microvascular perfusion in diabetic CSVD, which was related to MRI markers and cognitive function. OCTA might be a valuable potential measurement for the early diagnosis of CSVD.

Hippocampal amide proton transfer values are associated with cerebral small vessel disease imaging markers and total burden: a community-based cross-sectional study.

Neurodegeneration has been suggested to be associated with cerebral small vessel disease (CSVD). The association between different CSVD imaging markers and the extent of neurodegeneration could be indirectly confirmed by examining the relationship between CSVD imaging markers and the hippocampal amide proton transfer (APT) values. The associations between hippocampal APT values with CSVD imaging markers and CSVD total load need to be further validated. The aim of this study was to investigate potential variations in hippocampal APT values among individuals with CSVD imaging markers and varying degrees of CSVD total burden. A cross-sectional study (retrospective analysis of prospectively-acquired data) was conducted at Nanxishan Hospital of Guangxi Zhuang Autonomous Region. From May 2020 to June 2021, 165 individuals (age, 40-76 years; male/female, 103/62) were included in this study. The inclusion criteria for the participants were as follows: The presence of lacunar infarction (LI), and/or cerebral microbleed (CMB); moderate-to-severe enlarged perivascular space (EPVS) (>20); deep white matter hyperintensity (WMH) > Fazekas 2 or periventricular WMH > Fazekas. The exclusion criteria comprised the following: History of craniocerebral operation; Cases with significant pathology incidentally identified during magnetic resonance (MR) scan; Drug or alcohol abuse. The differences of hippocampal APT values between CSVD imaging makers presence or absence groups and different CSVD total burden groups were compared using independent t-test and one-way analysis of variance (ANOVA). The correlations between APT values and CSVD imaging markers were analyzed using Pearson correlation analysis. A mediation analysis model was used to investigate the mediating effect of the hippocampal APT values in the association between CSVD total loads and Montreal Cognitive Assessment (MoCA) score was assessed. The hippocampal APT values among different CSVD total load groups were significantly different (P<0.001). The hippocampal APT values were significantly different between the imaging markers presence and absence groups. The P values for the LI, WMH EPVS, and CMB presence or absence groups were <0.001, <0.001, 0.034, and 0.002, respectively. The hippocampal APT values were significantly correlated with CMB (P<0.01), LI (P<0.01) and WMH (P<0.01). The mediation models demonstrated that the APT values of the hippocampus partially mediated the association between CSVD total load and MoCA score, the proportion of mediation attributable was calculated as 17.50%. Hippocampal APT values were associated with CSVD imaging markers and total burden. Hippocampal APT values may serve as a biomarker for the early detection of neurodegeneration in CSVD patients.

Cerebral white matter burden is linked to cognitive function in patients undergoing hemodialysis

Introduction Chronic kidney disease is related to neurodegeneration and structural changes in the brain which might lead to cognitive decline. The Fazekas scale used for assessing white matter hyperintensities (WMHs) was associated with poor cognitive performance. Therefore, this study investigated the associations between the mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), and Fazekas scale in patients under hemodialysis (HD). Methods The periventricular (PV) WMHs and deep WMHs (DWMHs) in brain magnetic resonance images of 59 patients under dialysis were graded using the Fazekas scale. Three cognition function tests were also performed, then multivariable ordinal regression and logistic regression were used to identify the associations between cognitive performance and the Fazekas scale. Results There were inverse associations between the three cognitive function tests across the Fazekas scale of PVWMHs (p = .037, .006, and .008 for MMSE, MoCA, and CASI, respectively), but the associations were attenuated in the DWMHs group. In CASI, significant differences were identified in short-term memory, mental manipulation, abstract thinking, language, spatial construction, and name fluency in the PVWMHs group. However, DWMHs were only significantly correlated with abstract thinking and short-term memory. Conclusion An inverse correlation existed between the Fazekas scale, predominantly in PVWMHs, and cognition in patients undergoing HD. The PVWMHs were associated with cognitive performance assessed by MMSE, MoCA, and CASI, as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.

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.

Association between white matter hyperintensities and altered cerebral blood flow in maintenance hemodialysis patients: a longitudinal study

ObjectivesTo explore changes in cerebral blood flow (CBF) and white matter in hemodialysis patients.MethodsThirty-three hemodialysis patients who underwent two brain MRI at an interval of three years and 33 age- and sex-matched healthy controls (HC) underwent structural and arterial spin-labeling MRI examinations. Intergroup differences in CBF in the gray matter, white matter, and whole matter, and regional white matter hyperintensities (WMH) were analyzed. Based on the changes in CBF between the baseline and follow-up groups, the hemodialysis patients were divided into two subgroups: an increased CBF group and a decreased CBF group. Differences in CBF and WMH between the subgroups and HC were analyzed.ResultsPatients undergoing hemodialysis exhibited increased cerebral watershed (CW) WMH, deep WMH, and periventricular WMH (P < 0.01). The CBF of patients with decreased CBF was higher than that of HC at baseline (,P < 0.01) and lower than that of HC at follow-up (P < 0.01). Compared with the increased CBF group, obvious development of deep WMH was found in the decreased CBF group for the gray matter, white matter, and whole matter (P < 0.01).ConclusionsWMH in hemodialysis patients were distributed in the deep white matter, periventricular white matter and CW, and progressed with the extension of hemodialysis duration. CBF in hemodialysis patients could manifest as both increased and decreased, and WMH in patients with decreased CBF developed severely with prolongation of hemodialysis duration.Advances in knowledgeThese findings provide a basis for exploring neuropathological changes of hemodialysis patients.

Discontinuity of deep medullary veins in SWI is associated with deep white matter hyperintensity volume and cognitive impairment in cerebral small vessel disease

BackgroundDiscontinuation of the deep medullary veins (DMVs) may be an early imaging marker for identifying cognitive impairment caused by cerebral small vessel disease (CSVD). However, this method lacks mechanistic exploration. We aimed to investigate whether the DMV score is related to CSVD imaging markers and cognitive impairment in patients with CSVD. MethodsThis retrospective study included patients with CSVD who completed DMV score and cognition (e.g., MMSE, MoCA) assessments, and underwent MRI scanning (T2-FLAIR for white matter hyperintensities (WMH) volume, T1-weighted MRI for brain parenchymal fractions (BPF) analysis, and SWI for assessment of DMV score). The CSVD imaging markers were quantitatively assessed using the AccuBrain® system. We assessed the diagnostic value of neuroimaging biomarkers for detecting CSVD-related cognitive impairment. In addition, we explored the relationship between the DMV score, CSVD imaging markers, and cognition using mediation analysis. ResultsNinety-four patients with CSVD were divided into a cognitive impairment group (n = 39) and a non-cognitive impairment group (n = 55). Higher DMV scores, larger WMH volumes, and smaller BPF were observed in the cognitive impairment group than those in the non-cognitive impairment group. Receiver operating characteristics (ROC) analysis revealed that the discovery value of the integration of patient age, BPF, whole WMH volume, and DMV score for cognitive impairment was 0.742, with a sensitivity and specificity of 79.5 % and 61.5 %, respectively. Mediation analysis showed mediation by WMH and BPF in the relationship between DMV score and cognitive impairment (all P < 0.05). LimitationsThis study did not evaluate the DMV score in subregions according to DMV anatomy. ConclusionsThe DMV score is significantly associated with cognitive impairment in patients with CSVD, and this association is mediated through WMH and BPF.

White Matter Hyperintensities as a Predictor of Aphasia Recovery

ObjectiveTo examine the relation between baseline white matter hyperintensities (WMH) and change in naming, content production, and efficiency after treatment in subacute aphasia. We hypothesized that more severe baseline WMH would result in less improvement with treatment. DesignRetrospective analysis of a cohort from a double-blind randomized controlled trial (RCT). SettingOutpatient clinical setting or participant home. ParticipantsWe retrospectively reviewed imaging and behavioral data for 52 participants with subacute aphasia due to left-hemisphere ischemic stroke enrolled in the RCT. RCT inclusion criteria: English proficiency, normal/corrected-to-normal hearing/vision, and no history of neurologic conditions other than the stroke resulting aphasia. One participant with a chronic right-hemisphere lesion was retained as she presented with no residual deficits on neurologic examination. Individuals with scalp sensitivities or on medications that lower seizure threshold or any N-methyl-D-aspartate (NMDA) antagonists were excluded. Of the 52 participants, for this analysis, 2 were excluded for not having a magnetic resonance imaging, and 7 were excluded for not participating in treatment or pre/post assessment for at least 1 outcome, resulting in final sample of 43 participants (20 women sex, M [SD] age=64.4 [11.9] and M [SD] education=14.9 [3.1] years). InterventionsParticipants received 15 sessions (2-3 times/week) of computerized lexical-semantic (ie, verification) treatment with [sham/active] transcranial direct current stimulation (tDCS). Sessions were approximately 45 minutes each (tDCS for first 20 minutes). Main Outcome MeasuresNaming accuracy, content units (CUs, a measure of semantically accurate production), and efficiency (ie, syllables/CU) on a picture description task. ResultsPeriventricular WMH severity was independently associated with recovery in picture naming for the active tDCS group. Deep WMH severity was associated with recovery for CU production for the sham tDCS group. ConclusionBaseline periventricular and deep WMH, among other factors, may be an important consideration for prognosis and treatment planning, especially when considered in conjunction with tDCS treatment.

Characterizing upper extremity fine motor function in the presence of white matter hyperintensities: A 7 T MRI cross-sectional study in older adults

BackgroundWhite matter hyperintensities (WMH) are a prevalent radiographic finding in the aging brain studies. Research on WMH association with motor impairment is mostly focused on the lower-extremity function and further investigation on the upper-extremity is needed. How different degrees of WMH burden impact the network of activation recruited during upper limb motor performance could provide further insight on the complex mechanisms of WMH pathophysiology and its interaction with aging and neurological disease processes. Methods40 healthy elderly subjects without a neurological/psychiatric diagnosis were included in the study (16F, mean age 69.3 years). All subjects underwent ultra-high field 7 T MRI including structural and finger tapping task-fMRI. First, we quantified the WMH lesion load and its spatial distribution. Secondly, we performed a data-driven stratification of the subjects according to their periventricular and deep WMH burdens. Thirdly, we investigated the distribution of neural recruitment and the corresponding activity assessed through BOLD signal changes among different brain regions for groups of subjects. We clustered the degree of WMH based on location, numbers, and volume into three categories; ranging from mild, moderate, and severe. Finally, we explored how the spatial distribution of WMH, and activity elicited during task-fMRI relate to motor function, measured with the 9-Hole Peg Test. ResultsWithin our population, we found three subgroups of subjects, partitioned according to their periventricular and deep WMH lesion load. We found decreased activity in several frontal and cingulate cortex areas in subjects with a severe WMH burden. No statistically significant associations were found when performing the brain-behavior statistical analysis for structural or functional data. ConclusionWMH burden has an effect on brain activity during fine motor control and the activity changes are associated with varying degrees of the total burden and distributions of WMH lesions. Collectively, our results shed new light on the potential impact of WMH on motor function in the context of aging and neurodegeneration.

Association between brain imaging biomarkers and continuous glucose monitoring-derived glycemic control indices in Japanese patients with type 2 diabetes mellitus

IntroductionAlthough type 2 diabetes mellitus (T2DM) is associated with alterations in brain structure, the relationship between glycemic control indices and brain imaging markers remains unclear. This study aimed to investigate...

Review Of Cerebral Microbleeds using FAZEKA Classification

Introduction: Cerebral microbleeds (CMBs), also known as cerebral microhemorrhages, are tiny hypointense foci discovered by susceptibility-weighted (SW) magnetic resonance imaging (MR). CMBs have been interpreted as asymptomatic lesions that may be identified by chance during a brain MRI. This study was done to understand the etiology and various imaging patterns of the cerebral microbleeds on MRI Materials &amp; Methods: This study was done with a sample size of 325 patients who underwent MRI Brain and diagnosed with CMB at our hospital. Detailed supportive history was taken and data was analysed. Results: Present study shows strong correlation between CMB’s and white matter changes. CMBs in parietal lobe found to have correlation with cognitive dysfunction. Lacunar infract is the most common subtype associated with the CMB’s Conclusion: The markers of microangiopathy on MRI brain are CMBs and white matter changes. Correlation of lobar CMBs with periventricular white matter hyperintensities and deep, infratentorial CMBs with deep white matter hyperintensities were found.  

Correlation between body composition and white matter hyperintensity in patients with acute ischemic stroke.

White matter hyperintensity (WMH) burden is associated with a higher risk of ischemic stroke. The relationship between WMH and obesity is somewhat controversial which might be interfered by different body composition such as skeletal muscle, fat and bone density. However, few researchers have evaluated the relationship between WMH burden and disaggregated body constituents in acute ischemic stroke (AIS) patients systematically. A total of 352 AIS patients were enrolled in this study. The subcutaneous adipose tissue, erector spinae muscle area and bone density were evaluated on the computed tomography scanning. The burden of WMH was evaluated using the Fazekas scale based on the fluid-attenuated inversion recovery sequence. The severity of overall WMH was defined as none-mild WMH (total Fazekas score 0-2) or moderate-severe WMH (total Fazekas score 3-6). Based on the severity of periventricular WMH (P-WMH) and deep WMH, patients were categorized into either a none-mild (Fazekas score 0-1) group or a moderate-severe (Fazekas score 2-3) group. We found that patients with moderate-severe WMH showed lower bone density and smaller erector spinae muscle area and subcutaneous adipose tissue than none-mild. The logistic regression analysis showed that the bone density was independently associated with moderate-severe overall WMH (odds radio = 0.98, 95% confidence interval, 0.972-0.992, P < .001) and similar results were found in the analyses according to P-WMH (odds radio = 0.98, 95% confidence interval, 0.972-0.992, P < .001). These findings suggest that among the AIS body composition, the bone density is independently associated with the severity of overall WMH and P-WMH.

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.

Impact of White Matter Hyperintensities on domain‐specific cognition in Southeast Asians

AbstractBackgroundDementia affects 55 million people worldwide, with 60% of the burden in Asia. White Matter Hyperintensities (WMH) is a key marker of small vessel disease, with high prevalence in Asian populations with prodromal and clinical dementia. WMH is described as: Deep White Matter Hyperintensities (DWMH), Periventricular Hyperintensities (PVH) or Fazekas‐Total (DWMH and PVH).However, association between WMH topography and performance in specific cognitive domains remains unexplored. Thus, this study aims to characterise the impact of Fazekas‐Total, DWMH and PVH on different cognitive domains.Method304 participants (mean age 60.6, mean education years 14.2, mean Montreal Cognitive Assessment 25.99, 43.8% males) from Biomarkers and Cognition Study, Singapore (Dementia Research Centre (Singapore)) met the inclusion criteria.Eight domains of cognition were tested: global cognition, learning and memory, language, executive function, complex‐attention, perceptual‐motor, social‐cognition, and processing speed.Normality tests, correlation analysis and stepwise regression (with Benjamini and Hochberg False Discovery Rate correction) were performed to understand association between Fazekas‐Total, DWMH, PVH on domains of cognition tested, accounting for age, education, and gender.Two approaches were used for data analysis: (1) by grouping participants as Mild Cognitive Impairment (MCI), Subjective Cognitive Decline (SCD) and Cognitively Normal (CN) as per the National Institute on Aging‐Alzheimer’s Association (NIA‐AA) criteria and (2) by grouping participants’ WMH as confluent (DWMH ≥2 and PVH ≥3) and non‐confluent.ResultHigher Fazekas‐Total was associated with slower processing speed (p = 0.0255, R = ‐0.039) in prodromal participants (MCI and SCD). Higher PVH was associated with slower processing speed in MCI (p = 0.017, R = ‐0.32) and CN (p = 0.017, R = ‐0.663) participants. Higher PVH was significantly associated with poorer learning and memory (p = 0.045, R = ‐0.043) in SCD participants. Higher DWMH was significantly associated with poorer learning and memory (p = 0.017, R = ‐0.765) in CN participants.ConclusionThese results demonstrate differential association between PVH, DWMH and cognitive domains, thus the location of WMH determines the affected cognitive domains. Therefore, it is worthwhile to assess PVH and DWMH in clinical cognitive outcomes separately and to understand the upstream pathobiology of DWMH and PVH.Furthermore, higher Fazekas‐Total was strongly associated with slower processing speed in prodromal participants and could be a marker of cognitive decline.

Vascular contribution to the preclinical Alzheimer’s disease pathological changes: Insights from the EPAD cohort

AbstractBackgroundThe role of cardiovascular risk factors and cerebral small vessel disease (CSVD) on the sequences of Alzheimer’s Disease (AD) pathological events remains to be determined.MethodWe included 1592 non‐demented participants from EPAD‐LCS (Table‐1). Linear models were used to study associations between the Framingham score (FRS) and CSF‐Aß1‐42; CSVD indices (visual assessment for perivascular spaces [PVS] in the basal ganglia [BG] and centrum‐semiovale [CS], periventricular and deep white matter hyperintensities [WMHs], presence of lobar or deep cerebral microbleeds [CMBs], and lacunes, and quantification of global and lobar WMH volumes) and Aß1‐42 and p‐Tau181, including an interaction between CSVD indices and Aß1‐42 for the latter. Hippocampal volumes (HCV) were quantified using LEAP. Structural equation models (SEM) were used to assess the association between clinical variables as described in Figure‐1. Models were corrected for age, sex, site and multiple comparisons.ResultHigher FRS scores were associated with lower CSF Aß1‐42 (ß = ‐0.18; p&lt;0.001) and higher P‐tau181 (ß = 0.21; p&lt;0.001). Aß1‐42 was negatively associated with all CSVD markers (all p&lt;0.001; Figure‐2). We found stronger association between Aß1‐42 and P‐tau181 in participants with higher Fazekas deep and periventricular (p‐interaction&lt;0.005) scores, and higher regional WMH (all p‐interactions&lt;0.005) volumes. Using SEM, the CSVD‐burden latent factor fully mediated the association between FRS and Aß1‐42 (indirect effect: ß = ‐0.03; p&lt;0.001). Aß1‐42 did not significantly predict the CSVD‐burden latent factor. We observed a significant direct effect of Aß1‐42 on P‐tau181 levels (ß = ‐0.14; p&lt;0.001) and HCV (ß = 0.06; p&lt;0.05), and of P‐tau181 levels onto HCV (ß = ‐0.05; p&lt;0.05). A significant indirect, but not direct, effect of the latent factor on both P‐tau181 (indirect effect: ß = 0.36; p &lt; 0.05) and HCV (indirect effect: ß = ‐0.24; p &lt; 0.05) through Aß1‐42 was observed.ConclusionExpression of cerebrovascular pathology fully mediates the effects of vascular risk factors on amyloid and accelerates manifestation of downstream biomarkers in the preclinical phases of AD, stressing the importance of vascular‐protective treatments.

Vascular contribution to the preclinical Alzheimer’s disease pathological changes: Insights from the EPAD cohort

AbstractBackgroundThe role of cardiovascular risk factors and cerebral small vessel disease (CSVD) on the sequences of Alzheimer’s Disease (AD) pathological events remains to be determined.MethodWe included 1592 non‐demented participants from EPAD‐LCS (Table‐1). Linear models were used to study associations between the Framingham score (FRS) and CSF‐Aβ1‐42; CSVD indices (visual assessment for perivascular spaces [PVS] in the basal ganglia [BG] and centrum‐semiovale [CS], periventricular and deep white matter hyperintensities [WMHs], presence of lobar or deep cerebral microbleeds [CMBs], and lacunes, and quantification of global and lobar WMH volumes) and Aβ1‐42 and p‐Tau181, including an interaction between CSVD indices and Aβ1‐42 for the latter. Hippocampal volumes (HCV) were quantified using LEAP. Structural equation models (SEM) were used to assess the association between clinical variables as described in Figure‐1. Models were corrected for age, sex, site and multiple comparisons.ResultHigher FRS scores were associated with lower CSF Aβ1‐42 (β = ‐0.18; p&lt;0.001) and higher P‐tau181 (β = 0.21; p&lt;0.001). Aβ1‐42 was negatively associated with all CSVD markers (all p&lt;0.001; Figure‐2).We found stronger association between Aβ1‐42 and P‐tau181 in participants with higher Fazekas deep and periventricular (p‐interaction&lt;0.005) scores, and higher regional WMH (all p‐interactions&lt;0.005) volumes.Using SEM, the CSVD‐burden latent factor fully mediated the association between FRS and Aβ1‐42 (indirect effect: β = ‐0.03; p&lt;0.001). Aβ1‐42 did not significantly predict the CSVD‐burden latent factor. We observed a significant direct effect of Aβ1‐42 on P‐tau181 levels (β = ‐0.14; p&lt;0.001) and HCV (β = 0.06; p&lt;0.05), and of P‐tau181 levels onto HCV (β = ‐0.05; p&lt;0.05). A significant indirect, but not direct, effect of the latent factor on both P‐tau181 (indirect effect: β = 0.36; p &lt; 0.05) and HCV (indirect effect: β = ‐0.24; p &lt; 0.05) through Aβ1‐42 was observed.ConclusionExpression of cerebrovascular pathology fully mediates the effects of vascular risk factors on amyloid and accelerates manifestation of downstream biomarkers in the preclinical phases of AD, stressing the importance of vascular‐protective treatments.

Relationship between a novel virtual reality test of mild functional difficulties and cerebrovascular disease

AbstractBackgroundIt is well known that mild cognitive impairment (MCI) is associated with subtle functional decline. However, standardized and cost‐effective methods for the objective quantification of mild functional difficulties are lacking. Here we report preliminary validity data for a novel, non‐immersive virtual‐reality task (Virtual Kitchen Challenge [VKC]) against brain markers of cerebrovascular disease and in contrast to a conventional, self‐report measure of function.MethodTwenty (n = 14 healthy control, n = 6 MCI) community‐dwelling older adults aged 60+ completed neuropsychological testing, including the Functional Activities Questionnaire (FAQ), and the VKC, which requires completion of simulated breakfast and lunch tasks on a touch‐screen computer. White matter hyperintensity (WMH) volumes from Fluid Attenuation Inversion Recovery (FLAIR) MRI sequences were derived using the UBO detector, a cluster‐based WMH extraction pipeline based on k‐nearest neighbors (k‐NN) algorithm. WMH volumes were calculated in SPM’s DARTEL space, precluding the need to adjust for intracranial volume (ICV).ResultMCI participants reported significantly more functional difficulties than healthy controls (FAQ U = 76.50 p = .002) and obtained marginally slower completion times on the VKC (U = 60.00, p = .138). VKC completion time was moderately associated with age (r = .441, p = .059) but relations with sex, race, and IQ were weak and not significant (all rs&lt;.195). VKC completion time significantly and strongly correlated with all WMH measures, even after controlling for age, sex, race, and IQ (total WMH r = .649, p = .031; deep WMH r = .615, p = .044; periventricular WMH r = .623, p = .041). By contrast, FAQ was not associated with WMH (rs&lt;.2, p&gt;.05 for all) or VKC completion time (r&lt;.1, p&gt;05) after controlling for age, sex, race, and IQ.ConclusionOur naturalistic, performance‐based measure of function (VKC) was not associated with race, sex, or premorbid IQ, but was strongly associated with neuroimaging markers of cerebrovascular disease (WMH). By contrast, a conventional self‐report measure of everyday functioning (FAQ) was not associated with neuroimaging measures (WMH). These results offer preliminary support for the VKC as a valid measure of early, subtle functional difficulties associated with cerebrovascular pathology that is not vulnerable to bias associated with race, sex, or premorbid IQ.