Search Results (42)

A key mechanism in the pathogenesis of cerebral small vessel disease (CSVD) is endothelial dysfunction associated with impaired metabolism of nitric oxide (NO) and its main substrate, L-arginine. The aim of the study was to assess parameters of L-arginine metabolism and their association with MRI-defined brain damage in CSVD patients. A total of 100 CSVD patients (according to MRI STRIVE standards) and cognitive impairment (CI) of varying severity, as well as 20 healthy volunteers, were analyzed. Levels of L-arginine and its metabolites—L-ornithine, L-citrulline, and asymmetric dimethylarginine (ADMA)—were measured; diffusion tensor MRI, MRI volumetry, and morphometry were performed. A threshold level of L-arginine (51.25 μmol/L) was identified, above which an association with CI was observed. Patients with L-arginine ≥ 51.25 μmol/L demonstrated poorer performance on cognitive tests (Stroop test, trail-making test (TMT)-B, TMT B–A, 10-word test) and more severe brain damage, reflected by greater severity of MRI markers (white matter hyperintensities, microbleeds), changes in brain component volumes, cortical atrophy in specific regions, and impairment of white matter microstructural integrity. The obtained data indicate a pathogenetic link between disturbances in L-arginine homeostasis and the development of CSVD with CI and support the need for further studies aimed at refining approaches to their correction. Full article

Introduction: Remote ischaemic conditioning (RIC) is a promising treatment for neurological disorders. It involves cycles of temporary ischaemic stimulus, usually applied to a limb, and has shown significant improvement in neurological function in many trials. This review focuses on identifying and summarising the biomarkers of RIC that can enhance clinical practice and understanding of its mechanisms. Methods: A search was conducted in MEDLINE and EMBASE up to August 2025 using terms related to ischaemic conditioning. Studies were included if they were RCTs involving cerebrovascular disease, used RIC as treatment, and measured mechanistic biomarkers. We extracted and summarised data on study design, participant characteristics, RIC intervention protocols (including timing, frequency, duration, and pressure), biomarker types and measurement methods, timing of biomarker assessment, and main findings relating biomarker changes to clinical outcomes. Results: The review identified twenty-one RCTs examining biomarkers, including serum biomarkers, imaging markers, and other physiological indicators. Key biomarkers identified include systemic inflammatory cytokines and various imaging markers such as cerebral blood flow (CBF), white matter hyperintensities (WMH), and brachial artery flow-mediated dilation (BA-FMD). Conclusions: The evidence suggests that RIC modulates various biomarkers linked to neuroprotection and recovery. Reliable biomarkers of RIC would enhance the understanding of its mechanisms and improve targeted therapies. The clinical utility of these biomarkers requires further validation through large-scale trials. Standardised protocols and longitudinal studies are essential for optimising RIC therapy and improving patient outcomes in stroke and cerebral small vessel disease. Future research should focus on expanding our understanding of these biomarkers and their interactions with RIC, leading to more personalised and effective treatments. Full article

Objective: White matter hyperintensity (WMH) is one of the most common and prominent changes seen in elderly individuals, especially on MRI. WMH is associated with serious conditions such as hemorrhagic and ischemic stroke, depression and dementia. Recently, the relationship between cerebral venous diameter and WMH was described. This study aimed to investigate the relationship between the Fazekas scale, which evaluates the severity of WMH, and cerebral vein diameters, age and clinical outcomes analysis. Materials and Methods: MRI images of 660 patients were examined retrospectively. FLAIR and SWI (MiniP) images were used to evaluate WMH and cerebral vein diameters. Internal cerebral veins (ICV), thalamostriate veins (TSV), anterior septal veins (ASV) and superior sagittal sinus (SSS) diameters were measured. Cerebral vein diameters were compared with age, WMH, hypertension, hyperlipidemia, diabetes mellitus, lacunar infarct and microhemorrhage presence. Results: In the presence of hypertension, hyperlipidemia, diabetes, lacunar infarction and microhemorrhage, Fazekas score, mean ICV-right, ICV-left, ASV-right, ASV-left, TSV-right and TSV-left values were significantly higher. The mean ICV-right, ICV-left, ASV-right, ASV-left, TSV-right and TSV-left values of the middle-aged and elderly groups were significantly higher than the young group. A strong positive correlation was observed between age and mean ICV-right, ICV-left, ASV-right and ASV-left values, while a moderate positive correlation was shown with TSV-right and TSV-left values. A weak negative correlation was determined with SSS values. Conclusions: Cerebral vein diameter increases with age and is associated with the severity of WMH. Clinicians can monitor cerebral vein diameter to predict the severity of WMH. Full article

Background: Sleep is a complex physiological process, crucial for cognitive functioning, emotional regulation, and overall health. Recent advances in genomics and neuroimaging have illuminated the intricate relationship between genetics, sleep architecture, and brain changes. This study investigated the association between sleep duration genetics, through a Sleep Duration Polygenic Index (Sleep PGI), and brain changes (total cortical thickness, white matter volume, gray matter volume, white matter hyperintensities volume) in cognitively healthy adults aged 20–80 years old. Methods: Using longitudinal data from the Reference Ability Neural Network (RANN) and Cognitive Reserve (CR) studies, we examined the impact of Sleep PGI on brain measures (total cortical thickness, gray matter volume, white matter volume, WMH volume) over time. Generalized Estimated Equations were used for the statistical analysis. Analysis was performed in the total sample (n = 94) and in three age-groups (young, middle, old). Results: Across age, higher Sleep PGI was associated with higher temporal WMH volumes over time. In models considering an interaction of age between Sleep PGI and time in study, age emerged as a significant moderator for outcomes of hippocampal volume, cortical white matter volume, and WMH volume (total, parietal) as outcomes. Conclusions: Sleep duration polygenic score was associated with changes in the brain in cognitively healthy adults. Genetic predisposition for longer sleep duration was associated with more favorable longitudinal trajectories against brain decline, a result mostly driven by younger adults. These findings underscore the importance of maintaining optimal sleep duration and the potential for personalized interventions to improve sleep and brain health. Full article

Objective: Oral frailty is associated with an increased risk of cognitive decline, yet practical tools for early identification remain limited. The Oral Frailty 5-item Checklist (OF-5), recently standardized in Japan, does not account for severe tooth loss, which is a known risk factor for brain atrophy. We developed a revised version of the OF-5 that includes the criterion of having nine or fewer teeth. This study aimed to validate the revised OF-5 as a screening tool for detecting early brain structural changes related to dementia risk in cognitively unimpaired older adults. Methods: We analyzed 732 cognitively unimpaired participants from a population-based Japanese cohort (baseline 2016–2018). Oral frailty was assessed using both the original OF-5 and the revised OF-5. Brain volumes were measured by MRI and processed with FreeSurfer. Associations between oral frailty status and regional brain volumes were tested using multivariable-adjusted models, with further adjustment for nutrient intake and food consumption. Results: The revised OF-5, which adds severe tooth loss (≥9 teeth) as a criterion, showed greater sensitivity in detecting dementia-related brain changes than the original version. With the original OF-5, oral frailty was associated only with reduced fusiform gyrus volume (1.088% vs. 1.109% of estimated total intracranial volume [eTIV]; p < 0.05). In contrast, the revised OF-5 detected broader changes: orally frail participants showed significantly higher white matter hyperintensity (WMH) volume (0.366% vs. 0.302% of eTIV; p < 0.05) and smaller volumes in the medial temporal lobe (1.824% vs. 1.856%), pars triangularis (0.401% vs. 0.412%), and fusiform gyrus (1.080% vs. 1.111%)—all p < 0.05 (FWE-corrected). These associations persisted after adjusting for nutrient intake and food consumption. Conclusions: The revised OF-5 improves identification of pre-symptomatic brain changes in cognitively healthy older adults, independent of nutrition. It may serve as a simple and practical tool for early screening of dementia risk in clinical and community settings. Full article

Background: Inflammatory arthritides (IAs) are systemic inflammatory syndromes that can affect diverse body tissues. Central nervous system involvement has been reported, but is considered rare. We investigated the relationship between cardiac and subclinical brain involvement in patients with IAs. Methods: We consecutively enrolled 25 patients with IAs and 31 as disease controls with non-autoimmune cardiovascular diseases (CVDs) reporting cardiac symptoms. Each participant underwent combined brain/heart magnetic resonance imaging (MRI). We also recruited 25 consecutive asymptomatic healthy controls without CVDs who underwent brain MRI. MRI scans were performed on a 1.5 T system. We investigated cardiac function/tissue characterization and the presence/localization of white matter hyperintensities (WMHs). Results: All groups had similar ages (p = 0.267), and 16 (64%) patients with IAs vs. 7 (23%) disease controls vs. 16 (64%) healthy controls were women (p = 0.001). WMHs were detected in ≥1 brain area in 15 (60%) patients with IAs and 16 (53%) disease controls (p = 0.620). WMHs were significantly less prevalent amongst healthy controls [two (8%)] compared to patients with IAs (p < 0.001). Amongst patients with IAs, an increased cardiac T2 ratio was associated with an increased probability of WMH occurrence [OR per 0.1 unit change (95% CI): 1.29 (1.05–1.59), p = 0.016], while a higher cardiac T2 ratio (per 0.1 unit change) and extracellular volume fraction (ECV) were associated with higher WMH lesion burdens [β (95% CI): 0.12 (0.03–0.20), p = 0.008 and 0.25 (0.00–0.49), p = 0.049, respectively]. Conclusions: Patients with IAs and cardiac symptoms had significantly higher subclinical WMH burdens compared to age/sex-matched healthy controls. Myocardial edema was associated with a greater WMH burden, potentially suggesting shared pathophysiologic substrates. Full article

Background/Objectives: Low-grade inflammation in the form of microglial activation may be involved in neurodegenerative and vascular dementias. Subcortical small-vessel disease (SSVD) is the main form of vascular dementia, associated with brain barrier dysfunction and endothelial and monocyte activation. IL-6 and IL-17A are known proinflammatory cytokines that contribute to the disruption of blood–brain barrier integrity and microvascular dysfunction, features that are central to SSVD pathophysiological pathways. We herein compared cerebrospinal fluid (CSF) IL-6 and IL-17A concentrations in SSVD and AD patients as well as control subjects and examined the potential associations among IL-6 and IL-17A levels with cognitive and ΜRΙ changes. The albumin quotient (Qalb) was also calculated. Methods: CSF IL-6 and IL-17A (18 SSVD, 17 AD, and 12 healthy controls) were measured with solid-phase sandwich ELISAs, while albumin levels were measured by immunonephelometry. MMSE, FAB, and the CLOX tests were used for cognitive assessment and MRI was used for atrophy and white matter hyperintensities. Results: Significantly elevated CSF levels of Qalb and IL-6 were found in SSVD patients compared to both AD (p = 0.02) and controls (p = 0.002), respectively. Moreover, CSF IL-6 levels displayed a significant inverse correlation with CLOX2 scores (r = −0.641, p = 0.02), as well as a positive correlation with the total normalized CSF volume (r = 0.7, p = 0.01). CSF IL-17A levels were found to be reduced in SSVD patients, compared to controls and AD patients (p < 0.0001 and p = 0.002, respectively). The IL-6/IL-17A ratio with a cut-off value > 1.004 displayed a sensitivity of 83.33% (95%CI; 60.78% to 94.16%) and a specificity of 68.97% (95%CI; 50.77% to 82.72%) for the discrimination of SSVD from AD patients and controls. Conclusions: In the present pilot single-center study, we found increased CSF IL-6 and IL-6/IL-17A ratio levels in SSVD patients that correlated with reduced scores in the CLOX2 test and increased CSF volume. These preliminary findings deserve further evaluation in larger cohorts in order to elucidate their potential as surrogate biomarkers for the discrimination of SSVD from AD pathology. Full article

To examine the association between post-stroke depression (PSD) and macrostructural and microstructural brain measures, and to explore whether changes in accelerometer-measured physical activity (PA) are associated with PSD, we conducted an exploratory study in UK Biobank with dementia-free participants diagnosed with at least one prior stroke. Eligible participants (n = 1186) completed an MRI scan. Depression was classified based on positive depression screening scores (PHQ-2 ≥ 3). Multivariate linear regression models assessed the relationships between depression and structural and diffusion measures generated from brain MRI scans. Logistic regression models were used to examine the relationship between accelerometer-measured daily PA and future depression (n = 367). Depression was positively associated with total white matter hyperintensities (WMHs) volume (standardized β [95% CI]—0.1339 [0.012, 0.256]; FDR-adjusted p-value—0.039), periventricular WMHs volume (standardized β [95% CI]—0.1351 [0.020, 0.250]; FDR-adjusted p-value—0.027), and reduced MD for commissural fibers (standardized β [95% CI]—−0.139 [−0.255, −0.024]; adjusted p-value—0.045). The odds of depression decreased by 0.3% for each daily minute spent in objectively measured light PA, while each minute spent in sleep from midnight to 6:00 AM was associated with a 0.9% decrease in the odds of depression. This early-stage analysis using a population cohort offers a scientific rationale for researchers using multimodal data sources to investigate the heterogenous nature of PSD and, potentially, identify stroke patients at risk of poor outcomes. Full article

Background/Objectives: The aim of the study was to evaluate the usefulness of vessel wall imaging and MRI in assessment of the post-COVID-19 changes in the brain. VWI is a progressive MRI technique that provides precise imaging of the pathological process in the wall of the vessel. It might help us to better understand the pathophysiology of COVID-19-related neurological lesions and may have an impact on management protocols. Methods: A total of 43 patients were included in the study; the post-COVID-19 group included 23 patients hospitalized for COVID-19 (mean age of the group: 53.52 years; 26% male, 74% female). The control group consisted of 20 patients from the general population who did not suffer from COVID-19 (mean age: 52.15 years; 35% male, 65% female). MRI examinations were performed on a 3T scanner (Biograph mMR, Siemens). The VW-MRI protocol included T1-weighted SPACE FS black-blood images, FLAIR images, SWI, and MRA. Results: Several radiological changes in post-COVID-19 patients were described: hyperintense foci in the white matter of the brain hemispheres, in the lower parts of the temporal lobes, and in the structures of the posterior cranial fossa; presence of engorgement of deep medullary veins or perivascular enhancement; presence of inflammatory vessel thickening in VWI images; changes in hippocampus size; presence of cortical atrophy; and thickening of the mucous membrane of the paranasal sinuses. The presence of atherosclerotic vessel thickening in VWI and the width of the third ventricle depended on the age of the patient. Conclusions: VWI and MRI may be useful in the assessment of post-COVID-19 lesions in the brain. Full article

Background/Objectives: Intracranial aneurysms (IAs) may be connected to interactions between large and small intracranial vessels. We aimed to investigate the association between IAs and cerebral small-vessel disease (CSVD) and assess CSVD impact on IA patient management. Methods: This retrospective study analyzed clinical data and MRI features of CSVD in 192 subarachnoid hemorrhage (SAH) patients: 136 with incidental IA, 147 with severe CSVD without SAH/IA, and 50 controls without SAH, IA, or severe CSVD. MRI assessments followed the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE), with a total burden of small-vessel disease (TBSVD) score calculated. Statistical analyses included forward selection and binary logistic regression. Results: TBSVD differed significantly across groups (p < 0.001), except between SAH and IA groups (p = 0.8). Controls had the lowest TBSVD (1.00; 1.22 ± 0.996), followed by SAH (2.00; 2.08 ± 1.013) and IA groups (2.00; 2.04 ± 1.141), with the highest in the CSVD group (1.00; 1.22 ± 0.996). White-matter hyperintensity (WMH) patterns varied with IA rupture status (p = 0.044); type A was prevalent in SAH patients and type D in the IA group. Incorporating MRI CSVD features and TBSVD into risk assessments did not enhance IA prediction or outcome models. Conclusions: IA patients exhibit a higher CSVD burden than controls, suggesting a link between small and large intracranial vessels. WMH patterns distinguish between ruptured and unruptured IA patients, offering potential markers for IA rupture risk assessment and signaling a paradigm shift in understanding IAs and CSVD. Full article

Objective: To compare white matter hyperintensities (WMHs) on T2-weighted magnetic resonance imaging (MRI) of patients with sudden sensorineural hearing loss (SSNHL) and analyze subpopulations with age-matched controls. Methods: T2-weighted MRI scans of 150 patients with SSNHL were assessed for WMHs and compared with the data of 148 healthy age-matched adults. Assessments of WMHs included independent grading of deep white matter hyperintensities (DWMHs) and periventricular hyperintensities (PVHs). WMH severity was visually rated using the Fazekas and Mirsen scales by two independent observers. Results: Fazekas grades for PVHs (p < 0.001) and DWMHs (p < 0.001) of SSNHL patients were found to be significantly greater than those of healthy participants. The average Mirsen grades for DWMHs of healthy and SSNHL patients were evaluated to be 0.373 ± 0.550 and 2.140 ± 0.859, respectively. Mirsen grades for DWMHs of SSNHL patients were found to be significantly greater (p < 0.001) than those of healthy participants. The Mirsen scale was found to have higher sensitivity (p < 0.001) than the Fazekas scale in grading PVHs and DWMHs. No significant difference (p = 0.24) was found in specificities between the two scales. Conclusions: Patients with sudden hearing loss have a much higher likelihood of having periventricular and deep white matter hyperintensities compared to age-matched controls. These findings indicate that sudden hearing loss patients are more likely to have microvascular changes in the brain, which may indicate a vascular and/or migraine origin to sudden sensorineural hearing loss. Full article

An association between subtle changes in T2 white matter hyper-intense signals (WMHSs) detected in fetal brain magnetic resonance imaging (fbMRI) and congenital cytomegalovirus (CMV) infection has been established. The research aim of this study is to compare children with congenital CMV infection with neurodevelopment outcome and hearing deficit with and without WMHSs in a historic prospective case study cohort of 58 fbMRIs. Of these, in 37 cases, fbMRI was normal (normal group) and WMHSs were detected in 21 cases (WMHS group). The median infection week of the WMHS group was earlier than the normal fbMRI group (8 and 17 weeks of gestation, respectively). The proportion of infants treated with valganciclovir in the WMHS group was distinctly higher. Hearing impairment was not significantly different between the groups. VABS scores in all four domains were within normal range in both groups. The median score of the motor skills corrected for week of infection was better in the WMHS group. A multivariate analysis using the week of infection interaction variable of WMHS and valganciclovir treatment showed better motor score outcomes in the valganciclovir treatment group despite an earlier week of infection. WMHSs were not associated with neurodevelopmental outcome and hearing deficit. In our cohort, valganciclovir treatment may have a protective effect on fetuses with WMHSs by improving neurodevelopmental outcome. Full article

Stroke and dementia have been linked to the appearance of white matter hyperintensities (WMHs). Meanwhile, diffusion tensor imaging (DTI) might capture the microstructural change in white matter early. Specific dietary interventions may help to reduce the risk of WMHs. However, research on the relationship between specific nutrients and white matter changes is still lacking. We aimed to investigate the causal effects of essential nutrients (amino acids, fatty acids, mineral elements, and vitamins) on WMHs and DTI measures, including fraction anisotropy (FA) and mean diffusivity (MD), by a Mendelian randomization analysis. We selected single nucleotide polymorphisms (SNPs) associated with each nutrient as instrumental variables to assess the causal effects of nutrient-related exposures on WMHs, FA, and MD. The outcome was from a recently published large-scale European Genome Wide Association Studies pooled dataset, including WMHs (N = 18,381), FA (N = 17,663), and MD (N = 17,467) data. We used the inverse variance weighting (IVW) method as the primary method, and sensitivity analyses were conducted using the simple median, weighted median, and MR-Egger methods. Genetically predicted serum calcium level was positively associated with WMHs risk, with an 8.1% increase in WMHs risk per standard deviation unit increase in calcium concentration (OR = 1.081, 95% CI = 1.006–1.161, p = 0.035). The plasma linoleic acid level was negatively associated with FA (OR = 0.776, 95% CI = 0.616–0.978, p = 0.032). Our study demonstrated that genetically predicted calcium was a potential risk factor for WMHs, and linoleic acid may be negatively associated with FA, providing evidence for interventions from the perspective of gene-environment interactions. Full article

Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers are of great significance for the early diagnosis and progression prediction of CSVD and have become a research focus because of their noninvasiveness and easy accessibility. Notably, many blood biomarkers have been reported to be associated with CSVD in a relatively large population, particularly serum neurofilament light chain (NfL), which has been regarded as a promising biomarker to track the variation trend in WMH and to predict the further status of white matter hyperintensities (WMH) and lacunar infarcts. And neuro-glio-vascular unit structure and blood–brain barrier function have been proposed as underlying mechanisms of CSVD. The article starts from the neuroimaging markers of CSVD, including recent small subcortical infarcts (RSSI), white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), enlarged perivascular spaces (EPVS), cerebral atrophy, and the combined small vessel disease score, and attempts to systematically review and summarize the research progress regarding the blood biomarkers of CSVD that form the changes in the neuro-glio-vascular unit structure and blood–brain barrier function. Full article

Background: Delayed Post-Hypoxic Leukoencephalopathy (DPHL), or Grinker’s myelinopathy, is a syndrome in which extensive changes are seen in the white matter of the cerebral hemispheres with MRI weeks or months after a hypoxic episode. T₂-weighted spin echo (T₂-wSE) and/or T₂-Fluid Attenuated Inversion Recovery (T₂-FLAIR) images classically show diffuse hyperintensities in white matter which are thought to be near pathognomonic of the condition. The clinical features include Parkinsonism and akinetic mutism. DPHL is generally regarded as a rare condition. Methods and Results: Two cases of DPHL imaged with MRI nine months and two years after probable hypoxic episodes are described. No abnormalities were seen on the T₂-FLAIR images with MRI, but very extensive changes were seen in the white matter of the cerebral and cerebellar hemisphere on divided Subtraction Inversion Recovery (dSIR) images. dSIR sequences may produce ten times the contrast of conventional inversion recovery (IR) sequences from small changes in T₁. The clinical findings in both cases were of cognitive impairment without Parkinsonism or akinetic mutism. Conclusion: The classic features of DPHL may only represent the severe end of a spectrum of diseases in white matter following global hypoxic injury to the brain. The condition may be much more common than is generally thought but may not be recognized using conventional clinical and MRI criteria for diagnosis. Reappraisal of the syndrome of DPHL to include clinically less severe cases and to encompass recent advances in MRI is advocated. Full article