OBJECTIVE: This study identified the factors affecting cerebral microbleed (CMBs) development. Moreover, their effects on intelligence and memory and association with stroke in patients with germinoma who had long-term follow-up were evaluated.
METHODS: This study included 64 patients with germinoma who were histologically and clinically diagnosed with and treated for germinoma. These patients were evaluated cross-sectionally, with a focus on CMBs on susceptibility-weighted magnetic resonance imaging (SWI), brain atrophy assessed through volumetric analysis, and intelligence and memory.
RESULTS: The follow-up period was from 32 to 412 (median: 175.5) months. In total, 43 (67%) patients had 509 CMBs and 21 did not have CMBs. Moderate correlations were observed between the number of CMBs and time from initial treatments and recurrence was found to be a risk factor for CMB development. Increased temporal CMBs had a marginal effect on the processing speed and visual memory, whereas brain atrophy had a statistically significant effect on verbal, visual, and general memory and a marginal effect on processing speed. Before SWI acquisition and during the follow-up periods, eight strokes occurred in four patients. All of these patients had ≥ 15 CMBs on SWI before stroke onset. Meanwhile, 33 patients with < 14 CMBs or 21 patients without CMBs did not experience stroke.
CONCLUSIONS: Patients with a longer time from treatment initiation had a higher number of CMBs, and recurrence was a significant risk factor for CMB development. Furthermore, brain atrophy had a stronger effect on memory than CMBs. Increased CMBs predict the stroke onset.

BACKGROUND: Atrophy of white and grey matter volumes occurs early in the brains of people with multiple sclerosis (pwMS) and has great clinical relevance. In clinical trials, brain atrophy can be quantified by magnetic resonance imaging (MRI) with automated software tools.
METHODS: In this study, we analyze volumes of various brain regions with the software \"md brain\" based on routine MRI scans of 53 pwMS in a real-world setting. We compare brain volumes of pwMS with an EDSS ≥ 3.5 and a disease duration ≥ 10 years to the brain volumes of pwMS with an EDSS < 3.5 and a disease duration < 10 years as well as with or without immunotherapy.
RESULTS: pwMS with an EDSS ≥ 3.5 and a disease duration ≥ 10 years had significantly lower volumes of the total brain, the grey matter and of the frontal, temporal, parietal and occipital lobe regions as compared to pwMS with an EDSS < 3.5 and a disease duration < 10 years. Regional brain volumes were significantly lower in pwMS without immunotherapy.
CONCLUSIONS: The study showed that higher EDSS, longer disease duration and absence of immunotherapy was associated with lower volumes in a number of brain regions. Further real-world studies may include larger patient cohorts in longitudinal analyses.

UNASSIGNED: The relative importance of different components of cognitive reserve (CR), as well as their differences by gender, are poorly established.
UNASSIGNED: To explore several dimensions of CR, their differences by gender, and their effects on cognitive performance and trajectory in a cohort of older people without relevant psychiatric, neurologic, or systemic conditions.
UNASSIGNED: Twenty-one variables related to the education, occupation, social activities, and life habits of 1,093 home-dwelling and cognitively healthy individuals, between 68 and 86 years old, were explored using factorial analyses to delineate several dimensions of CR. These dimensions were contrasted with baseline cognitive performance, follow-up over 5 years of participants\' cognitive trajectory, conversion to mild cognitive impairment (MCI), and brain volumes using regression and growth curve models, controlling for gender, age, marital status, number of medications, trait anxiety, depression, and ApoE genotype.
UNASSIGNED: Five highly intercorrelated dimensions of CR were identified, with some differences in their structure and effects based on gender. Three of them, education/occupation, midlife cognitive activities, and leisure activities, were significantly associated with late-life cognitive performance, accounting for more than 20% of its variance. The education/occupation had positive effect on the rate of cognitive decline during the 5-year follow up in individuals with final diagnosis of MCI but showed a reduced risk for MCI in men. None of these dimensions showed significant relationships with gray or white matter volumes.
UNASSIGNED: Proxy markers of CR can be represented by five interrelated dimensions. Education/occupation, midlife cognitive activities, and leisure activities are associated with better cognitive performance in old age and provide a buffer against cognitive impairment. Education/occupation may delay the clinical onset of MCI and is also associated with the rate of change in cognitive performance.

Inflammation is an important factor in Alzheimer\'s disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman\'s correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer\'s Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman\'s correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3-9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention.

Progression independent of relapse activity (PIRA) is prevalent among Caucasian patients with relapsing and remitting multiple sclerosis (RRMS). However, there is limited knowledge regarding the characteristics of PIRA in Asian patients with RRMS. Therefore, we retrospectively analyzed the clinical and radiological progression of 95 Japanese patients with RRMS during a 2-year observation period. PIRA was observed in three patients who were characterized by young age, large T2 lesion volume, and great reduction in brain volume. Despite having highly active disease, fewer patients with PIRA (33.3%) were treated with high-efficacy drugs compared with those without disease activity (60.7%).

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (β = -0.051, SE = 0.004, p < .001, per 10 years, and β = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (β = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (β = 0.067, SE = 0.007, p < .001 and β = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

The aim of this study was to employ artificial intelligence (AI)-based magnetic resonance imaging (MRI) brain volumetry to potentially distinguish between idiopathic normal pressure hydrocephalus (iNPH), Alzheimer\'s disease (AD), and age- and sex-matched healthy controls (CG) by evaluating cortical, subcortical, and ventricular volumes. Additionally, correlations between the measured brain and ventricle volumes and two established semi-quantitative radiologic markers for iNPH were examined. An IRB-approved retrospective analysis was conducted on 123 age- and sex-matched subjects (41 iNPH, 41 AD, and 41 controls), with all of the iNPH patients undergoing routine clinical brain MRI prior to ventriculoperitoneal shunt implantation. Automated AI-based determination of different cortical and subcortical brain and ventricular volumes in mL, as well as calculation of population-based normalized percentiles according to an embedded database, was performed; the CE-certified software mdbrain v4.4.1 or above was used with a standardized T1-weighted 3D magnetization-prepared rapid gradient echo (MPRAGE) sequence. Measured brain volumes and percentiles were analyzed for between-group differences and correlated with semi-quantitative measurements of the Evans\' index and corpus callosal angle: iNPH patients exhibited ventricular enlargement and changes in gray and white matter compared to AD patients and controls, with the most significant differences observed in total ventricular volume (+67%) and the lateral (+68%), third (+38%), and fourth (+31%) ventricles compared to controls. Global ventriculomegaly and marked white matter reduction with concomitant preservation of gray matter compared to AD and CG were characteristic of iNPH, whereas global and frontoparietally accentuated gray matter reductions were characteristic of AD. Evans\' index and corpus callosal angle differed significantly between the three groups and moderately correlated with the lateral ventricular volumes in iNPH patients [Evans\' index (r > 0.83, p ≤ 0.001), corpus callosal angle (r < -0.74, p ≤ 0.001)]. AI-based MRI volumetry in iNPH patients revealed global ventricular enlargement and focal brain atrophy, which, in contrast to healthy controls and AD patients, primarily involved the supratentorial white matter and was marked temporomesially and in the midbrain, while largely preserving gray matter. Integrating AI volumetry in conjunction with traditional radiologic measures could enhance iNPH identification and differentiation, potentially improving patient management and therapy response assessment.

BACKGROUND: Assessing the potential sources of bias and variability of the Centiloid (CL) scale is fundamental for its appropriate clinical application.
METHODS: We included 533 participants from AMYloid imaging to Prevent Alzheimer\'s Disease (AMYPAD DPMS) and Alzheimer\'s Disease Neuroimaging Initiative (ADNI) cohorts. Thirty-two CL pipelines were created using different combinations of reference region (RR), RR and target types, and quantification spaces. Generalized estimating equations stratified by amyloid positivity were used to assess the impact of the quantification pipeline, radiotracer, age, brain atrophy, and harmonization status on CL.
RESULTS: RR selection and RR type impact CL the most, particularly in amyloid-negative individuals. The standard CL pipeline with the whole cerebellum as RR is robust against brain atrophy and differences in image resolution, with 95% confidence intervals below ± 3.95 CL for amyloid beta positivity cutoffs (CL < 24).
CONCLUSIONS: The standard CL pipeline is recommended for most scenarios. Confidence intervals should be considered when operationalizing CL cutoffs in clinical and research settings.
CONCLUSIONS: We developed a framework for evaluating Centiloid (CL) variability to different factors. Reference region selection and delineation had the highest impact on CL values. Whole cerebellum (WCB) and whole cerebellum plus brainstem (WCB+BSTM) as reference regions yielded consistent results across tracers. The standard CL pipeline is robust against atrophy and image resolution variation. Estimated within- and between-pipeline variability (95% confidence interval) in absolute CL units.

The discovery that metabolic alterations often coexist with neurodegenerative conditions has sparked interest in the examination of metabolic regulatory factors as potential modulators of brain health. Here, we examined the role of adipokines (leptin, adiponectin, resistin, and IL6) and insulin on different markers of brain atrophy in participants on the spectrum of Alzheimer\'s Disease. We included 566 participants from the Alzheimer\'s Disease Neuroimaging Initiative (ADNI) dataset with 1063 follow-up time points (average follow-up: one year); and examined the association between metabolic regulatory factors and volumetric MRI values, white matter hyperintensities, and measures of cognitive impairment. Higher leptin, resistin, IL6, and insulin were associated with markers of cerebral atrophy, such as lower total brain volume, or higher ventricular volume. Higher leptin and resistin were also associated with greater impairment in daily life activities. Higher adiponectin was associated with lower ventricle volume. There was no association between adipokines or insulin with white matter hyperintensities. Our findings indicate a co-occurrence between alterations in metabolic regulatory factors and in brain volume along the preclinical to clinical spectrum of Alzheimer\'s Disease. These results suggest that strategies aimed at promoting metabolic health may positively impact brain health.

Anorexia nervosa (AN) is an eating disorder (ED) that has seen an increase in its incidence in the last thirty years. Compared to other psychosomatic disorders, ED can be responsible for many major medical complications, moreover, in addition to the various systemic impairments, patients with AN undergo morphological and physiological changes affecting the cerebral cortex. Through immunohistochemical studies on portions of postmortem human brain of people affected by AN and healthy individuals, and western blot studies on leucocytes of young patients and healthy controls, this study investigated the role in the afore-mentioned processes of altered redox state. The results showed that the brain volume reduction in AN could be due to an increase in the rate of cell death, mainly by apoptosis, in which mitochondria, main cellular organelles affected by a decreased dietary intake, and a highly compromised intracellular redox balance, may play a pivotal role.