As a potential preclinical stage of Alzheimer\'s dementia, subjective cognitive decline (SCD) reveals a higher risk of future cognitive decline and conversion to dementia. However, it has not been clear whether SCD status increases the clinical progression of older adults in the context of amyloid deposition, cerebrovascular disease (CeVD), and psychiatric symptoms. We identified 99 normal controls (NC), 15 SCD individuals who developed mild cognitive impairment in the next 2 years (P-SCD), and 54 SCD individuals who did not (S-SCD) from ADNI database with both baseline and 2-year follow-up data. Total white matter hyperintensity (WMH), WMH in deep (DWMH) and periventricular (PWMH) regions, and voxel-wise grey matter volumes were compared among groups. Furthermore, using structural equation modelling method, we constructed path models to explore SCD-related brain changes longitudinally and to determine whether baseline SCD status, age, and depressive symptoms affect participants\' clinical outcomes. Both SCD groups showed higher baseline amyloid PET SUVR, baseline PWMH volumes, and larger increase of PWMH volumes over time than NC. In contrast, only P-SCD had higher baseline DWMH volumes and larger increase of DWMH volumes over time than NC. No longitudinal differences in grey matter volume and amyloid was observed among NC, S-SCD, and P-SCD. Our path models demonstrated that SCD status contributed to future WMH progression. Further, baseline SCD status increases the risk of future cognitive decline, mediated by PWMH; baseline depressive symptoms directly contribute to clinical outcomes. In conclusion, both S-SCD and P-SCD exhibited more severe CeVD than NC. The CeVD burden increase was more pronounced in P-SCD. In contrast with the direct association of depressive symptoms with dementia severity progression, the effects of SCD status on future cognitive decline may manifest via CeVD pathologies. Our work highlights the importance of multi-modal longitudinal designs in understanding the SCD trajectory heterogeneity, paving the way for stratification and early intervention in the preclinical stage. PRACTITIONER POINTS: Both S-SCD and P-SCD exhibited more severe CeVD at baseline and a larger increase of CeVD burden compared to NC, while the burden was more pronounced in P-SCD. Baseline SCD status increases the risk of future PWMH and DWMH volume accumulation, mediated by baseline PWMH and DWMH volumes, respectively. Baseline SCD status increases the risk of future cognitive decline, mediated by baseline PWMH, while baseline depression status directly contributes to clinical outcome.

The neurological effects and underlying pathophysiological mechanisms of sports-related concussion (SRC) in active young boxers remain poorly understood. This study aims to investigate the impairment of white matter microstructure and assess changes in glymphatic function following SRC by utilizing neurite orientation dispersion and density imaging (NODDI) on young boxers who have sustained SRC. A total of 60 young participants were recruited, including 30 boxers diagnosed with SRC and 30 healthy individuals engaging in regular exercise. The assessment of whole-brain white matter damage was conducted using diffusion metrics, while the evaluation of glymphatic function was performed through diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS) index. A two-sample t-test was utilized to examine group differences in DTI and NODDI metrics. Spearman correlation and generalized linear mixed models were employed to investigate the relationship between clinical assessments of SRC and NODDI measurements. Significant alterations were observed in DTI and NODDI metrics among young boxers with SRC. Additionally, the DTI-ALPS index in the SRC group exhibited a significantly higher value than that of the control group (left side: 1.58 vs. 1.48, PFDR = 0.009; right side: 1.61 vs. 1.51, PFDR = 0.02). Moreover, it was observed that the DTI-ALPS index correlated with poorer cognitive test results among boxers in this study population. Repetitive SRC in active young boxers is associated with diffuse white matter injury and glymphatic dysfunction, highlighting the detrimental impact on brain health. These findings highlight the importance of long-term monitoring of the neurological health of boxers.

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual \"omics\" signature that distinguishes subjects with varying cognitive profiles.
RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging.
CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

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.

Decline in spatial context memory emerges in midlife, the time when most females transition from pre- to post-menopause. Recent evidence suggests that, among post-menopausal females, advanced age is associated with functional brain alterations and lower spatial context memory. However, it is unknown whether similar effects are evident for white matter (WM) and, moreover, whether such effects contribute to sex differences at midlife. To address this, we conducted a study on 96 cognitively unimpaired middle-aged adults (30 males, 32 pre-menopausal females, 34 post-menopausal females). Spatial context memory was assessed using a face-location memory paradigm, while WM microstructure was assessed using diffusion tensor imaging. Behaviorally, advanced age was associated with lower spatial context memory in post-menopausal females but not pre-menopausal females or males. Additionally, advanced age was associated with microstructural variability in predominantly frontal WM (e.g., anterior corona radiata, genu of corpus callosum), which was related to lower spatial context memory among post-menopausal females. Our findings suggest that post-menopausal status enhances vulnerability to age effects on the brain\'s WM and episodic memory.

Given that glioma cells tend to infiltrate and migrate along WM tracts, leading to demyelination and axonal injuries, Diffusion Tensor Imaging (DTI) emerged as a promising tool for identifying major \"high-risk areas\" of recurrence within the peritumoral brain zone (PBZ) or at a distance throughout the adjacents white matter tracts. Of our systematic review is to answer the following research question: In patients with brain tumor, is DTI able to recognizes within the peri-tumoral brain zone (PBZ) areas more prone to local (near the surgical cavity) or remote recurrence compared to the conventional imaging techniques?. We conducted a comprehensive literature search to identify relevant studies in line with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. 15 papers were deemed compatible with our research question and included. To enhance the paper\'s readability, we have categorized our findings into two distinct groups: the first delves into the role of DTI in detecting PBZ sub-regions of infiltration and local recurrences (n = 8), while the second group explores the feasibility of DTI in detecting white matter tract infiltration and remote recurrences (n = 7). DTI values and, within a broader framework, radiomics investigations can provide precise, voxel-by-voxel insights into the state of PBZ and recurrences. Better defining the regions at risk for potential recurrence within the PBZ and along WM bundles will allow targeted therapy.

UNASSIGNED: Brain medical image segmentation is a critical task in medical image processing, playing a significant role in the prediction and diagnosis of diseases such as stroke, Alzheimer\'s disease, and brain tumors. However, substantial distribution discrepancies among datasets from different sources arise due to the large inter-site discrepancy among different scanners, imaging protocols, and populations. This leads to cross-domain problems in practical applications. In recent years, numerous studies have been conducted to address the cross-domain problem in brain image segmentation.
UNASSIGNED: This review adheres to the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for data processing and analysis. We retrieved relevant papers from PubMed, Web of Science, and IEEE databases from January 2018 to December 2023, extracting information about the medical domain, imaging modalities, methods for addressing cross-domain issues, experimental designs, and datasets from the selected papers. Moreover, we compared the performance of methods in stroke lesion segmentation, white matter segmentation and brain tumor segmentation.
UNASSIGNED: A total of 71 studies were included and analyzed in this review. The methods for tackling the cross-domain problem include Transfer Learning, Normalization, Unsupervised Learning, Transformer models, and Convolutional Neural Networks (CNNs). On the ATLAS dataset, domain-adaptive methods showed an overall improvement of ~3 percent in stroke lesion segmentation tasks compared to non-adaptive methods. However, given the diversity of datasets and experimental methodologies in current studies based on the methods for white matter segmentation tasks in MICCAI 2017 and those for brain tumor segmentation tasks in BraTS, it is challenging to intuitively compare the strengths and weaknesses of these methods.
UNASSIGNED: Although various techniques have been applied to address the cross-domain problem in brain image segmentation, there is currently a lack of unified dataset collections and experimental standards. For instance, many studies are still based on n-fold cross-validation, while methods directly based on cross-validation across sites or datasets are relatively scarce. Furthermore, due to the diverse types of medical images in the field of brain segmentation, it is not straightforward to make simple and intuitive comparisons of performance. These challenges need to be addressed in future research.

Cognitive challenges and brain structure variations are common in autism spectrum disorder (ASD) but are rarely explored in middle-to-old aged autistic adults. Cognitive deficits that overlap between young autistic individuals and elderlies with dementia raise an important question: does compromised cognitive ability and brain structure during early development drive autistic adults to be more vulnerable to pathological aging conditions, or does it protect them from further decline? To answer this question, we have synthesized current theoretical models of aging in ASD and conducted a systematic literature review (Jan 1, 1980 - Feb 29, 2024) and meta-analysis to summarize empirical studies on cognitive and brain deviations in middle-to-old aged autistic adults. We explored findings that support different aging theories in ASD and addressed study limitations and future directions. This review sheds light on the poorly understood consequences of aging question raised by the autism community to pave the way for future studies to identify sensitive and reliable measures that best predict the onset, progression, and prognosis of pathological aging in ASD.

OBJECTIVE: Insomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure detection of involved brain circuits. The present study investigated whether structural brain connectivity deviations differ between recently discovered and validated insomnia subtypes.
METHODS: Structural and diffusion weighted 3-Tesla MRI data of four independent studies were harmonized. The sample consisted of 73 controls without sleep complaints and 204 participants with insomnia grouped into five subtypes based on their fingerprint of mood and personality traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age and sex evaluated group differences in structural connectivity strength, indicated by fractional anisotropy, streamline volume density and mean diffusivity, and evaluated within three different atlases.
RESULTS: Insomnia subtypes showed differentiating profiles of deviating structural connectivity which concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in four of the five subtypes: highly distressed, moderately distressed reward sensitive, slightly distressed low reactive and slightly distressed high reactive. Connectivity deviation profile significance ranged from p= 0.001 to p=0.049 for different resolutions of brain parcellation and connectivity weight.
CONCLUSIONS: Our results provide a first indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping of insomnia could be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.

We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we studied n = 9 cases without neurological disorders and n = 22 cases with neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (ALS, n = 8), Alzheimer\'s disease (AD, n = 8), Pick\'s disease (PiD, n = 3), and schizophrenia (n = 3). NPFF-immunopositive cells were located chiefly, but not exclusively, in the superficial white matter and constituted there a subpopulation of white matter interstitial cells (WMIC): Pyramidal-like and multipolar somata predominated in the gyral crowns, whereas bipolar and ovoid somata predominated in the cortex surrounding the sulci. Their sparsely ramified axons were unmyelinated and exhibited NPFF-positive bead-like varicosities. We found significantly fewer NPFF-immunopositive cells in the gray matter of the frontal, cingulate, and superior temporal gyri of both sporadic ALS and late-stage AD patients than in controls, and significantly fewer NPFF-positive cells in the subjacent as well as deep white matter of the frontal gyrus of these patients compared to controls. Notably, the number of NPFF-positive cells was also significantly lower in the hippocampal formation in AD compared to controls. In PiD, NPFF-positive cells were present in significantly lower numbers in the gray and white matter of the cingulate and frontal gyrii in comparison to controls. In schizophrenic patients, lower wNPFF cell counts in the neocortex were significant and global (cingulate, frontal, superior temporal gyrus, medial, and inferior gyri). The precise functions of NPFF-positive cells and their relationship to the superficial corticocortical white matter U-fibers are currently unknown. Here, NPFF immunohistochemistry and expression characterize a previously unrecognized population of cells in the human brain, thereby providing a new entry-point for investigating their physiological and pathophysiological roles.