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Introduction: White matter hyperintensities (WMHs), a major cerebral small vessel disease (cSVD) marker, may arise from different pathologies depending on their location. We explored clinical and genetic correlates of agnostically derived spatial WMH patterns in two longitudinal population-based cohorts (Three-City Study [3C]-Dijon, LIFE-Adult).
Methods: We derived seven WMH spatial patterns using Bullseye segmentation in 2878 individuals aged 65+ and explored their associations with vascular and genetic risk factors, cognitive performance, dementia and stroke incidence.
Results: WMHs in the frontoparietal and anterior periventricular region were associated with blood pressure traits, WMH genetic risk score (GRS), baseline and decline in general cognitive performance, incident all-cause dementia, and ischemic stroke. Juxtacortical-deep occipital WMHs were not associated with vascular risk factors and WMH GRS, but with incident all-cause dementia and intracerebral hemorrhage.
Discussion: Accounting for WMH spatial distribution is key to deciphering mechanisms underlying cSVD subtypes, an essential step towards personalized therapeutic approaches.
Highlights: We studied spatial patterns of WMHs in 2878 participants. Blood pressure was associated with frontoparietal and anterior PV WMHs. Anterior PV WMHs predicted dementia and stroke risk. Juxtacortical-deep occipital WMH burden was not associated with blood pressure or WMH genetic risk. Juxtacortical-deep occipital WMH burden predicted dementia and intracerebral hemorrhage.
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http://dx.doi.org/10.1002/alz.70053 | DOI Listing |
J Sep Sci
September 2025
Department of Analytical Chemistry, Faculty of Science, Palacký University Olomouc, Olomouc, Czech Republic.
The increasing use of engineered nanoparticles (NPs) in consumer and biomedical products has raised concern over their potential accumulation, transformation, and toxicity in biological systems. Accurate analytical methods are essential to detect, characterize, and quantify NPs in complex biological matrices. Inductively coupled plasma mass spectrometry (ICP-MS) has emerged as a leading technique due to its high sensitivity, elemental selectivity, and quantitative capabilities.
View Article and Find Full Text PDFActa Pharmacol Sin
September 2025
Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Bas
Recent investigations into the rapid antidepressant effects of ketamine, along with studies on schizophrenia-related susceptibility genes, have highlighted the GluN2A subunit as a critical regulator of both emotion and cognition. However, the specific impacts of acute pharmacological inhibition of GluN2A-containing NMDA receptors on brain microcircuits and the subsequent behavioral consequences remain poorly understood. In this study, we first examined the effects of MPX-004, a selective GluN2A NMDA receptor inhibitor, on behavior within the dorsomedial prefrontal cortex (dmPFC).
View Article and Find Full Text PDFJ Neurosci
September 2025
Department of Bioengineering, George Mason University, Fairfax, VA, United States,
In the hippocampal formation, cholinergic modulation from the medial septum/diagonal band of Broca (MSDB) is known to correlate with the speed of an animal's movements at sub-second timescales and also supports spatial memory formation. Yet, the extent to which sub-second cholinergic dynamics, if at all, align with transient behavioral and cognitive states supporting the encoding of novel spatial information remains unknown. In this study, we used fiber photometry to record the temporal dynamics in the population activity of septo-hippocampal cholinergic neurons at sub-second resolution during a hippocampus-dependent object location memory task using ChAT-Cre mice of both sexes.
View Article and Find Full Text PDFJ Safety Res
September 2025
Zachry Department of Civil and Environmental Engineering, Texas A&M University, USA.
Introduction: Pedestrian safety has become a critical concern with the rising global population of older adults. Older pedestrians face higher crash risks due to age-related physical limitations, yet road infrastructure often fails to address their specific needs. Most studies treat older adults as a single group, overlooking variations in mobility and behavior.
View Article and Find Full Text PDFNucleic Acids Res
September 2025
Department of Molecular Life Sciences and SIB Swiss Institute of Bioinformatics, University of Zurich, 8057 Zurich, Switzerland.
Spatial omics allow for the molecular characterization of cells in their spatial context. Notably, the two main technological streams, imaging-based and high-throughput sequencing-based, give rise to very different data modalities. The characteristics of the two data types are well known in spatial statistics as point patterns and lattice data.
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