The Canadian Stroke Best Practice Recommendations (CSPR) 7th edition includes this new module on the diagnosis and management of vascular cognitive impairment (VCI) with or without neurodegenerative disease. An expert writing group and people with VCI lived experience (PWLE) reviewed current evidence. Existing recommendations were reviewed and revised, and new recommendations added. Sections include definitions, signs and symptoms, screening, assessment, diagnosis, pharmacological and non-pharmacological management, secondary prevention, rehabilitation, and end-of-life care. PWLE were actively involved in all aspects of the development, ensuring their experiences are integrated. A unique VCI journey map, developed by PWLE, is included, and helped to motivate and anchor the recommendations. We encourage it to be displayed across healthcare settings to raise awareness and support persons with VCI. These VCI CSBPRs emphasize the need for integrated multidisciplinary care across the continuum. Evidence for the diagnosis and management of VCI continues to emerge and gaps in knowledge should drive future research.
Deciphering the diverse molecular mechanisms in living Alzheimer's disease (AD) patients is a big challenge but is pivotal for disease prognosis and precision medicine development.
Utilizing an optimal transport approach, we conducted graph-based mapping of transcriptomic profiles to transfer AD subtype labels from ROSMAP monocyte samples to ADNI and ANMerge peripheral blood mononuclear cells. Subsequently, differential expression followed by comparative pathway and diffusion pseudotime analysis were applied to each cohort to infer the progression trajectories. Survival analysis with real follow-up time was used to obtain potential biomarkers for AD prognosis.
AD subtype labels were accurately transferred onto the blood samples of ADNI and ANMerge living patients. Pathways and associated genes in neutrophil degranulation-like immune process, immune acute phase response, and IL-6 signaling were significantly associated with AD progression.
The work enhanced our understanding of AD progression in different subtypes, offering insights into potential biomarkers and personalized interventions for improved patient care.
Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course. With the emergence of anti-amyloid therapeutics, discrimination of LATE-NC from ADNC is critical and will lead to greater clinical recognition of amnestic patients without ADNC. Furthermore, co-pathology with LATE-NC may influence outcomes of these therapeutics. Thus there is a need to identify patients during life with likely LATE-NC. We propose criteria for clinical diagnosis of LATE as an initial framework for further validation. In the context of progressive memory loss and substantial hippocampal atrophy, criteria are laid out for probable (amyloid negative) or possible LATE (amyloid biomarkers are unavailable or when amyloid is present, but hippocampal neurodegeneration is out of proportion to expected pure ADNC).
Introduction: Cerebrovascular dysfunction plays a critical role in the pathogenesis of dementia and related neurodegenerative disorders. Recent omics-driven research has revealed associations between vascular abnormalities and transcriptomic alterations in brain vascular cells, particularly endothelial cells (ECs) and pericytes (PCs). However, the impact of these molecular changes on dementia remains unclear.
Methods: We conducted a comparative analysis of gene expression in ECs and PCs across neurodegenerative conditions, including Alzheimer's disease (AD), Huntington's disease, and arteriovenous malformation, utilizing transcriptomic data from published postmortem human tissue studies.
Results: We identified differentially expressed genes (DEGs) consistently dysregulated in ECs and PCs across these pathologies. Notably, several DEGs are linked to vascular cell zonation and genetic risks for AD and cerebral small vessel disease.
Discussion: Our findings provide insights into the cellular and molecular mechanisms underlying vascular dysfunction in dementia, highlight the knowledge gaps, and suggest potential novel vascular therapeutic targets, including genes not previously investigated in this context.
Highlights: Systematic review of differentially expressed genes (DEGs) in vascular cells from neurodegenerative single-nuclear RNA-sequencing (snRNA-seq) studies. Identify overlapping DEGs in multiple vascular cell types across studies. Examine functional relevance and associations with genetic risk for common DEGs. Outline future directions for the vascular omics field.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：