Post-Stroke Cognitive Impairment and Dementia

Circulation Research, Journal Year: 2022, Volume and Issue: 130(8), P. 1252 - 1271

Published: April 14, 2022

Poststroke cognitive impairment and dementia (PSCID) is a major source of morbidity mortality after stroke worldwide. PSCID occurs as consequence ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Cognitive manifesting clinical categorized vascular even in people with comorbid neurodegenerative pathology, which common elderly individuals can contribute to the expression PSCID. Manifestations cerebral small vessel disease, such covert brain infarcts, white matter lesions, microbleeds, cortical microinfarcts, are also patients likewise outcomes. Although studies historically varied approach timing methods diagnosis, most them demonstrate that older age, lower educational status, socioeconomic disparities, premorbid functional decline, life-course exposure risk factors, history prior increase Stroke characteristics, particular severity, lesion volume, location, multiplicity recurrence, influence risk. Understanding complex interaction between an acute event preexisting pathology remains priority will be critical for developing strategies personalized prediction, prevention, targeted interventions, rehabilitation. Current challenges field relate lack harmonization definition classification PSCID, approaches neurocognitive assessment, duration follow-up stroke. However, evolving knowledge on pathophysiology, neuroimaging, biomarkers offers potential applications may inform trials. Preventing cornerstone any strategy achieve optimal health. We summarize recent developments discuss future directions closing call action systematically include outcome assessment into poststroke outcome.

Language: Английский

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Exploring and validating associations between six systemic inflammatory indices and ischemic stroke in a middle-aged and old Chinese population

Aging Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: 37(1)

Published: Jan. 21, 2025

Abstract Background Inflammation and maladaptive immune mechanisms have been substantiated as integral components in the critical pathological processes of injury cascade ischemic stroke (IS). This study aimed to explore associations between six systemic inflammatory indices IS a Chinese population. Methods was case-control based on retrospective review electronic medical records from two hospitals Shandong Province, China. Systemic indices, including inflammation response index (SIRI), (SII), pan-immune-inflammation value (PIV), neutrophil lymphocyte ratio (NLR), platelet (PLR), monocyte (LMR), were calculated. Logistic regression models classification analyses employed evaluate discriminatory abilities. Results In total, 9392 participants aged 40–83 years old included discovery (3620 pairs IS-present cases healthy controls) validation (1076 IS-absent controls with mimics) datasets. After adjusting for potential confounding factors, found be associated all dataset, SIRI (odd [OR] 8.77, 95% confidence interval [CI] 7.48–10.33), SII (1.03, 1.01–1.04), PIV (1.01, 1.01–1.01), NLR (2.23, 2.08–2.39), PLR LMR (0.77, 0.75–0.78). Notably, only exhibited significant both datasets (0.88, 0.83–0.93), suggesting an independent protective role this index. SIRI, SII, PIV, NLR, showed good discriminative ability patients dataset (AUCs > 0.70). However, they performed poorly distinguishing mimics < 0.60). Conclusion provides valuable insights into IS, offering implications risk stratification. While these are indicators conditions, additional biomarkers may needed when differentiating other chronic conditions clinical practice.

Language: Английский

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Soluble Biomarkers of Cerebrovascular Pathologies

Stroke, Journal Year: 2024, Volume and Issue: 55(4), P. 801 - 811

Published: March 25, 2024

Vascular contributions to cognitive impairment and dementia (VCID) is an all-encompassing term that describes due cerebrovascular origins. With the advancement of imaging pathological studies, we now understand VCID often comorbid with Alzheimer disease. While researchers in disease field have been working for years establish test blood-based biomarkers diagnosis, prognosis, clinical therapy discovery, early detection, are their infancy also face challenges. heterogeneous, comprising many different entities (ischemic, or hemorrhagic), spatial temporal differences (acute chronic). This review highlights pathways aiding search sensitive specific dysfunction markers, promising candidates, explains ongoing initiatives discover biomarkers.

Language: Английский

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Production of Amyloid-β in the Aβ-Protein-Precursor Proteolytic Pathway Is Discontinued or Severely Suppressed in Alzheimer’s Disease-Affected Neurons: Contesting the ‘Obvious’

Genes, Journal Year: 2025, Volume and Issue: 16(1), P. 46 - 46

Published: Jan. 2, 2025

A notion of the continuous production amyloid-β (Aβ) via proteolysis Aβ-protein-precursor (AβPP) in Alzheimer's disease (AD)-affected neurons constitutes both a cornerstone and an article faith research field. The present Perspective challenges this assumption. It analyses relevant empirical data reaches unexpected conclusion, namely that AD-afflicted neurons, AβPP-derived Aβ is either discontinued or severely suppressed, concept that, if proven, would fundamentally change our understanding disease. This suppression, effectively self-suppression, occurs context global inhibition cellular cap-dependent protein synthesis as consequence neuronal integrated stress response (ISR) elicited by intraneuronal (iAβ; hence self-suppression) upon reaching certain levels. Concurrently with suppression AβPP proteolytic pathway, ISR activates human but not mouse powerful AD-driving pathway generating C99 fragment independently AβPP. study describes molecular mechanisms potentially involved these phenomena, propounds novel approaches to generate transgenic animal models AD, advocates for utilization cells-based disease, makes verifiable predictions, suggests experiments designed validate proposed concept, considers its potential therapeutic implications. Remarkably, it opens up possibility conventional AβPP, BACE enzymes, γ-secretase components also suppressed under conditions AD-affected resulting dyshomeostasis follows whereas AD triggered iAβ accumulated ISR-eliciting levels, unconventional (triggered stressors distinct from iAβ) forms, driven (or only) produced AβPP-independent we previously, mainly, possibly exclusively, generated cleaved at γ-site due ISR-caused deficiency (apparently, "substance X" predicted previous study), paradigm consistent dictum George Perry "central causative" AD. strategies only deplete driver abrogate reverse ameliorate dyshomeostasis, significant contributor pathology.

Language: Английский

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Lipids at the Nexus between Cerebrovascular Disease and Vascular Dementia: The Impact of HDL-Cholesterol and Ceramides

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4403 - 4403

Published: Feb. 23, 2023

Cerebrovascular diseases and the subsequent brain hypoperfusion are at basis of vascular dementia. Dyslipidemia, marked by an increase in circulating levels triglycerides LDL-cholesterol a parallel decrease HDL-cholesterol, turn, is pivotal promoting atherosclerosis which represents common feature cardiovascular cerebrovascular diseases. In this regard, HDL-cholesterol has traditionally been considered as being protective from prospective. However, emerging evidence suggests that their quality functionality play more prominent role than shaping health possibly cognitive function. Furthermore, lipids embedded lipoproteins another key discriminant modulating disease, with ceramides proposed novel risk factor for atherosclerosis. This review highlights HDL lipoprotein repercussion on Additionally, manuscript provides up-to-date picture impact saturated omega-3 fatty acids levels, ceramide metabolism.

Language: Английский

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Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study

Stroke, Journal Year: 2023, Volume and Issue: 54(5), P. 1303 - 1311

Published: April 7, 2023

Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim this study was investigate associations between concentrations systemic inflammatory biomarkers after ischemic stroke and impairment.The Nor-COAST (Norwegian Cognitive Impairment After Stroke) a prospective observational multicenter cohort study, including patients hospitalized with acute 2015 2017. Inflammatory biomarkers, TCC (terminal C5b-9 complement complex) 20 cytokines, were analyzed plasma, collected at baseline, 3-, 18 months poststroke, using ELISA multiplex assay. Global outcome assessed Montreal Assessment (MoCA) scale. We investigated plasma baseline MoCA score 18-, 36-month follow-ups; 3 18- association these follow-up. used mixed linear regression adjusted for age sex.We included 455 survivors stroke. Higher 7 significantly associated lower 36 months; TCC, IL (interleukin)-6, MIP (macrophage protein)-1α 3, 18, (P<0.01). No biomarker either or months, whereas higher IL-6 MIP-1α measured both particularly strongly (P<0.01).Higher scores up poststroke. This most pronounced phase following stroke.URL: https://www.gov; Unique identifier: NCT02650531.

Language: Английский

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Heart brain axis in health and disease: role of innate and adaptive immunity

Cardiovascular Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 24, 2024

Abstract The importance of the brain–heart interaction has been increasingly recognized as a critical physiological axis that is altered in disease. In this review, we explore intricate relationship between central nervous system and cardiovascular health, focusing particularly on immunological mechanisms influence course both neurological diseases. While previous studies have established key role autonomic (ANS) linking brain heart, more recent expanded our understanding multifaceted inter-organ interactions. As such, circulating mediators include immune cells adaptive innate their secreted immunogenic factors come into focus along bidirectional communication. Hence, review briefly discuss contribution ANS then heart-to-brain brain-to-heart axes, illustrating how diseases affect cognitive functions pathologies lead to cardiac complications.

Language: Английский

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CRTC1 is a potential target to delay aging-induced cognitive deficit by protecting the integrity of the blood-brain barrier via inhibiting inflammation

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2023, Volume and Issue: 43(7), P. 1042 - 1059

Published: April 22, 2023

Aging can cause attenuation in the functioning of multiple organs, and blood-brain barrier (BBB) breakdown could promote occurrence disorders central nervous system during aging. Since inflammation is considered to be an important factor underlying BBB injury aging, vascular endothelial cell senescence serves as a critical pathological basis for destruction integrity. In current review, we have first introduced concepts related aging-induced cognitive deficit integrity damage. Thereafter, reviewed potential relationship between disruption cognition role inflammation, senescence, injury. We also briefly function CREB-regulated transcription co-activator 1 (CRTC1) CRTC1 changes well roles CRTC1/cyclooxygenase-2 (COX-2) regulating Finally, mechanisms been summarized propose that promising target delay by protecting through promoting inhibition inflammation-mediated senescence.

Language: Английский

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Single-nucleus RNA sequencing of midbrain blood-brain barrier cells in schizophrenia reveals subtle transcriptional changes with overall preservation of cellular proportions and phenotypes

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(11), P. 4731 - 4740

Published: Oct. 3, 2022

The midbrain is an extensively studied brain region in schizophrenia, view of its reported dopamine pathophysiology and neuroimmune changes associated with this disease. Besides the dopaminergic system, contains other cell types that may be involved schizophrenia pathophysiology. neurovascular hypothesis postulates both neurovasculature structure functioning blood-brain barrier (BBB) are compromised schizophrenia. In present study, potential alteration BBB patients was investigated by single-nucleus RNA sequencing post-mortem tissue (15 cases 14 matched controls). We did not identify relative abundance major types, nor sub-populations, However, we identified differentially expressed genes cells as compared to controls, including have previously been related such FOXP2 PDE4D. These transcriptional were limited ependymal pericytes, suggesting broadly affected

Language: Английский

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Linking evidence for targeted blood biomarkers in post-stroke cognitive impairment and dementia

Frontiers in Stroke, Journal Year: 2025, Volume and Issue: 3

Published: Jan. 7, 2025

With improvements in acute stroke treatment and more patients surving the period, identification prognostication of post-stroke disability is paramount. Post-stroke cognitive impairment dementia (PSCID) severely impacts morbidity mortality survivors. While clinical factors imaging are useful identifying at risk for PSCID, blood-based biomarkers sorely needed to provide cost-effective greatest risk. Furthermore, can inform biologic basis PSCID lead potential targets. This narrative review attempts summarize currently available research on use fluid measure quantify using a framework proposed DISCOVERY Network study PSCID. In this framework, blood divided into broad pathologic categories including inflammation, neurodegeneration, neuroaxonal injury, vascular injury. Key that have been as relevant include interleukin-6, C-reactive protein, β-amyloid 42:40 ratio, neurofilament light chain, 10 angiogenic molecules. Critical assessment prior studies includes defining sample collection period assess temporal pattern biomarker levels relation an incident event. addition comprehensive review, we performed protein-protein network analysis putative (surprisingly) find they exist highly connected interaction centered inflammatory neurodegenerative suggesting shared biology underlies pathogenesis Both literature point role combinatorial methodology enhance specificity sensitivity prognostic highlights emerging evaluating while also informing underlying creates synergy between dementia.

Language: Английский

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