Vascular cognitive impairment – Past, present, and future challenges

Badji, Atef; Youwakim, Jessica; Cooper, Alexandra; Westman, Eric; Marseglia, Anna

doi:10.1016/j.arr.2023.102042

Cited by 9 publications

(5 citation statements)

References 202 publications

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“…The global prevalence of VCI has been steadily increasing in recent years [ 26 ]. VCI has been recognized to have a significant detrimental effect on the quality of life and prognostic outcomes of patients with CVD, underscoring the importance of identifying diagnostic indicators that can facilitate early clinical intervention [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events

Li,

Gu,

Wang

et al. 2024

BMC Neurol

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Background The global prevalence of VCI has increased steadily in recent years, but diagnostic biomarkers for VCI in patients with non-disabling ischemic cerebrovascular incidents (NICE) remain indefinite. The primary objective of this research was to investigate the relationship between peripheral serological markers, white matter damage, and cognitive function in individuals with NICE. Methods We collected clinical data, demographic information, and medical history from 257 patients with NICE. Using the MoCA upon admission, patients were categorized into either normal cognitive function (NCF) or VCI groups. Furthermore, they were classified as having mild white matter hyperintensity (mWMH) or severe WMH based on Fazekas scores. We then compared the levels of serological markers between the cognitive function groups and the WMH groups. Results Among 257 patients with NICE, 165 were male and 92 were female. Lymphocyte count (OR = 0.448, P < 0.001) and LDL-C/HDL-C (OR = 0.725, P = 0.028) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age and inflammation markers but a lower MoCA score, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.765, P < 0.001) and LDL-C/HDL-C (AUC = 0.740, P < 0.001) had an acceptable diagnostic value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups. Conclusion Lymphocyte count, LDL-C/HDL-C were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.

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Section: Discussionmentioning

confidence: 99%

The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events

Li,

Gu,

Wang

et al. 2024

BMC Neurol

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“…The dysregulation of cerebral perfusion is a prevalent cause underlying VCI. Perfusion is the fundamental process in which blood circulates through an intricate network of tiny vessels within tissue to facilitate the crucial exchange of oxygen and other essential molecules [ 28 ]. Maintaining this process is crucial in the brain for sustaining homeostasis and ensuring the proper functioning of the neurovascular unit (NVU) [ 29 ].…”

Section: Pathophysiological Mechanisms Of Vcimentioning

confidence: 99%

“…A similar decrease in proteins such as claudin-5, occludins, and zonula occludens-1 is also observed in the cortical areas of those suffering from Alzheimer’s disease [ 46 ]. Interestingly, elevated levels of tight junction proteins in the peripheral blood have been detected in individuals with coronary heart disease, stroke, and intracranial hemorrhage, with particularly higher concentrations of occluding and claudin-5 in these conditions [ 28 ]. These increased levels could signify endothelial dysfunction in patients with VCI, suggesting a breach in the integrity of the BBB.…”

Section: Pathophysiological Mechanisms Of Vcimentioning

confidence: 99%

Potential Intersections between lncRNA, Vascular Cognitive Impairment, and Immunization Strategies: Insights and Future Directions

Fan,

Xiao,

Zhang

2024

Vaccines

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Vascular cognitive impairment (VCI) encompasses a wide range of cognitive disorders stemming from cerebrovascular issues, such as strokes or small vessel disease. These conditions often pose challenges to traditional diagnostic approaches due to their multifactorial nature and varied clinical presentations. Recently, next-generation sequencing (NGS) technologies have provided detailed analyses of long non-coding RNAs (lncRNAs) in the molecular pathobiology of VCI. These new findings help with molecular-based diagnostics and treatments of VCI. Within this realm, the concept of immune modulation, especially through specific vaccinations, emerges as a promising therapeutic strategy in VCI mitigation. In this review, we comprehensively elucidate the function of lncRNAs in VCI, emphasizing the advanced understanding of VCI’s molecular underpinnings made possible through NGS technologies. Significant focus is placed on the immune system’s role in VCI, particularly the neuroinflammatory processes which are consequential to cerebrovascular abnormalities. We believe that lncRNAs participate in regulating these immunological pathways, potentially guiding the development of vaccines targeting VCI. In this context, we propose a novel perspective: using knowledge about lncRNA profiles and functions to guide vaccine development, we can potentially exploit the body’s immune response to mitigate or prevent VCI. This approach has the potential to revolutionize VCI management by introducing targeted immunization strategies informed by molecular signatures, a concept that remains largely unexplored in current research endeavors. In addition, we summarize current progress and propose future directions, advocating for robust, interdisciplinary studies to validate the potential intersections between lncRNA landscapes, VCI pathology, and immunology. This review aims to spur innovative research and promote the development of lncRNA-informed vaccine strategies as proactive interventions against the cognitive consequences of VCI.

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“…Starting with subjective cognitive decline and progressing to dementia, it encompasses the full range of vascular brain pathologies that affect cognition. 1 , 2 The etiology is multifactorial, including small vessel diseases and large vessel infarcts. However, the exact pathogenesis of VCI remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR₂/SRC pathway in vascular cognitive impairment mice

Gao,

Chen,

Yin

et al. 2024

CNS Neurosci Ther

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AimTo explore the neuroprotective potential of hyperforin and elucidate its underlying molecular mechanisms involved in its therapeutic effects against vascular cognitive impairment (VCI).MethodsThe active compounds and possible targets of Hypericum perforatum L. that may be effective against VCI were found by network pharmacology in this research. We utilized bilateral common carotid artery occlusion (BCCAO) surgery to induce a VCI mouse model. Morris water maze (MWM) and Y‐maze tests were used to assess VCI mice's cognitive abilities following treatment with hyperforin. To evaluate white matter lesions (WMLs), we utilized Luxol fast blue (LFB) stain and immunofluorescence (IF). Neuroinflammation was assessed using IF, western blot (WB), and enzyme‐linked immunosorbent assay (ELISA). The effects of hyperforin on microglia were investigated by subjecting the BV2 microglial cell line to oxygen–glucose deprivation/reperfusion (OGD/R) stimulation. The expressions of VEGFR2, p‐SRC, SRC, VEGFA, and inflammatory markers including IL‐10, IL‐1β, TNF‐α, and IL‐6 were subsequently assessed.ResultsThe VEGFR2/SRC signaling pathway is essential for mediating the protective properties of hyperforin against VCI according to network pharmacology analysis. In vivo findings demonstrated that hyperforin effectively improved BCCAO‐induced cognitive impairment. Furthermore, staining results showed that hyperforin attenuated WMLs and reduced microglial activation in VCI mice. The hyperforin treatment group's ELISA results revealed a substantial decrease in IL‐1β, IL‐6, and TNF‐α levels. According to the results of in vitro experiments, hyperforin decreased the release of pro‐inflammatory mediators (TNF‐α, IL‐6, and IL‐1β) and blocked microglial M1‐polarization by modulating the VEGFR2/SRC signaling pathway.ConclusionHyperforin effectively modulated microglial M1 polarization and neuroinflammation by inhibiting the VEGFR2/SRC signaling pathways, thereby ameliorating WMLs and cognitive impairment in VCI mice.

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Vascular cognitive impairment – Past, present, and future challenges

Cited by 9 publications

References 202 publications

The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events

The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events

Potential Intersections between lncRNA, Vascular Cognitive Impairment, and Immunization Strategies: Insights and Future Directions

Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR₂/SRC pathway in vascular cognitive impairment mice

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Vascular cognitive impairment – Past, present, and future challenges

Cited by 9 publications

References 202 publications

The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events

The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events

Potential Intersections between lncRNA, Vascular Cognitive Impairment, and Immunization Strategies: Insights and Future Directions

Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR2/SRC pathway in vascular cognitive impairment mice

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Hyperforin ameliorates neuroinflammation and white matter lesions by regulating microglial VEGFR₂/SRC pathway in vascular cognitive impairment mice