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INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis. METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes. RESULTS: CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function. DISCUSSION: The predefined hypothesis on the association between CVR and a global cognitive score was validated in three independent analysis sites, providing support for CVR as a biomarker in VCID. HIGHLIGHTS: This study measured a novel functional index of small arteries referred to as cerebrovascular reactivity (CVR). CVR was positively associated with global cognition in older adults. This finding was observed in three independent cohorts at three sites. Our statistical analysis plan was predefined before beginning data collection.

Background: Vascular cognitive impairment is frequent, in mild (mVCI) or severe forms (vascular dementia). Objective: To do a randomized controlled-trial to evaluate the impact of physical activity on cognition (primary outcome), neurocognitive measures, quality of life, functional status, and physical function (secondary outcomes), in patients with mVCI. Methods: A hundred and four patients with mVCI (mean age 71.2 years; 53 women) were randomized for a six-month intervention of moderate physical activity (60-minute sessions, 3 times/week) (n = 53) or best-practice "usual care" (n = 51). Comprehensive evaluations of primary and secondary outcomes included an objective measure of physical activity through accelerometry at baseline and after intervention. Results: Mean session attendance was 58%. Adverse events were negligible. After 6 months, no significant primary outcome change was observed, either in the intervention or 'usual care' group. The intervention group improved significantly in some secondary outcomes in physical function - aerobic capacity (U = 403; p = 0.000) and agility (U = 453; p = 0.005) after 6 months. Regardless of randomization arm, a post-hoc analysis based on fulfilling at least 21.5 minutes/day of moderate or 10.7 minutes/day of vigorous physical activity (World Health Organization-WHO standards) revealed improvements. These were not only in motor capacity but also on the global measure of cognition, executive functions and memory. Conclusions: Physical activity was safe and beneficial regarding domains of physical function. No significant cognitive decline was registered over 6-months, regardless of intervention allocation. Larger samples, longer follow-ups and focus on intervention adherence are needed to fully analyze the impact of WHO recommendations for physical activity in mVCI populations. [ABSTRACT FROM AUTHOR]

Background: Cognitive deficits following ischemic stroke significantly impair quality of life, highlighting the need for effective interventions. This study evaluates the efficacy and safety of extended N-Pep-12 dietary supplementation in enhancing cognitive recovery post-stroke. Methods: In this randomized, open-label, controlled study, 106 patients with supratentorial ischemic stroke were enrolled to receive either 90mg N-Pep-12 or no supplementation daily for 360 days and were followed-up for 360 days. Cognitive function and emotional well-being were assessed using established neuropsychological scales at baseline, 90 days, and 360 days post-stroke. Safety was monitored through adverse events and mortality rates. Results: Significant improvements were observed in the N-Pep-12 group compared to controls, particularly in the Montreal Cognitive Assessment scores at both 90 and 360 days, and in the Digit Symbol Coding scores at 360 days, suggesting enhanced cognitive recovery with extended N-Pep-12 supplementation. A linear regression for a composite outcome analysis at day 360 further confirmed the efficacy of N-Pep-12 in contributing to cognitive improvement. Safety profiles were favorable, with no significant adverse effects attributed to N-Pep-12. Conclusions: Extended dietary supplementation with N-Pep-12 appears to offer a safe and effective approach to support cognitive recovery in ischemic stroke survivors. These findings underscore the potential of the supplement as an add-on intervention for managing post-stroke cognitive impairments. [ABSTRACT FROM AUTHOR]

Background: Post-diagnostic care for people with vascular cognitive impairment (VCI) typically involves multiple professions and disjointed care pathways not specifically designed to aid VCI needs. Objective: Exploring perspectives of healthcare professionals on post-diagnostic care for people with VCI. Methods: We conducted a qualitative focus group study. We used purposive sampling to include healthcare professionals in different compositions of primary and secondary care professionals per focus group. Thematic saturation was reached after seven focus groups. Transcripts were iteratively coded and analyzed using inductive thematic analysis. Results: Forty participants were included in seven focus groups (4–8 participants). Results showed knowledge and awareness of VCI as prerequisites for adequate post-diagnostic care, and for pre-diagnostic detection of people with VCI (theme 1). In light of perceived lack of differentiation between cognitive disorders, participants shared specific advice regarding post-diagnostic care for people with VCI and informal caregivers (theme 2). Participants thought current care for VCI was fragmented and recommended further integration of care and collaboration across settings (theme 3). Conclusions: People with VCI and their caregivers risk getting stuck in a "no man's land" between post-diagnostic care pathways; challenges lie in acknowledgement of VCI and associated symptoms, and alignment between healthcare professionals. Education about the symptoms and consequences of VCI, to healthcare professionals, people with VCI and caregivers, may increase awareness of VCI and thereby better target care. Specific attention for symptoms common in VCI could further tailor care and reduce caregiver burden. Integration could be enhanced by combining expertise of dementia and stroke/rehabilitation pathways. [ABSTRACT FROM AUTHOR]

Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another 20% of vascular diseases contribute to a mixed dementia picture. Therefore, the vascular contribution to dementia affects 20 million people currently and will increase markedly in the next few decades, particularly in lower- and middle-income countries. In this review, we discuss the mechanisms of vascular cognitive impairment (VCI) and review management. VCI refers to the spectrum of cerebrovascular pathologies that contribute to any degree of cognitive impairment, ranging from subjective cognitive decline, to mild cognitive impairment, to dementia. While acute cognitive decline occurring soon after a stroke is the most recognized form of VCI, chronic cerebrovascular disease, in particular cerebral small-vessel disease, can cause insidious cognitive decline in the absence of stroke. Moreover, cerebrovascular disease not only commonly co-occurs with Alzheimer's disease (AD) and increases the probability that AD pathology will result in clinical dementia, but may also contribute etiologically to the development of AD pathologies. Despite its enormous health and economic impact, VCI has been a neglected research area, with few adequately powered trials of therapies, resulting in few proven treatments. Current management of VCI emphasizes prevention and treatment of stroke and vascular risk factors, with most evidence for intensive hypertension control. Reperfusion therapies in acute stroke may attenuate the risk of VCI. Associated behavioral symptoms such as apathy and poststroke emotionalism are common. We also highlight novel treatment strategies that will hopefully lead to new disease course-modifying therapies. Finally, we highlight the importance of including cognitive endpoints in large cardiovascular prevention trials and the need for an increased research focus and funding for this important area. [ABSTRACT FROM AUTHOR]

Background: There are major challenges in determining the etiology of vascular cognitive impairment (VCI) clinically, especially in the presence of mixed pathologies, such as vascular and amyloid. Most recently, two criteria (American Heart Association/American Stroke Association (AHA/ASA) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)) have been proposed for the clinical diagnosis of VCI but have not as yet been validated using neuroimaging. Aims: This study aims to determine whether the AHA/ASA and DSM-V criteria for VCI can distinguish between cases with predominantly vascular pathology and cases with mixed pathology. Methods: A total of 186 subjects were recruited from a cross-sectional memory clinic–based study at the National University Hospital, Singapore. All subjects underwent clinical and neuropsychological assessment, magnetic resonance imaging (MRI) and carbon 11-labeled Pittsburgh Compound B ([11C] PiB) positron emission tomography (PET) scans. Diagnosis of the etiological subtypes of VCI (probable vascular mild cognitive impairment (VaMCI), possible VaMCI, non-VaMCI, probable vascular dementia (VaD), possible VaD, non-VaD) were performed following AHA/ASA and DSM-V criteria. Brain amyloid burden was determined for each subject with standardized uptake value ratio (SUVR) values ⩾1.5 classified as amyloid positive. Results: Using κ statistics, both criteria had excellent agreement for probable VaMCI, probable VaD, and possible VaD (κ = 1.00), and good for possible VaMCI (κ = 0.71). Using the AHA/ASA criteria, the amyloid positivity of probable VaMCI (3.8%) and probable VaD (15%) was significantly lower compared to possible VaMCI (26.7%), non-VaMCI (33.3%), possible VaD (73.3%), and non-VaD (76.2%) (p < 0.001). Similarly, using the DSM-V criteria, the amyloid positivity of probable VaMCI (3.8%) and probable VaD (15%) was significantly lower compared to possible VaMCI (26.3%), non-VaMCI (32.1%), possible VaD (73.3%), and non-VaD (76.2%) (p < 0.001). In both criteria, there was good agreement in differentiating individuals with non-VaD and possible VaD, with significantly higher (p < 0.001) global [11C]-PiB SUVR, from individuals with probable VaMCI and probable VaD, who had predominant vascular pathology. Conclusion: The AHA/ASA and DSM-V criteria for VCI can identify VCI cases with little to no concomitant amyloid pathology, hence supporting the utility of AHA/ASA and DSM-V criteria in diagnosing patients with predominant vascular pathology. Data access statement: Data supporting this study are available from the Memory Aging and Cognition Center, National University of Singapore. Access to the data is subject to approval and a data sharing agreement due to University policy. [ABSTRACT FROM AUTHOR]

Background: State-of-the-art stroke treatment significantly reduces lesion size and stroke severity, but it remains unclear whether these therapeutic advances have diminished the burden of post-stroke cognitive impairment (PSCI). Aims: In a cohort of patients receiving modern state-of-the-art stroke care including endovascular therapy, we assessed the frequency of PSCI and the pattern of domain-specific cognitive deficits, identified risk factors for PSCI, and determined the impact of acute PSCI on stroke outcome. Methods: In this prospective monocentric cohort study, we examined patients with first-ever anterior circulation ischemic stroke without pre-stroke cognitive decline, using a comprehensive neuropsychological assessment ⩽10 days after symptom onset. Normative data were stratified by demographic variables. We defined PSCI as at least moderate (<1.5 standard deviation) deficits in ⩾2 cognitive domains. Multivariable regression analysis was applied to define risk factors for PSCI. Results: We analyzed 329 non-aphasic patients admitted from December 2020 to July 2023 (67.2 ± 14.4 years old, 41.3% female, 13.1 ± 2.7 years of education). Although most patients had mild stroke (median National Institutes of Health Stroke Scale (NIHSS) 24 h = 1.00 (0.00; 3.00); 87.5% with NIHSS ⩽ 5), 69.3% of them presented with PSCI 2.7 ± 2.0 days post-stroke. The most severely and often affected cognitive domains were verbal learning, episodic memory, executive functions, selective attention, and constructive abilities (39.1%–51.2% of patients), whereas spatial neglect was less frequent (18.5%). The risk of PSCI was reduced with more years of education (odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.23–0.99) and right hemisphere lesions (OR = 0.47, 95% CI = 0.26-0.84), and increased with stroke severity (NIHSS 24 h, OR = 4.19, 95% CI = 2.72-6.45), presence of hyperlipidemia (OR = 1.93, 95% CI = 1.01–3.68), but was not influenced by age. After adjusting for stroke severity and depressive symptoms, acute PSCI was associated with poor functional outcome (modified Rankin Scale > 2, F = 13.695, p < 0.001) and worse global cognition (Montreal Cognitive Assessment (MoCA) score, F = 20.069, p < 0.001) at 3 months post-stroke. Conclusion: Despite modern stroke therapy and many strokes having mild severity, PSCI in the acute stroke phase remains frequent and associated with worse outcome. The most prevalent were learning and memory deficits. Cognitive reserve operationalized as years of education independently protects post-stroke cognition. [ABSTRACT FROM AUTHOR]

Background: This study aims to explore the therapeutic effects of the Qi Teng Mai Ning recipe on ischemic stroke and vascular cognitive impairment through its potential to modulate cellular autophagy, with a focus on identifying its active ingredients and their target proteins. Methods: The study began with the identification of active ingredients in the Qi Teng Mai Ning recipe. It proceeded to screen the gene expression omnibus database for ischemic stroke and vascular cognitive impairment-associated differentially expressed mRNAs and to identify cellular autophagy-related proteins via the Human Autophagy Database. These proteins were annotated with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functions and subjected to molecular docking with the recipe's core active ingredients. In vitro cell experiments were conducted on hypoxic HT22 cells, involving CCK8 assay, lentiviral transfection to silence autophagy related 9B (ATG9B), immunofluorescence staining, and qPCR validation to investigate the effects of the recipe on autophagy. Results: The analysis identified 104 active ingredients targeting 408 proteins and forming a complex ingredient-target network. Intersecting 55 ischemic stroke-related and 909 vascular cognitive impairment-related differentially expressed mRNAs revealed 14 co-expressed mRNAs. Molecular docking showed quercetin, kaempferol, myrcene, and conferone as key ingredients targeting autophagy-related proteins. Cellular experiments indicated that the recipe significantly enhanced cell viability under hypoxic conditions, reduced apoptosis, and modulated the expression of autophagy-related factors, thereby decreasing apoptosis rates in HT22 cells. Conclusion: The Qi Teng Mai Ning recipe offers protective effects against ischemic stroke and vascular cognitive impairment by modulating autophagy-related proteins. Its efficacy highlights the potential of traditional Chinese medicine in treating these conditions, though further research is needed to fully understand its mechanisms and clinical applications. [ABSTRACT FROM AUTHOR]

Background: Hypertension‐induced impairment of the cerebral artery network contributes to cognitive impairment. Characterizing the structure and function of cerebral arteries may facilitate the understanding of hypertension‐related pathological mechanisms and lead to the development of new indicators for cognitive impairment. Purpose: To investigate the associations between morphological features of the intracranial arteries distal to the circle of Willis on time‐of‐flight MRA (TOF‐MRA) and cognitive performance in a hypertensive cohort. Study Type: Prospective observational study. Population: 189 hypertensive older males (mean age 64.9 ± 7.2 years). Field Strength/Sequence: TOF‐MRA sequence with a 3D spoiled gradient echo readout and arterial spin labeling perfusion imaging sequence with a 3D stack‐of‐spirals fast spin echo readout at 3T. Assessment: The intracranial arteries were segmented from TOF‐MRA and the total length of distal arteries (TLoDA) and number of arterial branches (NoB) were calculated. The mean gray matter cerebral blood flow (GM‐CBF) was extracted from arterial spin labeling perfusion imaging. The cognitive level was assessed with short‐term and long‐term delay‐recall auditory verbal learning test (AVLT) scores, and with montreal cognitive assessment. Statistical Tests: Univariable and multivariable linear regression were used to analyze the associations between TLoDA, NoB, GM‐CBF and the cognitive assessment scores, with P < 0.05 indicating significance. Results: TLoDA (r = 0.314) and NoB (r = 0.346) were significantly correlated with GM‐CBF. Multivariable linear regression analyses showed that TLoDA and NoB, but not GM‐CBF (P = 0.272 and 0.141), were significantly associated with short‐term and long‐term delay‐recall AVLT scores. These associations remained significant after adjusting for GM‐CBF. Data Conclusion: The TLoDA and NoB of distal intracranial arteries on TOF‐MRA are significantly associated with cognitive impairment in hypertensive subjects. Level of Evidence: 2 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Background: Although its incidence is relatively low, delayed-onset poststroke cognitive decline (PSCD) may offer valuable insights into the "vascular contributions to cognitive impairment and dementia," particularly concerning the roles of vascular and neurodegenerative mechanisms. We postulated that the functional segregation observed during post-stroke compensation could be disrupted by underlying amyloid pathology or cerebral small vessel disease (cSVD), leading to delayed-onset PSCD. Methods: Using a prospective stroke registry, we identified patients who displayed normal cognitive function at baseline evaluation within a year post-stroke and received at least one subsequent assessment. Patients suspected of pre-stroke cognitive decline were excluded. Decliners [defined by a decrease of ≥3 Mini- Mental State Examination (MMSE) points annually or an absolute drop of ≥5 points between evaluations, confirmed with detailed neuropsychological tests] were compared with age- and stroke severity-matched non-decliners. Index-stroke MRI, resting-state functional MRI, and 18F-florbetaben PET were used to identify cSVD, functional network attributes, and amyloid deposits, respectively. PET data from age-, sex-, education-, and apolipoprotein E-matched stroke-free controls within a community-dwelling cohort were used to benchmark amyloid deposition. Results: Among 208 eligible patients, 11 decliners and 10 matched non-decliners were identified over an average follow-up of 5.7 years. No significant differences in cSVD markers were noted between the groups, except for white matter hyperintensities (WMHs), which were strongly linked with MMSE scores among decliners (rho = 0.85, p < 0.01). Only one decliner was amyloid-positive, yet subthreshold PET standardized uptake value ratios (SUVR) in amyloid-negative decliners inversely correlated with final MMSE scores (rho = 0.67, p = 0.04). Decliners exhibited disrupted modular structures and more intermingled canonical networks compared to non-decliners. Notably, the somato-motor network's system segregation corresponded with the decliners' final MMSE (rho = 0.67, p = 0.03) and was associated with WMH volume and amyloid SUVR. Conclusion: Disruptions in modular structures, system segregation, and internetwork communication in the brain may be the pathophysiological underpinnings of delayed-onset PSCD. WMHs and subthreshold amyloid deposition could contribute to these disruptions in functional brain networks. Given the limited number of patients and potential residual confounding, our results should be considered hypothesis-generating and need replication in larger cohorts in the future. [ABSTRACT FROM AUTHOR]

Vascular cognitive impairment (VCI) is a heterogenous form of cognitive impairment that results from cerebrovascular disease. It is a result of both genetic and non‐genetic factors. Although much research has been conducted on the genetic contributors to other forms of cognitive impairment (e.g. Alzheimer's disease), knowledge is lacking on the genetic factors associated with VCI. A better understanding of the genetics of VCI will be critical for prevention and treatment. To begin to fill this gap, the genetic contributors are reviewed with VCI from the literature. Phenome‐wide scans of the identified genes are conducted and genetic variants identified in the review in large‐scale resources displaying genetic variant‐trait association information. Gene set are also carried out enrichment analysis using the genes identified from the review. Thirty one articles are identified meeting the search criteria and filters, from which 107 unique protein‐coding genes are noted related to VCI. The phenome‐wide scans and gene set enrichment analysis identify pathways associated with a diverse set of biological systems. This results indicate that genes with evidence of involvement in VCI are involved in a diverse set of biological functions. This information can facilitate downstream research to better dissect possible shared biological mechanisms for future therapies. [ABSTRACT FROM AUTHOR]

Vascular cognitive impairment (VCI) denotes a wide range of cognitive deficiencies resulting from cerebrovascular risk factors and cerebrovascular diseases. Sirtuin 1 (SIRT1), as a deacetylase, can mediate the deacetylation of histones and non-histone proteins. It is involved in regulating multiple pathophysiological processes of VCI, including neuroinflammation reduction, oxidative stress inhibition, cell apoptosis decrease, and blood-brain barrier protection, serving as a target for VCI treatment. This paper summarizes SIRT1 and the molecular mechanisms of targeting SIRT1 in order to provide a reference for the clinical treatment of VCI.

Background: Neurofilament Light Chain (NfL) is a biomarker of axonal injury elevated in mild cognitive impairment (MCI) and Alzheimer's disease dementia. Blood NfL also inversely correlates with cognitive performance in those conditions. However, few studies have assessed NfL as a biomarker of global cognition in individuals demonstrating mild cognitive deficits who are at risk for vascular-related cognitive decline. Objective: To assess the relationship between blood NfL and global cognition in individuals with possible vascular MCI (vMCI) throughout cardiac rehabilitation (CR). Additionally, NfL levels were compared to age/sex-matched cognitively unimpaired (CU) controls. Method: Participants with coronary artery disease (vMCI or CU) were recruited at entry to a 24-week CR program. Global cognition was measured using the Montreal Cognitive Assessment (MoCA) and plasma NfL level (pg/ml) was quantified using a highly sensitive enzyme-linked immunosorbent assay. Results: Higher plasma NfL was correlated with worse MoCA scores at baseline (β = −.352, P =.029) in 43 individuals with vMCI after adjusting for age, sex, and education. An increase in NfL was associated with worse global cognition (b [SE] = −4.81[2.06], P =.023) over time, however baseline NfL did not predict a decline in global cognition. NfL levels did not differ between the vMCI (n = 39) and CU (n = 39) groups (F (1, 76) = 1.37, P =.245). Conclusion: Plasma NfL correlates with global cognition at baseline in individuals with vMCI, and is associated with decline in global cognition during CR. Our findings increase understanding of NfL and neurobiological mechanisms associated with cognitive decline in vMCI. [ABSTRACT FROM AUTHOR]

Ridengnaxi E, Yan Wang Department of Rehabilitation Medicine, Inner Mongolia Autonomous Region People’s Hospital, Hohhot, People’s Republic of ChinaCorrespondence: Yan Wang, Department of Rehabilitation Medicine, Inner Mongolia Autonomous Region People’s Hospital, No. 20 of Zhaowuda Road, Saihan District, Hohhot, 010017, People’s Republic of China, Tel/Fax +86 18148253963, Email wangyanyw26@126.comAbstract: Vagus nerve stimulation (VNS) is acknowledged as a highly effective therapy for various neurological conditions, including refractory epilepsy, depression, Alzheimer’s disease (AD), migraine, and stroke. Presently, there is an increasing focus on understanding the impact of VNS on cognitive aspects. Numerous studies suggest that VNS suppresses the body’s inflammatory response, leading to enhanced cognitive function in patients. Vascular cognitive impairment (VCI) is a severe cognitive dysfunction syndrome resulting from prolonged chronic cerebral hypoperfusion (CCH), where the primary pathogenesis is CCH-induced neuroinflammation. In this paper, we present a comprehensive overview of the research advancements in using VNS for treating VCI and discuss that VNS improves cognitive function in VCI patients by suppressing neuroinflammation, offering insights into a potential novel approach for addressing this condition.Keywords: cholinergic anti-inflammatory pathway, chronic cerebral hypoperfusion, cognition, neuroinflammation, vagus nerve stimulation, vascular cognitive impairment

Intermittent fasting (IF), a dietary pattern alternating between eating and fasting periods within a 24-hour cycle, has garnered recognition for its potential to enhance both healthspan and lifespan in animal models and humans. It also shows promise in alleviating age-related diseases, including neurodegeneration. Vascular cognitive impairment (VCI) spans a severity range from mild cognitive deficits to severe cognitive deficits and loss of function in vascular dementia. Chronic cerebral hypoperfusion has emerged as a significant contributor to VCI, instigating vascular pathologies such as microbleeds, blood-brain barrier dysfunction, neuronal loss, and white matter lesions. Preclinical studies in rodents strongly suggest that IF has the potential to attenuate pathological mechanisms, including excitotoxicity, oxidative stress, inflammation, and cell death pathways in VCI models. Hence, this supports evaluating IF in clinical trials for both existing and at-risk VCI patients. This review compiles existing data supporting IF’s potential in treating VCI-related vascular and neuronal pathologies, emphasizing the mechanisms by which IF may mitigate these issues. Hence providing a comprehensive overview of the available data supporting IF’s potential in treating VCI by emphasizing the underlying mechanisms that make IF a promising intervention for VCI.

Sijing Li,1– 3 Zijian Xiao1,2 1Department of Neurology, Multi-Omics Research Center for Brain Disorders, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 2Clinical Research Center for Immune‑Related Encephalopathy of Hunan Province (The First Affiliated Hospital), Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 3Department of Clinical Laboratory Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, People’s Republic of ChinaCorrespondence: Zijian Xiao, Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China, Email zijian6340@21cn.comAbstract: Vascular Cognitive Impairment (VCI) is a condition where problems with brain blood vessels lead to a decline in cognitive abilities, commonly affecting the elderly and placing a significant burden on both patients and their families. Compared to medication and surgery, Transcranial Magnetic Stimulation (TMS) is a non-invasive treatment option with fewer risks and side effects, making it particularly suitable for elderly patients. TMS not only assesses the excitability and plasticity of the cerebral cortex, but its effectiveness in treating Vascular Cognitive Impairment (VCI) and its subtypes has also been validated in numerous clinical trials worldwide. However, there is still a lack of review on the physiological mechanisms of TMS treatment for VCI and its specific clinical application parameters. Therefore, this article initially provided a brief overview of the risk factors, pathological mechanisms, and classification of VCI. Next, the article explained the potential physiological mechanisms of TMS in treating VCI, particularly its role in promoting synaptic plasticity, regulating neurotransmitter balance, and improving the function of the default mode network. Additionally, The article also summarizes the application of rTMS in treating VCI and its subtypes, VCI-related sleep disorders, and the use of TMS in follow-up studies of VCI patients, providing empirical evidence for the clinical application of TMS and rTMS technologies.Keywords: transcranial magnetic stimulation, mild cognitive impairment, post-stroke dementia, VCI-related sleep disorders, following up VCI patients, physiological mechanism

Background: The Montreal Cognitive Assessment (MoCA) is a valuable tool for detecting cognitive impairment, widely used in many countries. However, there is still a lack of large sample normative data and whose cut-off values for detecting cognitive impairment is considerable controversy. Methods: The assessment conducted in this study utilizes the MoCA scale, specifically employing the Mandarin-8.1 version. This study recruited a total of 3,097 healthy adults aged over 20 years. We performed multiple linear regression analysis, incorporating age, gender, and education level as predictor variables, to examine their associations with the MoCA total score and subdomain scores. Subsequently, we established normative values stratified by age and education level. Finally, we included 242 patients with vascular cognitive impairment (VCI) and 137 controls with normal cognition, and determined the optimal cut-off value of VCI through ROC curves. Results: The participants in this study exhibit a balanced gender distribution, with an average age of 54.46 years (SD = 14.38) and an average education period of 9.49 years (SD = 4.61). The study population demonstrates an average MoCA score of 23.25 points (SD = 4.82). The multiple linear regression analysis indicates that MoCA total score is influenced by age and education level, collectively accounting for 46.8% of the total variance. Higher age and lower education level are correlated with lower MoCA total scores. A score of 22 is the optimal cut-off value for diagnosing vascular cognitive impairment (VCI). Conclusion: This study offered normative MoCA values specific to the Chinese adults. Furthermore, this study indicated that a score of 26 may not represent the most optimal cut-off value for VCI. And for detecting VCI, a score of 22 may be a better cut-off value. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (CSVD) is a prevalent vascular disorder that has been consistently associated with vascular cognitive impairment (VCI). The diagnosis of CSVD continues to rely on magnetic resonance imaging (MRI). Epidemiological data indicate that the characteristic MRI features of CSVD, including white matter hyperintensity (WMH) and lacunar infarction, are very common among individuals over 40  years of age in community studies. This prevalence poses a significant burden on many low- and middle-income families. The amygdala plays a crucial role in integrating sensory and associative information to regulate emotional cognition. Although many previous studies have linked alterations in the amygdala to various diseases, such as depression, there has been little research on CSVD-associated alterations in the amygdala due to the complexity of CSVD. In this paper, we summarize the various imaging features of CSVD and discuss the correlation between amygdala changes and VCI. We also explore how new neuroimaging methods can assess amygdala changes early, laying a foundation for future comprehensive exploration of the pathogenesis of CSVD. [ABSTRACT FROM AUTHOR]

Background: Vascular cognitive impairment (VCI) manifests in memory impairment, mental slowness, executive dysfunction, behavioral changes, and visuospatial abnormalities, significantly compromising the quality of daily life for patients and causing inconvenience to caregivers. Neuroimaging serves as a crucial approach to evaluating the extent, location, and type of vascular lesions in patients suspected of VCI. Nevertheless, there is still a lack of comprehensive bibliometric analysis to discern the research status and emerging trends concerning VCI neuroimaging. Objective: This study endeavors to explore the collaboration relationships of authors, countries, and institutions, as well as the research hotspots and frontiers of VCI neuroimaging by conducting a bibliometric analysis. Methods: We performed a comprehensive retrieval within the Core Collection of Web of Science, spanning from 2000 to 2023. After screening the included literature, CiteSpace and VOSviewer were utilized for a visualized analysis aimed at identifying the most prolific author, institution, and journal, as well as extracting valuable information from the analysis of references. Results: A total of 1,024 publications were included in this study, comprising 919 articles and 105 reviews. Through the analysis of keywords and references, the research hotspots involve the relationship between neuroimaging of cerebral small vessel disease (CSVD) and VCI, the diagnosis of VCI, and neuroimaging methods pertinent to VCI. Moreover, potential future research directions encompass CSVD, functional and structural connectivity, neuroimaging biomarkers, and lacunar stroke. Conclusion: The research in VCI neuroimaging is constantly developing, and we hope to provide insights and references for future studies by delving into the research hotspots and frontiers within this field. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine the alterations in aberrant brain activity and network connectivity between individuals with mild and major vascular cognitive impairment (VCI). Materials and methods: A total of 114 patients with cerebral small vessel disease (CSVD) were included in this study, comprising 61 individuals with mild VCI (mean age, 55.7  ±  6.9  years; male, 42.6%) and 53 cases with major VCI (mean age, 57.6  ±  5.5  years; male, 58.5%). Additionally, 53 age-, gender-, and educationmatched healthy subjects were recruited as normal controls (NC) (mean age, 54.9  ±  7.9  years; male, 52.9%). All participants underwent neuropsychological assessments and magnetic resonance imaging scans. One-way analysis of variance was used to compare fractional amplitude of low-frequency fluctuation (fALFF) values among the three groups. Two-sample t-tests were conducted to assess functional connectivity matrices between different groups for each connection. Moreover, mediation analyses were performed to explore the mediating effect of aberrant brain activity on the relationship between cognitive impairment and CSVD total burden. Results: VCI patients exhibited aberrant brain activity in regions such as the right thalamus (THA_R), right cuneus (CUN_R), left postcentral gyrus (PoCG_L), right postcentral gyrus (PoCG_R), right median cingulate, paracingulate gyri (PCG_R), and left precuneus (PCUN_L). Reduced positive functional connectivity was predominantly observed among nodes including PCUN_L, CUN_R, PoCG_L, PoCG_R, right posterior cingulate (PCG_R), and left occipital gyrus (IOG_L) in VCI patients. The aberrant baseline brain activity and disrupted brain network were more pronounced with worsening cognitive function. Increased fALFF values in THA_R, CUN_R, and PoCG_L mediated cognitive impairment in CSVD patients. Conclusion: Abnormal brain activities in THA_R, CUN_R, and PoCG_L, along with their associated abnormal functional connections, play a significant role in VCI. The study revealed a progressive increase in aberrant brain activity and network connectivity with advancing stages of VCI. [ABSTRACT FROM AUTHOR]

Objective: Executive dysfunction is a core symptom of vascular cognitive impairment (VCI), which seriously affects patients' prognosis. This paper aims to investigate the effectiveness of rTMS on executive function in VCI. Methods: The databases selected for this study included Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, China Science and Technology Journal Database (VIP), and China Biology Medicine Disc (CBM). The screening times were conducted from the time of library construction until August 23, 2023. The inclusion criteria for this metaanalysis were randomized controlled trials (RCTs) on rTMS for VCI, which include executive function scores. The primary metrics were executive subscale scores of the Cognitive Comprehensive Scale and total scores of the Executive Specificity Scale. The secondary metrics were subscale scores of the Executive Specificity Scale. The quality of each eligible study was assessed using the Cochrane Risk of Bias tool. Meta-analysis and bias analysis were performed using Stata (version 16.0) and RevMan (version 5.3). Results: A total of 20 high-quality clinical RCTs with 1,049 samples were included in this paper. The findings from the primary outcomes revealed that within the rTMS group, there were significantly higher scores observed for the executive sub-item on the cognitive composite scale (SMD = 0.93, 95% CI = 0.77-1.08, p < 0.00001, I2 = 14%) and the total score on the executive specific scale (SMD = 0.69, 95% CI = 0.44-0.94, p < 0.00001, I2 = 0%) compared to the control group. As for the secondary outcome measures, as shown by the Trail Making Test-A (time) (MD = -35.75, 95% CI = -68.37 to -3.12, p = 0.03, I2 = 55%), the Stroop-C card (time) (SMD = -0.46, 95% CI = -0.86 to -0.06, p = 0.02, I2 = 0%) and the Stroop-C card (correct number) (SMD = 0.49, 95% CI = 0.04-0.94, p = 0.03, I2 = 0%), the experimental group shorts time and enhances accuracy of executive task in comparison to the control group. Subgroup analysis of the main outcome demonstrated that intermittent theta burst stimulation (iTBS), higher frequency, lower intensity, longer duration, and combined comprehensive therapy exhibited superior efficacy. Conclusion: rTMS is effective in the treatment of the executive function of VCI. The present study has some limitations, so multi-center, large-sample, objective indicators and parameters are needed to further explore in the future. [ABSTRACT FROM AUTHOR]

Cognitive impairment (CI), which is highly prevalent, especially among the elderly, leads to decreases in patients' quality of life, impairments to daily activities, and an increased risk of dementia and mortality. Much attention is currently being paid to moderate CI. This article discusses the diagnostic criteria and possible clinical variants of this syndrome. The high rate of progression of moderate CI to dementia makes it necessary to identify risk groups and carry out preventive measures. Correction of potentially modifiable risk factors is regarded as a promising approach to therapy. Sufficient physical and mental activity, proper diet, and normalization of sleep, visual acuity, and hearing are needed. Preventing stroke and controlling cardiovascular risk factors may reduce the risk of progression from mild CI to dementia. [ABSTRACT FROM AUTHOR]

Objectives. To establish the specific features of impairments to executive functions (EF) and attention at the initial stages of vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Materials and methods. A total of 80 patients aged over 50 years with VCI or AD, as well as 29 healthy volunteers (control group), took part in the study. Cognitive functions were assessed using the following tests: the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment Scale (MoCA), the Executive Function Interview Technique (EXIT-25), the Frontal Assessment Battery (FAB), the clock drawing test, the 12-word memory test, the verbal association test (literal and categorical), the trail-making test (TMT A and B), the symbol-digit substitution test (SDST), the Stroop test, and Benton's visual memory test. A mandatory criterion for inclusion in the study was availability of a brain MRI scan in T1, T2, FLAIR, DWI, and SWI modes acquired during year preceding recruitment. Results. The AD and VCI groups were comparable in age, gender, education, and the severity of CI. Impairments in attention and EF were noted in both VCI and AD and were somewhat more marked in AD. Qualitative analysis of the individual components of EF showed that the VCI and AD groups had comparable impairments in cognitive control as compared with the control group, while AD was characterized by a more significant decrease in intellectual flexibility than VCI. Concentration of attention was affected equally in patients with VCI and AD; differences from the control group were significant (p < 0.05). In the memory domain, auditory-verbal and semantic memory were found to suffer to a much greater extent in AD, while both conditions were characterized by identical involvement of the visual modality. Conclusions. Impairments to attention and EF are not specific to the subcortical type of CI. AD even in its early stages is characterized by significant impairments to attention and EF, while the EF component intellectual flexibility suffers to a greater extent at the onset of AD than VCI. Memory impairments are not specific to AD; visual memory impairment comparable to AD is noted as early as the onset stage of VCI. These data can be used for early neuropsychological diagnostics and the differential diagnosis of CI. [ABSTRACT FROM AUTHOR]

Objectives. To study the features of and relationships between neuropsychological and metabolic indicators in patients with cognitive disorders (CD) of the Alzheimer's and vascular types of different severities Materials and methods. A total of 177 patients took part, including 85 with Alzheimer's disease (AD) and 92 with vascular CD (VCD). All patients underwent comprehensive neuropsychological examination; 18F-deoxyglucose positron emission tomography was performed in 17 patients with AD and 15 patients with VCD. Results. The greatest changes in patients with AD were noted in the mnestic domain, indicators being significantly different from those of patients with VCD even at the pre-dementia stage. Neurodynamic and dysregulatory disorders were predominant in patients with VCD. Patients with AD showed symmetrical bilateral decreases in metabolic activity in the parietal and temporal cortex, often in combination with marked hypometabolism in the hippocampal region. Patients with VCD showed areas of decreased metabolism in different locations and of different sizes, mainly in the projection of the basal ganglia and in the prefrontal and parietal areas of the cortex, as well as in the cingulate gyrus, providing indirect confi rmation of the mechanism of uncoupling of subcortical and cortical structures. In patients with AD, impaired metabolic activity in the hippocampal region correlated with impaired temporal and spatial orientation (ϱ = –0.54, p < 0.05) and memory impairment (ϱ = –0.71, p < 0.005). Hypometabolism of the parietal lobe cortex was linked with the total score on the Mini Mental State Examination (ϱ = –0.8, p < 0.001), the 10-word memory test (ϱ = –0.89, p < 0.001 and ϱ = –0.82, p < 0.001), visuospatial impairment (ϱ = –0.64, p < 0.01), and the categorical association test (ϱ = –0.73, p < 0.005). In patients with VCD, dysregulatory disorders correlated with hypometabolism in the thalamus (ϱ = –0.56, p < 0.05), prefrontal cortex (ϱ = –0.64, p < 0.05), and cingulate gyrus (anterior sections) (ϱ = –0.53, p < 0.05). Conclusions. The results obtained here indicate that there are differences in CD and cerebral metabolism between patients with AD and VCD. [ABSTRACT FROM AUTHOR]

Intermittent fasting (IF), a dietary pattern alternating between eating and fasting periods within a 24-hour cycle, has garnered recognition for its potential to enhance both healthspan and lifespan in animal models and humans. It also shows promise in alleviating age-related diseases, including neurodegeneration. Vascular cognitive impairment (VCI) spans a severity range from mild cognitive deficits to severe cognitive deficits and loss of function in vascular dementia. Chronic cerebral hypoperfusion has emerged as a significant contributor to VCI, instigating vascular pathologies such as microbleeds, blood-brain barrier dysfunction, neuronal loss, and white matter lesions. Preclinical studies in rodents strongly suggest that IF has the potential to attenuate pathological mechanisms, including excitotoxicity, oxidative stress, inflammation, and cell death pathways in VCI models. Hence, this supports evaluating IF in clinical trials for both existing and at-risk VCI patients. This review compiles existing data supporting IF's potential in treating VCI-related vascular and neuronal pathologies, emphasizing the mechanisms by which IF may mitigate these issues. Hence providing a comprehensive overview of the available data supporting IF's potential in treating VCI by emphasizing the underlying mechanisms that make IF a promising intervention for VCI. [ABSTRACT FROM AUTHOR]

Vascular cognitive impairment (VCI) encompasses cognitive disorders associated with cerebrovascular disease, often manifesting as white matter lesions (WMLs), irrespective of precise triggers. The integrity of white matter is essential for neural communication and cognitive function maintenance. Persistent cerebral hypoperfusion-induced WMLs are now acknowledged as a key driver of VCI and dementia, though their exact formation mechanism remains unclear. Recent studies link pericyte dysfunction to diverse brain disorders like Alzheimer disease. However, the exact pathological connection between pericyte dysfunction and cognitive impairment in VCI remains unexplored. In this study, we aimed to examine whether pericyte dysfunction could impact WMLs and cognitive impairment in a rat VCI model. Using a rat model of chronic cerebral hypoperfusion-induced VCI through two-vessel occlusion (2VO), we verified that 2VO induced both WMLs and cognitive impairment. Notably, the number of pericytes in the brain was significantly altered after 2VO. Furthermore, we observed significantly increased capillary constrictions at pericyte bodies in the brains of 2VO-induced rats compared to sham-operated rats, accompanied by reduced cerebral blood flow (CBF). To tackle this issue, we administered CGS21680, a specific adenosine A2A subtype receptor agonist, intranasally twice a day for 7 days. We found that rats treated with CGS21680 exhibited a significant increase in CBF at 7 and 14 days after 2VO, compared to the vehicle group. Moreover, capillary lumens beneath pericytes also increased after the CGS21680 treatment. Importantly, the treatment led to substantial improvements in WMLs and cognitive impairment compared to the vehicle group. Our findings suggest a critical role of pericyte dysfunction in WMLs and cognitive impairment within the rat VCI model. This insight contributes to our understanding of pathogenesis and offers prospects for targeted intervention in VCI. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Cerebral small vessel disease (SVD) is a common cause of stroke/vascular dementia with few effective treatments. Neuroinflammation and increased blood‐brain barrier (BBB) permeability may influence pathogenesis. In rodent models, minocycline reduced inflammation/BBB permeability. We determined whether minocycline had a similar effect in patients with SVD. METHODS: MINERVA was a single‐center, phase II, randomized, double‐blind, placebo‐controlled trial. Forty‐four participants with moderate‐to‐severe SVD took minocycline or placebo for 3 months. Co‐primary outcomes were microglial signal (determined using 11C‐PK11195 positron emission tomography) and BBB permeability (using dynamic contrast‐enhanced MRI). RESULTS: Forty‐four participants were recruited between September 2019 and June 2022. Minocycline had no effect on 11C‐PK11195 binding (relative risk [RR] 1.01, 95% confidence interval [CI] 0.98–1.04), or BBB permeability (RR 0.97, 95% CI 0.91–1.03). Serum inflammatory markers were not affected. DISCUSSION: 11C‐PK11195 binding and increased BBB permeability are present in SVD; minocycline did not reduce either process. Whether these pathophysiological mechanisms are disease‐causing remains unclear. INTERNATIONAL CLINICAL TRIALS REGISTRY PORTAL IDENTIFIER: ISRCTN15483452 Highlights: We found focal areas of increased microglial signal and increased blood‐brain barrier permeability in patients with small vessel disease.Minocycline treatment was not associated with a change in these processes measured using advanced neuroimaging.Blood‐brain barrier permeability was dynamic but MRI‐derived measurements correlated well with CSF/serum albumin ratio.Advanced neuroimaging is a feasible outcome measure for mechanistic clinical trials. [ABSTRACT FROM AUTHOR]

Cerebrovascular fragility and cerebral microhemorrhages (CMH) contribute to age-related cognitive impairment, mobility defects, and vascular cognitive impairment and dementia, impairing healthspan and reducing quality of life in the elderly. Insulin-like growth factor 1 (IGF-1) is a key vasoprotective growth factor that is reduced during aging. Circulating IGF-1 deficiency leads to the development of CMH and other signs of cerebrovascular dysfunction. Here our goal was to understand the contribution of IGF-1 signaling on vascular smooth muscle cells (VSMCs) to the development of CMH and associated gait defects. We used an inducible VSMC-specific promoter and an IGF-1 receptor (Igf1r) floxed mouse line (Myh11-CreERT2 Igf1rf/f) to knockdown Igf1r. Angiotensin II in combination with L-NAME-induced hypertension was used to elicit CMH. We observed that VSMC-specific Igf1r knockdown mice had accelerated development of CMH, and subsequent associated gait irregularities. These phenotypes were accompanied by upregulation of a cluster of pro-inflammatory genes associated with VSMC maladaptation. Collectively our findings support an essential role for VSMCs as a target for the vasoprotective effects of IGF-1, and suggest that VSMC dysfunction in aging may contribute to the development of CMH. [ABSTRACT FROM AUTHOR]

Dilation of perivascular spaces (PVS) in the brain may indicate poor fluid drainage due to the accumulation of perivascular cell debris, waste, and proteins, including amyloid-beta (Aβ). No prior study has assessed whether plasma Aβ levels are related to PVS in older adults without dementia. Independently living older adults (N = 56, mean age = 68.2 years; Standard deviation (SD) = 6.5; 30.4% male) free of dementia or clinical stroke were recruited from the community and underwent brain MRI and venipuncture. PVS were qualitatively scored and dichotomized to low PVS burden (scores 0-1,) or high PVS burden (score>1). Plasma was assayed using a Quanterix Simoa Kit to quantify Aβ42 and Aβ40 levels. A significant difference was observed in plasma Aβ42/Aβ40 ratio between low and high PVS burden, controlling for age (F[1, 53] = 5.59, p = 0.022, η2 = 0.10), with lower Aβ42/Aβ40 ratio in the high PVS burden group. Dilation of PVS is associated with a lower plasma Aβ42/Aβ40 ratio, which may indicate higher cortical amyloid deposition. Future longitudinal studies examining PVS changes, and the pathogenesis of AD are warranted.

Vascular cognitive impairment (VCI) is a clinical syndrome that arises from cerebrovascular issues and associated risk factors, resulting in difficulties in at least one area of cognitive function. VCI has emerged as the second most prevalent type of dementia following Alzheimer's disease, yet there is no effective clinical treatment. Botch, an endogenous Notch1 antagonist, demonstrates neuroprotective effects by inhibiting neuroinflammatory responses mediated through the Notch pathway. While its role in stroke-induced neuroinflammation is well-established, its involvement in VCI remains largely unexplored. This study investigates the role and potential mechanisms of Botch in a rat model of cognitive impairment caused by bilateral common carotid artery occlusion (BCCAO). Firstly, we observed that Botch levels were down-regulated in BCCAO rats, which correlated with increased release of inflammatory cytokines and neuronal damage. Microglia in BCCAO rats released interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), and complement component 1q (C1q), leading to the activation of neurotoxic C3+ A1 reactive astrocytes. Then, the down-regulation of Botch exacerbated microglia-mediated inflammation, activated C3+ A1 astrocytes, worsened neuronal damage, and led to a decline in cognitive function. Conversely, the re-expression of Botch alleviated C3+ astrocyte activation, inhibited neuronal damage, and improved mental function. In conclusion, Botch plays a crucial role in inhibiting neuroinflammation induced by type A1 reactive astrocytes. It achieves this by blocking the activation of microglia triggered by the Notch pathway. Ultimately, it inhibits neuronal damage to play a neuroprotective role. These findings suggest that Botch may represent a novel potential target for treating VCI.

Objective: The aim was to predict the effectiveness of using frailty, defined by the frailty index (FI), for predicting recurrent pneumonia and death in patients 50 years and older with vascular cognitive impairment (VCI) during long-term hospitalization. Measurements: This retrospective cohort study was conducted at a teaching hospital in western China and included VCI patients aged ≥50 years undergoing long-term hospitalization. The relevant data were collected from the electronic medical record system. The FI was based on 31 parameters and groups were defined using a cutoff value (0.2) as robust (FI

The management of patients with cognitive impairment (CI) is one of the urgent problems of modern medicine. Vascular CI (VCI) is the second most common cause of dementia after Alzheimer's disease. The diagnosis of VCI is based on the results of a neuropsychological examination, the presence of clinical and neuroimaging signs of cerebrovascular disease, and the absence of data for other causes of CI. Socio-psychological methods, stroke prevention, correction of vascular risk factors, and stimulation of patients to regular physical and mental activity are of leading importance in the management of patients with VCI. The effectiveness and safety of citicoline in VCI are discussed.

Vascular cognitive impairments are the expression of complex interactions between vascular etiology, risk factors (brain diseases, white matter lesions, etc.) and cellular changes at the brain level. Consequently, vascular cognitive impairment is highly dependent on the location, extent (volume of brain tissue affected) and number of lesions. Memory impairment is not necessarily characteristic of vascular cognitive decline, usually having an evolution with episodic exacerbations and multiple cerebrovascular attacks (cumulative effect), thus producing a gradual deterioration. In recent years, the concept of mild cognitive impairment has emerged as a potential form of predementia, but which can progress to different types of dementia, including Alzheimer's disease or vascular dementia. This review presents recent data related to the etiological and risk factors of cognitive decline after stroke, the associated neuropsychological and behavioral changes, the clinical forms/diagnosis and general principles of vascular dementia therapy. As preliminary conclusions, the Hachinski score is a very useful tool in differentiating vascular dementia from Alzheimer's dementia. A score greater than 7 points (especially when associated with imaging and anamnestic criteria) suggests a vascular etiology of dementia, whereas a score of 4 points or less excludes such an etiology. Although it is not the only factor involved, vascular etiology is still intensively studied because it is the only one that can be prevented and treated.

Zhenjie Teng,1– 3 Jing Feng,4 Xiaohua Xie,2 Jing Xu,2 Xin Jiang,2 Peiyuan Lv1– 3 1Department of Neurology, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Neurology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Hebei Provincial Key Laboratory of Cerebral Networks and Cognitive Disorders, Shijiazhuang, People’s Republic of China; 4Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Peiyuan Lv, Department of Neurology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel/Fax +86 31185988906, Email peiyuanlu2@163.comBackground: Total cerebral small vessel disease (CSVD) burden score is an important predictor of vascular cognitive impairment (VCI). However, few predictive models of VCI in type 2 diabetes mellitus (T2DM) patients have included the total CSVD burden score, especially in the early stage of VCI.Objective: To develop and validate a nomogram that includes the total CSVD burden score to predict mild VCI in patients with T2DM.Methods: A total of 322 eligible participants with T2DM who were divided into mild and normal cognitive groups were enrolled in this retrospective study. Demographic data, laboratory data and imaging markers of CSVD were collected. The total CSVD burden score was calculated by combining the different CSVD markers. Step-backward multivariable logistic regression analysis with the Akaike information criterion was applied to select significant predictors and develop a best-fit predictive nomogram. The performance of the nomogram was assessed in terms of discriminative ability, calibrated ability, and clinical usefulness.Results: The nomogram model consisted of five variables: age, education, hemoglobin A1c level, serum homocysteine level, and total CSVD burden score. A nomogram with these variables showed good discriminative ability (area under the receiver operating characteristic curve was 0.801 in internal verification). In addition, the Hosmer-Lemeshow test (χ2 =9.226, P=0.417) and bootstrap-corrected calibration plot indicated that the nomogram had good calibration. The Brier score of the predictive model was 0.178. Decision curve analysis demonstrated that when the threshold probability ranged between 16% and 98%, the use of the nomogram to predict mild VCI in patients with T2DM provide a greater net benefit.Conclusions: The nomogram, composed of age, education, stroke, HbA1c level, Hcy level, and total CSVD burden score, had good predictive accuracy and may provide clinicians with a practical tool for predicting the risk of mild VCI in T2DM patients.Keywords: vascular cognitive impairment, mild cognitive impairment, cerebral small vessel disease, type 2 diabetes mellitus, nomogram

Abstract 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

The dementia epidemic, attributed to aging populations, represents a growing socio-economic burden. It is estimated that in 2019 about 55 million people worldwide were living with dementia. With many possible causes of dementia and the possibility of mixed dementia combining Alzheimer's disease (AD) and vascular dementia the question is whether diagnostic uncertainty exists or whether diagnostic constructs based on single etiologies are incorrect. Vascular Cognitive Impairment and Dementia (VCID) designates the extent of cognitive dysfunctions from the most benign state to that of dementia, of vascular origin. We reviewed epidemiological, pathophysiological and clinical data on VCID with a focus on VaD, as well as key data on the development of a new therapeutic solution, SaiLuoTong (MLC-SLT). From documentary research executed on different web sources (PubMed, Clintrials.gov, Z-library and Google), our initial selection for the short review of VCID and VaD was based on keywords contained in each paragraph subtitles of this article with exclusion of publications in a language other than English or published before 2010. For the review of SaiLuoTong development, there was just the language exclusion criterion. Sorted by relevance and publication date, 47 references were selected from 140 shortlisted for review. With new evidence-based classification systems, vascular cognitive impairment was proposed as umbrella term covering all forms of cognitive deficits related to vascular causes. The scope of application expanded with the VCID which includes VaD and mixed pathologies. No drugs are approved for the treatment of VaD by major Western regulatory agencies, while some traditional Chinese medicines are registered in China. VCID treatment should have a dual focus: managing the underlying cerebrovascular disease and dementia symptoms. This is the objective set for the development of the MLC-SLT, the essential data of which are reviewed in detail. To strengthen VCID and VaD research, consensus groups should attempt to consolidate scattered local research initiatives into coordinated international programs. In two VaD clinical trials, MLC-SLT improved cognitive symptoms and activities of daily living, with good safety and potential diseasemodifying effect. In a placebo-controlled study in 325 patients with mild to moderate VaD and randomized according to a delayed-start design, MLC-SLT demonstrated significant improvement in memory tests and performance in executive function tasks, expanding its place in the management of VCID. At week 26, changes in VADAS-cog scores (SD) from baseline were 23.25 (0.45) for MLCSLT 180 mg bid), 23.05 (0.45) for MLC-SLT 120 mg bid (both p < 0.0001), and 20.57 (0.45) for placebo (p = 0.15). At week 52, differences between both groups MLCSLT and placebo were 2.67 and 2.48, respectively (p < 0.0001), without significant difference between MLC-SLT groups. [ABSTRACT FROM AUTHOR]

The morbidity and mortality associated with vascular cognitive impairment (VCI) generally increase steeply, and health systems will face increasing demand for services. The present study aims to screen key genes to give new insight into the mechanisms and treatment of VCI based on bioinformatic approaches combined with biological experiments in rats. The gene expression data of VCI patients contained in the GSE122063 data set were downloaded from the Gene Expression Omnibus. We performed a weighted gene co-expression network analysis to identify a hub module and 44 hub genes. Two hundred and seventy-seven differentially expressed genes (DEGs) were analyzed using R software by the "limma" package. STRING database was used to construct protein–protein interaction (PPI) network, after which 36 hub genes were identified through Cytoscape. Functional enrichment analysis revealed that these genes from the yellow module and 277 DEGs were mainly associated with these pathways, such as Staphylococcus aureus infection, complement, and coagulation cascades. These biological functions are related to inflammatory cell activation and inflammatory response. The key genes of VCI were the overlapping hub genes from the yellow module and the PPI network. The expressions of hub genes in rats were determined by quantitative reverse transcription-polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence. In conclusion, C1QA, C1QB, C1QC, CD163, and FCGR2A were highly expressed in the hippocampus of VCI rats, and they can serve as candidate biomarkers for the diagnosis and prognosis of VCI. Finally, molecular docking results suggested that 5 genes interact with Bisphenol A. These findings open a new avenue to investigate molecular mechanisms for preventing or treating VCI. [ABSTRACT FROM AUTHOR]

Background: Post-stroke cognitive impairment (PSCI) represents a serious post-stroke complication with poor cognitive consequences. A vascular consequence after a stroke is that the occurrence and progression of PSCI may be closely related to blood pressure (BP). Thus, we systematically reviewed and performed a meta-analysis of the literature to examine the correlations between BP and PSCI. Methods: We systematically queried databases, including PubMed, the Cochrane Library, Embase, and Scopus, and conducted metaanalyses on studies reporting odds ratios (ORs) related to the association between BP and PSCI. Two authors autonomously assessed all titles, abstracts, and full texts and extracted data following the Meta-Analysis of Observational Studies in Epidemiology guidelines. The quality of the studies was evaluated using the modified Newcastle-Ottawa scale. Results: Meta-analyses incorporated 12 articles comprising a cumulative participant cohort of 21,732 individuals. The quality assessment indicated good in five studies, fair in one study, and poor in six. Through meta-analyses, we found that hypertension, systolic or diastolic BP (SBP or DBP) was significantly associated with PSCI (OR 1.53, 95% confidence interval (CI), 1.18-1.99; p = 0.001, I2 = 66%; OR 1.13, 95% CI, 1.05-1.23; p = 0.002, I2 = 52%; OR 1.38, 95% CI, 1.11-1.72; p = 0.004, I2 = 90%, respectively). In the subgroup analysis, SBP <120 mmHg, 120-139 mmHg, 140-159 mmHg, 160-179 mmHg, and DBP =100 mmHg highly predicted the occurrence of PSCI (OR 1.15, p = 0.0003; OR 1.26, p = 0.010; OR 1.15, p = 0.05; OR 1.02, p = 0.009; OR 1.96, p < 0.00001, respectively). However, the predictive effect of BP for PSCI declines when SBP =180 mmHg and DBP =99 mmHg (p > 0.05). Statistical heterogeneity was moderate to high, and publication bias was detected in SBP for PSCI. Conclusions: Considering the multifactorial etiology of PSCI, it is difficult to conclude that BP is an independent risk factor for PSCI. Given the restricted inclusion of studies, caution is advised when interpreting the findings from this meta-analysis. Subsequent investigations with substantial sample sizes are essential to exploring BP as a prospective target for addressing PSCI. Trial Registration Number: CRD42023437783 from PROSPERO. [ABSTRACT FROM AUTHOR]

Introduction: The impact of intracerebral hemorrhage (ICH) on cognition and the determinants of cognitive recovery early after ICH remain elusive. In this post hoc analysis of the intracerebral hemorrhage deferoxamine (iDEF) trial, we examined the trajectories of cognitive impairment and the determinants of early cognitive recovery after ICH. Methods: We examined baseline factors associated with a 90-day cognitive outcome and constructed generalized linear mixed models to examine the trajectory of cognitive function over time among iDEF participants. Cognition was measured by the Montreal Cognitive Assessment (MoCA) scores on days 7, 30, and 90. Results: 291 were available for analysis under the trial’s modified intention-to-treat definition (38% female, mean age 60.3 ± 12.0 years, median NIHSS 13, IQR 8–18). The median baseline ICH volume was 12.9 IQR (6.4–26.0) mL; 59 (20%) of the ICH cases were lobar, 120 (41%) had intraventricular extension. There was an overall significant increase in total MOCA score with time (p < 0.0001). Total MOCA score increased by an estimated 3.9 points (95% CI: 3.1, 4.7) between the day 7 and day 30 assessments and by an additional 2.9 points (95% CI: 2.2, 3.6) between the day 30 and day 90 assessments. Despite the overall improvement, 134 of 205 (65%) patients with an available 90-day MoCA score remained cognitively impaired with a score <26 on day 90. Older age, higher NIHSS score, baseline ICH volume, intraventricular hemorrhage, and perihematoma edema had an adjusted negative impact on cognitive recovery. Conclusions: Although ICH survivors exhibit significant improvement of cognitive status over the first 3 months, cognitive performance remains impaired in the majority of patients. Among factors independently associated with worse cognitive recovery, higher baseline ICH, intraventricular blood and perihematomal edema volumes, are potential therapeutic targets that merit further exploration. [ABSTRACT FROM AUTHOR]

Background and Purpose: Stroke is a leading cause of global morbidity and mortality, indicating the necessity and urgency of effective prevention and treatment. Remote ischemic conditioning (RIC) is a convenient, simple, non‐intrusive, and effective method that can be easily added to the treatment regime of stroke patients. Animal experiments and clinical trials have proved the neuroprotective effects of RIC on brain injury including (examples of neuroprotective effects). This neuroprotection is achieved by raising brain tolerance to ischemia, increasing local cerebral blood perfusion, promoting collateral circulations, neural regeneration, and reducing the incidence of hematomas in brain tissue. This current paper will summarize the studies within the last 2 years for the comprehensive understanding of the use of RIC in the treatment of stroke. Methods: This paper summarizes the clinical research progress of RIC on stroke (ischemic stroke and hemorrhagic stroke (HS)). This paper is a systematic review of research published on registered clinical trials using RIC in stroke from inception through November 2022. Four major databases (PUBMED, WEB OF SCIENCE, EMBASE, and ClinicalTrials.gov) were searched. Results: Forty‐eight studies were identified meeting our criteria. Of these studies, 14 were in patients with acute ischemic stroke with onset times ranging from 6 h to 14 days, seven were in patients with intravenous thrombolysis or endovascular thrombectomy, 10 were in patients with intracranial atherosclerotic stenosis, six on patients with vascular cognitive impairment, three on patients with moyamoya disease, and eight on patients with HS. Of the 48 studies, 42 were completed and six are ongoing. Conclusions: RIC is safe, feasible, and effective in the treatment of stroke. Large‐scale research is still required to explore the optimal treatment options and mechanisms of RIC in the future to develop a breakthrough in stroke prevention and treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: With the increasing number of patients with cognitive impairment, nonpharmacological ways to delay cognitive impairment have attracted people's attention, such as lifestyle changes and nutritional supplementation. Folic acid supplementation appears to be a promising treatment option. However, it remains controversial whether folic acid supplementation is effective in delaying adult's cognitive impairment. Therefore, we conducted a meta‐analysis to analyze the effects of folic acid supplementation on different cognitive impairments. Methods: We systematically searched PubMed, Web of Science, EMbase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), WanFang and VIP databases for randomized controlled trials on January 22, 2024. The included population comprised those diagnosed with cognitive impairment. We included trials that compared folic acid treatment with placebo, other dosing regimens, or other intervention controls. Conducting quality evaluation of included studies according to the Cochrane Risk of Bias tool. Statistical analyses were performed using Review Manager software. Results: Twenty‐two trials, including 3604 participants, met inclusion criteria. Compared with controls, the cognitive function of Alzheimer's disease (AD) patients showed improvement with folic acid supplementation: supplementation with < 3 mg (standardized mean differences (SMD) = 0.15, 95% confidence interval (CI) –0.10 to 0.41), and supplementing with ≥ 3 mg folic acid could improve cognitive function in AD patients (SMD = 1.03, 95% CI 0.18 to 1.88). Additionally, it reduced homocysteine (HCY) levels (mean differences (MD) = –4.74, 95% CI –8.08 to –1.39). In mild cognitive impairment (MCI) patients, cognitive function improved with folic acid supplementation: supplementation with > 400 μg (SMD = 0.38, 95% CI 0.13 to 0.63), and supplementation with ≤ 400 μg (SMD = 1.10, 95% CI 0.88 to 1.31). It also reduced HCY levels at intervention ≤ 6 months (MD = –3.93, 95% CI –5.05 to –2.82) and intervention > 6 months (MD = –4.38, 95% CI –5.15 to –3.61). However, supplementing with folic acid did not improve cognitive function in vascular cognitive impairment (VCI) patients, with folic acid supplements < 3 mg (SMD = –0.07, 95% CI –0.23 to –0.08), folic acid supplements ≥ 3 mg (SMD = 0.46, 95% CI –0.57 to 1.49), however, it reduced HCY levels at intervention > 6 months (MD = –5.91, 95% CI –7.13 to –4.69) and intervention ≤ 6 months (MD = –11.15, 95% CI –12.35 to –9.95). Conclusions: Supplement folic acid is beneficial to the cognitive profile of patients with MCI, supplementation with ≥ 3 mg folic acid can improve cognitive function in AD patients. [ABSTRACT FROM AUTHOR]

Aim: To explore the neuroprotective potential of hyperforin and elucidate its underlying molecular mechanisms involved in its therapeutic effects against vascular cognitive impairment (VCI). Methods: The 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. Results: The 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. Conclusion: Hyperforin effectively modulated microglial M1 polarization and neuroinflammation by inhibiting the VEGFR2/SRC signaling pathways, thereby ameliorating WMLs and cognitive impairment in VCI mice. [ABSTRACT FROM AUTHOR]

Aphasia is a communication disorder resulting from stroke and/or neurodegenerative conditions which involve the left cerebral hemisphere. It is a debilitating disorder affecting a person's ability to speak, understand, read, and write. Its impact on daily life necessitates therapeutic strategies to aid patients with aphasia. In this special report, the authors speculate whether current pharmacotherapeutic strategies are effective in treating aphasia. The authors look at aphasia caused by different conditions and how this could impact therapy before providing the reader with their expert perspectives. The aim of this paper is for the reader to gain a clearer understanding of the efficacy of the current pharmacotherapeutic treatment paradigms as well as potential future developments. The exploration of pharmacotherapy for aphasia in vascular brain disorders and neurodegenerative diseases has received much attention in recent years with various therapeutic strategies having been put forward. In terms of whether pharmacotherapy is effective for the treatment of aphasia, there is still no clear-cut answer. Further research is needed with more studies requiring a greater emphasis on language and communication deficits. Biomarkers may also help clinicians provide their patients with a more personalized treatment plan. [ABSTRACT FROM AUTHOR]

Background: Carotid stenosis, even in the clinically asymptomatic stage, causes cognitive impairment, silent lesions, and hemispheric changes. The corpus callosum (CC) is crucial for hemispheric cortical integration and specialization. Purpose: To examine if CC morphology and connectivity relate to cognitive decline and lesion burden in asymptomatic carotid stenosis (ACS). Study Type: Retrospective, cross‐sectional. Population: 33 patients with unilaterally severe (70%) ACS and 28 demographically and comorbidity‐matched controls. A publicly available healthy adult lifespan (ages between 18 and 80; n = 483) MRI dataset was also included. Field Strength/Sequence: A 3.0 T; T1 MPRAGE and diffusion weighted gradient echo‐planar imaging sequences. Assessment: Structural MRI and multidomain cognitive data were obtained. Midsagittal CC area, circularity, thickness, integrity, and probabilistic tractography were calculated and correlated with cognitive tests and white matter hyperintensity. Fractional anisotropy, mean diffusivity (MD), and radial diffusivity were determined from DTI. Statistical Tests: Independent two‐sample t‐tests, χ2 tests, Mann–Whitney U, locally weighted scatterplot smoothing (LOWESS) curve fit, and Pearson correlation. A P value < 0.05 was considered statistically significant. Results: Patients with ACS demonstrated significant reductions in callosal area, circularity, and thickness compared to controls. The callosal atrophy was significantly correlated with white matter hyperintensity size (r = −0.629, P < 0.001). Voxel‐wise analysis of diffusion measures in the volumetric CC showed that ACS patients exhibited significantly lower fractional anisotropy and higher MD and radial diffusivity in the genu and splenium of the CC than controls. Further lifespan trajectory analysis showed that although the midsagittal callosal area, circularity, and thickness exhibited age‐related decreases, the values in the ACS patients were significantly lower in all age groups. Data Conclusion: Midsagittal callosal atrophy and connectivity reflect the load of silent lesions and the severity of cognitive decline, respectively, suggesting that CC degeneration has potential to serve as an early marker in ACS. Level of Evidence: 3 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to investigate the relationship between blood–brain barrier (BBB) permeability and cognitive functioning in healthy older adults and individuals with neurodegenerative diseases. Methods and Results A total of 124 participants with Alzheimer disease, cerebrovascular disease, or a mix Alzheimer's and cerebrovascular diseases and 55 controlparticipants underwent magnetic resonance imaging and neuropsychological testing. BBB permeability was measured with dynamic contrast‐enhanced magnetic resonance imaging and white matter injury was measured using a quantitative diffusion‐tensor imaging marker of white matter injury. Structural equation modeling was used to examine the relationships between BBB permeability, vascular risk burden, white matter injury, and cognitive functioning. Vascular risk burden predicted BBB permeability (r=0.24, P

Background: Vascular cognitive impairment (VCI) is the second leading cause of dementia. Cognitive impairment is a common consequence of VCI. However, there is no effective treatment for VCI and the underlying mechanism of its pathogenesis remains unclear. This study to investigate whether artesunate (ART) can improve the learning and memory function in rats with VCI by down-regulating he level of autophagy in cerebral cortex neurons. Methods: The models for VCI were the rat bilateral common carotid artery occlusion (BACCO), which were randomized into three groups including the sham operation group (Sham), model + vehicle group (Model) and model + ART group (ART). Then the animal behaviors were recorded, as well as staining the results of cortical neurons. Western blot was performed to determine the protein expressions of LC3BⅡ/Ⅰ, p-AMPK, p-mTOR, and Beclin-1. Results: Behavioral outcomes and the protein expressions in Model group were supposedly affected by the induction of autophagy in cerebral cortex neurons. Compared to the Model group, ART improved memory impairment in VCI rats. And the expression of LC3BⅡ/Ⅰ, p-AMPK/AMPK, Beclin-1 is significant decreased in the ART group, while significant increases of p-mTOR/mTOR were showed. These results suggest that ART improved learning and memory impairment in VCI rats by down-regulating the level of autophagy in cerebral cortex neurons. Conclusion: The results suggest that autophagy occurs in cerebral cortex neurons in rats with VCI. It is speculated that ART can improve learning and memory impairment in VCI rats by down-regulating the level of autophagy in cerebral cortex neurons.

Post-stroke cognitive impairment is related to the effects of the acute stroke and pre-stroke brain health. We tested whether diffusion tensor imaging (DTI) can detect acute, global effects of stroke and predict post-stroke cognitive performance. Patients with stroke or TIA enrolled in a prospective cohort study were included if they had 1) at least one DTI acquisition at acute presentation, 24 hours, 5 days, or 30 days, and 2) follow-up testing with the telephone Montreal Cognitive Assessment (T-MoCA) at 30 and/or 90 days. A whole brain, white-matter skeleton excluding the infarct was used to derive mean global DTI measures for mean diffusivity (MD), fractional anisotropy (FA), free water (FW), FW-corrected MD (MDtissue), and FW-corrected FA (FAtissue). In 74 patients with ischemic stroke or TIA, there was a transient 4.2% increase in mean global FW between acute presentation and 24 hours (p = 0.024) that returned to initial values by 30 days (p = 0.03). Each acute global DTI measure was associated with 30-day T-MoCA score (n = 61, p = 0.0011-0.0076). Acute global FW, MD, FA and FAtissue were also associated with 90-day T-MoCA (n = 56, p = 0.0034-0.049). Transient global FW elevation likely reflects stroke-related interstitial edema, whereas other global DTI measures are more representative of pre-stroke brain health.

Abstract Hypertension (HTN) affects over 1.2 billion individuals worldwide and is defined as systolic blood pressure (BP) ≥ 140 mmHg and diastolic BP ≥ 90 mmHg. Hypertension is also considered a high risk factor for cerebrovascular diseases, which may lead to vascular cognitive impairment (VCI). VCI is associated with executive dysfunction and is also a transitional stage between hypertension and vascular dementia. Hence, it is essential to establish a reliable approach to diagnosing the severity of VCI. In 28 HTN (51–83 yrs; 18 males, 10 females) and 28 healthy controls (HC) (51–75 yrs; 7 males, 21 females), we investigated which regions demonstrate alterations in the resting-state functional connectome due to vascular cognitive impairment in HTN by using the amplitude of the low-frequency fluctuations (ALFF), regional homogeneity (ReHo), graph theoretical analysis (GTA), and network-based statistic (NBS) methods. In the group comparison between ALFF/ReHo, HTN showed reduced spontaneous activity in the regions corresponding to vascular or metabolic dysfunction and enhanced brain activity, mainly in the primary somatosensory cortex and prefrontal areas. We also observed cognitive dysfunction in HTN, such as executive function, processing speed, and memory. Both the GTA and NBS analyses indicated that the HTN demonstrated complex local segregation, worse global integration, and weak functional connectivity. Our findings show that resting-state functional connectivity was altered, particularly in the frontal and parietal regions, by hypertensive individuals with potential vascular cognitive impairment.