Vascular Dementia Research Articles

Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia.

Central nervous system parvalbumin-positive interneurons (PV-INs) are crucial and highly vulnerable to various stressors. They also play a significant role in the pathological processes of many neuropsychiatric diseases, especially those associated with cognitive impairment, such as Alzheimer's disease (AD), vascular dementia (VD), Lewy body dementia, and schizophrenia. Although accumulating evidence suggests that the loss of PV-INs is associated with memory impairment in dementia, the precise molecular mechanisms remain elusive. In this review, we delve into the current evidence regarding the physiological properties of PV-INs and summarize the latest insights into how their loss contributes to cognitive decline in dementia, particularly focusing on AD and VD. Additionally, we discuss the influence of PV-INs on brain development, the variations in their characteristics across different types of dementia, and how their loss affects the etiology and progression of cognitive impairments. Ultimately, our goal is to provide a comprehensive overview of PV-INs and to consider their potential as novel therapeutic targets in dementia treatment.

Z-Ligustilide: A Potential Therapeutic Agent for Atherosclerosis Complicating Cerebrovascular Disease

Atherosclerosis (AS) is one of the major catalysts of ischemic cerebrovascular disease, and the death and disease burden from AS and its cerebrovascular complications are increasing. Z-ligustilide (Z-LIG) is a key active ingredient in Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort. In this paper, we first introduced LIG’s physicochemical properties and pharmacokinetics. Then, we reviewed Z-LIG’s intervention and therapeutic mechanisms on AS and its cerebrovascular complications. The mechanisms of Z-LIG intervention in AS include improving lipid metabolism, antioxidant and anti-inflammatory effects, protecting vascular endothelium, and inhibiting vascular endothelial fibrosis, pathological thickening, and plaque calcification. In ischemic cerebrovascular diseases complicated by AS, Z-LIG exerts practical neuroprotective effects in ischemic stroke (IS), transient ischemic attack (TIA), and vascular dementia (VaD) through anti-neuroinflammatory, anti-oxidation, anti-neuronal apoptosis, protection of the blood-brain barrier, promotion of mitochondrial division and angiogenesis, improvement of cholinergic activity, inhibition of astrocyte proliferation, and endoplasmic reticulum stress. This paper aims to provide a basis for subsequent studies of Z-LIG in the prevention and treatment of AS and its cerebrovascular complications and, thus, to promote the development of interventional drugs for AS.

White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status.

Placental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment. MarkVCID consortium participants ≥55 years old with plasma PlGF and brain MRI were included. We tested cross-sectionally whether FW mediated the associations between PlGF and WMH, or PlGF and cognition, measured using the Clinical Dementia Rating (CDR) scale and an executive function (EF) composite (Uniform Data Set version 3 [UDS3]-EF). For 370 participants (mean age 72), a higher PlGF was associated with higher FW, higher WMH, and higher CDR, but not UDS3-EF. Higher FW was associated with higher WMH, higher CDR, and lower UDS3-EF. FW explained 26% of the association between PlGF and CDR and 73% of the association between PlGF and WMH. Elevated PlGF may contribute to WMH and cognitive impairment through white matter FW accumulation. NCT06284213 HIGHLIGHTS: PlGF is a promising blood-based biomarker for vascular cognitive impairment. In MarkVCID, higher PlGF was associated with accumulated white matter FW on MRI. FW mediated the association between higher PlGF and MRI-visible white matter injury. FW mediated the association between PlGF and worse CDR scale. PlGF may contribute to cognitive dysfunction via accumulated interstitial fluid.

Blood-brain barrier disruption and microglial activation during hypoxia and post-hypoxic recovery in aged mice

Abstract Hypoxia triggers blood-brain barrier disruption and a strong microglial activation response around leaky cerebral blood vessels. These events are greatly amplified in aged mice which is translationally relevant because aged patients are far more likely to suffer hypoxic events from heart or lung disease, and because of the pathogenic role of blood-brain barrier breakdown in vascular dementia. Importantly, it is currently unclear if disrupted cerebral blood vessels spontaneously repair and if they do, whether surrounding microglia deactivate. In this study we addressed these questions by exposing aged (20 months old) mice to chronic mild hypoxia (8% O2) for 7 days and then returned them to normoxic conditions for 7 or 14 days, before evaluating blood-brain barrier disruption and microglial activation at the different timepoints. Seven days chronic mild hypoxia triggered marked blood-brain barrier disruption, as measured by extravascular leak of fibrinogen and red blood cells, which led to enhanced microglial activation, as measured by Mac-1 and CD68 levels. Interestingly, while return to normoxia promoted spontaneous repair of damaged blood vessels, the surrounding microglia remained persistently activated and were slow to deactivate. Chronic mild hypoxia also triggered neuronal loss that resulted in irreversible cognitive decline as measured by the novel object recognition test. Taken together, these findings describe an important disconnect between vascular repair and microglial deactivation in aged mice, which likely contributes to prolonged neuroinflammation. As hypoxia occurs in many age-related conditions, our data have important implications for the pathogenic role of hypoxia in the induction and progression of vascular dementia.

Endothelial Cell Senescence Effect on the Blood-Brain Barrier in Stroke and Cognitive Impairment.

Age is an important risk factor of stroke, cognitive decline, and dementia. Senescent endothelial cells (ECs) accumulate with advancing age through exposure to cellular stress, such as that exerted by hypertension and diabetes. These senescent ECs have altered characteristics, such as altered tight junction proteins, use of a more indiscriminate transcellular transport system, increased inflammation, and increased immune cell interactions. ECs are the main component of the blood-brain barrier (BBB), separating the brain from systemic circulation. As senescent ECs accumulate in the BBB, their altered functioning results in the disruption of the barrier. They have inadequate barrier-forming properties, disrupted extracellular matrix, and increased transcytosis, resulting in an overly permeable barrier. This disruption of the BBB can have important effects in stroke and cognitive impairment, as presented in this review. Besides increasing the permeability of the BBB, senescent ECs can also impair angiogenesis and vascular remodeling, which in ischemic stroke may increase risk of hemorrhagic transformation and worsen outcomes. Senescent ECs may also contribute to microvascular dysfunction, with disruption of cerebral perfusion and autoregulation. These may contribute to vascular cognitive impairment along with increased permeability. With an aging population, there is growing interest in targeting senescence. Several ongoing trials have been evaluating whether senolytics can slow aging, improve vascular health, and reduce the risk of stroke and cognitive decline.

Ultrastructural features of the brain of patients with cognitive impairment in Alzheimer’s disease and vascular dementia

BACKGROUND: Nowadays, due to the increase in life expectancy, the problem of cognitive disorders, quite often found in elderly people and being a formidable syndrome of a number of neurodegenerative diseases, is extremely relevant. According to epidemiological data, the most common causes of cognitive dysfunction are Alzheimer’s disease and cerebrovascular diseases, accounting for about 90% of all cases. AIM: to investigate the morphological features underlying the development of cognitive disorders in Alzheimer’s disease and cerebrovascular pathology. MATERIALS AND METHODS: According to our developed and patented method of preparation of sectional material for electron microscopy а detailed study of the brain of elderly patients with Alzheimer’s disease and cerebrovascular pathology was carried out using electron microscopy on autopsy material. RESULTS: Electron microscopy of the brains of patients with Alzheimer’s disease often reveals large extracellular reticulate-fiber structures closely adjacent to myelin fibers, which are part of a fibrous plaque. In vascular dementia, irregularly shaped hyperchromic masses with heterogeneous contents are found in the neuropil, which may represent future so-called “diffuse” plaques. In Alzheimer’s disease, fragments of future “diffuse” plaques are also observed in the cytoplasm of some cortical oligodendrocytes. In all deceased with Alzheimer’s disease, synaptic changes were found in the form of roughly granular disintegration of the entire synaptocomplex, i.e., synaptic vesicles, mitochondria, and the synaptic cleft proper. CONCLUSION: This study provides an opportunity to take a new look at some questions of etiology and pathogenesis of such a disease as cognitive disorders, which is not easy to diagnose and treat.

Liver enzyme and risk of vascular dementia: A univariable and multivariable Mendelian randomization of European descent

AbstractBackgroundObservational studies have indicated a link between liver enzymes and dementia, but the causal relationship remains uncertain. We conducted a two‐sample Mendelian randomization (MR) study to investigate potential causal links between liver function markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and γ‐glutamyltransferase [GGT]) and various forms of dementia (all‐cause dementia, Alzheimer's disease [AD], vascular dementia [VaD], and frontotemporal dementia [FTD]).MethodsGenome‐wide association study (GWAS) data of liver enzyme levels with 517 single nucleotide polymorphisms from 315,572 individuals of European descent were considered as exposures. Additional GWAS data on dementia from the FinnGen consortium and the UK Biobank were used as outcomes. The causal relationship was evaluated using univariable MR (UVMR) and multivariable MR (MVMR) methods. UVMR approaches such as inverse variance weighting (IVW), MR‐Egger, weighted median, simple mode, and weighted mode were used, with IVW as primary. MVMR techniques, such as extended versions of IVW, MR‐Egger, and Q‐minimization methods, were used to assess causal effects. The robustness of the MR analysis findings was verified through heterogeneity, horizontal pleiotropy, and leave‐one‐out analyses.ResultsMVMR analysis demonstrated that a genetically determined one standard deviation rise in blood GGT levels was associated with an increased risk of VaD (IVW: odds ratio = 1.007, 95% confidence interval = 1.002–1.011, p = 0.010). These findings remained consistent after adjusting for confounding variables in MVMR analysis. Sensitivity analyses further supported the causal relationship. However, no significant links were observed between ALT, AST, ALP, and all‐cause dementia, VaD, AD, or FTD.ConclusionsOur study suggests clinical implications, demonstrating that high blood GGT concentrations are potential causal risk factors for VaD in European populations. Further research is needed to uncover the underlying biological mechanisms between GGT and VaD and validate the clinical relevance of early prevention and intervention strategies.

The cerebellar glucose metabolism in moyamoya vasculopathy and its correlation with neurocognitive performance after cerebral revascularization surgery: a [18F]FDG PET study.

The vascular cognitive impairment (VCI) is quite common in moyamoya vasculopathy (MMV). However, the abnormality of cerebellar glucose metabolism in MMV and its relationship with patients' neurocognitive performance were few reported. In this study, we aimed to investigate the relationship between neurocognitive performance and cerebellar glucose metabolism. Furthermore, the cerebellar glucose metabolism changes after combined revascularization surgery were also researched. We retrospectively analyzed the 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography ([18F]FDG PET) images and their neuropsychological scales in 93 eligible MMV patients by comparing their cerebellar standardized uptake values ratio (SUVR) and metabolic covariant network (MCN) among different neurocognitive groups. Then, forty-two MMV patients with VCI who underwent combined revascularization surgery were prospectively observed. According to their neuropsychological performance at 6-month follow-up, these patients were assigned to cognitive improved group (n = 22) and non-improved group (n = 20). The cerebellar SUVR and MCN changes were also analyzed. SUVR of right Lobule VI/Crus II/VIII decreased when cognitive impairment progression (P < 0.05, Least-Significant Difference [LSD] post hoc analysis). The cerebellar glucose metabolic pattern can be divided into two parts, in which the cerebellar posterior lobe was positively related to patients' neurocognitive performance, while the vermis and anterior lobe showed negative relationship with the neurocognitions (P < 0.001). Further MCN analysis expound that the degree of right Lobule VI/Crus II/VIII displayed decreased tendency as cognitive impairment worsened (P < 0.05, LSD post hoc analysis). After revascularization surgery, the SUVR of right cerebellar posterior lobe significantly promoted in improved group (P < 0.001). Besides, we also witnessed the SUVR improvement in left cerebral hemisphere, thalamus, and red nucleus (P < 0.001). The MCN analysis revealed that the posterior connective strength improvement among right Lobule VI and several cerebral regions significantly correlated with memory and executive screening (MES) score (P < 0.001, false discovery rate corrected). We found that the hypometabolism of cerebellar posterior lobe, especially in the right Lobule VI, was associated with MMV patients' neuropsychological performance, while the anterior lobe and vermis showed opposites tendencies. Combined revascularization surgery improved the posterior cerebellar metabolism and was associated with favorable neurocognitive outcomes, which might be related to the activation of cortico-rubral-cerebellar pathway.

Implications of Modifiable and Non-Modifiable Determinants of Dementia for Public Health Policies and Prevention Strategies

Dementia, characterized by cognitive decline and memory deterioration, poses a significant and growing global health challenge. Alzheimer's disease (AD) is the most common form, with others including Lewy body dementia (LBD), frontotemporal dementia (FTD), and vascular dementia (VaD). The World Health Organization estimates that 55 million people worldwide are affected, a number projected to triple by 2050. This essay explores both non-modifiable and modifiable determinants of dementia and their implications for public health policies and prevention efforts. Non-modifiable determinants include age, genetics, and sex, all of which significantly influence dementia risk. Ageing is the primary risk factor, with genetic factors such as mutations in APP, PSEN1, and PSEN2, and the APOE 4 allele increasing susceptibility. Women, due to their longer lifespan and hormonal differences, are at a higher risk compared to men. Modifiable determinants encompass lifestyle factors and medical conditions, notably diet, physical activity, alcohol and tobacco use, hypertension, and diabetes. Effective public health policies, like the WHO's Global Action Plan, emphasize early intervention and lifestyle modifications. Integrating these determinants into policy making requires a balanced approach, considering the dynamic nature of modifiable factors and the specific needs of an aging population. The essay underscores the need for comprehensive public health education, destigmatization of dementia, and an inclusive healthcare infrastructure to enhance dementia prevention and care, ultimately reducing the societal burden of this condition.

The Promising Potency of Sodium–Glucose Cotransporter 2 Inhibitors in the Prevention of and as Treatment for Cognitive Impairment Among Type 2 Diabetes Patients

Type 2 diabetes mellitus (T2DM), accounting for the majority of diabetes mellitus prevalence, is associated with an increased risk of cognition decline and deterioration of cognition function in diabetic patients. The sodium–glucose cotransporter 2 (SGLT2), located in the renal proximal tubule, plays a role in urine glucose reabsorption. SGLT2 inhibitors (SGLT2i), have shown potential benefits beyond cardiac and renal improvement in preventing and treating cognitive impairment (CI), including mild cognitive impairment, Alzheimer’s disease and vascular dementia in T2DM patients. Studies suggest that SGLT2i may ameliorate diabetic CI through metabolism pathways, inflammation, oxidative stress, neurotrophic factors and AChE inhibition. Clinical trials and meta-analyses have reported significant and insignificant results. Given their vascular effects, SGLT2i may offer unique protection against vascular CI. This review compiles mechanisms and clinical evidence, emphasizing the need for future analysis, evaluation, trials and meta-analyses to verify and recommend optimal SGLT2i selection and dosage for specific patients.

Identification of isoAsp7-Aβ as a major Aβ variant in Alzheimer's disease, dementia with Lewy bodies and vascular dementia.

The formation of amyloid-β (Aβ) aggregates in brain is a neuropathological hallmark of Alzheimer's disease (AD). However, there is mounting evidence that Aβ also plays a pathogenic role in other types of dementia and that specific post-translational Aβ modifications contribute to its pathogenic profile. The objective of this study was to test the hypothesis that distinct types of dementia are characterized by specific patterns of post-translationally modified Aβ variants. We conducted a comparative analysis and quantified Aβ as well as Aβ with pyroglutamate (pGlu3-Aβ and pGlu11-Aβ), N-truncation (Aβ(4-X)), isoaspartate racemization (isoAsp7-Aβ and isoAsp27-Aβ), phosphorylation (pSer8-Aβ and pSer26-Aβ) or nitration (3NTyr10-Aβ) modification in post mortem human brain tissue from non-demented control subjects in comparison to tissue classified as pre-symptomaticAD (Pre-AD), AD, dementia with Lewy bodies and vascular dementia. Aβ modification-specific immunohistochemical labelings of brain sections from the posterior superior temporal gyrus were examined by machine learning-based segmentation protocols and immunoassay analyses in brain tissue after sequential Aβ extraction were carried out. Our findings revealed that AD cases displayed the highest concentrations of all Aβ variants followed by dementia with Lewy bodies, Pre-AD, vascular dementia and non-demented controls. With both analytical methods, we identified the isoAsp7-Aβ variant as a highly abundant Aβ form in all clinical conditions, followed by Aβ(4-X), pGlu3-Aβ, pGlu11-Aβ and pSer8-Aβ. These Aβ variants were detected in distinct plaque types of compact, coarse-grained, cored and diffuse morphologies and, with varying frequencies, in cerebral blood vessels. The 3NTyr10-Aβ, pSer26-Aβ and isoAsp27-Aβ variants were not found to be present in Aβ plaques but were detected intraneuronally. There was a strong positive correlation between isoAsp7-Aβ and Thal phase and a moderate negative correlation between isoAsp7-Aβ and performance on the Mini Mental State Examination. Furthermore, the abundance of all Aβ variants was highest in APOE 3/4 carriers. In aggregation assays, the isoAsp7-Aβ, pGlu3-Aβ and pGlu11-Aβ variants showed instant fibril formation without lag phase, whereas Aβ(4-X), pSer26-Aβ and isoAsp27-Aβ did not form fibrils. We conclude that targeting Aβ post-translational modifications, and in particular the highly abundant isoAsp7-Aβ variant, might be considered for diagnostic and therapeutic approaches in different types of dementia. Hence, our findings might have implications for current antibody-based therapies of AD.

Vascular Cognitive Impairment

ABSTRACT OBJECTIVE Vascular cognitive impairment is a major contributor to age-associated cognitive decline, both independently and as a contributor to mixed dementia syndromes. This article reviews the current understanding of how vascular dysfunction contributes to cognitive impairment and dementia risk in older individuals and includes updated diagnostic criteria and treatment recommendations. LATEST DEVELOPMENTS Clinical and research criteria have been evolving to more accurately determine the full prevalence of vascular cognitive impairment. The Boston Criteria version 2.0 for cerebral amyloid angiopathy now includes multiple punctate MRI T2 white matter hyperintensities and MR-visible perivascular spaces in addition to previously described T2* hemorrhagic signatures. MR-visible perivascular spaces are associated with both vascular cognitive impairment and Alzheimer disease, potentially linking cerebrovascular dysfunction to neurodegenerative disorders through its role in brain waste clearance. The American Heart Association’s goal for cardiovascular health promotion, “Life’s Essential 8,” has been updated to include sleep health and acknowledges psychological well-being and social determinants of health as fundamental components necessary to achieve optimal cardiovascular health for all adults. ESSENTIAL POINTS Vascular cognitive impairment is a common and often underrecognized contributor to cognitive impairment in older individuals, with heterogeneous etiologies requiring individualized treatment strategies. Effective cerebrovascular disease risk factor modification starting in midlife is critical to reducing the risk of Alzheimer disease and related dementias, with the goal of preventing vascular brain injury and maintaining cognitive reserve in the presence of nonvascular age-related brain pathologies.

Neuroimaging in Dementia.

This article captures the current literature regarding the use of neuroimaging measures to study neurodegenerative diseases, including early- and late-onset Alzheimer disease, vascular cognitive impairment, frontotemporal lobar degeneration disorders, dementia with Lewy bodies, and Parkinson disease dementia. In particular, the article highlights significant recent changes in novel therapeutics now available for the treatment of Alzheimer disease and in defining neurodegenerative disease using biological frameworks. Studies summarized include those using structural and functional MRI (fMRI) techniques, as well as metabolic and molecular emission tomography imaging (ie, positron emission tomography [PET] and single-photon emission computerized tomography [SPECT]). Neuroimaging measures are considered essential biomarkers for the detection and diagnosis of most neurodegenerative diseases. The recent approval of anti-amyloid antibody therapies has highlighted the importance of MRI and PET techniques in treatment eligibility and monitoring for associated side effects. Given the success of the initial biomarker-based classification system for Alzheimer disease (the amyloid, tau, neurodegeneration [A/T/N] framework), researchers in vascular cognitive impairment have created similar techniques for biomarker-based diagnosis. Further, the A/T/N framework for Alzheimer disease has been updated to include several pathologic targets for biomarker detection. Neurodegenerative diseases have a major health impact on millions of patients around the world. Neuroimaging biomarkers are rapidly becoming major diagnostic tools for the detection, monitoring, and treatment of neurodegenerative diseases. This article educates readers about the current literature surrounding the use of neuroimaging tools in neurodegenerative diseases along with recent important developments in the field.

Deep Learning Model for Prediction of Dementia Severity based on EEG Signals

This study aimed to determine variations in the electroencephalograms (EEGs) of 15 individuals who were diagnosed with mild cognitive impairment (MCI) following stroke, 5 individuals suffering from vascular dementia (VD) and 15 healthy normal control (NC) individuals who performed a working memory task. Conventional filters including notch and bandpass filters were utilised to remove noise from the EEG data. The proposed method comprises computing the estimates of the attention entropy (AttEn), bubble entropy (BubbEn) and symbolic dynamic entropy (SyDyEn) of univariate data sequence features. The long short-term memory (LSTM) deep learning neural network was used to automatically classify dementia severity through noninvasive EEG-based recordings. The LSTM classification result with AttEn exceeds an average of 88.9% than BubbEn and SyDyEn, with classification results of 69.2% and 77.7%, respectively. The analysis of the brain EEG-based dementia severity dataset suggests that AttEn could potentially serve as a biomarker for detecting dementia severity. AttEn can capture relevant patterns and features in the EEG data and may be indicative of the severity of dementia with LSTM RNN to differentiate patients with VD, patients with MCI and NC individuals.

Assessing the Role of VISTA in Vascular Cognitive Impairment: Addressing Limitations and Exploring Future Research Directions [Letter

Assessing the Role of VISTA in Vascular Cognitive Impairment: Addressing Limitations and Exploring Future Research Directions [Letter

An overview of the relationship between inflammation and cognitive function in humans, molecular pathways and the impact of nutraceuticals

Inflammation has been associated with cognitive decline, whether in the peripheral or central nervous systems. The primary mechanism involves the response of microglia, an immune cell in the brain, which generates pro-inflammatory mediators such as cytokines, chemokines, and adhesion molecules. The excessive production of pro-inflammatory mediators may accelerate the damage to neurons, contributing to the development of neurodegenerative diseases such as Alzheimer’s disease, mild cognitive impairment, and vascular dementia, as well as a general decline in cognitive function. Various studies have supported the correlation between elevated pro-inflammatory mediators and a decline in cognitive function, particularly in aging and age-related neurodegenerative diseases. Moreover, this association has also been observed in other inflammatory-related conditions, including post-operative cognitive impairment, diabetes, stroke, obesity, and cancer. However, the interaction between inflammatory processes and cognitive function in humans remains unclear and varies according to different health conditions. Therefore, this review aims to consolidate and evaluate the available evidence from original studies as well as meta-analyses in order to provide a greater understanding of the inflammatory process in connection with cognitive function in humans. Furthermore, relevant biological cellular processes, putative inflammatory biomarkers, and the role of nutraceuticals on the interaction between cognitive performance and inflammatory status are outlined.

REPLY: Hippocampal atrophy and white matter lesions as predictors of the transition from VMCI to vascular dementia: Implications for early intervention

REPLY: Hippocampal atrophy and white matter lesions as predictors of the transition from VMCI to vascular dementia: Implications for early intervention

Association between hypertension, diabetes, depression, and serum calcium with the risk of all-cause and vascular dementia: findings from the UK biobank.

The associations between serum calcium levels and the risk of all-cause dementia and vascular dementia (VaD) are not well understood. Additionally, the potential roles of hypertension, diabetes, and depression in this association need to be explored. This study aimed to investigate the links between serum calcium and all-cause dementia and VaD and to assess the role of hypertension, diabetes, and depression in that association. For this cohort study, data were extracted from the UK Biobank, a population-based longitudinal survey with baseline assessments from 2006 to 2010 in England, Wales, and Scotland. A total of 363 182 participants without dementia at baseline were included. Cases of all-cause dementia and VaD were identified through database linkage until December 31, 2022. The hazards of all-cause dementia and VaD were estimated using Cox proportional hazards regression models. Mediation analyses were performed to evaluate the mediation effect of hypertension, diabetes, and depression. During a median follow-up of 13.8years, 5 836 cases of all-cause dementia and 1 301 cases of VaD were identified. Participants with higher levels of serum calcium (in the third and fourth quartile, > 2.37 to ≤ 2.43mmol/L and > 2.43mmol/L) had a lower risk of all-cause dementia compared to those in the first quartile (≤ 2.32mmol/L) (Hazard Ratio [HR] [95% Confidence Interval (CI)] in Q3: 0.87 (0.81-0.93), HR [95% CI] in Q4: 0.90 [0.84-0.97]). For VaD, HRs (95% CIs) in the second, third, and fourth quartiles were 0.80 (0.69-0.93), 0.76 (0.65-0.89), and 0.80 (0.69-0.93), respectively. Hypertension, diabetes, and depression significantly explained 18.67%, 2.57%, and 18.91% of the mediation effects on serum calcium-related dementia, respectively. Diabetes and depression contributed 1.85% and 15.34% of mediation effects on the association between serum calcium and the risk of VaD. This study found that individuals with higher serum calcium levels (> 2.37mmol/L) had a reduced risk of developing dementia. Hypertension, diabetes, and depression significantly mediated the association. These findings highlight the significance of considering serum calcium levels as a potential indicator for the development of dementia. Further, optimizing the treatment of associated diseases and managing risk factors, particularly for individuals with lower serum calcium levels, is important.

Anti-RGMa neutralizing antibody ameliorates vascular cognitive impairment in mice

Repulsive Guidance Molecule A (RGMa) is well-recognized for its role in axon guidance. Recent studies have unveiled its diverse functions under pathological conditions within the central nervous system, such as spinal cord injury, multiple sclerosis, and Parkinson’s disease. In this study, we explored the involvement of RGMa and the therapeutic effects of an anti-RGMa neutralizing antibody in a mouse model of vascular dementia (VaD). The VaD mouse model was established using the bilateral common carotid artery stenosis (BCAS) method. Immunohistochemical analysis revealed that these mice exhibited increased RGMa expression in the hippocampus, which coincided with reduced neurogenesis and impaired cholinergic innervation. These alterations manifested as cognitive impairments in the BCAS mice. Significantly, treatment with anti-RGMa neutralizing antibody reversed these pathological changes and cognitive deficits. Our findings suggest that RGMa plays a pivotal role in VaD pathology within the hippocampus and propose the anti-RGMa antibody as a promising therapeutic avenue for treating VaD.

Palliative Home Care Based on Clinically Relevant Scientific Measures: A Cross-Sectional Study.

Introduction: Measuring palliative care needs of patients with multiple complex illnesses and their family, is essential for providing quality clinical care. The integrated palliative care outcome scale (IPOS) is a scientifically verified measure of patients' physical, emotional symptoms, and their palliative care communication and practical needs. The patients in this study require palliative care due to both their end-of-life heart failure (HF) and vascular dementia. Purpose: The purposes are to describe and compare home palliative care needs measured by the family caregivers (N = 20) and patients (N = 20) IPOS scores and to examine whether the patient IPOS total score can predict patient HF health status and caregiving burden scores. Methods: This study uses explanatory research design with rigorous methods for obtaining information from multiple sources. Descriptive, Cohen's Kappa (k) statistics comparing patient and caregiver IPOS scores and regression analyses to examine the patient IPOS scores impact on patient HF health status and caregiving burden scores were used. Results: There was significant agreement between patient and caregiver ratings on 16 out of 17 IPOS items (k = .34 to .80). Regression analyses found that the patient IPOS total score significantly predicted patients' HF health status (β = -.50, P < .05), and caregiving burden scores (β = .57, P < .01). Conclusion: Patients' and their caregivers' IPOS scores agreement indicates palliative care needs can be consistently identified. The patient IPOS total scores can predict patients' HF health status and caregiving burden. These measures provide information directly applicable for health professionals guiding palliative home care.