Mechanisms of mitophagy and oxidative stress in cerebral ischemia-reperfusion, vascular dementia, and Alzheimer's disease.

Neurological diseases have consistently represented a significant challenge in both clinical treatment and scientific research. As research has progressed, the significance of mitochondria in the pathogenesis and progression of neurological diseases has become increasingly prominent. Mitochondria serve not only as a source of energy, but also as regulators of cellular growth and death. Both oxidative stress and mitophagy are intimately associated with mitochondria, and there is mounting evidence that mitophagy and oxidative stress exert a pivotal regulatory influence on the pathogenesis of neurological diseases. In recent years, there has been a notable rise in the prevalence of cerebral ischemia/reperfusion injury (CI/RI), vascular dementia (VaD), and Alzheimer's disease (AD), which collectively represent a significant public health concern. Reduced levels of mitophagy have been observed in CI/RI, VaD and AD. The improvement of associated pathology has been demonstrated through the increase of mitophagy levels. CI/RI results in cerebral tissue ischemia and hypoxia, which causes oxidative stress, disruption of the blood-brain barrier (BBB) and damage to the cerebral vasculature. The BBB disruption and cerebral vascular injury may induce or exacerbate VaD to some extent. In addition, inadequate cerebral perfusion due to vascular injury or altered function may exacerbate the accumulation of amyloid ß (Aß) thereby contributing to or exacerbating AD pathology. Intravenous tissue plasminogen activator (tPA; alteplase) and endovascular thrombectomy are effective treatments for stroke. However, there is a narrow window of opportunity for the administration of tPA and thrombectomy, which results in a markedly elevated incidence of disability among patients with CI/RI. It is regrettable that there are currently no there are still no specific drugs for VaD and AD. Despite the availability of the U.S. Food and Drug Administration (FDA)-approved clinical first-line drugs for AD, including memantine, donepezil hydrochloride, and galantamine, these agents do not fundamentally block the pathological process of AD. In this paper, we undertake a review of the mechanisms of mitophagy and oxidative stress in neurological disorders, a summary of the clinical trials conducted in recent years, and a proposal for a new strategy for targeted treatment of neurological disorders based on both mitophagy and oxidative stress.

The Effects of Physical Activity on Experimental Models of Vascular Dementia: A Systematic Review and Meta-Analysis.

Background: Physical activity is associated with improved brain health and cognition in humans. However, the validity, range, and quality of evidence for the beneficial outcomes linked to exercise in experimental models of vascular dementia (VaD) have not been evaluated. We performed a systematic review and meta-analysis of studies that assessed the effect of exercise intervention on models of VaD to provide an unbiased and comprehensive determination of the cognitive function and brain morphology benefits of exercise. Summary: A systematic search in three databases as well as study design characteristics and experimental data extraction were completed in December 2021. We investigated the effects of exercise on cognitive function and brain-morphology outcomes in VaD models. Twenty-five studies were included for systematic review, while 21 studies were included in the meta-analysis. These studies included seven models of VaD in rats (60%, 15 studies), mice (36%, 9 studies), and pigs (4%, 1 study). None of the included studies used aged animals, and the majority of studies (80%) used only male animals. Key Message Exercise improves cognition but increased neuro-inflammation in VaD models: Exercise improved cognitive function as well as some markers of brain morphology in models of VaD. However, exercise increased anxiety and neuro-inflammatory signals in VaD models. Further, we observed increased reporting anomalies such as a lack of blinding to group treatment or data analysis and randomization of animals to groups. Our report could help in the appropriate design of experimental studies seeking to investigate the effects of exercise as a non-pharmacological intervention on VaD models with a high translational impact.

Should dietary restrictions be imposed on Alzheimer's Disease patients affected by type 2 diabetes?

INTRODUCTION: Antidiabetic drugs, reduction of carbohydrates intake, maintaining normal weight and physical activity are the cornerstone of diabetes 2 treatment. METHODS: This opinion article is not intended to challenge hundreds of studies unequivocally demonstrating the benefits of a healthy lifestyle including appropriate diet in controlling the consequences of T2DM. The article questions whether the benefits of dietary restrictions for the management of T2D in older adults who are already demented, are worth the potential detrimental effects on quality of life for the patients and their caregivers, as well as the effects of dietary restrictions on frailty, sarcopenia. DISCUSSION: However, the benefit of dietary restrictions including carbohydrates restrictions, might not manifest in elderly Alzheimer and vascular dementia patients with type 2 diabetes. On the contrary, such restrictions might hinder the patients' and caregiver's quality of life and encumber attempts to maintain normal weight in a population which tends to be underweight. Therefore, the benefit/risk ratio of dietary restriction should be weighed in this population on an individual basis.

Inhibition of histone methyltransferase promotes cognition and mitochondrial function in vascular dementia model.

Vascular dementia (VD) is one of the most common forms of dementia worldwide, characterized by problems with reasoning, planning, judgment, and memory. This study investigated the effect of a histone methyltransferase inhibitor on cognition and mitochondrial function in a rat model of VD, as well as its impact on H2O2-induced neurotoxicity in hippocampal neuronal cultures. In the in vivo experiments, VD was induced by bilateral occlusion of the common carotid artery (CCA) for one month. The histone methyltransferase inhibitor, BIX01294, was administered intracerebroventricularly for one month (22.5 µg.kg-1 three times/week). On day 30, behavioral tests, including the novel object recognition test and elevated plus maze test, were conducted. Mitochondrial enzyme activities, including aconitase, α-ketoglutarate dehydrogenase (α-KG), complex I, and complex IV, were evaluated in the hippocampus of rats following CCA ligation. In the in vitro experiments, the effect of BIX01294 (50-600 µM) on H2O2 (400 µM)-induced cytotoxicity in hippocampal neuronal cells was assessed using the MTT assay. Flow cytometry was performed to evaluate apoptosis. Our findings revealed that BIX01294 effectively improved memory function, Krebs cycle enzyme activity, and mitochondrial function in the rat model of VD. Moreover, in vitro results showed that BIX01294 at a concentration of 100 µM significantly reversed the cytotoxicity and apoptosis induced by H2O2 in neuronal cells. These findings suggest that BIX01294 may have the potential to improve VD complications by reducing oxidative stress and inhibiting histone methylation.

Comparison of subjective cognitive decline and polygenic risk score in the prediction of all-cause dementia, Alzheimer's disease and vascular dementia.

BACKGROUND: Polygenic risk scores (PRS) and subjective cognitive decline (SCD) are associated with the risk of developing dementia. It remains to examine whether they can improve the established cardiovascular risk factors aging and dementia (CAIDE) model and how their predictive abilities compare. METHODS: The CAIDE model was applied to a sub-sample of a large, population-based cohort study (n = 5,360; aged 50-75) and evaluated for the outcomes of all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VD) by calculating Akaike's information criterion (AIC) and the area under the curve (AUC). The improvement of the CAIDE model by PRS and SCD was further examined using the net reclassification improvement (NRI) method and integrated discrimination improvement (IDI). RESULTS: During 17 years of follow-up, 410 participants were diagnosed with dementia, including 139 AD and 152 VD diagnoses. Overall, the CAIDE model showed high discriminative ability for all outcomes, reaching AUCs of 0.785, 0.793, and 0.789 for all-cause dementia, AD, and VD, respectively. Adding information on SCD significantly increased NRI for all-cause dementia (4.4%, p = 0.04) and VD (7.7%, p = 0.01). In contrast, prediction models for AD further improved when PRS was added to the model (NRI, 8.4%, p = 0.03). When APOE ε4 carrier status was included (CAIDE Model 2), AUCs increased, but PRS and SCD did not further improve the prediction. CONCLUSIONS: Unlike PRS, information on SCD can be assessed more efficiently, and thus, the model including SCD can be more easily transferred to the clinical setting. Nevertheless, the two variables seem negligible if APOE ε4 carrier status is available.

Danggui-Shaoyao-San (DSS) ameliorating cognitive impairment in ischemia-reperfusion vascular dementia mice through miR-124 regulating PI3K/Akt signaling pathway.

Vascular dementia (VD) is a disease characterized by cognitive impairment and memory loss due to brain cell damage caused by cerebral vascular ischemia. Danggui-Shaoyao-San (DSS) has been used clinically to treat diseases for centuries. The VD model was established by bilateral common carotid artery (BCCA) repeated ischemia-reperfusion (I/R) and caudal bleeding. Target prediction of DSS and miR-124 in PI3K/Akt signaling pathway by network pharmacology. The effect of DSS on cognitive dysfunction were evaluated through methods such as behavioral experiments, cerebral blood flow monitoring, HE and Nissl staining, western blot, and q-PCR. Prediction result showed that both DSS and miR-124 could target Akt1. DSS treatment significantly reduced hippocampal cell damage, improved learning and memory ability. Mechanically, DSS treatment up-regulated the expression levels of PI3K and Akt protein, and its gene. Bcl-2/Bax index is up-regulated and cell apoptosis reduced. LC3II/LC3I index decreased and autophagy of brain cells increased. Moreover, DSS down-regulated the expression level of miR-124. And inhibition of miR-124 up-regulate the expression of PI3K, Akt. These results suggested that DSS can reduce the content of miR-124 in the hippocampus of VD mice, thus regulating the PI3K/Akt signaling pathway and improving the learning and memory ability of VD mice.

Efficacy of 5 and 10 mg donepezil in improving cognitive function in patients with dementia: a systematic review and meta-analysis.

Objective: The purpose of this study was to compare donepezil at 5 mg and 10 mg/day against a placebo to systematically evaluate its effectiveness in improving cognitive function among patients suffering from dementia at any stage. Method: For this systematic review and meta-analysis, we looked up Medline, Scopus, Embase, Web of Science, and The Cochrane Library for articles on the efficacy of donepezil in dementia published in the past 20 years and summarized the placebo and intervention data. Initially, a total of 2,272 articles were extracted using our search query and after the inclusion and exclusion criteria set for extraction of data, 18 studies were included in this review using PRISMA flowchart. The ADAS-cog and MMSE assessment scales were used for measuring the outcomes using IBM SPSS 29.0 for the meta-analysis. Result: The meta-analysis comprised a total of 18 RCTs (randomized controlled trials) that were randomized to receive either donepezil 5 mg/day (n = 1,556), 10 mg/day (n = 2050) or placebo (n = 2,342). Meta-analysis concerning efficacy showed that donepezil at 10 mg/day significantly improved the MMSE score (g: 2.27, 95%CI: 1.25-3.29) but could not substantially reduce the ADAS-cog. At 5 mg/day donepezil, an overall slight improvement in MMSE score (Hedges' g: 2.09, 95%CI: 0.88-3.30) was observed. Conclusion: Both donepezil 5 mg/day and 10 mg/day doses demonstrated improved cognitive functions for patients with dementia, however results indicated that the 10 mg/day dose was more efficacious.

Effect of Different Durations of Treatment With Antihypertensive Drugs With Anticholinergic Effects on the Risk of Dementia: A Target Trial Emulation Study.

Studying the effect of duration of treatment on prognostic outcomes using real-world data is challenging because only people who survive for a long time can receive a treatment for a long time. Specifying a target trial helps overcome such challenge. We aimed to estimate the effect of different durations of treatment with antihypertensive drugs with anticholinergic properties (AC AHT) on the risk of vascular dementia and Alzheimer's disease by emulating a target trial using the UK CPRD GOLD database (2001-2017). Comparing treatment for 3-6 years versus ≤3 years yielded null results for both types of dementia. Comparing a longer duration of treatment, >6 years versus ≤3 years, yielded a 10-year risk ratio of 0.69 (95% CI, 0.54-0.90) for vascular dementia and 0.91 (95% CI, 0.77-1.10) for Alzheimer's disease. For illustration, we performed an analysis that failed to emulate a target trial by assigning exposure categories using post-baseline information, obtaining implausible beneficial estimates. Our findings indicate a modest benefit of longer duration of treatment with AC AHT on vascular dementia and highlight the value of the target trial emulation to avoid selection bias in the evaluation of the effect of different durations of treatment.

Clinical application of whole genome sequencing in young onset dementia: challenges and opportunities.

INTRODUCTION: Young onset dementia (YOD) by its nature is difficult to diagnose. Despite involvement of multidisciplinary neurogenetics services, patients with YOD and their families face significant diagnostic delays. Genetic testing for people with YOD currently involves a staggered, iterative approach. There is currently no optimal single genetic investigation that simultaneously identifies the different genetic variants resulting in YOD. AREAS COVERED: This review discusses the advances in clinical genomic testing for people with YOD. Whole genome sequencing (WGS) can be employed as a 'one stop shop' genomic test for YOD. In addition to single nucleotide variants, WGS can reliably detect structural variants, short tandem repeat expansions, mitochondrial genetic variants as well as capture single nucleotide polymorphisms for the calculation of polygenic risk scores. EXPERT OPINION: WGS, when used as the initial genetic test, can enhance the likelihood of a precision diagnosis and curtail the time taken to reach this. Finding a clinical diagnosis using WGS can reduce invasive and expensive investigations and could be cost effective. These advances need to be balanced against the limitations of the technology and the genetic counseling needs for these vulnerable patients and their families.

Risk of Dementia in Different Types of Cancer Survivors: A Nationwide Cohort Study.

OBJECTIVES: The association between specific types of malignancies and the subsequent risk of dementia remains unknown. DESIGN: A retrospective population-based cohort study based on data from Taiwan National Health Insurance Research Database. SETTING AND PARTICIPANTS: We recruited 32,250 patients who survived malignancies and 322,500 controls between 1998 and 2011 and followed them up until the end of 2013. MEASUREMENTS: Diagnoses of dementia (including Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia) was made during the follow-up period. Cox regression analyses were performed after adjusting for potential confounders. A sensitivity analysis was conducted to exclude patients with prodromal dementia. RESULTS: Cancer survivors were more likely to develop AD (hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.38-2.06), unspecified dementia (HR: 1.19, 95% CI: 1.07-1.32), and any dementia (HR: 1.26, 95% CI: 1.16-1.37) compared with controls after adjusting for potential confounders. Importantly, cancers of the digestive and genitourinary organs seem to be associated with AD, unspecified dementia, and any dementia, whereas only malignant neoplasms of the brain are more likely to develop into VaD. Sensitivity analyses after exclusion of the first three or five years of observation and after exclusion of case enrollment before 2009 or 2007 showed consistent findings. CONCLUSION: Cancer survivors are at higher risk of subsequent dementia. Different types of cancer survivors may contribute to variable risks of specific dementias. Further studies are necessary to investigate the underlying mechanisms in cancer survivors and patients with dementia.

Exploring the causal role of immune cells in vascular dementia: A bidirectional mendelian randomization study.

BACKGROUND: The aim of this study was to explore the causal association between immune cells and VaD based on a two-sample bidirectional Mendelian randomization study. METHODS: Bidirectional two-sample MR analyses based on pooled datasets from publicly available genome-wide association studies were performed using inverse variance weighted (IVW), weighted median (WE), and MR-Egger regressions to evaluate the causal relationships between immune cells and vascular dementia. Heterogeneity was assessed using Cochran's Q statistic. The reliability of the MR analysis results was verified by using the MR-PRESSO method for outlier detection, the MR-Egger method for horizontal multivariate analysis, and the leave-one-out method for sensitivity analysis. RESULTS: Specifically, 27 immunophenotypes were associated with VaD pathogenesis, including Sw mem %lymphocyte (P = 0.043), CD38 on CD20- (P = 0.039), CD11c+ monocyte AC (P = 0.024), DC AC (P = 0.002), CCR2 on CD62L+ myeloid DC (P = 0.039), Resting Treg %CD4 (P = 0.042), Activated & resting Treg %CD4+ (P = 0.038), CD28+ CD45RA- CD8br %CD8br (P = 0.047), NK %CD3- lymphocyte (P = 0.042), CD45 on B cell (P = 0.029), FSC-A on NKT (P = 0.033), CD45 on CD33br HLA DR+ CD14- (P = 0.039) were significantly correlated with increased VaD risk. Additionally, four immune phenotypes, namely, CD19 on CD20-, Resting Treg %CD4, Activated & resting Treg %CD4+, and CD11c+ monocyte AC, showed bidirectional effects on VaD. CONCLUSIONS: MR analysis revealed potential causal relationships between certain immune cells and VaD. Our preliminary exploration through immune cell infiltration analysis highlights the significant value of immune cells in VaD. Therefore, this study may provide a new perspective for the prevention and treatment of VaD.

Machine and deep learning algorithms for classifying different types of dementia: A literature review.

The cognitive impairment known as dementia affects millions of individuals throughout the globe. The use of machine learning (ML) and deep learning (DL) algorithms has shown great promise as a means of early identification and treatment of dementia. Dementias such as Alzheimer's Dementia, frontotemporal dementia, Lewy body dementia, and vascular dementia are all discussed in this article, along with a literature review on using ML algorithms in their diagnosis. Different ML algorithms, such as support vector machines, artificial neural networks, decision trees, and random forests, are compared and contrasted, along with their benefits and drawbacks. As discussed in this article, accurate ML models may be achieved by carefully considering feature selection and data preparation. We also discuss how ML algorithms can predict disease progression and patient responses to therapy. However, overreliance on ML and DL technologies should be avoided without further proof. It's important to note that these technologies are meant to assist in diagnosis but should not be used as the sole criteria for a final diagnosis. The research implies that ML algorithms may help increase the precision with which dementia is diagnosed, especially in its early stages. The efficacy of ML and DL algorithms in clinical contexts must be verified, and ethical issues around the use of personal data must be addressed, but this requires more study.

Does Vascular Dementia Exist? Report of Two Cases Previously Diagnosed with Vascular Dementia Treated by Means of Ventriculoatrial Shunts.

Vascular dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. While new therapeutic modalities have been available for Alzheimer's disease, there is currently no effective treatment for VaD. We encountered two cases with VaD who recovered their cognitive function to normal levels after ventriculoatrial shunt (VA shunt). Both cases complained cognitive impairment shortly after cerebral infarctions. Their brain images showed ventricular dilatation without the findings of disproportionately enlarged subarachnoid space hydrocephalus, which is regarded as characteristic for idiopathic normal pressure hydrocephalus (iNPH). Both cases were initially diagnosed as VaD by board neurosurgeons. However, since they showed positive response to lumbar tap test, VA shunts were performed. Both cases recovered their cognitive function to normal level. Their excellent cognitive outcomes after VA shunts indicate that many iNPH patients with lacunar infarcts may possibly be misdiagnosed as VaD.

Genetic evidence for causal association between migraine and dementia: a mendelian randomization study.

BACKGROUND: There is an association between migraine and dementia, however, their causal relationship remains unclear. This study employed bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal relationship between migraine and dementia and its subtypes: Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). METHODS: Summary-level statistics data were obtained from publicly available genome-wide association studies (GWAS) for both migraine and five types of dementia. Single nucleotide polymorphisms (SNPs) associated with migraine and each dementia subtype were selected. MR analysis was conducted using inverse variance weighting (IVW) and weighted median (WM) methods. Sensitivity analyses included Cochran's Q test, MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, the intercept of MR-Egger, and leave-one-out analysis. RESULTS: Migraine showed a significant causal relationship with AD and VaD, whereas no causal relationship was observed with all-cause dementia, FTD, or DLB. Migraine may be a potential risk factor for AD (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 0.02-0.14; P = 0.007), while VaD may be a potential risk factor for migraine (OR: 1.04; 95% CI: 0.02-0.06; P = 7.760E-5). Sensitivity analyses demonstrated the robustness of our findings. CONCLUSION: Our study suggest that migraine may have potential causal relationships with AD and VaD. Migraine may be a risk factor for AD, and VaD may be a risk factor for migraine. Our study contributes to unraveling the comprehensive genetic associations between migraine and various types of dementia, and our findings will enhance the academic understanding of the comorbidity between migraine and dementia.

Efficacy and safety of ginkgo biloba extract combined with donepezil hydrochloride in the treatment of Chinese patients with vascular dementia: A systematic review meta-analysis.

Objective: To conduct a meta-analysis of the effectiveness and safety of ginkgo biloba extract combined with donepezil hydrochloride vs. donepezil for the treatment of vascular dementia (VaD). Methods: Four English databases (PubMed, EMBASE, Web of Science, Cochrane Library) and four Chinese databases [the China National Knowledge Infrastructure Wanfang DATA, the Chongqing VIP Database (VIP), China Biomedical Database (CBM)] were manually searched for literature published from dates of the inception of the databases to September 2023. The randomized controlled trials (RCTs) of ginkgo biloba extract with donepezil hydrochloride vs. donepezil for the treatment of VaD were included. Relevant literature was screened, and the data in the included studies were extracted for quality assessment according to the Risk of bias tool. Results: A total of 1,309 participants were enrolled in the 15 RCTs. Of these, 656 participants were in the experimental group (ginkgo biloba extract combined with donepezil) and 653 participants were in the control group (donepezil).The results showed that combination therapy was superior to donepezil alone, and there were statistically significant differences in several outcomes including RR in change for total effective rate (1.28, 95% confidence intervals 1.20, 1.38, p < 0.001), MD in change for Mini-Mental State Examination score (2.98, 95%CI 2.31, 3.65, p < 0.001), Barthel Index score (8.55,95%CI 1.11, 15.99, p = 0.024), Activity of Daily Living Scale (ADL)score (10.11,95% CI 7.16,13.07,p < 0.001). Conclusion: Ginkgo biloba extract combined with donepezil dramatically improved the total effective rate, MMSE, BI and ADL scores, and decreased homocysteine (HCY), plasma viscosity (PV), whole blood viscosity at high cut (BVH) and whole blood viscosity at low cut (BVL) in VaD patients, while the effect on mean flow velocity and pulse index (PI) of middle cerebral artery (MCA) is not obvious. However, more relevant high-quality RCTs are needed to validate these results. Systematic Review Registration: Identifier CRD42023474678.

Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

Changes in Alzheimer's disease blood biomarkers in kidney failure before and after kidney transplant.

INTRODUCTION: Alzheimer's disease (AD) blood biomarkers show promise for clinical diagnosis but their reliability in chronic kidney disease (CKD) is debated. This study investigates the impact of kidney transplant (KT) on AD biomarkers in CKD. METHODS: We assessed AD biomarkers in 46 CKD patients pre-KT, at 12 weeks and 12 months post-KT, with baseline measures from 13 non-CKD controls. Using linear mixed models, we examined associations with participant groups, estimated glomerular filtration rate (eGFR) and cognition. RESULTS: CKD patients showed elevated levels of neurofilament light (117 ± 72 vs. 11 ± 5 pg/mL), phosphorylated tau 181 (75 ± 42 vs. 13 ± 8 pg/mL), glial fibrillary acidic protein (193 ± 127 vs. 94 ± 39 pg/mL), amyloid ß 42 (17 ± 5 vs. 5 ± 1 pg/mL), and amyloid ß 40 (259 ± 96 vs. 72 ± 17 pg/mL) compared to controls. Post-KT, biomarker levels approached normal with improved eGFR, paralleled by enhanced cognitive function. DISCUSSION: AD blood biomarker elevations in CKD are reversible with improved kidney function through KT. Highlights: AD biomarker levels are extremely high in severe CKD.AD biomarker levels are higher in patients with kidney failure on dialysis when compared to CKD patients not on dialysis.These elevations in AD biomarker levels in kidney failure are reversable and decrease dramatically after kidney transplantation.The change in biomarker levels after transplantation align with changes in kidney function.The change in biomarker levels after transplantation align with changes in cognitive function.

Repetitive transcranial magnetic stimulation impacts the executive function of patients with vascular cognitive impairment: a systematic review and meta-analysis.

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 meta-analysis 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, I 2 = 14%) and the total score on the executive specific scale (SMD = 0.69, 95% CI = 0.44-0.94, p < 0.00001, I 2 = 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, I 2 = 55%), the Stroop-C card (time) (SMD = -0.46, 95% CI = -0.86 to -0.06, p = 0.02, I 2 = 0%) and the Stroop-C card (correct number) (SMD = 0.49, 95% CI = 0.04-0.94, p = 0.03, I 2 = 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.Systematic review registration:https://www.crd.york.ac.uk/prospero/, CRD42023459669.