Causal Association between Circulating Metabolites and Dementia: A Mendelian Randomization Study.

The causal association of circulating metabolites with dementia remains uncertain. We assessed the causal association of circulating metabolites with dementia utilizing Mendelian randomization (MR) methods. We performed univariable MR analysis to evaluate the associations of 486 metabolites with dementia, Alzheimer's disease (AD), and vascular dementia (VaD) risk. For secondary validation, we replicated the analyses using an additional dataset with 123 metabolites. We observed 118 metabolites relevant to the risk of dementia, 59 of which were lipids, supporting the crucial role of lipids in dementia pathogenesis. After Bonferroni adjustment, we identified nine traits of HDL particles as potential causal mediators of dementia. Regarding dementia subtypes, protective effects were observed for epiandrosterone sulfate on AD (OR = 0.60, 95% CI: 0.48-0.75) and glycoproteins on VaD (OR = 0.89, 95% CI: 0.83-0.95). Bayesian model averaging MR (MR-BMA) analysis was further conducted to prioritize the predominant metabolites for dementia risk, which highlighted the mean diameter of HDL particles and the concentration of very large HDL particles as the predominant protective factors against dementia. Moreover, pathway analysis identified 17 significant and 2 shared metabolic pathways. These findings provide support for the identification of promising predictive biomarkers and therapeutic targets for dementia.

Causal association between blood leukocyte counts and vascular dementia: a two-sample bidirectional Mendelian randomization study.

While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis.

[Correlations between serum BDNF, IL-18 and hs-CRP levels in patients with acute cerebral infarction and vascular cognitive impairment].

OBJECTIVE: To explore the correlations between serum levels of brain-derived neurotrophic factor (BDNF), interleukin-18 (IL-18) and hypersensitivity C-reactive protein (hs-CRP) in patients with acute cerebral infarction and vascular cognitive impairment (VCI), and to provide some clinical bases for early prevention of VCI. METHODS: A total of 160 patients with acute cerebral infarction admitted in Department of Neurology of Jincheng People' s Hospital from May 2019 to April 2020 were enrolled in this study and were devided into three groups according to whether or not combined with cognitive impairment, including no cognitive impairment group (NCI, 57 cases), vascular cognitive impairment no dementia group (VCIND, 56 cases) and vascular dementia group (VaD, 47 cases). The cognitive function of all the patients were evaluated by Montreal cognitive assessment (MoCA). The National Institute of Health stroke scale (NIHSS) was used to assess the degree of neurological deficit (mild-, moderate-, severe-neurologic deficit group). The infarct size was calculated by Pullicino' s method (small-, middle-, large-infarct group). The levels of serum BDNF and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA), and serum levels of hs-CRP were measured by immunoturbidimetry during the acute phase (0-7 d), recovery period (15-30 d) and 6 months after cerebral infarction. The effects of varying degrees of neurological deficits and different size of infarction on BDNF, IL-18 and hs-CRP were observed. The levels of serum BDNF, IL-18 and hs-CRP in the patients of the three groups with acute, convalescent and six-month cerebral infarction were compared, and their correlations with VCI were analyzed. RESULTS: Serum BDNF level and MoCA scores in mild-neurologic deficit group and small-infarct group were significantly higher than those in moderate- and severe-deficit group, middle- and large-infarct group, respectively (P < 0.05). Their levels of IL-18 and hs-CRP were significantly lower than those in moderate- and severe-deficit group, middle- and large-infarct group, respectively (P < 0.05). The levels of serum BDNF in NCI group, VCIND group and VaD group during the acute phase, convalescence and 6 months after cerebral infarction were in a significant decline, and the differences during the acute phase and recovery period were statistically significant (P < 0.05). The levels of IL-18 and hs-CRP during the acute phase, recovery period and 6 months after cerebral infarction showed a significant increasing trend with significance (P < 0.05). Correlation analysis revealed that the levels of BDNF was positively correlated with MoCA scores but negatively correlated with the severity of cognitive impairment while the expression levels of IL-18 and hs-CRP were negatively correlated with MoCA scores but positively correlated with the severity of cognitive impairment. CONCLUSION: Serum BDNF, IL-18 and hs-CRP are involved in the pathological process of occurrence and development of VCI in the patients with acute cerebral infarction. BDNF has a protective effect on VCI while IL-18 and hs-CRP cause severe cognitive impairment. The levels of serum BDNF、IL-18 and hs-CRP in the patients with acute ischemic cerebral infarction are closely related to the severity of cognitive impairment and can be used as biomarkers of early diagnosis of VCI.

Red Cell Distribution Width and Dementia Among Rural-Dwelling Older Adults: The MIND-China Study.

BACKGROUND: Evidence has emerged that anemia is associated with dementia, but data on the relationships of red blood cell distribution width (RDW) with dementia and cognitive function in older adults are sparse. OBJECTIVE: We sought to investigate the associations of RDW with dementia and global cognitive performance among rural-dwelling Chinese older adults and further to examine their associations by anemia status. METHODS: This population-based cross-sectional study included 5,115 participants (age≥65 years, 57.0%women) in the baseline examination (March-September 2018) of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-CHINA). We collected data through face-to-face interviews, clinical examinations, and laboratory tests. Global cognitive function was evaluated using the Mini-Mental State Examination (MMSE). We defined dementia, Alzheimer's disease (AD), and vascular dementia (VaD) following the respective international criteria. Data were analyzed using multinomial logistic and general linear regression models. RESULTS: Of all participants, 300 were diagnosed with dementia, including 195 with AD and 95 VaD. The multiple-adjusted odds ratio of dementia associated with quartiles of RDW were 1.45 (95%CI: 0.87-2.44), 1.00 (reference), 1.77 (1.07-2.93), and 2.28 (1.40-3.72). Similar J-shaped patterns existed for the association of RDW with odds ratio of AD and VaD. Anemia was not significantly associated with dementia. The J-shaped associations of RDW with dementia and subtypes were statistically evident only among participants without anemia. There was an inverted J-shaped relationship between RDW quartiles and ß-coefficients of MMSE score. CONCLUSION: There is a J-shaped association between RDW level and likelihood of dementias among rural-dwelling Chinese older adults, especially among people without anemia.

Decreased Levels of Serum IL-34 Associated with Cognitive Impairment in Vascular Dementia.

OBJECTIVE: Interleukin- (IL-) 34 is a new type of cytokine with neuroprotective effects discovered in recent years. However, the relationship between IL-34 and vascular dementia (VaD) has not yet been elucidated. The purpose of this study is to determine whether IL-34 is involved in cognitive impairment of VaD. METHODS: From January 2017 to December 2020, 84 VaD patients and 60 healthy controls who attended Qingpu Branch of Zhongshan Hospital were prospectively included in the study. Once included in the study, demographic features of all research subjects are collected. They include age, gender, education, white blood cells (WBC), neutrophil, lymphocyte, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC). Meanwhile, the Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function of participants. The serum IL-34 level was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was no significant difference between the demographic features of VaD patients and healthy controls (p > 0.05). However, the serum IL-34 levels of VaD patients and healthy controls are 27.6 ± 3.9 pg/ml and 41.8 ± 6.0 pg/ml, respectively, and there is a significant statistical difference between them (p < 0.001). The results of bivariate correlation analysis showed that serum IL-34 levels were significantly positively correlated with MoCA scores (r = 0.371, p = 0.023). Further regression analysis showed that IL-34 was still correlated with MoCA after adjusting for demographic features (ß = 0.276, p = 0038). CONCLUSIONS: Serum IL-34 levels in VaD patients were significantly reduced, which may be an independent predictor of cognitive impairment in VaD patients.

Relationship of Homocysteine Plasma Levels with Mild Cognitive Impairment, Alzheimer's Disease, Vascular Dementia, Psychobehavioral, and Functional Complications.

BACKGROUND: Alzheimer's disease (AD) may be a vascular disorder with neurodegenerative consequences opening possibility of preventing AD by targeting vascular risk factors including homocysteine. OBJECTIVE: The study aims were to assess homocysteine distribution in different forms and severity of cognitive impairment (CogI) [mild cognitive impairment (MCI), probable AD (Prob-AD), possible AD (Poss-AD), and vascular dementia (VaD)] and in NoCogI, and to estimate possible association between hyperhomocysteinemia levels with functional deficit severity and psychobehavioral complications. METHODS: In total, 929 (M = 366, F = 563; mean age of 72.55±6.24 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. Homocysteine serum was set on two levels: between 0 and 10µmol/L and > 10µmol/L. For each patient, blood concentration of folate, vitamin B12, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), cholesterol, triglycerides, and glycemia were measured. RESULTS: CogI patients demonstrated significantly a higher frequency of homocysteine > 10 (p = 0.003), than NoCogI patients. Patients with moderate and severe dementia had a higher frequency of homocysteine > 10 (p < 0.0001), than MCI and mild dementia. Poss-AD and VaD had a higher frequency of homocysteine > 10 (p = 0.003), than Prob-AD patients. Homocysteine > 10 frequency is directly proportional to increased neuropsychiatric symptom severity (p < 0.0001), and functional impairment severity respectively for ADL (p < 0.0001) and IADL (p < 0.0001). CONCLUSION: Higher homocysteine level seems to be significantly related to cognitive impairment frequency and severity, possible AD and VaD, neuropsychiatric symptom severity, and functional impairment severity.

Diagnostic and prognostic blood biomarkers in vascular dementia: From the viewpoint of ischemic stroke.

Reliable quantitative blood biomarkers are important in vascular dementia (VaD) because early diagnosis and therapeutic intervention are effective in preventing progression of dementia. Although many blood biomarkers for acute ischemic stroke (AIS) or VaD have been reported, there are few reliable blood biomarkers. VaD and AIS have similar pathological conditions that are associated with small vessel disease (SVD) such as oxidative stress, inflammation, endothelial dysfunction, and neuronal injury. Therefore, it may be possible to find superior blood biomarkers of VaD among AIS blood biomarkers. Owing to recent developments, noncoding RNAs such as microRNA and long noncoding RNA, which can be analyzed using a single drop of blood, are also particularly reliable VaD markers because they stably reflect brain tissue damage. A multimarker combining several blood biomarkers or artificial intelligence technology may also be beneficial to compensate for insufficiencies of a single blood biomarker. This review describes the blood biomarkers of VaD and how they are related to blood biomarkers of AIS.

The Relationship between Serum Amyloid A Level and Cognitive Dysfunction in Patients with Vascular Dementia: Preliminary Findings.

OBJECTIVE: This study was aimed at investigating the relationship between serum amyloid A (SAA) levels and cognitive dysfunction in patients with vascular dementia (VAD). METHODS: Using cross-sectional research methods, 146 patients with VAD were selected as the VAD group and 70 normal people were selected as the NC group. Upon admission, the clinical and biochemical characteristics of the two groups of study subjects were collected, and the MMSE scale was used to assess cognitive function. A sandwich enzyme-linked immunosorbent assay was used to detect SAA levels. RESULTS: There was no significant difference in clinical data and biochemical characteristics in the VAD group (p > 0.05). Compared with the VAD group, the NC group has a higher level of education (p < 0.05). The SAA level of the VAD group was higher than that of the NC group, and there was a significant difference (p < 0.05). Spearman correlation analysis showed that SAA and MMSE in the VAD group were negatively correlated. Further multiple regression analysis showed that the serum amyloid A level is an independent risk factor for cognitive dysfunction in VAD patients. CONCLUSION: The level of SAA in VAD patients is significantly increased, which can be used as a potential peripheral blood marker to predict cognitive impairment in VAD patients.

Plasma and cerebrospinal fluid ABeta42 for the differential diagnosis of Alzheimer's disease dementia in participants diagnosed with any dementia subtype in a specialist care setting.

BACKGROUND: Dementia is a syndrome that comprises many differing pathologies, including Alzheimer's disease dementia (ADD), vascular dementia (VaD) and frontotemporal dementia (FTD). People may benefit from knowing the type of dementia they live with, as this could inform prognosis and may allow for tailored treatment. Beta-amyloid (1-42) (ABeta42) is a protein which decreases in both the plasma and cerebrospinal fluid (CSF) of people living with ADD, when compared to people with no dementia. However, it is not clear if changes in ABeta42 are specific to ADD or if they are also seen in other types of dementia. It is possible that ABeta42 could help differentiate ADD from other dementia subtypes. OBJECTIVES: To determine the accuracy of plasma and CSF ABeta42 for distinguishing ADD from other dementia subtypes in people who meet the criteria for a dementia syndrome. SEARCH METHODS: We searched MEDLINE, and nine other databases up to 18 February 2020. We checked reference lists of any relevant systematic reviews to identify additional studies. SELECTION CRITERIA: We considered cross-sectional studies that differentiated people with ADD from other dementia subtypes. Eligible studies required measurement of participant plasma or CSF ABeta42 levels and clinical assessment for dementia subtype. DATA COLLECTION AND ANALYSIS: Seven review authors working independently screened the titles and abstracts generated by the searches. We collected data on study characteristics and test accuracy. We used the second version of the 'Quality Assessment of Diagnostic Accuracy Studies' (QUADAS-2) tool to assess internal and external validity of results. We extracted data into 2 x 2 tables, cross-tabulating index test results (ABeta42) with the reference standard (diagnostic criteria for each dementia subtype). We performed meta-analyses using bivariate, random-effects models. We calculated pooled estimates of sensitivity, specificity, positive predictive values, positive and negative likelihood ratios, and corresponding 95% confidence intervals (CIs). In the primary analysis, we assessed accuracy of plasma or CSF ABeta42 for distinguishing ADD from other mixed dementia types (non-ADD). We then assessed accuracy of ABeta42 for differentiating ADD from specific dementia types: VaD, FTD, dementia with Lewy bodies (DLB), alcohol-related cognitive disorder (ARCD), Creutzfeldt-Jakob disease (CJD) and normal pressure hydrocephalus (NPH). To determine test-positive cases, we used the ABeta42 thresholds employed in the respective primary studies. We then performed sensitivity analyses restricted to those studies that used common thresholds for ABeta42. MAIN RESULTS: We identified 39 studies (5000 participants) that used CSF ABeta42 levels to differentiate ADD from other subtypes of dementia. No studies of plasma ABeta42 met the inclusion criteria. No studies were rated as low risk of bias across all QUADAS-2 domains. High risk of bias was found predominantly in the domains of patient selection (28 studies) and index test (25 studies). The pooled estimates for differentiating ADD from other dementia subtypes were as follows: ADD from non-ADD: sensitivity 79% (95% CI 0.73 to 0.85), specificity 60% (95% CI 0.52 to 0.67), 13 studies, 1704 participants, 880 participants with ADD; ADD from VaD: sensitivity 79% (95% CI 0.75 to 0.83), specificity 69% (95% CI 0.55 to 0.81), 11 studies, 1151 participants, 941 participants with ADD; ADD from FTD: sensitivity 85% (95% CI 0.79 to 0.89), specificity 72% (95% CI 0.55 to 0.84), 17 studies, 1948 participants, 1371 participants with ADD; ADD from DLB: sensitivity 76% (95% CI 0.69 to 0.82), specificity 67% (95% CI 0.52 to 0.79), nine studies, 1929 participants, 1521 participants with ADD. Across all dementia subtypes, sensitivity was greater than specificity, and the balance of sensitivity and specificity was dependent on the threshold used to define test positivity. AUTHORS' CONCLUSIONS: Our review indicates that measuring ABeta42 levels in CSF may help differentiate ADD from other dementia subtypes, but the test is imperfect and tends to misdiagnose those with non-ADD as having ADD. We would caution against the use of CSF ABeta42 alone for dementia classification. However, ABeta42 may have value as an adjunct to a full clinical assessment, to aid dementia diagnosis.

Utility of Plasma Neurofilament Light in the 1Florida Alzheimer's Disease Research Center (ADRC).

BACKGROUND: Plasma NfL (pNfL) levels are elevated in many neurological disorders. However, the utility of pNfL in a clinical setting has not been established. OBJECTIVE: In a cohort of diverse older participants, we examined: 1) the association of pNfL to age, sex, Hispanic ethnicity, diagnosis, and structural and amyloid imaging biomarkers; and 2) its association to baseline and longitudinal cognitive and functional performance. METHODS: 309 subjects were classified at baseline as cognitively normal (CN) or with cognitive impairment. Most subjects had structural MRI and amyloid PET scans. The most frequent etiological diagnosis was Alzheimer's disease (AD), but other neurological and neuropsychiatric disorders were also represented. We assessed the relationship of pNfL to cognitive and functional status, primary etiology, imaging biomarkers, and to cognitive and functional decline. RESULTS: pNfL increased with age, degree of hippocampal atrophy, and amyloid load, and was higher in females among CN subjects, but was not associated with Hispanic ethnicity. Compared to CN subjects, pNfL was elevated among those with AD or FTLD, but not those with neuropsychiatric or other disorders. Hippocampal atrophy, amyloid positivity and higher pNfL levels each added unique variance in predicting greater functional impairment on the CDR-SB at baseline. Higher baseline pNfL levels also predicted greater cognitive and functional decline after accounting for hippocampal atrophy and memory scores at baseline. CONCLUSION: pNfL may have a complementary and supportive role to brain imaging and cognitive testing in a memory disorder evaluation, although its diagnostic sensitivity and specificity as a stand-alone measure is modest. In the absence of expensive neuroimaging tests, pNfL could be used for differentiating neurodegenerative disease from neuropsychiatric disorders.

Increased Levels of Serum Neuregulin 1 Associated with Cognitive Impairment in Vascular Dementia.

OBJECTIVE: Neuregulin 1 (NRG 1) is a member of the epidermal growth factor (EGF) family and is believed to play an important role in neuroplasticity. However, the relationship between NRG 1 and vascular dementia (VaD) is poorly understood. The purpose of this study is to explore the correlation between neuregulin 1 and VaD. Patients and Methods. From October 2018 to September 2020, 93 VaD patients and 79 control populations who attended Liaocheng People's Hospital were included in the study. Baseline characteristics including age, gender, years of education, HDL, LDL, FBG, SBP, and DBP are collected. At the same time, peripheral blood was collected, and the concentration of serum NRG 1 was detected by enzyme-linked immunosorbent assay (ELISA). All research subjects received professional cognitive function assessment. RESULTS: A total of 93 VaD patients and 79 controls were enrolled. There was no significant difference in age, gender, years of education, HDL, LDL, FBG, SBP, and DBP between the two groups (p > 0.05). However, compared with the control group, VaD patients have lower MoCA and higher serum NRG 1 levels, and the difference is statistically significant (p < 0.001). The correlation analysis of MoCA and baseline characteristics showed that the MoCA score in VaD was significantly negatively correlated with serum NRG 1 (r = -0.374, p = 0.036). The results of multivariate regression showed that the MoCA score of VaD patients was only associated with NRG 1 (ß = 0.258, p = 0.012). CONCLUSIONS: The concentration of serum NRG 1 in VaD patients is significantly increased, which may be an independent risk factor for cognitive impairment in VaD patients.

Elevated Levels of Serum Neurofilament Light Chain Associated with Cognitive Impairment in Vascular Dementia.

OBJECTIVE: Vascular dementia (VaD) is a progressive neurodegenerative disease with cognitive decline caused by cerebrovascular factors. Despite the great progress made in the past decade, VaD still lacks effective treatments and peripheral blood biomarkers. In this study, we tested the level of peripheral blood neurofilament light chain (NfL) in VaD patients and explored its relationship with cognitive impairment. METHOD: A total of 176 study subjects including 80 normal controls (NC) and 96 VaD patients were included in our study. Upon admission, we collected clinical and biochemical characteristics of all research subjects. We also evaluate the Montreal cognitive assessment scale (MoCA) scores of all subjects. The serum NfL level was measured by the single-molecule array (Simoa) method. RESULTS: The years of education in the NC group and VaD group were (11.65 ± 3.04) years and (10.53 ± 3.87) years, respectively. Compared with VaD patients, the NC group has a higher level of education (p = 0.037). Furthermore, the results of Simoa indicated that VaD subjects had higher serum NfL levels compared with the NC group [(8.49 ± 2.37) pg/ml vs. (19.26 ± 4.71) pg/ml, p < 0.001]. In terms of other clinical and biochemical characteristics, there was no significant difference between VaD and NC. The Spearman correlation analysis indicated that educational years have a significant positive correlation with MoCA scores (r = 0.238, p = 0.041), while age and serum NfL levels have a significantly negative correlation with MoCA scores (age: r = -0.213, p = 0.040; NfL: r = -0.395, p = 0.027). However, further multiple regression analysis showed that only serum NfL level might serve as an independent risk factor for cognitive decline in VaD (ß = 0.317, p = 0.021). CONCLUSION: The serum NfL levels in VaD subjects are significantly elevated, which may be used as a potential peripheral blood marker for predicting cognitive impairment in patients with VaD.

Increased blood BACE1 activity as a potential common pathogenic factor of vascular dementia and late onset Alzheimer's disease.

Late onset Alzheimer disease (LOAD) is traditionally considered as a separate disease from vascular dementia (VAD). However, growing evidence suggests that ß-amyloid (Aß) accumulation, that initiates LOAD-related neurodegeneration, is preceded by vascular events. Previous in vitro studies showed that ß-secretase 1 (BACE1), the key-enzyme of amyloidogenesis, is upregulated by cerebrovascular insult; moreover, its activity is increased both in brain and serum of LOAD patients. We aimed to investigate whether BACE1 serum activity is altered also in dementias related, or not, to cerebrovascular disease. Thus, we evaluated serum BACE1 activity in a sample of individuals, including patients with LOAD (n. 175), VAD (n. 40), MIXED (LOAD/VAD) dementia (n. 123), other types of dementia (n. 56), and healthy Controls (n. 204). We found that BACE1 was significantly higher not only in LOAD (+ 30%), but also in VAD (+ 35%) and MIXED dementia (+ 22%) (p < 0.001 for all), but not in the other types of dementia (+ 10%). Diagnostic accuracy was 77% for LOAD, 83% for VAD, and 77% for MIXED dementia. In conclusion, we showed for the first time that the increase in peripheral BACE1 activity is a common feature of LOAD and VAD, thus underlying a further pathogenic link between these two forms of dementia.

The effect of scalp electroacupuncture combined with Memantine in patients with vascular dementia: A retrospective study.

Currently there is no effective treatment for vascular dementia (VaD). Pharmacological treatment often lead to severe complications and require drug dosage adjustment. This study investigated the effect of scalp electroacupuncture combined with Memantine in VaD. The safety and antioxidative effect of scalp electroacupuncture were also explored.A retrospective study was conducted and data of inpatients of Linyi Central Hospital with VaD between June 2017 and May 2018 were collected and sorted. The patients were divided into scalp electroacupuncture-medication (A), scalp electroacupuncture (B) and medication (control) (C) groups, in which Memantine was prescribed as medication. Cognitive function, activities of daily living and quality of life assessed by Montreal Cognitive Assessment (MoCA), Barthel index and dementia quality of life questionnaire; the contents of superoxide dismutase, lipid peroxide and nitric oxide in blood samples; and adverse reaction were compared.Data from a total of 150 patients were collected (Group A, n = 55; Group B, n = 50; Group C, n = 45). The post-treatment/follow-up Montreal Cognitive Assessment, Barthel index and dementia quality of life questionnaire scores were significantly improved in all groups compared to pre-treatment (groups A and B, P<.01; group C, P<.05). The improvements were significant for groups A vs C, B vs C (P<0.01, both), and group A vs B (P<.05). The post-treatment/follow-up levels of lipid peroxide and nitric oxide decreased significantly while superoxide dismutase increased significantly in groups A and B compared to pre-treatment (P<.01, both). The differences were significant for groups A vs C, and B vs C (P < .01, both), but not significant between groups A and B (P > .05). There were no significant adverse events occurred during the study and follow-up.In combined treatment, scalp electroacupuncture works in parallel with Memantine and significantly increase the therapeutic effect in VaD with no significant adverse events. Scalp electroacupuncture may have the potential to serve as an option or alternative treatment for VaD. Scalp electroacupuncture may alleviate VaD symptoms through its antioxidative mechanism.

Association of Serum FAM19A5 with Cognitive Impairment in Vascular Dementia.

OBJECTIVE: Family with sequence similarity 19 member A5 (FAM19A5), a novel chemokine-like peptide, is a secreted protein mainly expressed in the brain. FAM19A5 was recently found to be involved in a variety of neurological diseases; however, its correlation with vascular dementia (VaD) remains unclear. The aim of the study is to explore the association between serum FAM19A5 and cognitive impairment in subjects with VaD. METHOD: 136 VaD subjects and 81 normal controls were recruited in the study. Their demographic and clinical baseline data were collected on admission. All subjects received Mini-Mental State Examination (MMSE) evaluation, which was used to test their cognitive functions. A sandwich enzyme-linked immunosorbent assay (ELISA) was applied to detect the serum levels of FAM19A5. RESULTS: No significant differences were found between the two groups regarding the demographic and clinical baseline data (p > 0.05). The serum FAM19A5 levels were significantly higher compared to normal controls (p < 0.001). The Spearman correlation analysis indicated that serum FAM19A5 levels and MMSE scores have a significant negative correlation in VaD patients (r = -0.414, <0.001). Further multiple regression analysis indicated that serum FAM19A5 levels were independent risk predictors for cognitive functions in VaD (ß = 0.419, p = 0.031). CONCLUSION: The serum FAM19A5 level of VaD patients is significantly increased, which may serve as a biomarker to predict cognitive function of VaD.

Therapeutic and Diagnostic Potential of microRNAs in Vascular Cognitive Impairment.

Vascular cognitive impairment (VCI) is the second most common type of dementia that accounts for 15 to 30%. To date, VCI still lacks an effective therapeutic strategy and an objective diagnostic tool. MicroRNAs (miRNAs) are a class of small non-coding RNAs that control gene expression at the post-translational level, playing an essential role in the pathogenesis of VCI. Moreover, accumulating evidence has indicated that miRNAs could be used as therapeutic strategies and diagnostic biomarkers of diseases. In this review, we summarize various mechanisms of miRNA-based therapeutics and candidate miRNAs for clinical diagnosis in VCI. Results showed that miRNAs participate in VCI via different mechanisms, including neuronal death, inflammation, oxidative stress, blood-brain barrier permeability, and synaptic translation. Circulating miRNAs of VCI have been detected in serum, plasma, and cerebrospinal fluid with various diagnostic power. Taking together, miRNAs are a potential biomarker for being a therapeutic agent and a diagnostic tool of VCI.

Serum Uric Acid Concentration in Patients with Cerebrovascular Disease (Ischemic Stroke and Vascular Dementia).

INTRODUCTION: Significance of serum uric acid (UA) in cerebrovascular disease still remains controversial. UA is most abundant natural antioxidant in human plasma. Its antioxidant properties might protect against free radical damage, thereby reducing the risk of oxidative stress-related cognitive impairment and dementia. AIM: In our investigation, we determine the level of UA in 100 male patients diagnosed with the first ischemic brain stroke (blood samples were collected during the acute phase and post-acute phase), 100 male patients diagnosed with vascular dementia and 100 male healthy volunteers (control group). METHODS: UA was determined using DIMENSION LxR automatic analyzer. Measurement of UA concentration was based on an enzymatic method (range 208-428 µmol/L). RESULTS: The prevalence of hyperuricemia among ischemic stroke and vascular dementia patients was 30% and 8%, respectively. Serum UA concentration was higher 7 and 14 days after the stroke compared to the acute phase (24-48 hours after hospitalization) and these concentrations were significantly higher than those measured in the control group. UA levels measured at 24-48 hours after the first symptoms of ischemic stroke were strongly correlated with those measured after 7 days of treatment (r = 0.79, p = 0.001) or after 14 days (r = 0.839, p = 0.0049). No significant differences were found between ischemic stroke and vascular dementia groups. CONCLUSION: UA concentrations were higher in ischemic stroke and vascular dementia groups than in controls. UA increase may reflect vascular atherosclerosis and tissue hypoxia. UA monitoring in patients with cerebrovascular disease is essential, because UA is more harmful than protective.

Electrophysiological differences in cortical excitability in different forms of dementia: A transcranial magnetic stimulation and laboratory biomarkers study.

BACKGROUND: The aim of the present study was to identify neurophysiologic markers to differentiate between Alzheimer dementia (AD), Vascular dementia (VaD), and Parkinson's disease dementia (PDD), and to examine their relationship to levels of transforming growth factor ß1 (TGFß1). METHODS: The study included 15 patients with each type of dementia (AD, VaD, PDD) and 25 control subjects. Dementia patients were diagnosed according to the DiagnosticandStatisticalManualofMentalDisorders4thedition-revised(DSM-IV-R). Modified Mini Mental State Examination (MMMSE), motor cortex excitability including resting and active motor thresholds (rMT, aMT), input-output (I/O) curve, contralateral and ipsilateral silent periods (cSP, iSP), short-interval intracortical inhibition (SICI) at 1,2 and 4ms, and serum levels of TGFß1 were examined. RESULTS: There were no significant differences between groups with regards to age, sex, education or socioeconomic level. There was significant neuronal hyperexcitability in the form of reduced rMT and aMT and a shallower I/O curve in all three groups of dementia compared with the control group. The durations of cSP and iSP were longer in AD and PDD groups compared with the control group, whereas there were no significant differences in VaD. SICI was less effective in the three dementia groups than in the control group at intervals of 4ms. Serum levels of TGFß1 were significantly elevated in all dementia groups in comparison with the control group. There was a significant negative correlation between serum level of TGFß1 and cSP, iSP, and SICI across all patients and a significant negative correlation between serum level of TGFß1 and iSP duration in AD. CONCLUSION: Although motor thresholds were reduced in all patients, measures of SICI, cSP and iSP could distinguish between dementia groups. Serum level of TGFß1 negatively correlated with iSP specifically in the AD group. This suggests that levels of TGFß1 may relate to GABAergic dysfunction in dementia.