Association of Depression and Cognitive Performance in US Older Adults: A Secondary Analysis of Cross-Sectional Data Using NHANES 2013-2014.

INTRODUCTION: Depression has been associated with cognitive performance, but whether sociodemographic and clinical characteristics might influence this association is not well elaborated. This study aimed to further explore this relationship in older adults. METHODS: This cross-sectional study is based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. A total of 1,433 individuals with complete information on depressive symptoms and cognitive function variables were included in this study. Patient Health Questionnaire 9 (PHQ-9) score ≥10 as the cutoff to identify cases of depression in our study. We defined poor cognitive performance as a composite cognitive score <47. Logistic regression models were used to examine the association of depression with cognitive performance (model 1). We progressively adjusted the covariates as confounders (model 2: model 1 + age, and gender; model 3: model 2 + race, education level, family income, drinking, and smoking; model 4: model 3 + overweight, arthritis, hyperlipidemia, diabetes, hypertension, heart failure, coronary heart disease, heart attack, stroke, and cancer). We then conducted subgroup, interaction, and restricted cubic spline (RCS) analyses to examine this association. RESULTS: The prevalence of poor cognitive performance was 36.6% (53/145) in the depression group and 14.1% (182/1,288) in the non-depression group. In the fully adjusted model, depression was significantly associated with poor cognitive performance (adjusted odds ratio: 2.25; 95% confidence interval: 1.31-3.81). The results were robust to sensitivity analyses. Gender and education level may modify the association between depression and poor cognitive performance. RCS analysis revealed that the PHQ-9 score was related to poor cognitive performance in a nonlinear manner (p for nonlinearity <0.001), and exhibited a J-shaped curve. CONCLUSION: Depression is associated with poor cognitive performance in US older adults. Early recognition and treatment of depression may be potential intervention strategies to protect cognitive health.

An AS-qPCR-based method for the detection of Alzheimer's disease-related SNPs.

Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases in the world and has a strong genetic predisposition. At present, there is still no effective method for the early diagnosis and prevention of AD. Accumulating evidence shows the association of several loci with AD risk, such as apolipoprotein E (APOE) and translocase of outer mitochondrial membrane 40 (TOMM40). However, for routine disease diagnosis in clinics, genotype detection methods based on gene sequencing technology are time-consuming and excessively costly. Thus, in this study, we developed a high-sensitivity, low-cost, and convenient single nucleotide polymorphism (SNP) detection assay method based on allele-specific quantitative polymerase chain reaction (AS-qPCR) technology, which can be used to determine the SNP genotype in APOE and TOMM40. A total of 40 patients were recruited from the outpatient department of the memory clinic of Dongzhimen Hospital, Beijing University of Chinese Medicine. The SNP detection assay method includes three steps. First, positive plasmids with different genotypes (TT/CC/TC) in APOE rs429358, rs7412, and TOMM40 rs11556505 were prepared. Second, 3'-T/3'-C primers were designed to amplify these positive plasmids for each SNP site. Finally, we calculated the log10 of the copy number ratio for each positive plasmid, and the genotype interpretation interval was established. Based on this method, we investigated whether the SNPs in 40 patients could be accurately calculated using AS-qPCR technology. The accuracy of SNP detection was verified by PCR-Pooling sequencing. The results showed that SNP genotypes assessed by AS-qPCR technology corresponded perfectly to the results obtained by conventional DNA sequencing. We have developed a genotype detection method for AD based on AS-qPCR, which can be performed easily, rapidly, accurately, and at low cost. The method will contribute to the early diagnosis of patients with late-onset Alzheimer's and the detection of large clinical samples in the future.

Plasma repressor element 1-silencing transcription factor levels are decreased in patients with Alzheimer's disease.

BACKGROUND: Repressor element 1-silencing transcription (REST)/neuron-restrictive silencer factor is considered a new therapeutic target for neurodegenerative disorders such as Alzheimer's disease (AD). However, the relationship between AD and REST remains unclear. This study aimed to 1) examine plasma REST levels and REST gene levels in AD patients and 2) further explore the pathological relationships between REST protein levels and cognitive decline in clinical conditions, including medial temporal lobe atrophy. METHODS: Participants (n = 252, mean age 68.95 ± 8.78 years) were recruited in Beijing, China, and then divided into a normal cognition (NC) group (n = 89), an amnestic mild cognitive impairment (aMCI) group (n = 79), and an AD dementia group (n = 84) according to diagnostic criteria. All participants underwent neuropsychological assessments, laboratory tests, and neuroimaging scans (magnetic resonance imaging) at baseline. Plasma REST protein levels and the distribution of REST single nucleotide polymorphisms (SNPs) were compared among the three groups. Correlations between cognitive function, neuro-imaging results, and REST levels were determined by a multivariate linear regression analysis. RESULTS: The plasma REST levels in both the NC group (430.30 ± 303.43)pg/ml and aMCI group (414.27 ± 263.39)pg/ml were significantly higher than that in the AD dementia group (NC vs AD dementia group, p = 0.034; aMCI vs AD dementia group, p = 0.033). There was no significant difference between the NC and aMCI groups (p = 0.948). No significant difference was found among the three groups regarding the genotype distribution (rs2227902 and rs3976529 SNPs) of the REST gene. The REST level was correlated with the left medial temporal lobe atrophy index (r = 0.306, p = 0.023). After 6 months of follow-up, the REST level in the NC group was positively correlated with the change in the Mini-Mental State Examination score (r = 0.289, p = 0.02). CONCLUSION: The plasma REST protein level is decreased in AD dementia patients, which is associated with memory impairment and left temporal lobe atrophy and may have potential value for clinical diagnosis of AD dementia.

Tianzhi granule improves cognition and BPSD of vascular dementia: a randomized controlled trial.

BACKGROUND AND PURPOSE: Tianzhi granule (TZ) is usually used for patients with vascular dementia (VaD) in China. The aim was to assess the effect of TZ by a randomized clinical trial (RCT). METHODS: A 24-week RCT was conducted in 16 centres. Participants were grouped into TZ, donepezil or placebo. The co-primary outcomes were the Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog) and Clinician's Interview-based Impression of Change-plus caregiver information (CIBIC-plus). RESULTS: A total of 543 patients with mild to moderate VaD were enrolled, of whom 242 took TZ granules, 241 took donepezil, and 60 took placebo. The least-squares mean changes from baseline and 95% CI were 6.20 (5.31, 7.09) (TZ group), 6.53 (5.63, 7.42) (donepezil group) and 3.47 (1.76, 5.19) (placebo group), both TZ and donepezil showed small but significantly improvement compared with placebo group. The percent of improvement on the global impression which was measured by CIBIC-plus was 73.71% in TZ and 58.18% in placebo, there was significant different between TZ and placebo group (P = 0.004). No significant differences were observed between TZ and donepezil. No significant differences of adverse events were found. CONCLUSIONS: TZ and donepezil could bring symptomatic benefit for mild to moderate VaD. Trial registration The protocol had retrospectively registered at clinical trial.gov, Unique identifier: NCT02453932, date of registration: May 27, 2015; https://www.clinicaltrials.gov/ct2/show/NCT02453932?term=NCT02453932&rank=1.

Increased substantia nigra echogenicity correlated with visual hallucinations in Parkinson's disease: a Chinese population-based study.

As a noninvasive technique, transcranial sonography (TCS) of substantia nigra (SN) has gradually showed its effectiveness not only in diagnosis but also in understanding clinical features of Parkinson's Disease (PD). This study aimed to further evaluate TCS for clinical diagnosis of PD, and to explore the association between sonographic manifestations and visual hallucinations (VH). A total of 226 subjects including 141 PD patients and 85 controls were recruited. All participants received TCS. A series of rating scales to evaluate motor and non-motor symptoms were performed in PD patients. Results showed that 172 subjects were successfully assessed by TCS. The area of SN was greater in PD patients than that in controls (P < 0.001). As receiver-operating characteristic (ROC) curve analysis showed, the best cutoff value for the larger SN echogenicity size was 23.5 mm2 (sensitivity 70.3%, specificity 77.0%). Patients with VH had larger SN area (P = 0.019), as well as higher Non-Motor Symptoms Scale (NMSS) scores (P = 0.018). Moreover, binary logistic regression analysis indicated that SN hyperechogenicity (odds ratio = 4.227, P = 0.012) and NMSS scores (odds ratio = 0.027, P = 0.042) could be the independent predictors for VH. In conclusion, TCS can be used as an auxiliary diagnostic tool for Parkinson's disease. Increased SN echogenicity is correlated with VH in Parkinson's disease, possibly because the brain stem is involved in the mechanism in the onset of VH. Further studies are needed to confirm these findings.

A new age-related cutoff of medial temporal atrophy scale on MRI improving the diagnostic accuracy of neurodegeneration due to Alzheimer's disease in a Chinese population.

BACKGROUND: Visual rating scales are still the most popular tools in assessing atrophy degrees of whole brain and lobes. However, the false negative rate of the previous cutoff score of visual rating scales was relatively high for detecting dementia of Alzheimer's type (DAT). This study aimed to evaluate the diagnostic value of new cutoffs of visual rating scales on magnetic resonance imaging for discriminating DAT in a Chinese population. METHODS: Out of 585 enrolled subjects, 296 participants were included and diagnosed as normal cognition (NC)(n = 87), 138 diagnosed as amnestic mild cognitive impairment (aMCI), and 71 as dementia of Alzheimer's type (DAT). Receiver operating characteristic (ROC) curve analyses were used to calculate the diagnostic value of visual rating sales (including medial temporal atrophy (MTA), posterior atrophy rating scale (PA),global cortical atrophy scale (GCA) and medial temporal-lobe atrophy index (MTAi))for detecting NC from DAT . RESULTS: Scores of MTA correlated to age and Mini-mental state examination score. When used to detect DAT from NC, the MTA showed highest diagnostic value than other scales, and when the cutoff score of 1.5 of MTA scale, it obtained an optimal sensitivity (84.5%) and specificity (79.1%) respectively, with a 15.5% of false negative rate. Cutoff scores and diagnostic values were calculated stratified by age. For the age ranges 50-64, 65-74, 75-84 years, the following cut-offs of MTA should be used, ≥1.0(sensitivity and specificity were 92.3 and 68.4%), ≥1.5(sensitivity and specificity were 90.4 and 85.2%), ≥ 2.0(sensitivity and specificity were 70.8 and 82.3%) respectively. All of the scales showed relatively lower diagnostic values for discriminating aMCI from NC. CONCLUSIONS: The new age-based MTA cutoff showed better diagnostic accuracy for detecting DAT than previous standard, the list of practical cut-offs proposed here might be useful in clinical practice.

Adding Chinese herbal medicine to conventional therapy brings cognitive benefits to patients with Alzheimer's disease: a retrospective analysis.

BACKGROUND: Conventional therapy (CT) such as donepezil and memantine are well-known short-term treatments for the symptoms of Alzheimer's disease (AD). The efficacy of them, however, drops below baseline level after 9 months. In China, herbal therapy as a complementary therapy is very popular. Should conventional therapy combined with herbal therapy (CT + H) make add-on benefit? METHODS: In this retrospective cohort study, 344 outpatients diagnosed as probable dementia due to AD were collected, with the treatment of either CT + H or CT alone in clinical settings. All the patients were examined with coronary MRI scan. Cognitive functions were obtained by mini-mental state examination (MMSE) every 3 months with the longest follow-up of 24 months. RESULTS: Most of the patients were initially diagnosed with mild (MMSE = 21-26, n = 177) and moderate (MMSE = 10-20, n = 137) dementia. At 18 months, CT+ H patients scored on average 1.76 (P = 0.002) better than CT patients, and at 24 months, patients scored on average 2.52 (P < 0.001) better. At 24 months, the patients with improved cognitive function (△MMSE ≥ 0) in CT + H was more than CT alone (33.33% vs 7.69%, P = 0.020). Interestingly, patients with mild AD received the most robust benefit from CT + H therapy. The deterioration of the cognitive function was largely prevented at 24 months (ΔMMSE = -0.06), a significant improvement from CT alone (ΔMMSE = -2.66, P = 0.005). CONCLUSIONS: Compared to CT alone, CT + H significantly benefited AD patients. A symptomatic effect of CT + H was more pronounced with time. Cognitive decline was substantially decelerated in patients with moderate severity, while the cognitive function was largely stabilized in patients with mild severity over two years. These results imply that Chinese herbal medicines may provide an alternative and additive treatment for AD.

Herbal formula GAPT prevents beta amyloid deposition induced Ca(2+)/Calmodulin-dependent protein kinase II and Ca(2+)/Calmodulin-dependent protein phosphatase 2B imbalance in APPV717I mice.

BACKGROUND: Synaptic dysfunction is one of the pathological characteristics of Alzheimer's disease (AD), which is directly related to the progressive decline of cognitive function. CaMKII and CaN have been found to play important roles in memory processes and synaptic transmission. So present study aimed to elucidate relationships between CaMKII, CaN and cognitive decline in APPV717I mice, and to reveal whether the cognitive improving effects of GAPT is conducted through rebalance CaMKII and CaN. METHODS: Three-month-old-male APPV717I mice were randomly divided into ten groups (n = 12 per group) and received intragastrically administrated vehicle, donepezil or different doses of herbal formula GAPT for 8 or 4 months. Three-month-old male C57BL/6 J mice was set as vehicle control. RESULTS: Immunohistochemistry analysis showed that there were CaMKII expression decrease in the CA1 region of APPV717I transgenic mice, while the CaMKII expression of donepezil or GAPT treated transgenic mice were all increased. And there were CaN expression increase in the brain cortex of APPV717I transgenic mice, while there were decrease of CaN expression in donepezil or GAPT treated transgenic group. Western blot analysis showed the similar expression pattern without significant difference. CONCLUSION: GAPT extract have showed effectiveness in activating the expression of CaMKII and inhibiting the expression of CaN either before or after the formation of amyloid plaques in the brain of APPV717I transgenic mice, which may in certain way alleviated neuron synaptic dysfunction in AD.

[Treatment of vascular dementia by Chinese herbal medicine: a systematic review of randomized controlled trials of clinical studies].

OBJECTIVE: Chinese herbal medicine has been extensively used in the treatment of vascular dementia (VaD), but lacked systematic review on its efficacy and safety. So we conducted a systematic review to assess the efficacy and safety of Chinese herbal medicine in treating VaD. METHODS: CNKI, CBM, PubMed, and Wiley Online Library were retrieved for randomized trials (RCTs) on Chinese herbal medicine treating VaD patients. Randomized parallel control trials by taking Chinese herbal medicine as one treatment method and placebos/cholinesterase inhibitors/Memantine hydrochloride as the control were included. Quality rating and data extraction were performed. RevMan5.2.0 Software was used for meta-analysis. Standardized mean difference (SMD) at 95% confidence interval (CI) was used to indicate effect indicators of results. RESULTS: Seven RCTs met the inclusive criteria. Totally 677 VaD patients were randomly assigned to the treatment group and the control group. Descriptive analyses were performed in inclusive trials. The cognitive function was assessed in all trials. Results showed Mini-Mental state examination (MMSE) score was better in the Chinese herbal medicine group than in the placebo group, but with no significant difference when compared with the donepezil group (P > 0.05). Adverse reactions were mainly manifested as gastrointestinal symptoms such as abdominal pain in the Chinese herbal medicine group. But they occurred more in the donepezil group than in the Chinese herbal medicine group. CONCLUSIONS: The methodological quality of included trials was poor with less samples. Results of different trials were lack of consistency. Present evidence is not sufficient to prove or disapprove the role of Chinese herbal medicine in improving clinical symptoms and outcome indicators of VaD patients. Their clinical efficacy and safety need to be supported by more higher quality RCTs.

The Chinese version of story recall: a useful screening tool for mild cognitive impairment and Alzheimer's disease in the elderly.

BACKGROUND: Decline in verbal episodic memory is a core feature of amnestic mild cognitive impairment (aMCI). The delayed story recall (DSR) test from the Adult Memory and Information Processing Battery (AMIPB) discriminates MCI from normal aging and predicts its conversion to Alzheimer's dementia. However, there is no study that validates the Chinese version of the DSR and reports cut-off scores in the Chinese population. METHODS: A total of 631 subjects were screened in the memory clinics of Dongzhimen Hospital, Beijing University of Chinese Medicine, China. 249 were considered to have normal cognition (NC), 134 met diagnostic criteria for MCI according to the MCI Working Group of the European Consortium on Alzheimer's Disease, and 97 met criteria for probable Alzheimer's disease (AD) according to the NINCDS/ADRDA criteria, 14 exhibited vascular dementia (VaD), and 50 had a diagnosis of another type of dementia. Receiver operating characteristic (ROC) curve analyses were used to calculate the story recall cutoff score for detecting MCI and AD. Normative data in the NC group were obtained as a function of age and education. RESULTS: In this Chinese sample, the normative mean DSR score was 28.10 ± 8.54 in the 50-64 year-old group, 26.22 ± 8.38 in the 65-74 year-old group, and 24.42 ± 8.38 in the 75-85 year-old group. DSR performance was influenced by age and education. The DSR test had high sensitivity (0.899) and specificity (0.799) in the detection of MCI from NC using a cut-off score of 15.5. When the cutoff score was 10.5, the DSR test obtained optimal sensitivity (0.980) and specificity (0.938) in the discrimination of AD from NC. Cutoff scores and diagnostic values were calculated stratified by age and education. CONCLUSIONS: The Chinese version of the DSR can be used as a screening tool to detect MCI and AD with high sensitivity and specificity, and it could be used to identify people at high risk of cognitive impairment.

Gout or Hyperuricemia and Dementia Risk: A Meta-Analysis of Observational Studies.

Background: As a natural antioxidant, uric acid has neuroprotective effects. The association between uric acid levels and dementia risk was reported by previous studies. However, recently published studies showed that the relationship between uric acid and dementia risk might be heterogeneous in dementia subtypes. Objective: This study aimed to clarify the relationship between hyperuricemia (or gout) and dementia. Methods: The PubMed and Web of Science databases were systematically searched up to April 2024 to identify relevant studies. A meta-analysis was conducted using hazard ratios (HR) or odds ratios (OR) and 95% confidence interval (CI) as pooled indicators. Heterogeneity between the studies was examined using Cochran's Q statistic and I2 statistic. Subgroup analyses were conducted for gender and age. Stratification analysis, sensitivity analyses and meta-regression were conducted to explore possible explanations for heterogeneity. Publication bias was assessed by funnel plot and Egger's test. Results: A total of 11 studies met the inclusion criteria including 2,928,152 participants were abstracted. Hyperuricemia (or gout) did not reduce the overall risk of dementia (OR/HR = 0.92, 95% CI: 0.81-1.05) and vascular dementia (OR/HR = 0.74, 95% CI: 0.53-1.05), but may have a protective effect against Alzheimer's disease (OR/HR = 0.82, 95% CI: 0.70-0.96). Subgroup analysis showed that a lower risk of dementia was observed in men (OR/HR = 0.83, 95% CI: 0.77-0.90) and patients whose age under 65 (OR/HR = 0.83, 95% CI: 0.72-0.95). Conclusions: Patients with gout or hyperuricemia have a low risk of Alzheimer's disease.

Comparative efficacy of various exercise interventions on sleep in patients with cognitive impairment: a systematic review and meta-analysis.

Background: Sleep disturbances are an early indicator of cognitive impairment and exacerbate its progression. While pharmacological treatments for sleep disorders exist, their side-effect profile includes an increased risk of falls and the potential to exacerbate cognitive impairment. Non-pharmacological treatments such as physical exercise should be considered. However, uncertainties persist. We aimed to assess the potential benefits of exercise interventions on sleep in patients with cognitive impairment and determine the specific effects of various exercise modalities. Materials and methods: A systematic search was performed on seven databases for eligible studies published before Nov 2022. Randomized controlled trials of exercise for patients with cognitive impairment (mild cognitive impairment and Alzheimer's disease) were included. All analyses were conducted using RevMan version 5.4. Meta-analysis and The Grading of Recommendations Assessment Development and Evaluations (GRADE) quality ratings were performed on sleep quality and objective sleep data. Results: A total of 8 randomized controlled trials were included with a sample size of 486 subjects. For patients with cognitive impairment, physical exercise had a beneficial effect on sleep quality [MD = -3.55 (-5.57, -1.32), Z = 3.13, p = 0.002] and total sleep time [MD = 33.77 (23.92, 43.62), Z = 6.72, P < 0.00001]. No improvement was found in sleep efficiency and nocturnal awakening time. Subgroup analysis showed that multi-component exercise produced superior results. Conclusion: Physical exercise may improve sleep quality and total sleep time for patients with cognitive impairment. Multi-component exercise designed individually is more effective. Large-scale randomized controlled trials with objective sleep outcome measurements are warranted.Clinical trial registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022377221.

[Assessment of the results of syndrome in clinical trials of dementia treated by Chinese herbal medicine].

Chinese medical syndrome efficacy, as a second efficacy indicator, has been widely used in clinical trials of treating dementia by Chinese herbal medicine. The syndrome assessment tool is a key point in assessing the efficacy of Chinese medical syndrome. The syndrome assessment tool for dementia used nowadays needs to be optimized in content, reliability, and validity. In this paper, the authors reviewed some problems correlated with the design of Chinese medical assessment questionnaire on the basis of Chinese medical theories by combining the common requirements for questionnaire development.

Systematic review: clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis.

Background: The number of reported cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has gradually increased since its discovery in 2007, while there are no uniform treatment guidelines. Objective: To summarize the clinical characteristics of patients with anti-NMDAR encephalitis and to analyze the factors affecting the disease prognosis. Methods: A systematic analysis of medical records was conducted, and PubMed, Embase, and Cochrane Library were searched from January 1, 2011, to December 31, 2021. Data were extracted, analyzed, and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Results: This study included 472 case reports. Most patients had prodromal symptoms of about 2 weeks, including psychiatric symptoms (53.2%), flu-like symptoms (51.5%), and seizures (23.9%), among others. Poor prognoses were associated with patients who had autonomic instability (p = 0.010), central hypoventilation (p = 0.014), and ICU support (p = 0.002). Patients with a higher age of onset were more likely to develop central hypoventilation (OR 1.024, CI 1.006-1.042, p = 0.009), cognitive impairment (OR 1.023, CI 1.009-1.037, p = 0.001), and memory impairment (OR 1.034, CI 1.017-1.050, p < 0.001), whereas patients with a lower age were more likely to have seizures (OR 0.979, CI 0.965-0.993, p = 0.003). In this study, 97.0% of patients received immunotherapy, with the most commonly used treatment regimen being intravenous methylprednisolone (IVGC) and intravenous immunoglobulin (IVIG). When compared with other treatment regimens, the IVGC+IVIG regimen (p < 0.001) resulted in better prognoses. Conclusion: When encountering patients with fever, headache, and initial psychiatric symptoms of unknown etiology, clinicians should test their CSF for antibodies to distinguish autoimmune encephalitis. Patients with autonomic instability, central hypoventilation, and ICU support had poorer prognoses. Clinicians should be aware that older patients are more likely to develop central hypoventilation, cognitive impairment, and memory impairment, while younger patients are more likely to develop seizures. The IVGC+IVIG treatment regimen has better prognoses than others. This study includes case reports, which have obvious selection bias, and there are no unified standards to measure the severity of the disease. Therefore, in the future, larger samples and randomized controlled trials are needed to evaluate the efficacy of different treatment regimens.

Peripheral Blood and Cerebrospinal Fluid Levels of YKL-40 in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

The pathogenesis associated with Alzheimer's disease (AD) is particularly complicated, and early diagnosis and course monitoring of the disease are not ideal based on the available core biomarkers. As a biomarker closely related to neuroinflammation, YKL-40 provides a potential scalable approach in AD, but its association remains controversial and inconclusive with AD. We conducted this study to assess the utility of YKL-40 levels in peripheral blood and cerebrospinal fluid (CSF) of AD patients and healthy controls (HCs) by meta-analysis. We systematically searched and screened relevant trials for comparing YKL-40 levels between AD patients and HCs in PubMed, Embase, Cochrane, and Web of Science, with a search deadline of 14 March 2023 for each database. A total of 17 eligible and relevant studies involving 1811 subjects, including 949 AD patients and 862 HCs, were included. The results showed that YKL-40 levels in the peripheral blood of AD patients and HCs did not possess significant differences. Subgroup analysis showed YKL-40 significantly differed in plasma (SMD = 0.527, 95%CI: [0.302, 0.752]; p = 0.000), but did not in serum. In the case of comparison with HCs, YKL-40 was significantly higher in CSF of AD patients (SMD = 0.893, 95%CI: [0.665, 1.121]; p = 0.000). Besides that, when we performed a combined analysis of total YKL-40 in both peripheral blood and CSF, overall YKL-40 concentrations were also significantly increased among AD patients (SMD = 0.608, 95%CI: [0.272, 0.943]; p = 0.000). YKL-40 provides support and rationale for the neuroinflammatory pathogenesis of AD. The significance of CSF levels of YKL-40 for early screening of AD is definite. Plasma levels of YKL-40 also appear to assist in discriminating AD patients from HCs, which facilitates early screening and monitoring of the natural course of AD.

Polygala tenuifolia and Acorus tatarinowii in the treatment of Alzheimer's disease: a systematic review and meta-analysis.

Background: The complexity of Chinese medicine treatment for Alzheimer's disease (AD) utilizing a multi-herb therapy makes the evidence in current studies insufficient. Herb pairs are the most fundamental form of multi-herb formulae. Among the Chinese herbal formulas for AD treatment, Polygala tenuifolia (PT) and Acorus tatarinowii (AT) appeared as the most commonly used herbal pairs in combination. Objective: The aim of this study is to evaluate the clinical efficacy and safety of the combination of PT and AT in the treatment of AD. Methods: We systematically searched and screened randomized controlled trials of pairing PT and AT for the treatment of AD patients in eight databases with a search deadline of June 26, 2023. Authors, year of publication, title, and basic information such as subject characteristics (age, sex, and race), course of disease, control interventions, dose, and treatment duration were extracted from the screened studies. Primary outcomes assessed included mini-mental state examination (MMSE), activities of daily living (ADL), and AD assessment scale-cognitive subscale (ADAS-cog), while secondary outcomes included efficiency and adverse events. The quality of the included studies was assessed using the Cochrane risk of bias tool. The mean difference with 95% confidence intervals (MD [95% CI]) and risk ratio (RR) was selected as the effect size, and the data were analyzed and evaluated using RevMan 5.4 and Stata 16. Results: A total of sixteen eligible and relevant studies involving 1103 AD participants were included. The combination of PT and AT plus conventional drugs was superior to single conventional drugs in MMSE [MD = 2.57, 95%CI: (1.44, 3.69); p < 0.00001; I 2 = 86%], ADL [MD = -3.19, 95%CI: (-4.29, -2.09); p < 0.00001; I 2 = 0%], and ADAS-cog scores [MD = -2.09, 95%CI: (-3.07, -1.10); p < 0.0001; I 2 = 0%]. The combination of PT and AT plus conventional drugs had a significantly more favorable benefit in clinical effectiveness [RR = 1.27, 95%CI: (1.12, 1.44); p = 0.0002; I 2 = 0%]. Adverse events were not increased with the combination of PT and AT plus conventional drugs compared to conventional drugs [RR = 0.65, 95%CI: (0.35, 1.19); p = 0.16; I 2 = 0%]. The experimental group treated with the combination of PT and AT alone for AD was comparable in MMSE, ADL, and ADAS-cog scores compared with the control group treated with single conventional drugs. Conclusion: Compared to single conventional drugs, the combination of PT and AT may be used as an alternative therapy to improve global cognition and functioning in AD, and the combination of PT and AT as adjunctive therapy appears to produce a better therapeutic response to AD in terms of efficacy without increasing the risk of adverse events. However, the very low to low quality of available evidence limits confidence in the findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023444156.

Peripheral high levels of CRP predict progression from normal cognition to dementia: A systematic review and meta-analysis.

OBJECTIVE: Several cross-sectional studies have demonstrated a relationship between inflammation and dementia. Uncertainty exists over the ability of C-reactive protein (CRP), one of the most investigated markers of inflammation, to predict the progression of normal cognition to dementia. A systematic review and meta-analysis were performed to assess whether high peripheral levels of CRP are associated with cognitive impairment and whether CRP is a risk factor for predicting progression from normal cognition to cognitive decline or dementia. METHODS: Literature published before November 2022 was retrieved from PubMed, Embase, and Web of Science. Prospective cohort studies that employed recognized evaluation instruments to assess global cognitive function or used accepted diagnostic criteria to ascertain dementia were selected. Subgroup analysis was conducted on specific cognitive domains and causes of dementia (i.e., Alzheimer's disease and vascular dementia). Odds ratios (ORs) and hazard ratios (HRs) were extracted and merged to facilitate data analysis. A random-effects model was used for the meta-analysis and a descriptive analysis of the data that could not be merged was conducted. RESULTS: A total of 13 articles (14 cohort studies) were included for meta-analysis and six articles were included for descriptive analysis. The results showed that high CRP levels were not related to future cognitive decline (OR = 1.115; 95 % CI: 0.830-1.497; p = 0.469) but were associated with an increased risk of conversion to dementia. (HR = 1.473; 95 % CI: 1.037-2.090; p = 0.0394). This association persisted after full adjustment for potential covariates, with an OR of 1.044 (95 % CI:0.767-1.421, p = 0.785) for cognitive decline and an HR of 1.429 (95 % CI:1.088-1.876, p = 0.010) for dementia. The subgroup analysis showed that a higher level of CRP was related to a decline in visual-spatial ability (OR = 1.402, 95 % CI: 1.045-1.882, p = 0.024) and the risk of conversion to vascular dementia (total effect size of OR and HR = 2.769, 95 % CI: 1.586-4.83, p = 0.000). CONCLUSIONS: Higher CRP levels as an indicator of chronic systemic inflammation cannot predict future cognitive decline but may indicate a higher risk of conversion to dementia.

Plasma ß-amyloid, tau, neurodegeneration biomarkers and inflammatory factors of probable Alzheimer's disease dementia in Chinese individuals.

Background: Plasma-derived ß-amyloid, tau, and neurodegeneration (ATN) biomarkers can accurately diagnose Alzheimer's disease (AD) and predict its progression. Few studies have investigated the relationship between plasma biomarkers and changes in plasma inflammatory markers in clinically diagnosed AD. Methods: Seventy-four participants were recruited, including 30 mild-to-moderate AD dementia patients and 44 normal controls (NC). All participants underwent neuropsychological testing and blood sampling for biomarker testing. AD was clinically diagnosed according to the National Institute on Aging-Alzheimer's Association (NIA-AA) core criteria and required age-mismatched hippocampal atrophy. We performed Single Molecule Array (Simoa), an ultra-sensitive enzyme-linked immunosorbent assay (ELISA), to examine plasma ATN markers, including ß-amyloid (Aß) 40, Aß42, p-tau181, total (t)-tau, neurofilament protein light chain (NfL), and inflammatory factors (TNF-α, IL-1ß, IL-6, and IL-8). Results: The level of the plasma Aß42/Aß40 ratio was significantly declined and the levels of the plasma p-tau181, NfL and TNF-α were significantly higher in the AD group than the NC group, but there was no significant difference in the levels of plasma t-tau, IL-1ß, IL-6, and IL-8 between the AD and NC groups. The levels of plasma p-tau181, NfL, Aß42/Aß40 ratio, and TNF-α were all associated with impairments in multiple cognitive domains. Among them, the plasma Aß42/Aß40 ratio, and the p-tau181 and TNF-α levels were associated with impairments in global cognition, memory, and visuospatial abilities, but not with executive function, only plasma NfL level was associated with executive function. Plasma NfL showed higher diagnostic performance in AD than in NC individuals (AUC = 0.833). A combined diagnostic prediction model of plasma Aß42/Aß40 ratio, p-tau 181, and NfL had the highest value than each factor alone (AUC = 0.902),with a sensitivity and specificity of 0.867 and 0.886, respectively. Conclusion: The levels of plasma ATN biomarkers (Aß42/Aß40 ratio, p-tua181, and NfL) were significantly changed in clinically diagnosed AD patients and they all associated with different domains of cognitive impairment. Plasma ATN biomarkers better differentiate mild-to-moderate AD dementia from NC when they are incorporated into diagnostic models together rather than individually. Plasma ATN biomarkers have the potential to be a screening tool for AD. However, the expression of inflammatory factors in AD patients requires further research.

Effect of hearing aids on cognitive functions in middle-aged and older adults with hearing loss: A systematic review and meta-analysis.

Objective: The study aimed to examine the effects of hearing aids on cognitive function in middle-aged and older adults with hearing loss. Data sources and study selection: PubMed, Cochrane Library, and Embase were searched for studies published before 30 March 2022. Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) were included in the search. Restriction was set on neither types, severity, or the time of onset of hearing impairment nor cognitive or psychiatric statuses. Data extraction and synthesis: Two independent reviewers extracted data and assessed the study quality of RCTs. Cognitive function outcomes were descriptively summarized and converted to standardized mean difference (SMD) in the meta-analysis. Meta-analysis was conducted in RCTs. Sub-group analyses were conducted by cognitive statuses, psychiatric disorders, and cognitive domains. Results: A total of 15 studies met the inclusion criteria, including five RCTs (n = 339) and 10 NRSIs (n = 507). Groups were classified as subjects without dementia or with normal global cognition, subjects with AD or dementia, and subjects with depressive symptoms. For subjects without dementia, improvements were found in global cognition, executive function, and episodic memory. For subjects with depressive symptoms, improvements were found in immediate memory, global cognition, and executive function. No improvement was found in subjects with AD or dementia. In total, four RCTs were included in the meta-analysis. For subjects without dementia (SMD = 0.11, 95% confidence interval [CI]: -0.15-0.37) and those with AD, no significant effect was found (SMD = -0.19, 95% CI: -0.65-0.28). For subjects without dementia, no significant effect was found in language (SMD = 0.14, 95% CI: -0.30-0.59) or general executive function (SMD = -0.04, 95% CI: -0.46-0.38). Further sub-group analysis found no significant effect in executive function (SMD = -0.27, 95% CI: -0.72-0.18) or processing speed (SMD = -0.02, 95% CI: -0.49-0.44). Conclusion: Hearing aids might improve cognitive performance in domains such as executive function in subjects without dementia. The effects on subjects with depressive symptoms remained unclear. No improvement was found in subjects with AD or dementia. Long-term RCTs and well-matched comparison-group studies with large sample sizes are warranted. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022349057.