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Abstract This meta-analysis aims to determine the efficacy of Epigallocatechin gallate (EGCG) in the treatment of myocardial ischemia–reperfusion injury (MIRI) and summarize the mechanisms involved. Literature from six databases including Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wan-Fang database, and VIP database (VIP) were systematically searched. All the analysis were conducted by R. Twenty-five eligible studies involving 443 animals were included in this meta-analysis. The results indicated that compared to controls, EGCG exerts a cardioprotective effect by reducing myocardial infarct size (SMD = −4.06; 95% CI: −5.17, −2.94; P

Abstract Background Aging population has led to an increased proportion of older adults and cognitively impaired. We designed a brief and flexible two-stage cognitive screening scale, the Dual-Stage Cognitive Assessment (DuCA), for cognitive screening in primary care settings. Method In total, 1,772 community-dwelling participants were recruited, including those with normal cognition (NC, n = 1,008), mild cognitive impairment (MCI, n = 633), and Alzheimer’s disease (AD, n = 131), and administered a neuropsychological test battery and the DuCA. To improve performance, the DuCA combines visual and auditory memory tests for an enhanced memory function test. Results The correlation coefficient between DuCA-part 1 and DuCA-total was 0.84 (P

Abstract Background Connectome mapping may reveal new treatment targets for patients with neurological and psychiatric diseases. However, the long-term delayed recall based-network with structural and functional connectome is still largely unknown. Our objectives were to (1) identify the long-term delayed recall-based cortex-hippocampus network with structural and functional connectome and (2) investigate its relationships with various cognitive functions, age, and activities of daily living. Methods This case-control study enrolled 131 subjects (73 amnestic mild cognitive impairment [aMCI] patients and 58 age- and education-matched healthy controls [HCs]). All subjects completed a neuropsychological battery, activities of daily living assessment, and multimodal magnetic resonance imaging. Nodes of the cortical-hippocampal network related to long-term delayed recall were identified by probabilistic fiber tracking and functional connectivity (FC) analysis. Then, the main and interaction effects of the network on cognitive functions were assessed by a generalized linear model. Finally, the moderating effects of the network on the relationships between long-term delayed recall and clinical features were analyzed by multiple regression and Hayes’ bootstrap method. All the effects of cortex-hippocampus network were analyzed at the connectivity and network levels. Results The result of a generalized linear model showed that the bilateral hippocampus, left dorsolateral superior frontal gyrus, right supplementary motor area, left lingual gyrus, left superior occipital gyrus, left superior parietal gyrus, left precuneus, and right temporal pole (superior temporal gyrus) are the left and right cortex-hippocampus network nodes related to long-term delayed recall (P < 0.05). Significant interaction effects were found between the Auditory Verbal Learning Test Part 5 (AVLT 5) scores and global properties of the left cortex-hippocampus network [hierarchy, clustering coefficient, characteristic path length, global efficiency, local efficiency, Sigma and synchronization (P < 0.05 Bonferroni corrected)]. Significant interaction effects were found between the general cognitive function/executive function/language and global properties of the left cortex-hippocampus network [Sigma and synchronization (P < 0.05 Bonferroni corrected)]. Conclusion This study introduces a novel symptom-based network and describes relationships among cognitive functions, brain function, and age. The cortex–hippocampus network constrained by the structural and functional connectome is closely related to long-term delayed recall.

Abstract Background Language deficits frequently occur during the prodromal stages of Alzheimer’s disease (AD). However, the characteristics of linguistic impairment and its underlying mechanism(s) remain to be explored for the early diagnosis of AD. Methods The percentage of silence duration (PSD) of 324 subjects was analyzed, including patients with AD, amnestic mild cognitive impairment (aMCI), and normal controls (NC) recruited from the China multi-center cohort, and the diagnostic efficiency was replicated from the Pitt center cohort. Furthermore, the specific language network involved in the fragmented speech was analyzed using task-based functional magnetic resonance. Results In the China cohort, PSD increased significantly in aMCI and AD patients. The area under the curve of the receiver operating characteristic curves is 0.74, 0.84, and 0.80 in the classification of NC/aMCI, NC/AD, and NC/aMCI+AD. In the Pitt center cohort, PSD was verified as a reliable diagnosis biomarker to differentiate mild AD patients from NC. Next, in response to fluency tasks, clusters in the bilateral inferior frontal gyrus, precentral gyrus, left inferior temporal gyrus, and inferior parietal lobule deactivated markedly in the aMCI/AD group (cluster-level P

Objective: This meta-analysis aimed to determine the efficacy of curcumin in preventing myocardial ischemia/reperfusion (I/R) injury in animal models.Methods: Studies published from inception to January 2023 were systematically searched in databases including PubMed, Web of Science, Embase, China’s National Knowledge Infrastructure (CNKI), Wan-Fang database, and VIP database (VIP). The SYRCLE’s RoB tool was used to determine methodological quality. Sensitivity analysis and subgroup analysis were performed when there was high heterogeneity. Publication bias was assessed using a funnel plot.Results: Thirty-seven studies involving 771 animals were included in this meta-analysis with methodology quality scores ranging from 4 to 7. The results indicated that curcumin treatment significantly improved myocardial infarction size standard mean difference (SMD) = −5.65; 95% confidence interval (CI): 6.94, −4.36; p < 0.01; I2 = 90%). The sensitivity analysis for infarct size showed that the results were stable and reliable. However, the funnel plot was asymmetric. The subgroup analysis included species, animal model, dose, administration, and duration. The results showed that the subgroup dose was statistically significant between subgroups. In addition, curcumin treatment improved cardiac function, myocardial injury enzymes, and oxidative stress levels in animal models of myocardial I/R injury. The funnel plot revealed that there is publication bias for creatine kinase and lactate dehydrogenase. Finally, we performed a meta-analysis of inflammatory cytokines and apoptosis index. The results showed that curcumin treatment downregulated serum inflammatory cytokine levels and myocardial apoptosis index.Conclusion: This meta-analysis suggests that curcumin has excellent potential for the treatment of myocardial I/R injury in animal models. However, this conclusion needs to be further discussed and verified in large animal models and human clinical trials.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42022383901.

ObjectiveThis meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in patients with glioma.MethodsPubMed, EMBASE, Web of Science, and the Cochrane library were searched from inception to January 2023 without language restriction. Primary outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The risk of bias was assessed by subgroup analysis, sensitivity analysis, and publication bias, including funnel plot, Egger’s test, and Begg’s test.ResultsA total of 20 studies involving 2,321 patients were included in this meta-analysis. In the analysis of the included phase III clinical trials, the forest plot showed that PD-1/PD-L1 inhibitors did not improve the OS (HR=1.15, 95% CI: 1.03-1.29, P=0.02, I2 = 14%) and PFS (HR=1.43, 95% CI: 1.03-1.99, P=0.03, I2 = 87%). In the single-arm analysis, the forest plot demonstrated that the 6-month OS was 71% (95% CI: 57%-83%, I2 = 92%), 1-year OS was 43% (95% CI: 33%-54%, I2 = 93%), and the 2-year OS was 27% (95% CI: 13%-44%, I2 = 97%). The pooled estimate of the median OS was 8.85 months (95% CI: 7.33-10.36, I2 = 91%). Furthermore, the result indicated that the 6-month PFS was 28% (95% CI: 18%-40%, I2 = 95%), 1-year PFS was 15% (95% CI: 8%-23%, I2 = 92%), and the 18-month PFS was 10% (95% CI: 3%-20%, I2 = 93%). The pooled estimate of the median PFS was 3.72 months (95% CI: 2.44-5.00, I2 = 99%). For ORR, the pooled estimate of ORR was 10% (95% CI: 2%-20%, I2 = 88%). We further analyzed the incidence of PD-1/PD-L1 inhibitor-related AEs, and the pooled incidence of AEs was 70% (95% CI: 58%-81%, I2 = 94%). The incidence of AEs ≥ grade 3 was 19% (95% CI: 11%-30%, I2 = 94%). The funnel plot for the median PFS and median OS was symmetric with no significant differences in Egger’s test and Begg’s test. The sensitivity analysis revealed that our results were stable and reliable.ConclusionThe results of this meta-analysis suggest that anti-PD-1/PD-L1 therapy is relatively safe but could not prolong survival in glioma. More randomized controlled trials are needed to confirm our results.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023396057.

Plasma amyloid-β (Aβ) was associated with brain Aβ deposition and Alzheimer’s disease (AD) development. However, changes of plasma Aβ over the course of cognitive decline in the Alzheimer’s continuum remained uncertain. We recruited 449 participants to this study, including normal controls (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, and non-AD dementia. All the participants underwent plasma Aβ42, Aβ40, and t-tau measurements with single-molecule array (Simoa) immunoassay and PET scan with 18F-florbetapir amyloid tracer. In the subgroup of Aβ-PET positive, plasma Aβ42 and Aβ42/Aβ40 ratio was significantly lower in AD than NC, SCD and MCI, yet SCD had significantly higher levels of plasma Aβ42 than both NC and MCI. In the diagnostic groups of MCI and dementia, participants with Aβ-PET positive had lower plasma Aβ42 and Aβ42/40 ratio than participants with Aβ-PET negative, and the increasing levels of plasma Aβ42 and Aβ42/40 ratio indicated lower risks of Aβ-PET positive. However, in the participants with SCD, plasma Aβ42 and Aβ40 were higher in the subgroup of Aβ-PET positive than Aβ-PET negative, and the increasing levels of plasma Aβ42 and Aβ40 indicated higher risks of Aβ-PET positive. No significant association was observed between plasma Aβ and Aβ-PET status in normal controls. These findings showed that, in the continuum of AD, plasma Aβ42 had a significantly increasing trend from NC to SCD before decreasing in MCI and AD. Furthermore, the predictive values of plasma Aβ for brain amyloid deposition were inconsistent over the course of cognitive decline.

Abstract Background Subtle cognitive decline (SCD) may represent a very early stage of objective cognitive impairment before mild cognitive impairment (MCI), with less neuronal damage and more functional reservation. Detecting individuals with SCD is imperative for dementia prevention and treatment. In this study, we aimed to compare the validations of three cognitive screening tests, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment-Chinese Version (MoCA-CV), and Memory and Executive Screening (MES), in identifying subtle cognitive decline. Methods A total of 407 individuals were recruited, including 147 cognitively normal controls (NC), 102 individuals with subtle cognitive decline (SCD) and 158 individuals with mild cognitive impairment (MCI) according to the operational neuropsychological criteria proposed by Jak and Bondi’s. All participants underwent standardized comprehensive neuropsychological tests and the three cognitive screening tests. Chi-square analysis was used to compare the cognitive performance among the groups of NC, SCD and MCI. Receiver operating characteristic (ROC) curves were used to evaluate the abilities of MMSE, MoCA-CV and MES in discriminating NC, SCD and MCI. Results Compared with NC, SCD showed a significant decline only in the tests of memory, such as Auditory Verbal Learning Test (AVLT), Rey-Osterrieth Complex Figure Test (CFT) and Prospective Memory Test (PrM) (P

Abstract Background For detecting mild cognitive impairment (MCI), brief cognitive screening tools are increasingly required for the advantage of time saving and no need for special equipment or trained raters. We aimed to develop a modified Chinese version of Mini‐Addenbrooke's Cognitive Examination (C‐MACE) and further evaluate its validation in detecting MCI. Methods A total of 716 individuals aged from 50 to 90 years old were recruited, including 431 cognitively normal controls (NC) and 285 individuals with MCI. The effect size of Cramer's V was used to explore which items in the Chinese version of Addenbrooke's Cognitive Examination‐III (ACE‐III‐CV) best associated with MCI and to form the C‐MACE. Receiver operating characteristic (ROC) analyses were carried out to explore the ability of C‐MACE, ACE‐III‐CV, Chinese version of Montreal Cognitive Assessment‐Basic (MoCA‐BC), and Mini‐Mental State Examination (MMSE) in discriminating MCI from NC. Results Five items with greatest effect sizes of Cramer's V were selected from ACE‐III‐CV to form the C‐MACE: Memory Immediate Recall, Memory Delayed Recall, Memory Recognition, Verbal Fluency Animal and Language Naming. With a total score of 38, the C‐MACE had a satisfactory classification accuracy in detecting MCI (area under the ROC curve, AUC = 0.892), superior to MMSE (AUC = 0.782) and comparable to ACE‐III‐CV (AUC = 0.901) and MoCA‐BC (AUC = 0.916). In the subgroup of Age > 70 years, Education ≤ 12 years, the C‐MACE got a highest classification accuracy (AUC = 0.958) for detecting MCI. Conclusion In the Chinese‐speaking population, C‐MACE derived from ACE‐III‐CV may identify MCI with a good classification accuracy, especially in aged people with low education.

Abstract Background Cholinesterase inhibitors and memantine have been approved for management of Alzheimer’s disease (AD), but there has been no consensus about the choice of various types and doses of drugs at different stages. Hence, we compared and ranked the efficacy and tolerability of these available drugs. Methods We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) published from database inception to July 21, 2017. The primary outcomes were the mean overall changes in cognitive function and responders who had any adverse events. We conducted a random-effects network meta-analysis. Results Forty-one RCTs were included in this study. Compared with placebo, galantamine 32 mg daily (standardized mean difference – 0.51, 95% credible interval – 0.67 to − 0.35), galantamine 24 mg daily (− 0.50, − 0.61 to − 0.40), and donepezil 10 mg daily (− 0.40, − 0.51 to − 0.29) were probably the most effective agents on cognition for mild to moderate AD, and memantine 20 mg combined with donepezil 10 mg (0.76, 0.39 to 1.11) was recommended for moderate to severe patients. Memantine showed the best profile of acceptability. Rivastigmine transdermal 15-cm2 patch was the best optional treatment both in function and global changes. None of the medicines was likely to improve neuropsychiatric symptoms through this analysis. Conclusions Pharmacological interventions have beneficial effects on cognition, function, and global changes, but not on neuropsychiatric symptoms, through current network meta-analysis. The choice of drugs may mainly depend on the disease severity and clinical symptoms.

Abstract Background Cognitive impairment is one of the non-motor symptoms in Parkinson’s disease (PD). In the present study, we aim to examine the cognitive function of non-demented Parkinson’s disease patients and compare the results between male and female patients as well as control groups in search of any gender effect. Methods Sixty PD Patients (30 males and 30 females) from the Movement Disorders Clinic at Huashan Hospital Affiliated to Fudan University were recruited to participate in the study. One hundred age and gender matched control subjects without neurological or psychiatric disorders were voluntarily recruited. The participants were administered measures of cognition in five domains including memory, language, spatial processing abilities, attention and executive function. Results PD patients attained significantly lower scores in the visual spatial function, language and attention/executive function compared with the control group. Anti-parkinsonian treated patients performed worse in Rey-copy score, Clock Drawing Test (CDT) and Verbal Fluency-City than untreated ones. In regard to gender differences, though no general cognitive differences were found in Mini-mental State Examination (MMSE), men surpassed women on Boston naming test (BNT) while women were superior on Auditory Verbal Learning Test-long (AVLT) delayed cued recall test. Conclusions Cognitive impairments were common in PD patients even in the absence of dementia. PD patients with anti-parkinsonian medication had worse cognitive impairment than untreated patients. Genders may have different manifestations of cognitive impairment in PD patients.

Objective To identify the sensitivity and specificity of Animal-City Alternating Form Fluency Test (ACFT) differentiating mild cognitive impairment (MCI) and Alzheimer's disease (AD) from normal controls. Methods A total of 121 MCI patients, 104 AD patients and 104 healthy controls, who were matched in sex, age and education level, were enrolled in this study. They performed Animal Category Verbal Fluency Test (AFT), City Category Verbal Fluency Test (CFT) and ACFT. A series of standard neuropsychological tests were also administered to reflect episodic memory, verbal ability, working memory, executive function and processing speed. The validity and related influencing factors of ACFT was evaluated. Results Compared with control group, the ACFT correct number in MCI and AD groups reduced significantly (P = 0.000, 0.000). Receiver operating characteristic (ROC) curve revealed the sensitivity and specificity of ACFT in discriminating MCI (P = 0.012, 0.030) and AD (P = 0.004, 0.003) from normal controls were higher than those of AFT and CFT. There was no correlation of correct number in ACFT with age and education (P > 0.05, for all). The correlations of ACFT with Stroop Color-Word Test (SCWT), Digital Symbol Substitution Test (DSST), Shape Trail Test (STT) and Digit Span Test (DS), all of which reflected attention and executive function, were significantly closer than those of AFT and CFT (P < 0.05, for all). Conclusions ACFT is more efficient in early cognitive impairment identification than the other traditional category verbal fluency tests. It is a new variant form of category verbal fluency test that could assess cognitive function and could be broadly applied in clinical practice. DOI: 10.3969/j.issn.1672-6731.2015.07.010

Objective To assess the efficacy of shortened neuropsychological tests for discernment of mild cognitive impairment (MCI) by comparing 3 shortened tests [Animal Fluency Test (AFT), Color Trail Test (CTT) B and Bells Test (BT)], and to provide information for developing brief cognitive screening tool. Methods One hundred and twenty MCI patients and 180 cognitive normal controls (NC) were assessed by a set of standardized comprehensive neuropsychological evaluation including Mini⁃Mental State Examination (MMSE), Auditory Verbal Learning Test (AVLT), Logical Memory Test (LM), Rey⁃Osterrieth Complex Figure Test (ROCFT), Clock Drawing Test (CDT), AFT, Boston Naming Test (BNT), Cancellation Test (CT), Digit Span Test (DS), Stroop Color ⁃ Word Test (CWT), CTT A and B, Similarity Test, BT, Clinical Dementia Rating Scale (CDR), Activities of Daily Living Scale (ADL), Self ⁃ Rating Depression Scale (SDS) and Geriatric Depression Scale (GDS). Results 1) AFT: the greatest difference was seen between MCI (12.65 ± 2.83) and NC (14.93 ± 2.49) in 45 s fluency test version (t = 7.315, P = 0.000). 2) CTT: there was significant difference between MCI (9.28 ± 3.53) and NC (13.43 ± 4.12) in terms of 1 min CTT version (t = 9.356, P = 0.000), and in which the differential efficacy nearly approached the full length version. 3) BT: there were significant differences between MCI and NC groups in all 4 scores including accuracy score, time, post⁃ advising accuracy score and total time (t = 4.164, 3.427, 3.616, 5.102, respectively; P = 0.000, for all). The average time for recancellation was 100 s. However, discerning efficacy was not obviously improved after recancellation. Conclusion Appropriately shortened version of Animal Fluency Test, Color Trail Test and Bells Test prensents the same discerning efficacy for MCI as the original versions. It is feasible for MCI screening. DOI：10.3969/j.issn.1672-6731.2010.03.014

DOI：10.3969/j.issn.1672-6731.2010.03.008

DOI：10.3969/j.issn.1672-6731.2010.02.009

Objective To develop Chinese Card Sorting Test (CCST) as an efficient, brief test for evaluating executive function in Chinese elderly. Methods Thirty ⁃ five patients with mild Alzheimer's disease (AD), 69 cases with mild cognitive impairment (MCI) [amnesic MCI⁃single domain (aMCI⁃s), 25; amnesic MCI⁃multiple domain (aMCI⁃m), 24; non⁃amnesic MCI (naMCI), 20] and 124 cognitively normal controls (NC) were administered a battery of neuropsychological tests including CCST. Three sets (including figures, words and numbers) of cards were adopted. Each set had 6 cards. Subjects were asked to sort cards according to shape, number, color and meaning. Full mark was 4 for each set and 12 for total 3 sets. Results 1) Comparison among NC, MCI and AD: according to test score, in NC group, Set Ⅱ was most difficult while Set Ⅰ was the easiest. However, in MCI and AD group, patients' scores were similar among 3 sets, which indicated that the discriminative efficacy was same among 3 sets. Set Ⅰ and Ⅲ sorting started with "color" and followed with "meaning". Set Ⅱ sorting started with "meaning". The accuracy score for Set Ⅱ was the lowest which may due to the inhibition effect of "meaning" against other sorting strategy (similar as "the Stroop effect"). "Number" was the most difficult and least adopted sorting dimension. There were few misclassification which indicated that the test design produced few misunderstanding. When the total score of CCST ≤ 6, the sensitivity and specificity for differentiating AD was 94.32% and 74.24%, respectively. When the total score of CCST ≤ 5, the sensitivity and specificity for differentiating AD was 74.35% and 89.52%, respectively. For subjects with low education, optimal cut⁃ off score should be selected as ≤ 5. For subjects with high education, optimal cut⁃off score should be set as ≤ 6. 2) Comparison among 3 MCI subgroups: the score in naMCI subgroup was the lowest (4.25 ± 2.07), while in aMCI ⁃ s subgroup was the highest (6.68 ± 1.65). The score in aMCI ⁃ m was between the 2 above subgroups (5.16 ± 2.26). There were significant differences among the 3 subgroups (P < 0.01, for all). CCST can be used to differentiate amnesic and non⁃amnesic MCI. There were significant differences between aMCI ⁃ s and naMCI for all 3 sets of cards. Significant differences only existed for Set Ⅱ between aMCI⁃m and naMCI. There were significant differences among 3 subgroups in "color" dimension. There were no differences among 3 subgroups in "number" and "meaning" dimension. There were significant differences between aMCI and naMCI in "color" and "number" dimension. There were no differences between aMCI and naMCI in "shape" and "meaning" dimension. Conclusion Chinese Card Sorting Test is an effective, rapid and usable test for differentiating amnesic and non⁃amnesic MCI. DOI：10.3969/j.issn.1672-6731.2010.02.014

As an important multifunctional protein involved in regulation of mitochondrial metabolism, CHCHD2 was identified as a causative gene for Parkinson's disease (PD), yet the relationship between CHCHD2 and neurodegenerative dementia is not well understood. We directly sequenced the entire coding region of CHCHD2 gene in 150 AD patients, 84 FTD patients, and 417 controls. Four rare putative pathogenic variants of CHCHD2, including rs142444896 (c.5C>T, p.P2L), rs752705344 (c.15C>G, p.S5R), rs145190179 (c.94G>A, p.A32T), and rs182992574 (c.255T>A, p.S85R) were identified from a cohort composed of 150 AD and 84 FTD patients. These results suggest that CH CHD2 gene play an important role in other neurodegenerative disorders from our dementia study in China. [ABSTRACT FROM AUTHOR]

Background: The relationship between alterations in thyroid function and cognitive deficits has been investigated in several previous studies. Hypo-or hyperthyroidism and, to a lesser extent, subclinical thyroid dysfunction can negatively affect cognitive performance. However, limited data are available on the potential association of thyroid function with mild cognitive impairment (MCI) and Alzheimer's disease (AD) in the elderly Chinese population. Methods: In the present study focusing on a population of elderly Chinese individuals ≥ 50 years of age, 77 cognitively normal controls, 64 patients with MCI, and 154 patients diagnosed with AD underwent assessment of thyroid status using thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) levels as variables. Cognitive function was evaluated with the aid of comprehensive neuropsychological tests, such as the Mini-Mental State Examination (MMSE) and Memory and Executive Screening (MES). Results: Overall, 88.1 % of the subjects displayed normal thyroid function, 4.7 % were diagnosed with clinical hypothyroidism, 3.1 % with subclinical hypothyroidism, and 4.1 % with subclinical hyperthyroidism. After adjusting for covariates (age, sex, education years and body mass index), no association was evident between mild cognitive impairment or AD and thyroid dysfunction. However, lower serum TSH was correlated with risk of AD (odds ratio [OR]: 2.78, 95 % confidence interval [95% CI]: 1.11-6.99). Conclusion: Neither hypothyroidism nor subclinical hyperthyroidism was associated with AD and MCI in this population-based elderly Chinese cohort. Our findings need to be confirmed in a longitudinal study. [ABSTRACT FROM AUTHOR]

Objective: Apolipoprotein E gene (APOE) polymorphisms contributing to the risk of sporadic Alzheimer's disease (AD) have been identified for decades, but it has not been investigated in large AD samples of Chinese Han population. Methods: We performed a cross-sectional study to explore the effect of APOE polymorphisms on sporadic AD in 875 sporadic AD patients and 1,195 cognitive normal controls of Chinese Han. Genotyping of APOE was determined by multiplex amplification refractory mutation system polymerase chain reaction. Results: APOE ε3ε4 and ε4ε4 genotypes increased AD risk with dosage effect. The odds ratio (OR) of ε3ε4 was 1.89 and the OR of ε4ε4 was 15.64 compared with that of ε3ε3 in all the subjects. E2ε3 genotype decreased AD risk in all the subjects (OR=0.64), female subgroup (OR=0.57), and late-onset AD subgroup (OR=0.60). However, neither ε2ε2 nor ε2ε4 affected AD risk. About the age at onset (AAO), the influence of APOE ε4 was only exhibited in late-onset AD subgroup, with 1 year lower in ε4-positive ones than negative ones. Further analysis did not show the dosage effect of ε4 pertinent to AAO, though the AAO of ε4ε4 patients decreased by 2 years. E2 did not affect the AAO of AD. Conclusion: APOE ε4 is a strong risk factor of AD risk in Chinese Han population, and APOE ε4ε4 genotype might be related to the AAO of late-onset AD. [ABSTRACT FROM AUTHOR]

Recent studies highlight a potential role of cholesterol metabolic disturbance in the pathophysiology of Alzheimer disease (AD). The adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1) gene resides within proximity of linkage peaks on chromosome 9q influence AD and plays a key role in cellular cholesterol efflux in the brain. Methods: We studied the role of R219K and V825I polymorphisms of ABCA1 in modulating the risk of AD in 321 AD patients and 349 comparisons of Chinese Han. Genotyping of R219K and V825I were performed by PCR-restriction fragment length polymorphism analysis. Results: The genotype distribution of R219K was different with more RK in total AD group (X² = 8. 705, df = 2, p = 0.013), late-onset AD (LOAD) group (X² = 10.636, df = 2, p = 0.005), APOE non-c4c4 group (X² = 9.900, df = 2, p = 0.007), and female AD group (X² = 8.369, df = 2, p = 0.015). Logistic regression manifested the risk of AD increased in RK carriers in total AD group (Wald = 6.102, df = 1, p = 0.014, odds ratio [OR]." 1.546, 95% confidence interval [95% CI]." 1.094-2.185), LOAD group (Wald = 7. 746, df = 1, p = 0.005, OR." 1.921, 95% CL" 1.213-3.041), and APOE non-ε4ε4 group (Wald = 6.399, df = 1, p = 0.011, OR: 1.586, 95% CL" 1.109-2.266). K allele (RK + KK) also increased the risk of AD compared with RR allele in LOAD group (Wald = 4. 750, df = 1, p = 0.029, OR." 1.619, 95% CI." 1.050-2.497). However, no discrepancy was found in V825I. In R219K, age at onset (AAO) was significantly lower by 4.9years on average in patients of KK genotype than those of RK in APOE ε4 carrying group and higher by 5.5 years in patients of KK genotype than those of RR in APOE ε4 noncarrying group. In V825I, AAO was diseased by 4.3 years in H genotype compared with W genotype in APOE ε4 noncarrying group and 3.4 years in APOE ε4ε4 noncarrying group. Conclusion: The results indicated that the RK genotype or K allele (RK + KK) of R219K may relate to the development of AD in the east of China. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI), defined as a transitional zone between normal cognition and dementia, requires a battery of formal neuropsychological tests administered by a trained rater for its diagnosis. The objective of this study was to develop a screening tool for MCI. Methods: One hundred ninety seven cognitively normal controls (NC), one hundred sixteen patients with amnestic MCI -single domain (aMCI-sd), one hundred ninety five patients with amnestic MCI-multiple domain (aMCI-md), and two hundred twenty eight patients with mild Alzheimer's disease (AD) were evaluated by comprehensive neuropsychological tests and by the Memory and Executive Screening (MES). Results: Correlation analysis showed that the three indicators of the MES were significantly negatively related with age (P<0.05), yet not related with education (P>0.05). There was no ceiling or floor effect. Test completion averaged seven minutes (421.14±168.31 seconds). The receiver operating characteristics (ROC) analyses performed on the aMCI-sd group yielded 0.89 for the area under the curve (AUC) (95% CI, 0.85-0.92) for the MES-total score, with sensitivity of 0.795 and specificity of 0.828. There was 81% correct classification rate when the cut-off was set at less than 75. Meanwhile, the aMCI-md group yielded 0.95 for the AUC (95% CI, 0.93-0.97) for the MES-total score, with sensitivity of 0.87 and specificity of 0.91, and 90% correct classification rate when the cut-off was set at less than 72. Conclusion: The MES, minimally time-consuming, may be a valid and easily administered cognitive screening tool with high sensitivity and specificity for aMCI, with single or multiple domain impairment. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of senile dementia, and the overall prevalence increases exponentially with age. It is well known that genetic variants may play an important role in the pathogenesis of this disorder. Recently, two independent large-scale genome-wide association studies (GWAS) identified 3 novel single nucleotide polymorphisms (SNPs) (rs11136000 within CLU, rs3851179 within PICALM and rs6656401 within CR1) that are associated with late-onset AD (LOAD), and these results have been replicated by other studies performed in the Caucasian population. Recently, an independent study failed to verify the association for the SNP within CLU in a Han Chinese population, indicating that there may be genetic heterogeneity in this association. In the present study, we studied the SNPs within PICALM and CR1 in 474 sporadic AD patients (SAD) and 591 unrelated age- and sex-matched healthy controls of Han Chinese descent. Our data revealed that the frequencies of both of these SNPs were not significantly difference between the SAD and control groups. Thus, the association between SNPs within PICALM, CR1, and SAD should be studied further in different ethnic groups. [ABSTRACT FROM AUTHOR]