Dual-stage cognitive assessment: a two-stage screening for cognitive impairment in primary care.

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 < 0.001). The correlation coefficients of DuCA-part 1 with Addenbrooke's Cognitive Examination III (ACE-III) and Montreal Cognitive Assessment Basic (MoCA-B) were 0.66 (P < 0.001) and 0.85 (P < 0.001), respectively. The correlation coefficients of DuCA-total with ACE-III and MoCA-B were 0.78 (P < 0.001) and 0.83 (P < 0.001), respectively. DuCA-Part 1 showed a similar discrimination ability for MCI from NC (area under curve [AUC] = 0.87, 95%CI 0.848-0.883) as ACE III (AUC = 0.86, 95%CI 0.838-0.874) and MoCA-B (AUC = 0.85, 95%CI 0.830-0.868). DuCA-total had a higher AUC (0.93, 95%CI: 0.917-0.942). At different education levels, the AUC was 0.83-0.84 for DuCA-part 1, and 0.89-0.94 for DuCA-total. DuCA-part 1 and DuCA-total's ability to discriminate AD from MCI was 0.84 and 0.93, respectively. CONCLUSION: DuCA-Part 1 would aid rapid screening and supplemented with the second part for a complete assessment. DuCA is suited for large-scale cognitive screening in primary care, saving time and eliminating the need for extensively training assessors.

Speech silence character as a diagnostic biomarker of early cognitive decline and its functional mechanism: a multicenter cross-sectional cohort study.

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 < 0.05, family-wise error (FWE) corrected). In the patient group (AD+aMCI), higher activation level of the right pars triangularis was associated with higher PSD in in both semantic and phonemic tasks. CONCLUSIONS: PSD is a reliable diagnostic biomarker for the early stage of AD and aMCI. At as early as aMCI phase, the brain response to fluency tasks was inhibited markedly, partly explaining why PSD was elevated simultaneously.

Validation of the Chinese version of Addenbrooke's cognitive examination III for detecting mild cognitive impairment.

OBJECTIVES: To evaluate the reliability and validity of Chinese version of Addenbrooke's Cognitive Examination III (ACE-III-CV) in the identification of mild cognitive impairment (MCI), and further investigate the optimal cutoff scores according to different age and education level. METHOD: A total of 716 individuals aged from 50 to 90 years old were recruited through internet-based and print advertisements, including 431 cognitively normal controls (NC) and 285 individuals with MCI according to an actuarial neuropsychological method put forward by Jak and Bondi. Besides the cognitive screening tests of ACE-III-CV, Mini-Mental State Examination (MMSE) and Chinese version of Montreal Cognitive Assessment-Basic (MoCA-BC), all the participants underwent a battery of standardized neuropsychological tests. Validations of the ACE-III-CV, MMSE, and MoCA-BC for detecting MCI from NC were determined by Receiver operating characteristic (ROC) curves. RESULTS: ACE-III-CV had a good reliability (Cronbach's coefficient α = 0.807, intraclass correlation coefficients for interrater and test-retest reliability were 0.95 and 0.93). According to the area under ROC curve (AUC), ACE-III-CV and MoCA-BC showed better ability than MMSE in detecting MCI. No significant difference was found between ACE-III-CV and MoCA-BC. The optimal cutoff scores of ACE-III-CV for screening MCI were 72 for individuals with 1-9 years of education, 78 for individuals with 10-15 years of education, and 80 for individuals with more than 16 years of education. CONCLUSION: The Chinese version of ACE-III-CV is a reliable and valid screening tool for detecting MCI. The optimal cutoff scores are closely related with education level.

A comparative study on the validations of three cognitive screening tests in identifying subtle cognitive decline.

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 < 0.01). However, MCI showed significant decline in all cognitive performances (P < 0.01). The scores of MMSE, MoCA-CV and MES all showed a progressive downward trend within the groups of NC, SCD and MCI (P < 0.001). In ROC Analyses for discriminating individuals with SCD from NC, the most appropriate MES cutoff was 84, with a sensitivity of 74.3%, a specificity of 60.8% and 0.738 for AUC (95%CI, 0.675-0.801). By contrast, MMSE and MOCA-CV had poor sensitivity (67.4 and 70.8%, respectively) and specificity (51.0 and 52.9%, respectively), and smaller AUCs (0.643 and 0.644, respectively) than the MES. CONCLUSION: As a screening test, MES is more efficacious in identifying SCD from normal controls than MMSE and MoCA-CV.

Mortality of Alzheimer's Disease Patients: A 10-Year Follow-up Pilot Study in Shanghai.

BACKGROUND: Identifying risk factors and mortality of individuals with Alzheimer's disease (AD) could have important implications for the clinical management of AD. OBJECTIVE: This pilot study aimed to examine the overall mortality of AD patients over a 10-year surveillance period in Shanghai, China. This study is an extension of our previous investigation on mortality of neurodegenerative diseases. METHODS: One hundred and thirty-two AD patients recruited from the memory clinics of two hospitals in Shanghai in 2007 were followed up until December 31, 2017 or death, representing a follow-up period of up to 10 years. Overall standardized mortality ratios (SMRs) were calculated, and predictors for survival at recruitment were estimated. RESULTS: Sixty-seven patients had died by December 31, 2017, and the SMR at 10 years of follow-up was 1.225 (95% confidence interval 0.944-1.563). Employing Cox's proportional hazard modeling, lower Mini-Mental State Examination score, and comorbid diabetes predicted poor survival in this cohort. CONCLUSION: This pilot study suggests a similar survival trend of patients with AD compared to the general population in Shanghai urban region. Poor cognitive status and comorbid diabetes had a negative impact on the survival of AD patients.

Pilot testing the caregiver self-management intervention for caregivers of relatives with dementia.

This study was designed to examine the feasibility of a caregiving self-management support program developed for caregivers of relatives with dementia in Shanghai. A total of 41 caregivers were recruited for a quasi-experimental study. The experimental group of 26 participants attended six bi-weekly social support group sessions. The control group of 15 participants received three monthly telephone instructions. All of participants received an illustrated caregiver educational booklet and three educational presentations during a six-month follow-up period. The results demonstrated a stronger sense of self-efficacy regarding the gathering of information about dementia care in both study groups compared to the baseline data. Caregivers participating in the group sessions reported better health-related quality of life, improved responses to behavioral disturbances, and efficacy in the management of stress than those who received telephone instructions. This study provided some preliminary information regarding ways to improve self-management for the target population in mainland China.

An abbreviated version of Silhouettes test: a brief validated mild cognitive impairment screening tool.

OBJECTIVES: To revise an abbreviated version of the Silhouettes subtest of the Visual Object and Space Perception (VOSP) battery in order to recognize mild cognitive impairment (MCI) and determine the optimal cutoffs to differentiate among cognitively normal controls (NC), MCI, and Alzheimer's Disease (AD) in the Chinese elderly. DESIGN: A cross-sectional validation study. SETTING: Huashan Hospital, Shanghai, China. SUBJECTS: A total of 591 participants: Individuals with MCI (n = 211), AD (n = 139) and NC (n = 241) were recruited from the Memory Clinic, Huashan Hospital, Shanghai, China. METHODS: Baseline neuropsychological battery (including VOSP) scores were collected from firsthand data. An abbreviated version of silhouettes test (Silhouettes-A) was revised from the original English version more suitable for the elderly, including eight silhouettes of animals and seven silhouettes of inanimate objects, with a score ranging from 0 to 15. RESULTS: Silhouettes-A was an effective test to screen MCI in the Chinese elderly with good sensitivity and specificity, similar to the Montreal cognitive assessment and superior to other single tests reflecting language, spatial, or executive function. However, it had no advantage in distinguishing MCI from AD. The corresponding optimal cutoff scores of Silhouettes-A were 10 for screening MCI and 8 for AD. CONCLUSION: Silhouettes-A is a quick, simple, sensitive, and dependable cognitive test to distinguish among NC, MCI, and AD patients.

Caregivers' attitude toward disclosure of Alzheimer's disease diagnosis in Urban China.

BACKGROUND: Disclosing the diagnosis of Alzheimer's disease (AD) to a patient is controversial. There is significant stigma associated with a diagnosis of AD or dementia in China, but the attitude of the society toward disclosure of such a diagnosis had not been formally evaluated prior to our study. Therefore, we aimed to evaluate the attitude toward disclosing an AD diagnosis to patients in China with cognitive impairment from their caregivers, and the factors that may affect their attitude. METHODS: We designed a 17-item questionnaire and administered this questionnaire to caregivers, who accompanied patients with cognitive impairment or dementia in three major hospitals in Shanghai, China. The caregiver's attitude toward disclosing the diagnosis of AD as evaluated by the questionnaire was compared to that of disclosing the diagnosis of terminal cancer. RESULTS: A majority (95.7%) of the 175 interviewed participants (mean 14.2 years of education received) wished to know their own diagnosis if they were diagnosed with AD, and 97.6% preferred the doctor to tell their family members if they were diagnosed with AD. If a family member of the participants suffered from AD, 82.9% preferred to have the diagnosis disclosed to the patient. "Cognitive impairment" was the most accepted term by caregivers to disclose AD diagnosis in Chinese. CONCLUSION: This study suggests most of the well-educated individuals in a Chinese urban area favored disclosing the diagnosis when they or their family members were diagnosed with AD.

Is thyroid status associated with cognitive impairment in elderly patients in China?

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.

Cardioprotective effect of epigallocatechin gallate in myocardial ischemia/reperfusion injury and myocardial infarction: a meta-analysis in preclinical animal studies.

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 < 0.01; I2 = 77%). The funnel plot revealed publication bias. Moreover, EGCG significantly improves cardiac function, serum myocardial injury enzyme, and oxidative stress levels in MIRI animal models. This meta-analysis demonstrates that EGCG exhibits therapeutic promise in animal models of MIRI. However, further validation is still needed in large animal models and large clinical studies.

The efficacy and safety of anti-PD-1/PD-L1 in treatment of glioma: a single-arm meta-analysis.

Objective: This meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in patients with glioma. Methods: PubMed, 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. Results: A 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. Conclusion: The 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 registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023396057.

Cardioprotective effect of curcumin on myocardial ischemia/reperfusion injury: a meta-analysis of preclinical animal studies.

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.

Brain amyloid-ß deposition associated functional connectivity changes of ultra-large structural scale in mild cognitive impairment.

In preclinical Alzheimer's disease, neuro-functional changes due to amyloid-ß (Aß) deposition are not synchronized in different brain lobes and subcortical nuclei. This study aimed to explore the correlation between brain Aß burden, connectivity changes in an ultra-large structural scale, and cognitive function in mild cognitive impairment. Participants with mild cognitive impairment were recruited and underwent florbetapir (F18-AV45) PET, resting-state functional MRI, and multidomain neuropsychological tests. AV-45 standardized uptake value ratio (SUVR) and functional connectivity of all participants were calculated. Of the total 144 participants, 72 were put in the low Aß burden group and 72 in the high Aß burden group. In the low Aß burden group, all connectivities between lobes and nuclei had no correlation with SUVR. In the high Aß burden group, SUVR showed negative correlations with the Subcortical-Occipital connectivity (r=-0.36, P = 0.02) and Subcortical-Parietal connectivity (r=-0.26, P = 0.026). Meanwhile, in the high Aß burden group, SUVR showed positive correlations with the Temporal-Prefrontal connectivity (r = 0.27, P = 0.023), Temporal-Occipital connectivity (r = 0.24, P = 0.038), and Temporal-Parietal connectivity (r = 0.32, P = 0.006). Subcortical to Occipital and Parietal connectivities had positive correlations with general cognition, language, memory, and executive function. Temporal to Prefrontal, Occipital, and Parietal connectivities had negative correlations with memory function, executive function, and visuospatial function, and a positive correlation with language function. In conclusion, Individuals with mild cognitive impairment with high Aß burden have Aß-related bidirectional functional connectivity changes between lobes and subcortical nuclei that are associated with cognitive decline in multiple domains. These connectivity changes reflect neurological impairment and failed compensation.

Mapping the long-term delayed recall-based cortex-hippocampus network constrained by the structural and functional connectome: a case-control multimodal MRI study.

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.

The polymorphism of the ATP-binding cassette transporter 1 gene modulates Alzheimer disease risk in Chinese Han ethnic population.

BACKGROUND: 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 (χ(2) = 8.705, df = 2, p = 0.013), late-onset AD (LOAD) group (χ(2) = 10.636, df = 2, p = 0.005), APOE non-ε4ε4 group (χ(2) = 9.900, df = 2, p = 0.007), and female AD group (χ(2) = 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% CI: 1.213-3.041), and APOE non-ε4ε4 group (Wald = 6.399, df = 1, p = 0.011, OR: 1.586, 95% CI: 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 4.9 years 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 II genotype compared with VV 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.

Memory and Executive Screening (MES): a brief cognitive test for detecting mild cognitive impairment.

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.

[Survey of comorbidities for hospitalized patients with cognitive disorders].

OBJECTIVE: To provide rationales for the prevention and treatment of elderly patients with cognitive disorders through comparing the comorbidities according to different etiologies and severities. METHODS: Six groups of different cognitive status were selected. There were 438 normal cognitive subjects (NC) from Jing'an community of Shanghai. Five other groups were from the Memory Clinic at our hospital from June 2006 to June 2010. There were subjective memory complaints (n = 443, SMC), mild cognitive impairment (n = 540, MCI), vascular cognitive impairment-non dementia (n = 119, VCI-ND), Alzheimer's disease (n = 337, AD) and vascular dementia (n = 54, VaD). All participants finished a battery of neuropsychological tests and completed the survey of such comorbidities as stroke, conscious disturbance, hypertension, diabetes, head injuries and excessive drinking. RESULTS: The comorbidity rates of diabetes were 11.4%, 9.9%, 16.1%, 14.2%, 12.4% and 18.5% in 6 groups (NC, SMC, MCI, VCI-ND, AD, VaD) respectively. There were no differences for overall or pairwise chi square tests. The rates of stroke, hypertension and excessive drinking in patients of VCI-ND and VaD were higher than those of SMC, MCI and AD. The comorbidity rates in the VCI-ND and VaD group were 54.6% vs 62.9% for stroke; 61.3% vs 79.6% for hypertension; 22.6% vs 37.0% for excessive drinking. Whereas in the SMC, MCI and AD groups, the rates were 9.4%, 10.9% and 3.0% for stroke; 44.9%, 47.2% and 42.1% for hypertension; 18.0%, 18.3% and 15.1% for excessive drinking. No distinct differences existed for the comorbidity rates among SMC, MCI and AD groups or among different degrees of AD. CONCLUSION: Etiologies rather than severities determine the different rates of comorbidities in the elders with cognitive impairment.

[Small-worldness of functional networks in Alzheimer's disease].

OBJECTIVE: To construct the functional networks of human brains by resting-state functional magnetic resonance imaging (fMRI) and examine whether or not the small-world property of functional brain networks changes in patients with Alzheimer disease (AD). METHODS: A total of 33 AD patients and 20 healthy old volunteers were recruited. Their cognitive functions were evaluated by the mini-mental state examination (MMSE) and Mattis dementia rating scale (DRS). The resting-state BOLD-fMRI data were acquired and preprocessed. Then the correlation coefficient of every pair of 90 regions was calculated and correlation matrix Z (N×N, N = 90) generated by Fisher Z transformation. The small-world property of functional brain networks was tested for AD patients and normal elders according to the definition of small-worldness. The changes of relevant parameters in AD patients were examined by two sample t-tests. RESULTS: Behavioral results: the MMSE scores of AD group and normal controls (NOR) were 20.60 ± 2.30 and 28.20 ± 1.80 respectively. The DRS scores of AD and NOR groups were 96.00 ± 10.82 and 123.22 ± 13.74 respectively. The MMSE and DRS scores were statistically different between two groups. Calculation of small-world parameters: Within the range of 0.1 ≤ Sparsity ≤ 0.4, both groups satisfied the small-world property. However, the clustering coefficient Cp and the average shortest path Lp of AD group were significantly higher than those of NOR group at each threshold (P < 0.05). CONCLUSIONS: The functional brain networks in AD patients still have the property of small-world. But the levels of Cp and Lp are higher in AD patients than those in normal controls. It suggests that the capacity of information transmission in functional brain networks and the ability of information integration in different brain regions in AD patients are impaired. This finding is of great importance in elucidating the pathological mechanisms of AD from the viewpoint of networks.

Validation of a modified Chinese version of Mini-Addenbrooke's Cognitive Examination for detecting mild cognitive impairment.

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.

Utility of Chinese Versions of Addenbrooke's Cognitive Examination: A Narrative Review.

Addenbrooke's cognitive examination (ACE) is a cognitive screening tool that has developed through three stages: ACE, ACE-Revised (ACE-R), and ACE-Ⅲ. In addition, mini-Addenbrooke's Cognitive Examination (M-ACE) and ACE mobile are the additional versions that is derived from ACE-III. ACE and its related versions show better performance than Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in detecting mild cognitive impairment in different neurological disorders. It has been translated into numerous languages, including Chinese. Through reviewing the history, validity, and comparison with other cognitive tests of Chinese versions of ACE, it aims to facilitate the clinical and scientific use, further development, improvement, and validation of Chinese versions of ACE in various neurological disorders and ultimately promote early identification and management of cognitive impairment in China.