S-Doping Regulated Iron Spin States in Fe-N-C Single-Atom Material for Enhanced Peroxidase-Mimicking Activity at Neutral pH.

Designing biomimetic nanomaterials with peroxidase (POD)-like activity at neutral pH remains a significant challenge. An S-doping strategy is developed to afford an iron single-atom nanomaterial (Fe1@CN-S) with high POD-like activity under neutral conditions. To the best of knowledge, there is the first example on the achievement of excellent POD-like activity under neutral conditions by regulating the active site structure. S-doping not only promotes the dissociation of the N─H bond in 3,3″,5,5″-tetramethylbenzidine (TMB), but also facilitates the desorption of OH* by the transformation of iron species' spin states from middle-spin (MS FeII) to low-spin (LS FeII). Meanwhile, LS FeII sites typically have more unfilled d orbitals, thereby exhibiting stronger interactions with H2O2 than MS FeII, which can enhance POD-like activity. Finally, a one-pot visual detection of glucose at pH 7 is performed, demonstrating the best selectivity and sensitivity than previous reports.

Cognitive profiles in adult-onset neuronal intranuclear inclusion disease: a case series from the memory clinic.

OBJECTIVE: This study aimed to analyze the characteristics of cognitive impairment in adult-onset neuronal intranuclear inclusion disease (NIID). METHODS: Seven patients with adult-onset NIID were collected consecutively from the memory clinic of Xuanwu hospital from February to December 2019. These cases were diagnosed with skin biopsy triggered by DWI high-intensity signals in corticomedullary junction on brain MRI. We used a battery of neuropsychological scales to detect the patient's performance in each cognitive domain, and made a detailed analysis on the characteristics of cognitive impairment. RESULTS: All seven cases had cognitive impairment, and four of them had met the criteria for dementia. The scores of Montreal Cognitive Assessment and Frontal Assessment Battery were abnormal in all patients. The executive dysfunction was confirmed by the abnormal scores of Trail Making Test (5/7, 71%) and Clock Drawing Test (4/7, 57%). Bad performance in Auditory Verbal Learning Test (6/7, 86%) demonstrated that the memory was also a very commonly impaired cognitive domain. The low score on the animal fluency (4/7, 57%), Boston Naming Test (3/7, 43%), and Pentagon and Cube Copying Test (4/7, 57%) indicated that the language and visuospatial skills were also impaired. Fazekas scores were significantly correlated to the global cognition, executive and language functions (r = 0.788-0.906, P < 0.05). CONCLUSIONS: There is obvious impairment in multiple cognitive domains in adult-onset NIID, and both the executive dysfunction and memory deficit are very common. Leukoencephalopathy may be the main course of cognitive impairment in adult-onset NIID.

PSEN1, PSEN2, and APP mutations in 404 Chinese pedigrees with familial Alzheimer's disease.

INTRODUCTION: The PSENs/APP mutation distribution in Chinese patients with familial Alzheimer's disease (FAD) remains unclear. We aimed to analyze the genetic features of Chinese FAD pedigrees with and without PSENs/APP mutations. METHODS: In total, 1330 patients with Alzheimer's disease (AD) or mild cognitive impairment in 404 pedigrees were enrolled from the Chinese Familial Alzheimer's Disease Network. PSENs/APP mutations and APOE frequencies were determined. RESULTS: In total, 13.12% of pedigrees carried PSENs/APP missense mutations, 3.71% carried PSENs/APP synonymous/untranslated region variants, and 83.17% did not carry PSENs/APP mutations. Eleven missense mutations were first identified. In patients without PSENs/APP mutations, 44.31% carried one APOEε4 allele, and 14.85% two APOEε4 alleles. DISCUSSION: The new PSENs/APP mutations indicate heterogeneity in AD pathogenesis between Chinese and other ethnic groups. The low mutation rate suggests the involvement of other genes/factors in Chinese FAD. APOEε4 might be a major gene for some FAD without PSENs/APP mutations.

[Association between exon polymorphisms of BACE2 gene with Alzheimer disease].

OBJECTIVE: To explore the association between ß-site APP-cleaving enzyme 2 gene exon polymorphisms with sporadic Alzheimer disease (AD) in a north Chinese Han population. METHODS: The exon regions of ß-site APP-cleaving enzyme 2 gene were sequenced randomly in 10 sporadic AD patients and 10 healthy controls from Beijing and Qinhuangdao, Hebei province during 2000-2008. Using SnaPshot or direct sequencing, we genotyped these polymorphisms of 348 sporadic AD patients and 294 healthy controls in a Chinese Han population. By genetic statistical assay, we studied the association between these polymorphisms and the risks for sporadic AD. RESULTS: The sequencing of all exon regions of ß-site APP-cleaving enzyme 2 gene revealed three polymorphisms of rs2252576C/T, rs1046210C/T and rs12149C/T. No association was detected between these three polymorphisms and sporadic AD even after statistical adjustments for age, gender and ApoEε4 status. CONCLUSIONS: There is not a linkage between exon region polymorphisms of ß-site APP-cleaving enzyme 2 gene and sporadic AD in a Chinese Han population.

Prevention of dementia using mobile phone applications (PRODEMOS): a multinational, randomised, controlled effectiveness-implementation trial.

BACKGROUND: The expected increase of dementia prevalence in the coming decades will mainly be in low-income and middle-income countries and in people with low socioeconomic status in high-income countries. This study aims to reduce dementia risk factors in underserved populations at high-risk using a coach-supported mobile health (mHealth) intervention. METHODS: This open-label, blinded endpoint, hybrid effectiveness-implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in people aged 55-75 years of low socioeconomic status in the UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome was change in cardiovascular risk factors, ageing, and incidence of dementia (CAIDE) risk score from baseline to after 12-18 months of intervention. Implementation outcomes were coverage, adoption, sustainability, appropriateness, acceptability, fidelity, feasibility, and costs assessed using a mixed-methods approach. All participants with complete data on the primary outcome, without imputation of missing outcomes were included in the analysis (intention-to-treat principle). This trial is registered with ISRCTN, ISRCTN15986016, and is completed. FINDINGS: Between Jan 15, 2021, and April 18, 2023, 1488 people (601 male and 887 female) were randomly assigned (734 to intervention and 754 to control), with 1229 (83%) of 1488 available for analysis of the primary effectiveness outcome. After a mean follow-up of 16 months (SD 2·5), the mean CAIDE score improved 0·16 points in the intervention group versus 0·01 in the control group (mean difference -0·16, 95% CI -0·29 to -0·03). 1533 (10%) invited individuals responded; of the intervention participants, 593 (81%) of 734 adopted the intervention and 367 (50%) of 734 continued active participation throughout the study. Perceived appropriateness (85%), acceptability (81%), and fidelity (79%) were good, with fair overall feasibility (53% of intervention participants and 58% of coaches), at low cost. No differences in adverse events between study arms were found. INTERPRETATION: A coach-supported mHealth intervention is modestly effective in reducing dementia risk factors in those with low socioeconomic status in the UK and any socioeconomic status in China. Implementation is challenging in these populations, but those reached actively participated. Whether this intervention will result in less cognitive decline and dementia requires a larger RCT with long follow-up. FUNDING: EU Horizon 2020 Research and Innovation Programme and the National Key R&D Programmes of China. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Estrogen metabolite 2-methoxyestradiol prevents hypertension in deoxycorticosterone acetate-salt rats.

PURPOSE: Our early work showed that the estrogen metabolite 2-methoxyestradiol (2ME) inhibits proliferation of vascular smooth muscle cells (SMCs) and vascular contractility through an endothelium-dependent mechanism. The aim of this study was to examine whether 2ME prevents the development of hypertension in rats. METHODS: A hypertensive model was established in uninephrectomized rats using deoxycorticosterone acetate (DOCA)-salt. Blood pressure in response to 2ME (treatment up to 10 weeks or single bolus) was monitored. RESULTS: Our results showed that systolic blood pressure, as measured by tail-cuff plethysmography, was significantly increased in conscious rats treated with DOCA-salt for 3-10 weeks. Co-treatment with 2ME (100-300 µg/kg), but not dimethyl sulfoxide (DMSO), completely prevented the increase in blood pressure of DOCA-salt rats. After 10-week treatment, the mean arterial blood pressure (MABP) of anesthetized rats measured using PowerLab Data Acquisition System was: 84 ± 16 mmHg in normotensive control rats and 150 ± 9 mmHg in DOCA-salt rats, which was similar to that of DMSO-treated rats. Treatment with 2ME at low or high doses reduced MABP of DOCA-salt rats close to that of control normotensive rats. In addition, MABP of hypertensive DOCA-salt rats was significantly reduced in response to a single injection of 2ME. Delayed administration of 2ME reduced the further increase of blood pressure in DOCA-salt rats. However, inhibition of 2ME production by entacapone did not significantly affect blood pressure in either control or DOCA-salt rats. CONCLUSIONS: 2ME treatment prevents the development of hypertension in DOCA-salt rats, implicating a therapeutic potential of 2ME in hypertension treatment.

Plasma Phosphorylated Tau181 and Amyloid-ß42 in Dementia with Lewy Bodies Compared with Alzheimer's Disease and Cognitively Healthy People.

BACKGROUND: Increasing evidence illustrates the value of plasma biomarkers of Alzheimer's disease (AD) to screen for and identify dementia with Lewy bodies (DLB). However, confirmatory studies are needed to demonstrate the feasibility of these markers. OBJECTIVE: To determine the feasibility of plasma tau phosphorylated at threonine 181 (p-tau181) and amyloid-ß42 (Aß42) as potential biomarkers to differentiate AD and DLB. METHODS: We evaluated plasma samples from patients with DLB (n = 47) and AD (n = 55) and healthy controls (HCs, n = 30), using ELISAs to measure p-tau181 and Aß42. Additionally, we examined neuropsychological assessment scores for participants. The plasma biomarkers were investigated for correlation with neuropsychological assessments and discriminant ability to identify DLB. RESULTS: Plasma p-tau181 was significantly lower in DLB than in AD and HCs. Plasma Aß42 was significantly higher in DLB than in AD but lower in DLB than in HCs. We found good correlations between plasma Aß42 and neuropsychological scores in the whole cohort, while p-tau181 was associated with cognitive status in DLB. In the distinction between DLB and HCs, plasma p-tau181 and Aß42 showed similar accuracy, while Aß42 showed better accuracy than p-tau181 in discriminating DLB and AD. CONCLUSION: In a single-center clinical cohort, we confirmed the high diagnostic value of plasma p-tau181 and Aß42 for distinguishing patients with DLB from HCs. Plasma Aß42 improved the differential diagnosis of DLB from AD.

Composite Indices of the Color-Picture Version of Boston Naming Test Have Better Discriminatory Power: Reliability and Validity in a Chinese Sample with Diverse Neurodegenerative Diseases.

BACKGROUND: The Boston Naming Test (BNT) is the most widely used measure to assess anomia. However, it has been criticized for failing to differentiate the underlying cognitive process of anomia. OBJECTIVE: We validated the color-picture version of BNT (CP-BNT) in a sample with diverse neurodegenerative dementia diseases (NDDs). We also verified the differential ability of the composite indices of CP-BNT across NDDs groups. METHODS: The present study included Alzheimer's disease (n = 132), semantic variant primary progressive aphasia (svPPA, n = 53), non-svPPA (n = 33), posterior cortical atrophy (PCA, n = 35), and normal controls (n = 110). We evaluated psychometric properties of CP-BNT for the spontaneous naming (SN), the percentage of correct responses on semantic cuing and word recognition cuing (% SC, % WR). Receiver operating characteristic analysis was used to examine the discriminatory power of SN alone and the composite indices (SN, % SC, and % WR). RESULTS: The CP-BNT had sufficient internal consistency, good convergent, divergent validity, and criterion validity. Different indices of CP-BNT demonstrated distinct cognitive underpinnings. Category fluency was the strongest predictor of SN (ß= 0.46, p < 0.001). Auditory comprehension tests highly associated with % WR (Sentence comprehension: ß= 0.22, p = 0.001; Word comprehension: ß= 0.20, p = 0.001), whereas a lower visuospatial score predicted % SC (ß= -0.2, p = 0.001). Composite indices had better predictability than the SN alone when differentiating between NDDs, especially for PCA versus non-svPPA (area under the curve increased from 63.9% to 81.2%). CONCLUSION: The CP-BNT is a highly linguistically relevant test with sufficient reliability and validity. Composite indices could provide more differential information beyond SN and should be used in clinical practice.

Acanthocytes Identified in Huntington's Disease.

Background: Neuroacanthocytosis (NA) and Huntington's disease (HD) are neurodegenerative conditions that share clinical symptoms and imaging findings, despite their distinct genetic etiologies. Usually, the presence of acanthocytes can help narrow the differential diagnosis of a familial choreiform disorder, as the diagnosis of NA syndrome is supported by the presence of acanthocytes in peripheral blood. In this study, we demonstrate four patients who present with HD and acanthocytosis. Methods: We retrieved the data of 40 HD patients with fresh peripheral blood screened for erythrocytes in our hospital from 2014 to 2022. Of these 40 patients, four patients with acanthocytes were recruited for this study. Patients' investigations included clinical and laboratory studies, HTT gene sequencing, and whole-exome sequencing. Fresh peripheral blood was screened for erythrocytes by scanning electron microscopy. Results: The four adult patients were Han Chinese and unrelated. The age ranged from 45 to 61 years, with a disease duration of 4-10 years. The main neurological features at diagnosis included progressive involuntary movements, psychiatric changes, and dementia. Genetic analysis showed an expansion at the HTT gene. The mean proportion of acanthocytes was mild (6-10%) elevated in patient one and high (>20%) elevated in patients 2-4 by scanning electron microscopy examination. Conclusion: Our study illustrates that HD can combine with acanthocytosis, which may expand the clinical phenotype. Even though the primary gene defect appears to be predominately directed at the brain, a peripheral defect can be seen in HD. Our study highlights the complexity and diversity of HD.

A Color-Picture Version of Boston Naming Test Outperformed the Black-and-White Version in Discriminating Amnestic Mild Cognitive Impairment and Mild Alzheimer's Disease.

Despite the ubiquity of the Boston naming test (BNT) in clinical practice and research, concerns have been expressed about its poor quality pictures, insufficient psychometric properties, and cultural bias in non-English language backgrounds. We modified the black-and-white BNT with a set of color pictures since color effects have been suggested to improve naming accuracy in the visual naming test. This study aimed to examine and compare the reliability and validity of the color-picture version of BNT (CP-BNT) and the black-and-white version of BNT (BW-BNT) to differentiate amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD) from the cognitive normals. This study included two subgroups, and each subgroup had 101 normal controls, 51 aMCI, and 52 mild AD. One subgroup undertook BW-BNT and the other conducted CP-BNT. The reliability, convergent and discriminant validity, and the diagnostic accuracy of two versions of BNT were evaluated. The CP-BNT showed a greater area under the curve (AUC) than the BW-BNT for aMCI (80.3 vs.s 69.4%) and mild AD (93.5 vs. 77.6%). The CP-BNT also demonstrated better convergent validity with CDR global scores and better reliability (Cronbach's coefficient 0.66 for the CP-BNT vs. 0.55 for the BW-BNT). At the optimal cutoff value of spontaneous naming, the CP-BNT demonstrated improved sensitivity and specificity for differentiating mild AD from NC with a higher positive predictive value, negative predictive value, and lower false-positive rate. Compared with BW-BNT, CP-BNT is a more reliable and valid test to assess cognitive and naming impairment.

Needs and views on healthy lifestyles for the prevention of dementia and the potential role for mobile health (mHealth) interventions in China: a qualitative study.

OBJECTIVES: Over the coming decades, China is expected to face the largest worldwide increase in dementia incidence. Mobile health (mHealth) may improve the accessibility of dementia prevention strategies, targeting lifestyle-related risk factors. Our aim is to explore the needs and views of Chinese older adults regarding healthy lifestyles to prevent cardiovascular disease (CVD) and dementia through mHealth, supporting the Prevention of Dementia using Mobile Phone Applications (PRODEMOS) study. DESIGN: Qualitative semi-structured interview study, using thematic analysis. SETTING: Primary and secondary care in Beijing and Tai'an, China. PARTICIPANTS: Older adults aged 55 and over without dementia with an increased dementia risk, possessing a smartphone. Participants were recruited through seven hospitals participating in the PRODEMOS study, purposively sampled on age, sex, living area and history of CVD and diabetes. RESULTS: We performed 26 interviews with participants aged 55-86 years. Three main themes were identified: valuing a healthy lifestyle, sociocultural expectations and need for guidance. First, following a healthy lifestyle was generally deemed important. In addition to generic healthy behaviours, participants regarded certain specific Chinese lifestyle practices as important to prevent disease. Second, the sociocultural context played a crucial role, as an important motive to avoid disease was to limit the care burden put on family members. However, time-consuming family obligations and other social values could also impede healthy behaviours such as regular physical activity. Finally, there seemed to be a need for reliable and personalised lifestyle advice and for guidance from a health professional. CONCLUSIONS: The Chinese older adults included in this study highly value a healthy lifestyle. They express a need for personalised lifestyle support in order to adopt healthy behaviours. Potentially, the PRODEMOS mHealth intervention can meet these needs through blended lifestyle support to improve risk factors for dementia and CVD. TRIAL REGISTRATION NUMBER: ISRCTN15986016; Pre-results.

[Relationship between computed tomography perfusion imaging and prognosis in hyperacute cerebral infarction].

OBJECTIVE: To explore the diagnostic valves of computed tomography perfusion imaging (CTP) in hyperacute cerebral infarction patients and examine the correlation of time period from symptom onset to examination and CTP parameters. METHODS: Non-enhancement CT and CTP were performed on 75 patients with acute cerebral infarction of internal carotid system within 8 hours of symptom onset at our department from January 2006 to May 2008. National Institute of Health Stroke Scale score (NIHSS), Barthel index (BI) and modified Rankin scale (mRS) were assessed at the same day, days 14 and 90 after stroke onset respectively for neurological function impairment, activity of daily living and extent of disability in prognosis. RESULTS: (1) All CTP parameters in ischemic region had no correlation with time period from symptom onset to examination (P > 0.05). No significant differences were found between the patients with > 3 hours and < 3 hours after stroke onset in terms of the above parameters; (2) the areas of CBF (cerebral blood flow) on ischemic region significantly correlated with NIHSS at the day of symptom onset (r = 0.391, P < 0.001), Day 14 (r = 0.564, P < 0.001) and Day 90 (r = 0.549, P < 0.001) after symptom onset. CBV (cerebral blood volume) and TTP (time-to-peak) on ischemic region significantly correlated with the evaluation indices of predicting clinical outcomes at the day of symptom onset, Days 14 and 90 (P < 0.01). CBF, CBV, rCBF (regional CBF) and rCBV (regional CBV) correlated only with some of the clinical outcome scores. CONCLUSION: Time period after symptom onset can not reflect the ischemic extent and volume of cerebral infarction. But CTP may evaluate the severity and prognosis of acute cerebral infarction patients. The area of abnormal perfusion is the most sensitive parameter.

Dementia with Lewy bodies research consortia: A global perspective from the ISTAART Lewy Body Dementias Professional Interest Area working group.

Dementia with Lewy bodies (DLB) research has seen a significant growth in international collaboration over the last three decades. However, researchers face a challenge in identifying large and diverse samples capable of powering longitudinal studies and clinical trials. The DLB research community has begun to focus efforts on supporting the development and harmonization of consortia, while also continuing to forge networks within which data and findings can be shared. This article describes the current state of DLB research collaborations on each continent. We discuss several established DLB cohorts, many of whom have adopted a common framework, and identify emerging collaborative initiatives that hold the potential to expand DLB networks and diversify research cohorts. Our findings identify geographical areas into which the global DLB networks should seek to expand, and we propose strategies, such as the creation of data-sharing platforms and the harmonization of protocols, which may further potentiate international collaboration.

Prevention of dementia using mobile phone applications (PRODEMOS): protocol for an international randomised controlled trial.

INTRODUCTION: Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%-40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk. METHODS AND ANALYSIS: The prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness-implementation hybrid design, taking place in the UK and China. People are eligible if they are 55-75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention. ETHICS AND DISSEMINATION: The PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London-Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People's Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN15986016.

The Efficacy of COGnitive tRaining in patiEnts with Amnestic mild coGnitive impairmENT (COG-REAGENT): Protocol for a Multi-Center Randomized Controlled Trial.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is often the prodromal stage of Alzheimer's disease (AD). Although previous studies have suggested that computerized cognitive training is an effective non-pharmacological intervention for aMCI, large-sample, randomized controlled studies are warranted to provide a high level of evidence. OBJECTIVE: To identify the efficacy of computerized cognitive training for aMCI. METHODS: This study will include 260 patients diagnosed with aMCI from 8 centers in China. A computerized multi-domain adaptive training program will be used in this study, and the targeted cognitive domains include memory, attention, language, and executive function. The patients will be randomized into either a cognitive-training group or an active-control group. The intervention is a 12-week internet-based cognitive training performed for 40 minutes per day, 4 days a week. Neuropsychological assessments and structural and functional MRI will be obtained at baseline, at the end of the intervention, and 6 months after randomization. The primary outcome will be the global cognitive function score assessed by Montreal Cognitive Assessment. The secondary outcomes include changes in other neuropsychological assessments and neuroplasticity changes measured by structural and functional MRI. RESULTS: The trial is currently ongoing, and it is anticipated that recruitment will be completed in December 2020. CONCLUSION: This multi-center, large-sample, randomized controlled trial will investigate the short and long-term effects of computerized cognitive training in patients with aMCI. Furthermore, the combination of functional and structural MRI results will also reveal the underlying mechanisms of the effect of intervention.

Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study.

BACKGROUND: China has a large population of older people, but has not yet undertaken a comprehensive study on the prevalence, risk factors, and management of both dementia and mild cognitive impairment (MCI). METHODS: For this national cross-sectional study, 46 011 adults aged 60 years or older were recruited between March 10, 2015, and Dec 26, 2018, using a multistage, stratified, cluster-sampling method, which considered geographical region, degree of urbanisation, economic development status, and sex and age distribution. 96 sites were randomly selected in 12 provinces and municipalities representative of all socioeconomic and geographical regions in China. Participants were interviewed to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, and family history, and then completed a neuropsychological testing battery administered by a psychological evaluator. The prevalence of dementia (Alzheimer's disease, vascular dementia, and other dementias) and MCI were calculated and the risk factors for different groups were examined using multivariable-adjusted analyses. FINDINGS: Overall age-adjusted and sex-adjusted prevalence was estimated to be 6·0% (95% CI 5·8-6·3) for dementia, 3·9% (3·8-4·1) for Alzheimer's disease, 1·6% (1·5-1·7) for vascular dementia, and 0·5% (0·5-0·6) for other dementias. We estimated that 15·07 million (95% CI 14·53-15·62) people aged 60 years or older in China have dementia: 9·83 million (9·39-10·29) with Alzheimer's disease, 3·92 million (3·64-4·22) with vascular dementia, and 1·32 million (1·16-1·50) with other dementias. Overall MCI prevalence was estimated to be 15·5% (15·2-15·9), representing 38·77 million (37·95-39·62) people in China. Dementia and MCI shared similar risk factors including old age (dementia: odds ratios ranging from 2·69 [95% CI 2·43-2·98] to 6·60 [5·24-8·32]; MCI: from 1·89 [1·77-2·00] to 4·70 [3·77-5·87]); female sex (dementia: 1·43 [1·31-1·56]; MCI: 1·51 [1·43-1·59]); parental history of dementia (dementia: 7·20 [5·68-9·12]; MCI: 1·91 [1·48-2·46]); rural residence (dementia: 1·16 [1·06-1·27]; MCI: 1·45 [1·38-1·54]); fewer years of education (dementia: from 1·17 [1·06-1·29] to 1·55 [1·38-1·73]; MCI: from 1·48 [1·39-1·58] to 3·48 [3·25-3·73]); being widowed, divorced, or living alone (dementia: from 2·59 [2·30-2·90] to 2·66 [2·29-3·10]; MCI: from 1·58 [1·44-1·73] to 1·74 [1·56-1·95]); smoking (dementia: 1·85 [1·67-2·04]; MCI: 1·27 [1·19-1·36]), hypertension (dementia: 1·86 [1·70-2·03]; MCI: 1·62 [1·54-1·71] for MCI), hyperlipidaemia (dementia: 1·87 [1·71-2·05]; MCI: 1·29 [1·21-1·37]), diabetes (dementia: 2·14 [1·96-2·34]; MCI: 1·44 [1·35-1·53]), heart disease (dementia: 1·98 [1·73-2·26]; MCI: 1·17 [1·06-1·30]), and cerebrovascular disease (dementia: 5·44 [4·95-5·97]; MCI: 1·49 [1·36-1·62]). Nine of these risk factors are modifiable. INTERPRETATION: Dementia and MCI are highly prevalent in China and share similar risk factors. A prevention strategy should be developed to target the identified risk factors in the MCI population to thwart or slow down disease progression. It is also crucial to optimise the management of dementia and MCI as an important part of China's public health system. FUNDING: Key Project of the National Natural Science Foundation of China, National Key Scientific Instrument and Equipment Development Project, Mission Program of Beijing Municipal Administration of Hospitals, Beijing Scholars Program, Beijing Brain Initiative from Beijing Municipal Science & Technology Commission, Project for Outstanding Doctor with Combined Ability of Western and Chinese Medicine, and Beijing Municipal Commission of Health and Family Planning.

Trajectories of Multidimensional Caregiver Burden in Chinese Informal Caregivers for Dementia: Evidence from Exploratory and Confirmatory Factor Analysis of the Zarit Burden Interview.

BACKGROUND: Despite its popularity, the latent structure of 22-item Zarit Burden Interview (ZBI) remains unclear. There has been no study exploring how caregiver multidimensional burden changed. OBJECTIVE: The aim of the work was to validate the latent structure of ZBI and to investigate how multidimensional burden evolves with increasing global burden. METHODS: We studied 1,132 dyads of dementia patients and their informal caregivers. The caregivers completed the ZBI and a questionnaire regarding caregiving. The total sample was randomly split into two equal subsamples. Exploratory factor analysis (EFA) was performed in the first subsample. In the second subsample, confirmatory factor analysis (CFA) was conducted to validate models generated from EFA. The mean of weighted factor score was calculated to assess the change of dimension burden against the increasing ZBI total score. RESULTS: The result of EFA and CFA supported that a five-factor structure, including role strain, personal strain, incompetency, dependency, and guilt, had the best goodness-of-fit. The trajectories of multidimensional burden suggested that three different dimensions (guilt, role strain and personal strain) became the main subtype of burden in sequence as the ZBI total score increased from mild to moderate. Factor dependency contributed prominently to the total burden in severe stage. CONCLUSION: The five-factor ZBI is a psychometrically robust measure for assessing multidimensional burden in Chinese caregivers. The changes of multidimensional burden have deepened our understanding of the psychological characteristics of caregiving beyond a single total score and may be useful for developing interventions to reduce caregiver burden.

Autologous peripheral blood stem cell transplantation for severe multiple sclerosis.

We describe the results of a clinical trial to evaluate the feasibility and toxicity of autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with progressive multiple sclerosis (MS). Fifteen patients (all patients with secondary progressive MS) were enrolled. The median expanded disability status scale (EDSS) score at baseline was 6.0 (range, 4.5-7.5). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. In 9 patients, CD34+ cell selection was performed with a CliniMACS cell selection system, and 6 patients accepted infusion of unmodified peripheral blood stem cells. The modified BEAM (carmustine, teniposide, cytarabine, and melphalan) was the sole conditioning regimen used. The adverse effects included infections, mucositis, transient hepatotoxicity, and diarrhea. Three patients had flares of neurologic deterioration during mobilization, 8 patients had the same manifestation during transplantation, and 2 patients had similar flares within 3 months of transplantation. Six patients experienced continuous neurologic improvement after transplantation, 5 patients experienced neurologic progression, and 4 patients had stabilization of their disease. The confirmed progression-free rate was 63.8% at 49 months. The results of lymphocyte purging were no better than for no purging. Auto-HSCT proved to be safe and beneficial for some MS patients. Further studies are needed to establish the merit of this procedure for MS patients.

[Transrectal high-intensity focused ultrasound for treatment of benign prostatic hyperplasia: report of 262 cases].

OBJECTIVE: To explore the application of transrectal high-intensity focused ultrasound (HIFU) for treatment of benign prostatic hyperplasia (BPH). METHODS: From Dec. 2002 to Dec. 2006, 262 BPH patients underwent transrectal HIFU ablative therapy. After the treatment, IPSS, QOL score, peak uroflow rate and prostatic volume measured by TRUS were used for evaluation. RESULTS: After 1 to 3 years' follow-up, IPSS, QOL score, and prostatic volume all decreased, while the peak uroflow rate increased obviously (P<0.01). Mild hematuria was noted in all the cases after the treatment, and epididymitis was found in 7 cases (2.7%), short-term hematospermia in 66 cases (25.2%), retrograde ejaculation in 35 cases (13.4%), and urethro-rectal fistula in 1 case (0.3%). No urinary incontinence was found in these cases. TURP was performed in 18 cases (6.8%) in 3 years after the treatment due to an excessively large volume of the prostates or bladder neck contracture. CONCLUSION: HIFU is effective and safe in the treatment of BPH which causes minimal invasion, absence of intraoperative bleeding, good tolerance and few complications, and is especially suitable in elderly patients.

Lack of association between the polymorphisms of beta-site APP-cleaving enzyme 2 (BACE2) 5'-flanking region and sporadic Alzheimer's disease.

Amyloid beta-peptide (A beta) plays a central role in the pathogenesis of Alzheimer's disease (AD). A beta is produced by sequential cleavage of the amyloid precursor protein (APP) by two enzymes referred to as beta- and gamma-secretase. beta-secretase is of more importance, as it catalyses the rate-limiting step in the production of A beta. Although beta-site APP-cleaving enzyme 1 (BACE1) is known to cleave APP at the beta-secretase site as required for the generation of A beta, the role of its homologue BACE2 is controversial. For seeking the correlation of the BACE2 promoter with sporadic AD (SAD), we performed a case-control study in a Chinese Han population. In the study, we sequenced the 2641 bp fragment of the 5'-flanking region of BACE2 gene and found three polymorphisms which are -320C/- (rs11316732), -1541A/T (rs9975138) and -1904C/T (rs28656880). Definitive genotyping these markers and apolipoprotein E (APOE) polymorphism were surveyed using restriction enzyme digestion and direct sequencing in 359 SAD patients and 334 controls. We failed to find any association between these three polymorphisms and SAD even after statistical adjustment for age, gender and APOE epsilon 4 status. Our data do not support that there is a linkage between the 5'-flanking region polymorphisms of BACE2 and SAD in the Chinese Han population.