Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study.

Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer's disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer's disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer's disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10-19, 2.49 × 10-23, 1.35 × 10-67, and 4.81 × 10-9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P < 5.0 × 10-8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer's disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer's disease, suggesting that our models can predict Alzheimer's disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer's disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer's disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.

Blood neuro-exosomal synaptic proteins predict Alzheimer's disease at the asymptomatic stage.

INTRODUCTION: Exosomes are an emerging candidate for biomarkers of Alzheimer's disease (AD). This study investigated whether exosomal synaptic proteins can predict AD at the asymptomatic stage. METHODS: We conducted a two-stage-sectional study (discovery stage: AD, 28; amnestic mild cognitive impairment [aMCI], 25; controls, 29; validation stage: AD, 73; aMCI, 71; controls, 72), a study including preclinical AD (160) and controls (160), and a confirmation study in familial AD (mutation carriers: 59; non-mutation carriers: 62). RESULTS: The concentrations of growth associated protein 43 (GAP43), neurogranin, synaptosome associated protein 25 (SNAP25), and synaptotagmin 1 were lower in AD than in controls (P < .001). Exosomal biomarker levels were correlated with those in cerebrospinal fluid (R2  = 0.54-0.70). The combination of exosomal biomarkers detected AD 5 to 7 years before cognitive impairment (area under the curve = 0.87-0.89). DISCUSSION: This study revealed that exosomal GAP43, neurogranin, SNAP25, and synaptotagmin 1 act as effective biomarkers for prediction of AD 5 to 7 years before cognitive impairment.

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.

The APOE ε4 exerts differential effects on familial and other subtypes of Alzheimer's disease.

INTRODUCTION: The genetic risk effects of apolipoprotein E (APOE) on familial Alzheimer's disease (FAD) with or without gene mutations, sporadic AD (SAD), and normal controls (NC) remain unclear in the Chinese population. METHODS: In total, 15 119 subjects, including 311 FAD patients without PSEN1, PSEN2, APP, TREM2, and SORL1 pathogenic mutations (FAD [unknown]); 126 FAD patients with PSENs/APP mutations (FAD [PSENs/APP]); 7234 SAD patients; and 7448 NC were enrolled. The risk effects of APOE ε4 were analyzed across groups. RESULTS: The prevalence of the APOE ε4 genotype in FAD (unknown), FAD (PSENs/APP), SAD, and NC groups was 56.27%, 26.19%, 36.23%, and 19.54%, respectively. Further, the APOE ε4 positive genotype had predictive power for FAD (unknown) risk (odds ratio: 4.51, 95% confidence interval: 3.57-5.45, P < .001). DISCUSSION: APOE ε4 positive genotype may cause familial aggregation, and the investigation of multiple interventions targeting APOE pathological function to reduce the risk for this disease warrants attention.

Adult-onset vanishing white matter disease with the EIF2B2 gene mutation presenting as menometrorrhagia.

BACKGROUND: Vanishing white matter disease (VWMD) is one of the most prevalent inherited leukoencephalopathies, which generally presents in childhood as a progressive disorder while less beginning in adulthood. The present report describes the clinical, neuroimaging, and genetic findings of a female patient with adult-onset VWMD. In addition, to provide a clearer delineation of the clinical and genetic characteristics of female adult-onset VWMD patients, 32 genetically confirmed female adult-onset EIF2B-mutated cases are summarized. CASE PRESENTATION: The patient described here suffered from long-term menometrorrhagia prior to manifesting progressive neurological impairments that included tremors, bilateral pyramidal tract injury, cerebellar ataxia, and dementia. To the best of our knowledge, this is the first female patient with adult-onset VWMD suffering from long-term menometrorrhagia attributed to the c.254 T > A and c.496A > G mutations in the EIF2B2 gene; the c.496A > G mutation has not been reported in previous studies. The patient also exhibited metabolic dysfunction. The present findings widen the spectrum of phenotypic heterogeneity observed in VWMD patients. CONCLUSIONS: The present report summarizes 33 female patients with adult-onset VWMD to provide an overview of the clinical and genetic characteristics of this disorder and ovarioleukodystrophy. The mean age of clinical onset in female patients with adult-onset VWMD was 36.8 years and the neurological symptoms primarily included motor and cognitive dysfunction such as paraparesis, cerebellar ataxia, and executive deficits. In addition, ovarian failure occurred in all of these female patients and usually preceded the neurological symptoms. Furthermore, several patients also suffered from metabolic dysfunction. All 33 patients had mutations on EIF2B1-5, and of these, the c.338 G > A mutation in the EIF2B5 gene (p.Arg113His) was the most common. These findings suggest that clinicians should be aware of adult-onset forms of VWMD as well as its typical magnetic resonance imaging (MRI) and clinical characteristics although this pathology is usually recognized as a pediatric disorder. No curative treatment is presently available, and thus early recognition is important to prevent triggering events and to allow for genetic counseling.

Neurosarcoidosis: clinical characteristics, diagnosis, and treatment in eight Chinese patients.

Neurosarcoidosis is relatively rare and has diverse manifestations. The clinical characteristics, diagnosis, treatment, and outcome for neurosarcoidosis in China are poorly understood. We retrospectively analyzed the clinical features, laboratory and imaging results, treatment, and outcomes in patients who met the criteria for definite or probable neurosarcoidosis in Xuan Wu Hospital of Capital Medical University from 2000 to 2015. Eight patients were included in this study, accounting for 5.84% of all cases with sarcoidosis. The mean age at onset was 50.25 years, and 75% of the patients were female. Five cases had a prior diagnosis of extraneurologic sarcoidosis, leading to a shorter lag time between onset of symptoms and diagnosis (3.4 vs. 16.2 months). Neurological symptoms were the first clinical feature of sarcoidosis in three cases, and no patients presented isolated nervous system manifestation. The most common symptom was sensory disturbance, and the most common site of nervous system involvement was brain parenchyma and meninges. Disturbance of consciousness, seizures, hydrocephalus, and abnormal CSF assays were associated with poor prognosis. All patients were treated with corticosteroids and one was also given azathioprine. Five patients had complete or partial improvement, one remained stabilized, and two deteriorated and died. Neurosarcoidosis is difficult to diagnose early and might be associated with a poor prognosis. Tissue biopsy for a definitive diagnosis and aggressive therapy with corticosteroids plus other alternative immunosuppressive treatment should be recommended in China.

The cost of Alzheimer's disease in China and re-estimation of costs worldwide.

INTRODUCTION: The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain. METHODS: We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD. RESULTS: The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015. DISCUSSION: China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide.

Monetary costs of Alzheimer's disease in China: protocol for a cluster-randomised observational study.

BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia. International multilateral cost-of-illness (COI) studies have revealed that the cost of treating this disease is huge, which places a significant burden on patients' families and their healthcare systems. However, no such studies have been conducted in China. This study estimates the monetary costs of patients with AD in mainland China. METHODS: This study planned to start in October 2015 and to finish in March 2016. It covered 30 provincial, municipal, and autonomous regions in mainland China. The sites and research centres in each region were selected randomly. The participating sites include Tier 3 hospitals, psychiatric hospitals, geriatric hospitals, nursing homes, and residences. More than 2500 patients with AD and their caregivers from all of the 81 research centres will be enrolled to fulfil the calculated sample size. The monetary costs of AD, which include direct medical costs, direct non-medical costs, and indirect costs, are being collected using the electronic medical record system and residence health system at each site; face-to-face interviews are being performed when necessary. Descriptive statistics will be used to summarise the patient characteristics and generalised linear models will be developed to calculate the costs. RESULTS: The main findings will include national and per patient annual monetary costs of AD in China. CONCLUSIONS: To the best of our knowledge, this is the first large-scale cluster-randomized observational study to estimate the economic burden of AD in Chinese patients. The methodology used was based on China's current healthcare system and is suitable for the purpose of the study. Because the burden of AD on patients, families, healthcare providers, and society is substantial and increasing, it is important and necessary to understand the economic burden caused by this disease. TRIAL REGISTRATION: Our trial was retrospectively registered on ClinicalTrials.gov, NCT02694445 , registered on 02/26/2016.

Consensus-based recommendations for the management of rapid cognitive decline due to Alzheimer's disease.

INTRODUCTION: Rapid cognitive decline (RCD) occurs in dementia due to Alzheimer's disease (AD). METHODS: Literature review, consensus meetings, and a retrospective chart review of patients with probable AD were conducted. RESULTS: Literature review showed that RCD definitions varied. Mini-Mental State Examination scores <20 at treatment onset, vascular risk factors, age <70 years at symptom onset, higher education levels, and early appearance of hallucinations, psychosis, or extrapyramidal symptoms are recognized RCD risk factors. Chart review showed that RCD (Mini-Mental State Examination score decline ≥3 points/year) is more common in moderate (43.2%) than in mild patients (20.1%; P < .001). Rapid and slow decliners had similar age, gender, and education levels at baseline. DISCUSSION: RCD is sufficiently common to interfere with randomized clinical trials. We propose a 6-month prerandomization determination of the decline rate or use of an RCD risk score to ensure balanced allocation among treatment groups.

The effects of DL-3-n-butylphthalide in patients with vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease: A multicentre, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Vascular cognitive impairment without dementia is very common among the aged and tends to progress to dementia, but there have been no proper large-scale intervention trials dedicated to it. Vascular cognitive impairment without dementia caused by subcortical ischemic small vessel disease (hereinafter, subcortical Vascular cognitive impairment without dementia) represents a relatively homogeneous disease process and is a suitable target for therapeutic trials investigating Vascular cognitive impairment without dementia. Preclinical trials showed that dl-3-n-butylphthalide (NBP) is effective for cognitive impairment of vascular origin. METHODS: In this randomized, double-blind, placebo-controlled trial, we enrolled patients aged 50-70 years who had a diagnosis of subcortical Vascular cognitive impairment without dementia at 15 academic medical centers in China. Inclusion criteria included a clinical dementia rating ≥0.5 on at least one domain and global score ≤0.5; a mini-mental state examination score ≥20 (primary school) or ≥24 (junior school or above); and brain magnetic resonance imaging consistent with subcortical ischemic small vessel disease. Patients were randomly assigned to NBP 200 mg three times daily or matched placebo (1:1) for 24 weeks according to a computer-generated randomization protocol. All patients and study personnel were masked to treatment assignment. Primary outcome measures were the changes in Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and clinician's interview-based impression of change plus caregiver input (CIBIC-plus) after 24 weeks. All patients were monitored for adverse events (AEs). Outcome measures were analyzed for both the intention-to-treat (ITT) population and the per protocol population. RESULTS: This study enrolled 281 patients. NBP showed greater effects than placebo on ADAS-cog (NBP change -2.46 vs. placebo -1.39; P = .03; ITT) and CIBIC-plus (80 [57.1%] vs. 59 [42.1%] patients improved; P = .01; ITT). NBP-related AE were uncommon and primarily consisted of mild gastrointestinal symptoms. DISCUSSION: Over the 6-month treatment period, NBP was effective for improving cognitive and global functioning in patients with subcortical vascular cognitive impairment without dementia and exhibited good safety.

Diagnosis and treatment of dementia in neurology outpatient departments of general hospitals in China.

INTRODUCTION: The status of dementia diagnosis and treatment of neurology outpatients in general hospitals in China remains unclear. METHODS: From neurology outpatients at 36 randomly selected hospitals, we first collected baseline data concerning the number of dementia doctors, memory clinics, and patients diagnosed with dementia. In stage 2, we intervened based on drawbacks discovered in stage 1, implementing a dementia initiative program. In stage 3, we reinvestigated the outpatients to determine the effects of intervention. RESULTS: After intervention, all 36 hospitals had established memory clinics (205 dementia doctors) compared with only 6 (47 dementia doctors) before intervention. The percentage of patients diagnosed with dementia significantly increased from 0.10% (536 dementia patients of 553,986 outpatients) in stage 1 to 0.41% (2482 dementia patients of 599,214 outpatients) in stage 3. DISCUSSION: Proper diagnosis and treatment are unavailable to many dementia patients because of a lack of dementia doctors and memory clinics in China.

The prevalence of dementia in urban and rural areas of China.

OBJECTIVE: The Chinese population has been aging rapidly and the country's economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas. METHODS: For the years 2008 to 2009, we performed a population-based cross-sectional survey with a multistage cluster sampling design. Residents aged 65 years and older were drawn from 30 urban (n = 6096) and 45 rural (n = 4180) communities across China. Participants were assessed with a series of clinical examinations and neuropsychological measures. Dementia, AD, and VaD were diagnosed according to established criteria via standard diagnostic procedures. RESULTS: The prevalence of dementia, AD, and VaD among individuals aged 65 years and older were 5.14% (95% CI, 4.71-5.57), 3.21% (95% CI, 2.87-3.55), and 1.50% (95% CI, 1.26-1.74), respectively. The prevalence of dementia was significantly higher in rural areas than in urban ones (6.05% vs. 4.40%, P < .001). The same regional difference was also seen for AD (4.25% vs. 2.44%, P < .001) but not for VaD (1.28% vs. 1.61%, P = .166). The difference in AD was not evident when the sample was stratified by educational level. Moreover, the risk factors for AD and VaD differed for urban and rural populations. CONCLUSIONS: A notably higher prevalence of dementia and AD was found in rural areas than in urban ones, and education might be an important reason for the urban-rural differences.

The prevalence of mild cognitive impairment and its etiological subtypes in elderly Chinese.

BACKGROUND: Epidemiologic studies on mild cognitive impairment (MCI) are limited in China. METHODS: Using a multistage cluster sampling design, a total of 10,276 community residents (6096 urban, 4180 rural) aged 65 years or older were evaluated and diagnosed with normal cognition, MCI, or dementia. MCI was further categorized by imaging into MCI caused by prodromal Alzheimer's disease (MCI-A), MCI resulting from cerebrovascular disease (MCI-CVD), MCI with vascular risk factors (MCI-VRF), and MCI caused by other diseases (MCI-O). RESULTS: The prevalences of overall MCI, MCI-A, MCI-CVD, MCI-VRF, and MCI-O were 20.8% (95% confidence interval [CI] = 20.0-21.6%), 6.1% (95% CI = 5.7-6.6%), 3.8% (95% CI = 3.4-4.2%), 4.9% (95% CI = 4.5-5.4%), and 5.9% (95% CI = 5.5-6.4%) respectively. The rural population had a higher prevalence of overall MCI (23.4% vs 16.8%, P < .001). CONCLUSIONS: The prevalence of MCI in elderly Chinese is higher in rural than in urban areas. Vascular-related MCI (MCI-CVD and MCI-VRF) was most common.

Rationale and design of a multicenter, phase 2 clinical trial to investigate the efficacy of traditional Chinese medicine SaiLuoTong in vascular dementia.

BACKGROUND: Vascular dementia (VaD) is the second most prevalent type of dementia among the aged, for whom limited pharmacologic options are available so far. SaiLuoTong capsule is a modern traditional Chinese medicine formula, which has been demonstrated to improve cognition of VaD by the reports of animal experiments and preliminary clinical trial. However, evaluation of this therapy in randomized multicenter trials is needed. In this article, we present the rationale and design of the SaiLuoTong in Vascular Dementia Study. METHODS: This phase 2 clinical trial of SaiLuoTong among patients with mild-to-moderate VaD is a 26-week, multicenter, randomized, double-blind, placebo-controlled study with a subsequent 26-week, open-label extension. After a 4-week placebo run-in period, participants are centrally randomized (1:1:1) to 3 groups: group A receives SaiLuoTong 360 mg per day for 52 weeks; group B receives SaiLuoTong 240 mg per day for 52 weeks; group C (the control group) are further randomly assigned to 2 groups in a 1:1 ratio and receives placebo during the double-blind phase, then SaiLuoTong 360 mg per day or SaiLuoTong 240 mg per day during the extension phase. The primary outcome measures include the VaD assessment scale cognitive subscale and the Alzheimer Disease Cooperative Study-clinical global impression of change. Safety measures include body weight, vital signs, electrocardiography, laboratory tests, and records of adverse events. Assuming an attrition rate of 20%, at least 372 patients are required to obtain a statistical power of 80%. RESULTS: The first patient was enrolled into the study in April 2012 and the completion of the study is expected in September 2014. CONCLUSIONS: The rigorous methodology of the study will hopefully move forward the scientific evaluation of traditional Chinese medicine in treatment of VaD. The results of the present study will provide high-quality evidence on the effect of SaiLuoTong in patients with VaD and has the potential to establish a novel therapeutic approach for this disorder.

Causal Relationship Between Ferritin and Neuropsychiatric Disorders: A Two-Sample Mendelian Randomization Study.

Background: Previous observational research has indicated a correlation between ferritin levels and neuropsychiatric disorders, although the causal relationship remains uncertain. Objective: The objective of this study was to investigate the potential causal link between plasma ferritin levels and neuropsychiatric disorders. Methods: A two-sample Mendelian randomization (MR) study was conducted, wherein genetic instruments associated with ferritin were obtained from a previously published genome-wide association study (GWAS). Summary statistics pertaining to neuropsychiatric disorders were derived from five distinct GWAS datasets. The primary MR analysis employed the inverse variance weighted (IVW) method and was corroborated by additional methods including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses were employed to identify potential pleiotropy and heterogeneity in the results. Results: The fixed effects IVW method revealed a statistically significant causal relationship between plasma ferritin level and the occurrence of Alzheimer's disease (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.00-1.12, p = 0.037), as well as Parkinson's disease (OR = 1.06, 95% CI: 1.00-1.13, p = 0.041). Various sensitivity analyses were conducted, which demonstrated no substantial heterogeneity or pleiotropy. Conversely, no compelling evidence was found to support a causal association between ferritin and amyotrophic lateral sclerosis, schizophrenia, or major depressive disorder. Conclusions: This MR study provides evidence at the genetic level for a causal relationship between plasma ferritin and an increased risk of Alzheimer's disease and Parkinson's disease. The exact genetic mechanisms underlying this connection necessitate further investigation.

Generation of human induced pluripotent stem cell line (XWHNi004-A) from a male with APOE gene mutation.

Genetic polymorphism of apolipoprotein E (APOE) confers differential susceptibility to Alzheimer's disease (AD), and APOE ɛ4 variants is the most powerful risk factor for this disease. Here, we report the generation of a human induced pluripotent stem cell (iPSC) line carrying the APOE ɛ4/ɛ4 genotype from peripheral blood mononuclear cells (PBMCs) isolated from a male with a family history of AD utilizing non-integrative Sendai virus vector. The iPSC maintains their original genotype, highly express endogenous pluripotency markers, displays a normal karyotype, and retains the ability to differentiate into cells representative of the three germ layers.

Generation of induced pluripotent stem cell line (XWHNi002-A) from a female with APP gene mutation.

The ß-amyloid precursor protein (APP) is a crucial pathogenic gene linked to Alzheimer's disease (AD). A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) isolated from a female with APP gene mutation utilizing non-integrative Sendai virus. The iPSC line exhibits high expression of pluripotency markers, retains the APP mutation, displays a normal karyotype, and has the ability to differentiate into normal teratoma tissue. This iPSC line represents a valuable cell model for investigating the pathological mechanisms and therapeutic strategies of AD.

Generation and characterization of a human induced pluripotent stem cell line (XWHNi001-A) derived from an Alzheimer's disease patient with mutation in the APP gene.

Mutations in the APP gene are popularly known as the second cause trigger the familial Alzheimer's disease (AD). We generated a human induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells isolated from an AD patient using non-integrative Sendai virus. The iPSC line highly expresses pluripotency markers, has the capacity to differentiate into the normal teratoma tissue, retains the APP mutation, and displays the normal karyotype. The iPSC line will provide a useful resource to study the pathogenesis and drugs screening of AD.

Culture Effects on the Chinese Version Boston Naming Test Performance and the Normative Data in the Native Chinese-Speaking Elders in Mainland China.

Background: The Chinese version of Boston Naming Test (BNT-C) is administered in China widely. However, the neuropsychological parameter of BNT-C in native Chinese-speaking elders in mainland China has not been explored systematically. The aim of this study was to explore cultural influences on BNT-C performance and establish norms among native Chinese-speaking elders in Beijing. Methods: A total of 161 native, Chinese-speaking, cognitively normal elders aged ≥55 years were enrolled from various communities in Beijing. The BNT-C was conducted on all the participants. The internal consistency, participants' familiarity, and naming accuracy were analyzed and compared with data from Chinese areas outside the mainland and from American published previously. The influencing factors and stratified norms for BNT-C were established. Results: The BNT-C showed good internal consistency (α = 0.738). Strong correlation between naming accuracy and object familiarity was found (r = 0.962, P < 0.001). Participants' familiarity and correct naming rate for many items were notably different between the Chinese-speaking elders and English-speaking elders in America. The difference in some items' correct naming rate also existed between Beijing, Taiwan, and Hongkong. Higher education was associated with higher scores, whereas age and gender had no effect on BNT-C performance. The recommended norms of total naming scores for elders with education ≤ 9 and >9 years were 16 and 23, respectively. Conclusion: The participants' familiarity with BNT items differed between different cultures, which further affected the naming accuracy and total scores. The education stratified norms established here are helpful for the better application of BNT-C in mainland China.

Detection of plasma Aß seeding activity by a newly developed analyzer for diagnosis of Alzheimer's disease.

OBJECTIVE: To evaluate the diagnostic value of plasma ß-amyloid (Aß) seeding activity measured using a newly developed instrument to distinguish Alzheimer's disease (AD) from other forms of dementia. METHODS: Seventy-nine AD patients, 64 non-AD dementia (NADD) patients, and 75 cognitively normal (NC) subjects were recruited in the study. To measure the levels of Aß seeding activity in the plasma samples, we have developed an AD-seeds protein analyzer. We used receiver operating characteristic (ROC) curves to quantify the ability of plasma Aß seeding activity to distinguish between AD and NADD or NC individuals. Spearman's correlation was used to examine the associations between plasma Aß seeding activity and global cognitive function or conventional AD biomarkers. RESULTS: The Aß seeding activities were 0.83 (0.58-1.16) A.U. in AD, 0.42 (0.04-0.74) A.U. in NADD and 0.42 (0.09-0.69) A.U. in NC, respectively. The Aß seeding activity was able to identify AD patients and distinguish them from NC or NADD with high accuracy (AUC = 0.85-0.86). In addition, the plasma Aß seeding activity showed a strong correlation with cognitive performance (mini-mental state examination, r = - 0.188; Montreal cognitive assessment, r = - 0.189; clinical dementia rating, r = 0.205) and conventional biomarkers (cerebrospinal fluid [CSF] Aß42/40, r = -0.227; CSF T-tau/Aß42, r = 0.239; CSF P-tau/Aß42, r = 0.259). CONCLUSION: Our results confirmed that plasma Aß seeding activity is an antibody-free and low-cost biomarker for the diagnosis of AD. TRIAL REGISTRATION: Trial registration number NCT04850053.