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Background: TAR DNA-binding protein-43 (TDP-43) and neurofilament light chain (NfL) are promising fluid biomarkers of disease progression for various dementia. Objective: We would explore whether blood levels of NfL and TDP-43 could predict the long-term progression to dementia, and the relationship of TDP-43 levels between cerebrospinal fluid (CSF) and blood. Methods: A total of 86 non-dementia elderly received 7-year follow-up, and were divided into 49 stable normal control (NC)/mild cognitive impairment (MCI) subjects, 19 subjects progressing from NC to MCI, and 18 subjects progressing from NC/MCI to dementia. Blood TDP-43 and NfL levels, and cognitive functions were measured in all subjects. Furthermore, another cohort of 23 dementia patients, including 13 AD and 10 non-AD patients received blood and CSF measurements of TDP-43. Results: In cohort 1, compared to stable NC/MCI group, there were higher levels of blood TDP-43 at baseline in subjects progressing from NC/MCI to dementia. The combination of baseline blood TDP-43 levels with demographics including age, education, and diabetes had the detection for dementia occurrence. Baseline blood levels of NfL are negatively associated with cognitive function at 7-year follow-up. In cohort 2, we found there were no relationship between CSF and blood levels of TDP-43. Moreover, the levels of TDP-43 in CSF was positively associated with the age of patients, especially in AD group. Conclusion: Single blood TDP-43 could not estimate dementia occurrence; however, TDP-43 combined with demographics has the predictive effect for dementia occurrence and NfL level is associated with a decrease of cognitive function.

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Background Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) includes a large spectrum of neurodegenerative disorders. Objective To identify the relationship of ErbB4 mutation and ALS/FTD. Methods Here, we report an atypical case of frontal variant behavioral abnormalities at the initial stage, a stable plateau stage of 5 years, and paralysis involving both upper and lower motor neurons followed by progressive cognitive dysfunction at the advanced stage. The clinical findings suggested a diagnosis of ALS/FTD, and genetic testing revealed erb-b2 receptor tyrosine kinase 4 (ErbB4) heterozygous mutation (c.2136 T>G, p.I712M), identified in an ALS pedigree previously. We modeled mutant ErbB4 protein through the SWISS-MODEL Server, and speculated on the structural change caused by the mutation. We also identified that ErbB4 (I712M) mutation led to reduced auto-phosphorylation of ErbB4 upon neuregulin-1 (NRG1) stimulation. Results A functional analysis of ErbB4 mutation demonstrated an obviously decreased auto-phosphorylation of ErbB4 involving in the pathogenesis of ALS/FTD. Conclusion We firstly found ErbB4 mutation to be identified in ALS/FTD.

Background: Yu Dafu, arguably one of the greatest writers in modern Chinese history, is characterized by critics as having a sentimental and decadent style. His life is clearly marked by mood bipolarity, and it seems that his creativity was affected by extreme emotional states. However, this link remains unclear. Methods: Yu’s self-assessments in his works and letters are analyzed from the perspective of current psychiatric classifications. Examples are extracted from his writing career and habits to help illuminate the relationship between mental disorders and literary creativity. Results: Yu’s writing career seems to be divided into four blocks. He was in a deep depression when he studied abroad and taught in China and experienced a hypomanic episode afterward, when he created a magazine and fell in love. The pattern of his mood changes is consistent with the symptoms of bipolar II disorder. His maintenance of a high degree of literary productivity alongside his anguish during depressive episodes may suggests mixed states. Conclusions: Mood changes shaped Yu’s life and writing career. Depressive and hypomanic moods enhanced his creativity in several ways, and some situations in his life indicate that writing and literary pursuits also have reverse effects on one’s mental state. The perspective that mental disorders are seen as a certain profile of literary career can help us to better understand the writers.

BackgroundMild cognitive impairment (MCI) is a transitional state between normal elderly people and dementia, with a higher risk of dementia transition. The primary purpose of the current study was to investigate whether routine blood and blood biochemical markers could be used to predict the onset of MCI.MethodsData was obtained from the cohort study on brain health of the elderly in Shanghai. A total of 1015 community elders were included in the current study. Based on clinical evaluation and the scores of Montreal Cognitive Assessment (MoCA), these participants were divided into the MCI (n=444) and cognitively normal groups (n=571). Then we tested their fasting blood routine and blood biochemical indexes, and collected their general demographic data by using a standard questionnaire.ResultsBy using binary logistic regression analysis and the ROC curve, we found that elevated fasting plasma glucose (p=0.025, OR=1.118, OR=1.014-1.233) was a risk factor for MCI.ConclusionsElevated fasting blood glucose may be a risk factor for mild cognitive impairment, but the above conclusions need to be verified by longitudinal studies.

Background: Sporadic dementias generally occur in older age and are highly polygenic, which indicates some patients transmitted in a poly-genes hereditary fashion.Objective: Our study aimed to analyze the correlations of genetic features with clinical symptoms in patients with degenerative dementia.Methods: We recruited a group of 84 dementia patients and conducted the whole exome sequencing (WES). The data were analyzed focusing on 153 dementia-related causing and susceptible genes.Results: According to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, we identified four reported pathogenic variants, namely, PSEN1 c.A344G, APP c.G2149A, MAPT c.G1165A, and MAPT c.G742A, one reported likely pathogenic variant, namely, PSEN2 c.G100A, one novel pathogenic variants, SQSTM1 c.C671A, and three novel likely pathogenic variants, namely, ABCA7 c.C4690T, ATP13A2 c.3135delC, and NOS3 c.2897-2A > G. 21 variants with uncertain significance in PSEN2, C9orf72, NOTCH3, ABCA7, ERBB4, GRN, MPO, SETX, SORL1, NEFH, ADCM10, and SORL1, etc., were also detected in patients with Alzheimer’s disease (AD) and frontotemporal dementia (FTD).Conclusion: The new variants in dementia-related genes indicated heterogeneity in pathogenesis and phenotype of degenerative dementia. WES could serve as an efficient diagnostic tool for detecting intractable dementia.

Obesity is a critical issue in patients with schizophrenia, which is considered to be brought about by both environmental and genetic factors. Apolipoprotein E (APOE) gene polymorphisms might be involved in the pathogenesis of schizophrenia, however, the effect of APOE gene polymorphism on obesity has never been investigated in Chinese aging with schizophrenia. This cross-sectional study was to investigate the effect of obesity on cognitive and psychiatric symptoms in elderly participants with schizophrenia. At the same time, we also discussed the inner link between APOE E4 and obesity. 301 elderly participants with schizophrenia and 156 normal controls were included in the study. Their cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and APOE gene polymorphism was determined by polymerase chain reaction (PCR). The prevalence of obesity in elderly schizophrenic patients and healthy controls accounted for 15.9% (48/301) and 10.3% (16/156), respectively, with no statistically significant difference. By using stepwise linear regression analysis, we found that elevated fasting blood glucose, hypertension, and hyperlipidemia were risk factors for obesity in elderly schizophrenic patients. Although there was no direct correlation between APOE E4 and obesity in patients with schizophrenia, it was significantly correlated with hyperlipemia(r = − 0.154, p = 0.008), suggesting that APOE E4 may induce obesity in elderly patients with schizophrenia through hyperlipemia, However, the above conclusions do not apply to the normal elderly. What’s more, we did not find a link between obesity and cognitive function or mental symptoms for both patients with schizophrenia and normal controls. APOE E4 is associated with hyperlipidemia in elderly schizophrenic patients, which may be a risk factor for obesity, however, the above conclusion does not apply to the normal elderly.

The purpose of this study is to investigate the complex connection between apathy and cognitive decline that remains unclear. A total of 1057 non-dementia elderly from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database received up to 13 years of follow-up and were divided into an apathy negative (−) group of 943 participants and an apathy positive (+) group of 114 participants through the Neuropsychiatric Inventory (NPI)-apathy subitem. Cerebrospinal fluid (CSF) AD biomarkers and amyloid β (Aβ) PET were measured, and their longitudinal changes were assessed using linear mixed-effects models. Risk factors for cognitive decline and apathy conversion were explored through the Cox proportional hazards model. Mediation effects of Aβ pathology on cognition were investigated using the causal mediation analysis. Apathy syndrome was associated with faster impairment of cognition and elevation of the Aβ burden. The effects of apathy on cognitive function and life quality were mediated by Aβ pathology, including CSF Aβ42/total tau ratio, and Aβ deposition in the prefrontal regions. Apathy syndrome was the risk factor for cognitive deterioration; meanwhile, frontal Aβ burden was the risk factor for apathy conversion. Apathy syndrome is an early manifestation of cognitive decline and there are bidirectional roles between apathy syndrome and Aβ pathology. Prefrontal Aβ pathology influenced the pathway from apathy to cognitive decline.

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

Background: The 4 allele of the apolipoprotein E (APOE) gene is known as a risk factor for cognitive impairment. How APOE e polymorphism affects the language and executive functions of healthy aging subjects remains less clear. Purpose: In this follow-up study, the relationship between APOE status and cognitive performance across various cognitive domains in healthy individuals (without dementia or mild cognitive impairment (MCI)) over 60 years old was investigated. Patients and methods: Based on multiplex amplification refractory mutation system polymerase chain reaction (PCR), 228 subjects (n=228; mean age: 70.59±8.07 years old; male %=40.8%) were divided into three groups, e2 (e2/e2 and e2/e3, n=35), e3 (e3/e3, n=152), and e4 (e2/e4, e3/e4, and e4/e4, n=41). Results: There was no statistical difference (p>0.05) in the general demographic data and neuropsychological tests among the three groups on the baseline; however, e4 group showed a greater drop rate (p

Short-term memory decline is the typical clinical manifestation of Alzheimer’s disease (AD). However, early-onset AD usually has atypical symptoms and may get misdiagnosed. In the present case study, we reported a patient who experienced symptoms of memory loss with progressive non-fluent aphasia accompanied by gradual social withdrawal. He did not meet the diagnostic criteria of AD based on the clinical manifestation and brain MRI. However, his cerebrospinal fluid examination showed a decreased level of beta-amyloid 42, and increased total tau and phosphorylated tau. Massive amyloid β-protein deposition by 11C-Pittsburgh positron emission tomography confirmed the diagnosis of frontal variant AD. This case indicated that early-onset AD may have progressive non-fluent aphasia as the core manifestation. The combination of individual and precision diagnosis would be beneficial for similar cases.

Subjective cognitive decline (SCD) is a high‐risk yet less understood status before developing Alzheimer's disease (AD). This work included 76 SCD individuals with two (baseline and 7 years later) neuropsychological evaluations and a baseline T1‐weighted structural MRI. A machine learning‐based model was trained based on 198 baseline neuroimaging (morphometric) features and a battery of 25 clinical measurements to discriminate 24 progressive SCDs who converted to mild cognitive impairment (MCI) at follow‐up from 52 stable SCDs. The SCD progression was satisfactorily predicted with the combined features. A history of stroke, a low education level, a low baseline MoCA score, a shrunk left amygdala, and enlarged white matter at the banks of the right superior temporal sulcus were found to favor the progression. This is to date the largest retrospective study of SCD‐to‐MCI conversion with the longest follow‐up, suggesting predictable far‐future cognitive decline for the risky populations with baseline measures only. These findings provide valuable knowledge to the future neuropathological studies of AD in its prodromal phase., In this article, we used a community‐based cohort of subjective cognitive decline (SCD) elderly subjects with 7‐year follow‐up and retrospectively identified individual SCD who had converted to mild cognitive impairment (MCI) during the follow‐up. After identifying progressive SCDs from stable SCDs, we constructed a machine learning‐based prediction model that successfully identified most progressive SCD individuals based on 198 morphometric features derived from structural MRI and 25 comprehensive clinical features. The striking finding is that as few as five neuroimaging and clinical features derived from baseline were able to predict cognitive impairment occurred 7 years later.

Background: Depressive symptoms are common comorbidities in schizophrenia. However, the effect of APOE E3 on depressive symptoms has never been investigated in an aging Chinese population with schizophrenia. This cross-sectional study aimed to investigate the effects of APOE E3 on blood lipid metabolism and depressive symptoms in elderly schizophrenics in China. Methods: Three Hundred and one elderly schizophrenics (161 males, age ranges from 60 to 92 years, with an average age of 67.31 ± 6.667) were included in the study. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). APOE gene polymorphism was determined by polymerase chain reaction (PCR). We assessed the correlations of GDS and serum low-density lipoprotein (LDL) with APOE genotypes. Results: The concentration of LDL in the Homozygous APOE E3 group was significantly higher than that in the non-homozygous APOE E3 group, while the scores of GDS of the Homozygous APOE E3 group were lower than that in the non-homozygous APOE E3 group. Using partial correlation analysis and controlling age, gender, duration of disease, and hyperlipidemia, we found that the scores of GDS were significantly correlated with LDL (r = −0.194, p = 0.016). Conclusions: APOE E3 is associated with less depressive symptoms and higher serum LDL in Chinese elderly patients with schizophrenia, and there is a negative correlation between depressive symptoms and LDL.

Background: The pathogenesis of dementia often starts several years prior to clinical onset during which the individual is asymptomatic. Existing strategies for the accurate diagnosis of early dementia are limited by high cost and the invasive nature of the procedures. Eye movement parameters associated with cognitive functions may be helpful in the early identification of dementia and in the development and evaluation of preventive and therapeutic strategies. Objective: We aimed to assess differences in eye movement parameters between healthy elderly individuals and patients with mild cognitive impairment (MCI). Furthermore, we examined the correlations between eye movement parameters with cognitive functions and specific hemispheric region and neural structures in individuals with MCI. Method: Eighty individuals with MCI without dementia (based on DSM-IV criteria) identified by community screening and 170 healthy controls were administered Chinese versions of MoCA and NTB, and a long (20 min) or short (5 min) version of a visual paired comparison (VPC) task. Two weeks later, 44 MCI patients and 107 healthy controls completed a retest of the VPC task, 44 MCI patients and 43 healthy controls among them administered a MRI. At the end of 1-year follow-up, a subset of 26 individuals with MCI and 57 healthy controls were administered the long version of VPC task and MoCA test again. Eye movement parameters and the relationship of eye movement parameters with cognitive functions and with changes in neural structures were compared between groups. Results: Patients with MCI were older, had less education, and had lower scores on cognitive tests than healthy controls. After adjustment for age and level of education, patients with MCI had lower novelty preference scores on the VPC than healthy controls. Using the logistic regression model, the amount of time that subjects focused on these novel images could predict MCI patients from normal elderly with an out of sample area under the receiver operator characteristic curve of 0.62. Furthermore, the cognition score of subjects whose novelty preference score was low decreased more remarkably in 1 year. For both the patient and control groups, VPC novelty preference was significantly correlated with verbal fluency and delayed and short-term memory function. Novelty preference score was also significantly correlated with the cortical thickness of several structures in the right hemisphere. Conclusion: Eye movement parameters are stable indicators to distinguish patients with MCI and cognitively normal subjects and are not affected by different testing versions and numbers. Additionally, the patients’ cognitive deficits and eye movement indices were correlated. Future longitudinal studies should further explore the clinical utility of eye movement parameters as early markers of MCI.

Subjective cognitive decline (SCD) is a high-risk yet less understood status years before Alzheimer’s disease (AD). This work included 76 SCD individuals with two (baseline and seven years later) neuropsychological evaluations and a baseline T1-MRI. A machine learning-based model was trained based on 198 baseline neuroimage features and a battery of 25 clinical measurements to discriminate 24 progressive SCDs from 52 stable SCDs. The SCD progression was satisfactorily predicted with combined features. A history of stroke, a low education level, a low baseline MoCA score, a shrunk left amygdala, and enlarged white matter at the banks of the right superior temporal sulcus favor the progression. This is to date the largest retrospective study of SCD-to-MCI conversion with the longest follow-up, suggesting predictable far-future cognitive decline for the risky populations with baseline measures only. These findings provide valuable knowledge to the future neuropathological studies of AD in its prodromal phase.

The clinical manifestation of frontal-variant Alzheimer’s disease (fvAD) is not typical, and it is difficult yet necessary to differentiate fvAD from frontal-variant frontal temporal dementia (fvFTD). We describe a patient with early-onset Alzheimer’s disease (AD) who presented with an fvFTD-like syndrome and apolipoprotein E ɛ3/ ɛ4 genotype. A brain amyloid imaging procedure, 11C-Pittsburgh compound B positron emission tomography (PET), supported the final diagnosis of AD. Our present case highlights the clinical variability that characterises early-onset AD. A multimodal approach is crucial when assessing rare forms of dementia.

Background: The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for China We speculated that the emigration rate of Wu

Background: Hypertension is considered as an independent risk factor for vascular mild cognitive impairment (vMCI) and vascular dementia (VaD). This study was performed to investigate the prevalence, influencing factors, and cognitive characteristics of vMCI and VaD in elderly patients with hypertension in China. Methods: In the cross-sectional study, we performed a cluster random sampling of 3246 people age 60 years and older across the country. All participants were interviewed and screened for hypertension. Among the 1495 hypertensive patients, 57 were diagnosed with vMCI and 48 with VaD according to the criteria of Petersen and DSM-IV, respectively. Logistic regression analyses were performed to evaluate risk and protective factors for vMCI and VaD with Hypertension. And we also assessed their cognitive function by a series of neuropsychological tests. Results: We finally found that: 1) the prevalence of vMCI and VaD in hypertension was 3.8% and 3.2%, respectively, which was much higher than that of normal controls (p

Background Neurotrophins including brain-derived neurotropic factor (BDNF) are implicated in the pathogenesis of major depressive disorder (MDD). Yet, the roles of brain-specific BDNF-related miRNAs miR-132 and miR-124 are unclear. Methods We enrolled 45 treatment-free patients with MDD, 32 citalopram-treated patients with MDD, and 32 healthy control subjects. Participants were assessed with the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). In a case-control sub-study, we followed 14 treatment-free patients who were subsequently treated with citalopram for 2 months. Enzyme-linked immunosorbent assay was used to detect plasma BDNF, and real-time polymerase chain reaction was used to quantify relative plasma miR-132 and miR-124 expression. Results Patients with MDD had significantly higher HAMA and HAMD scores than the control group, with the highest scores in the treatment-free MDD group. Plasma miR-132 in the treatment-free MDD group was 2.4-fold that in the control group and significantly higher than that in the citalopram-treated MDD group. Plasma miR-124 in the treatment-free MDD and citalopram-treated MDD groups was 1.8-fold and 4-fold that in the control group, respectively. Compared to the control group, plasma BDNF levels were increased in both MDD groups, but not significantly different between them. There was a positive correlation between miR-132 and HAMD and HAMA scores, whereas no significant correlations were identified for plasma miR-124 or BDNF. Limitations The range of neurotrophin-related MiRNAs and the number of follow-up cases were limited. Conclusions BDNF and miR-124 in plasma increase with depression and antidepressants. Plasma MiR-132 might be an indication for depression status.

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.

BACKGROUND Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type. OBJECTIVE To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer's disease (AD). METHODS The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naive AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: Alzheimer's Disease Cooperative Study; Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. RESULTS 222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (≥6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p

The population of early-onset Alzheimer’s disease (EOAD) accounts for 1%–2% of the total population of Alzheimer’s disease, and genetic mutations are more common in EOAD. The first symptom of the patient in the present case report was the decline in memories of recent events, and the disease progressed rapidly in the following 2 years. Genetic testing has revealed the presence of genetic mutations (c.A479G, p.N160S) of ACE, which causes the 160th codon of the ACE protein to change from aspartic acid to serine, and at the same time genotype of apolipoprotein E (APOE) is ɛ3/ɛ4. We think that this patient carries the mutation type of the sensitive gene ACE and the risk gene APOE of Alzheimer’s disease, and this is the reason why the disease progressed rapidly. Moreover, we discussed ACE genetic mutation’s meaning in EOAD progression.

Background Few studies have investigated the effects of blood glucose (BG) on cognitive function in community-dwelling elderly individuals carrying the apolipoprotein E (APOE) ε3 allele. Objective To explore the effect of high BG levels on cognitive function in APOE ε3-carrying, non-demented, community-dwelling older adults, as compared to their counterparts carrying the APOE ε4 or APOE ε2 alleles. Methods Within the China Longitudinal Ageing Study, we recruited 282 elderly adults without dementia. Data collected included demographic information; psychological measures; laboratory test results, including BG and plasma lipid levels; and APOE genotypes. We divided the participants into APOE ε2(ε2/ε2, ε2/ε3), ε3(ε3/ε3), and ε4(ε3/ε4, ε4/ε4) groups. Partial correlation analyses and multivariate linear regression analyses were utilized to compare the cognitive function and laboratory data between the APOE groups. White matter hyperintensity (WMH) was measured on magnetic resonance images in 77 participants. Results With adjustment for age, sex, education, and diabetes, higher BG in non-demented community-dwelling older adults was associated with cognitive decline in immediate memory and executive function. In the APOE ε3 group, elevated BG was associated with cognitive decline in immediate memory, executive function, and perceptual reasoning. In the APOE ε4 group, higher BG was also correlated with a decline in abstract reasoning. There was a trend for association between higher BG and more severe WMHs. Conclusion Worse cognitive function was correlated withApoEε3/ε3 genotype carriers with higher BG in community-dwelling older adults.

BackgroundDementia is a chronic brain disorder classified by four distinct diseases that impact cognition and mental degeneration. Each subgroup exhibits similar brain deficiencies and mutations. This review will focus on four dementia subgroups: Alzheimer’s disease, vascular dementia, frontotemporal dementia and dementia Lewy body.AimThe aim of this systematic review is to create a concise overview of unique similarities within dementia used to locate and identify new biomarker methods in diagnosing dementia.Methods123 300 articles published after 2010 were identified from PubMed, JSTOR, WorldCat Online Computer Library and PALNI (Private Academic Library Network of Indiana) using the following search items (in title or abstract): ‘Neurodegenerative Diseases’ OR ‘Biomarkers’ OR ‘Alzheimer’s Disease’ OR ‘Frontal Temporal Lobe Dementia’ OR ‘Vascular Dementia’ OR ‘Dementia Lewy Body’ OR ‘Cerebral Spinal Fluid’ OR ‘Mental Cognitive Impairment’. 47 studies were included in the qualitative synthesis.ResultsEvidence suggested neuroimaging with amyloid positron emission tomography (PET) scanning and newly found PET tracers to be more effective in diagnosing Alzheimer’s and amnesiac mental cognitive impairment than carbon-11 Pittsburgh compound-B radioisotope tracer. Newly created methods to make PET scans more accurate and practical in clinical settings signify a major shift in diagnosing dementia and neurodegenerative diseases.ConclusionVast improvements in neuroimaging techniques have led to newly discovered biomarkers and diagnostics. Neuroimaging with amyloid PET scanning surpasses what had been considered the dominant method of neuroimaging and MRI. Newly created methods to make PET scans more accurate and practical in clinical settings signify a major shift in diagnosing dementia pathology. Continued research and studies must be conducted to improve current findings and streamline methods to further subcategorise neurodegenerative disorders and diagnosis.

Mild cognitive impairment (MCI) is a neurological disorder that occurs in older adults involving cognitive impairments. It may occur as a transitional stage between normal aging and dementia such as Alzheimer’s disease (AD). Recent studies found that subjective cognitive decline (SCD) may be the early clinical precursor of dementia that precedes MCI. SCD individuals with normal cognition may already have some medial temporal lobe atrophy. This paper proposes a machine learning framework by combination of sparse coding and random forest to identify the informative biomarkers for prediction of clinical scores in SCD and MCI using structural magnetic resonance imaging (MRI). The volumetric features are computed from brain regions and the subregions of hippocampus and amygdala in MRIs. Then, sparse coding is applied to identify the relevant features. Finally, the proximity-based random forest is used to combine three sets of volumetric features and establish a regression model for predicting clinical scores. Our method has double feature selections to better explore the relevant features for prediction. Our method is evaluated with the T1-weighted structural MR images from 36 MCI, 112 SCD, 78 Normal Control (NC) subjects. The results demonstrate the effectiveness of proposed method.

Frontotemporal dementia includes a large spectrum of neurodegenerative disorders. Here, we report the case of a young patient with MAPT mutation G389R, who was 27 years old when he progressively developed severe behavioral disturbances. Initially, he presented with slowly progressive personality change. After 1 year, he exhibited moderate dementia with extrapyramidal and pyramidal symptoms. MRI showed frontotemporal atrophy. He rapidly progressed to severe dementia 3 years after onset. Genetic testing revealed a heterozygous guanine to cytosine mutation at the first base of codon 389 (c.1165G>A) of MAPT, the tau gene, resulting in a glycine to arginine substitution in the patient and two unaffected relatives. We predicted the model of mutant tau protein through I-TASSER software, and speculated the structural change of tau protein caused by mutant site. We also detected the MAPT gene transcript and methylation of samples from peripheral blood leucocytes in an attempt to explain the possible mechanisms of incomplete penetrance, although there were not positive findings. This case is remarkable because of the early onset and rapid progression of the disease.

The establishment of normative data and screening cut-points for cognitive tasks is important to ensure the effective and timely detection of mild cognitive impairment (MCI) and Alzheimer's disease (AD). These need to be culturally relevant and account for known factors that impact on cognition such as age, education, and gender. In this study, 1,068 elderly Chinese residents of Shanghai completed a comprehensive series of cognitive tasks as part of a community screening study with 1027 meeting criteria for analysis, age M(SD) = 72.54 (8.40). MCI was detected in 267 individuals, AD in 50, and 710 had normal cognition. Receiver Operator Characteristic curve analysis indicated that the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) best differentiated normal cognition from MCI and AD. We present suggested cut-points to differentiate between normal cognition and MCI and AD for the total sample, and when split according to education levels, age, and gender. Trends suggest that the MoCA was better suited to detecting MCI, and the MMSE was better for detecting AD. For younger and more educated participants, only a slight impairment was necessary to meet screening criteria, while a larger impairment was necessary for older and less educated participants. Both tasks had a high negative predictive values for MCI and AD, and variable positive predictive values. The cut-points presented can be used to inform future work using the MMSE and MoCA to screen for MCI and AD in older Chinese people. (PsycINFO Database Record

Background: China’s ageing population will lead to increased neurodegenerative illness and age-related mental health problems. Aims: The Chinese Longitudinal Ageing Study has been developed to better understand the impact of ageing on cognition and mental health. An overview of the sample, major diagnoses and results of the first wave of data collection is presented. Method: One thousand and sixty-eight elderly Chinese (42.2% male), mean age of 72.8 years (SD = 8.5) completed a comprehensive cognitive, psychosocial and mental health assessment. Results: Mean MMSE score was 24.73 (SD = 6.17). Primary generalised anxiety was detected in 0.4% of the sample. Sub-clinical depression and depressive disorder were diagnosed in 1.7% and 2.4% of the sample, respectively. Most (84.5%) reported subjective memory decline, however 66.5% had no cognitive impairment. Mild Cognitive Impairment (MCI) was detected in 25%, Alzheimer’s disease (AD) in 4.7%, vascular dementia in 2.5%, and mixed dementia in 1.3%. Cognition was worse in those 85+ years, but affective disorder rates were not. Conclusion: Higher rates of dementia were detected than previously reported in China. Normative data is presented for common cognitive and mental health assessment and screening tasks in a Chinese population. This suggests that the true incidence of dementia has been underestimated, and requires further investigation.

BackgroundWith an aggravated social ageing level, the number of patients with Alzheimer’s disease (AD) is gradually increasing, and mild cognitive impairment (MCI) is considered to be an early form of Alzheimer’s disease. How to distinguish diseases in the early stage for the purposes of early diagnosis and treatment is an important topic.AimsThe purpose of our study was to investigate the differences in brain cortical thickness and surface area among elderly patients with AD, elderly patients with amnestic MCI (aMCI) and normal controls (NC).Methods20 AD patients, 21 aMCIs and 25 NC were recruited in the study. FreeSurfer software was used to calculate cortical thickness and surface area among groups.ResultsThe patients with AD had less cortical thickness both in the left and right hemisphere in 17 of the 36 brain regions examined than the patients with aMCI or NC. The patients with AD also had smaller cerebral surface area both in the left and right hemisphere in 3 of the 36 brain regions examined than the patients with aMCI or NC. Compared with the NC, the patients with aMCI only had slight atrophy in the inferior parietal lobe of the left hemisphere, and no significant difference was found.ConclusionAD, as well as aMCI (to a lesser extent), is associated with reduced cortical thickness and surface area in a few brain regions associated with cognitive impairment. These results suggest that cortical thickness and surface area could be used for early detection of AD.

Frontotemporal dementia includes a large spectrum of neurodegenerative disorders. SQSTM1, coding for p62 protein, plays a vital role in the pathogenesis of FTD. Here, we report a case of a female patient with SQSTM1 mutation S224X, who was 59 years old when she initially exhibited memory decline, mild personality changes, and subtle atrophy of frontal/temporal lobes in magnetic resonance imaging (MRI). Genetic testing revealed a nonsense mutation of the SQSTM1 gene (S224X), resulting in premature termination of protein synthesis and a predicted truncated protein 217 amino acids shorter than the normal protein. Moreover, neither intact nor truncated SQSTM1 proteins was detectable in SQSTM1 S224X mutant overexpressing HEK-293T cells. We assayed for SQSTM1 cDNA in samples from the patient's peripheral leucocytes, and did not detect its mutation. The test of quantitative PCR showed significant decreased level of SQSTM1 mRNA from peripheral leucocytes of the patient compared to five dementia controls. Our results identify a novel pathogenic SQSTM1 S224X mutation in an atypical FTD patient accompanied with loss of SQSTM1/p62 protein expression probably due to SQSTM1 gene haploinsufficiency.

Using a combination of the Hopkins Verbal Learning Test (HVLT) and the Mini-Mental State Examination (MMSE), we investigated the prevalence of possible dementia (DEM) in community-dwelling elderly in Shanghai. Subsequently, we investigated significant risk factors for DEM and generated a DEM self-checklist for early DEM detection and case management. We found that among a total of 521 participants using a HVLT cut-off score of &lt, 19 and a MMSE cut-off score of &lt, 24, a total of 69 DEM cases were identified. Risk factors, such as advanced age (≥68 years), low education (no or primary level), self-reported history of hypertension, and self-reported subjective memory complaints (SMC) were significantly predictive of DEM. The presence of ≥3 out of four of the above mentioned risk factors can effectively discriminate DEM cases from non-DEM subjects.

OBJECTIVE To investigate the relationship between microRNA107 (miRNA107) and BACE1 messenger RNA (mRNA) gene expressions in plasma and their diagnostic capability to distinguish subjects with amnestic mild cognitive impairment from healthy controls. METHOD We recruited 97 patients with Alzheimer's disease according to diagnostic criteria of DSM-IV and National Institute of Neurologic and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association, 116 subjects with amnestic mild cognitive impairment, and 81 healthy controls from January 2012 to December 2012. The real-time PCR was used to quantify miRNA107 and BACE1 mRNA. The power of classification accuracies between patients with amnestic mild cognitive impairment and healthy controls was performed using linear discriminate analysis single or combining both the expression miRNA107 and BACE1 mRNA. RESULTS For patients with Alzheimer's disease, the miRNA107 expressions in plasma and cerebral spinal fluid were correlated (Pearson correlation = 0.665, P = .034). There were statistically significant correlations between plasma miRNA107 and BACE1 mRNA gene expression in Alzheimer's disease, amnestic mild cognitive impairment, and healthy control groups (r value = -0.316 [P = .002], -0.615 [P < .001], and -0.367 [P = .001], respectively). The overall classification accuracy of miRNA107 to discriminate between patients with amnestic mild cognitive impairment and healthy controls was 91.9%, with sensitivity of 98.3% and specificity of 82.7%. CONCLUSIONS The miRNA107 expression in plasma has a high capability to discriminate between patients with amnestic mild cognitive impairment and healthy controls. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01819545.

Alzheimer’s disease (AD) is the most common type of dementia, and promptly diagnosis of AD is crucial for delaying the development of disease and improving patient quality of life. However, AD detection, particularly in the early stages, remains a substantial challenge due to the lack of specific biomarkers. The present study was undertaken to identify and validate the potential of circulating miRNAs as novel biomarkers for AD. Solexa sequencing was employed to screen the expression profile of serum miRNAs in AD and controls. RT-qPCR was used to confirm the altered miRNAs at the individual level. Moreover, candidate miRNAs were examined in the serum samples of patients with mild cognitive impairment (MCI) and vascular dementia (VD). The results showed that four miRNAs (miR-31, miR-93, miR-143, and miR-146a) were markedly decreased in AD patients’ serum compared with controls. Receiver operating characteristic curve analysis demonstrated that this panel of four miRNAs could be used as potential biomarker for AD. Furthermore, miR-93, and miR-146a were significantly elevated in MCI compared with controls, and the panel of miR-31, miR-93 and miR-146a can be used to discriminate AD from VD. We established a panel of four serum miRNAs as a novel noninvasive biomarker for AD diagnosis.

Bone morphogenetic protein 6 (BMP6) has neuroprotective effects against various neuronal injuries, but its effect on amyloid-β (Aβ)-induced neurotoxicity remains unclear. We exposed rat hippocampal neurons to different concentrations of Aβ25-35 to induce neurotoxicity, and then treated cells with BMP6 to assess the neuroprotective effects. In vivo, we bilaterally injected Aβ1-40 into basal forebrain to simulate the neuropathological process of Alzheimer's disease (AD), and explored changes in the expression of BMP6 and LIMK1. Our data demonstrated that BMP6 prevented apoptosis induced by a high dose of Aβ25-35, and inhibited rod formation induced by low dose of Aβ25-35 in hippocampal neurons. Forebrain injection of Aβ1-40 led to a significant downregulation of BMP6, and inactivation of LIMK1 pathway in basal forebrain, whereas the opposite changes were observed in hippocampus. Our results suggest that BMP6 has neuroprotective effects against Aβ25-35. The BMP6 and LIMK1 pathways may have different expression patterns at different stages of AD, and be self-regulating via a negative feedback mechanism between different brain regions.

Most experts consider that memantine has a symptomatic treatment, but clinical trials have not yet provided compelling evidence to support a disease-modifying effect. We investigate the effects of memantine on clinical ratings; fluorodeoxyglucose positron emission tomography (FDG-PET) measurements, which can monitor disease-modifying effect; and cerebrospinal fluid (CSF) assays in patients with moderate to severe probable Alzheimer disease (AD) dementia. Twenty-two patients completed a 24-week, double-blind, placebo-controlled, randomized clinical trial of memantine, titrated up to 10 mg twice per day using the Severe Impairment Battery, AD Assessment Scale-Cognitive subscale, Mini-Mental State Examination, FDG-PET measurements of the regional cerebral metabolic rate for glucose (CMRgl), and CSF amyloid β (Aβ) and tau assays. An automated brain mapping algorithm and predefined regions of interest were each used to analyze treatment-related regional CMRgl effects. In comparison with the placebo group, the memantine treatment group had significantly less cognitive decline on the Severe Impairment Battery and significantly less CMRgl declines in regions preferentially affected by AD. There were no significant treatment effects on CSF Aβ₁₋₄₂, CSF Aβ₁₋₄₀, total tau, or phosphor-tau levels or ratios. This relatively small and brief randomized clinical trial suggests an association between memantine's clinical benefit and its effects on FDG-PET measurements in AD-affected brain regions. Larger and longer studies are needed to confirm these findings, extend them to earlier clinical and preclinical stages of AD, and help determine the extent to which FDG-PET should be qualified for use as a reasonably likely surrogate end point in the evaluation of putative AD-modifying treatments.

During visual fixation, the eyes are never completely still, but produce small involuntary movements, called “fixational eye movements,” including microsaccades, drift, and tremor. In certain neurological disorders, attempted fixation results in abnormal fixational eye movements with distinctive characteristics. Thus, determining how normal fixation differs from pathological fixation has the potential to aid early and differential noninvasive diagnosis of neurological disease as well as the quantification of its progression and response to treatment. Here, we recorded the eye movements produced by patients with Alzheimer’s disease, patients with mild cognitive impairment, and healthy age-matched individuals during attempted fixation. We found that microsaccade magnitudes, velocities, durations, and intersaccadic intervals were comparable in the three subject groups, but microsaccade direction differed in patients versus healthy subjects. Our results indicate that microsaccades are more prevalently oblique in patients with Alzheimer’s disease or mild cognitive impairment than in healthy subjects. These findings extended to those microsaccades paired in square-wave jerks, supporting the hypothesis that microsaccades and square-wave jerks form a continuum, both in healthy subjects and in neurological patients.

Wei Li,1,2 Tao Wang,1,2 Shifu Xiao1,2 1Alzheimer’s Disease and Related Disorders Center, 2Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China Background: Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer’s disease (AD), so identification of the related risk factors can be helpful. Although the association between type 2 diabetes mellitus (T2DM) and these modest changes in cognition is well established, whether T2DM will promote the transformation of MCI into AD is not a unified conclusion.Objective: This study aims to explore the relationship between T2DM and MCI in the elderly population living in the community in Shanghai, People’s Republic of China.Methods: A total of 197 participants were included in the study. They were screened for T2DM, hyperlipidemia, traumatic brain injury, and family history of dementia. The Mini-Mental State Examination and the Montreal Cognitive Assessment were used to assess cognitive function. The diagnosis of AD was made according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, whereas the diagnosis of MCI was made according to Petersen’s criteria. Then, we investigated the relation between T2DM and MCI.Results: A total of 82 (41.6%) participants had no cognitive impairment, 82 (41.6%) participants had MCI, and 33 (16.8%) participants had AD. Multivariate logistic regression models demonstrated that T2DM was a risk factor for AD (odds ratio =49.723, 95% CI =21.173–111.987).Conclusion: T2DM might be a risk factor for MCI progressing into AD. Keywords: T2DM, AD, MCI, risk factor

Rapid cognitive decline (RCD) occurs in dementia due to Alzheimer's disease (AD).Literature review, consensus meetings, and a retrospective chart review of patients with probable AD were conducted.Literature review showed that RCD definitions varied. Mini-Mental State Examination scores20 at treatment onset, vascular risk factors, age70 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.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.

This study investigated the relationship between education, cognitive and physical function in older age, and their respective impacts on activities of daily living (ADL). Data on 148 older participants from a community-based sample recruited in Shanghai, China, included the following measures: age, education, ADL, grip strength, balance, gait speed, global cognition and verbal memory. The majority of participants in the present cohort were cognitively and physically healthy and reported no problems with ADL. Twenty-eight percent of participants needed help with ADL, with the majority of this group being over 80 years of age. Significant predictors of reductions in functional independence included age, balance, global cognitive function (MMSE) and the gait measures. Cluster analysis revealed a protective effect of education on cognitive function that did not appear to extend to physical function. Consistency of such phenotypes of ageing clusters in other cohort studies may provide helpful models for dementia and frailty prevention measures.

Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low-density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE ε2 group (ε2/ε2 and ε2/ε3), APOE ε3 group (ε3/ε3), and APOE ε4 group (ε2/ε4, ε3/ε4 and ε4/ε4). Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE ε3/ε3 genotype exhibited the highest frequency (70.4%) among the subjects. Participants in the APOE ε3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE ε2 and APOE ε4 groups (P

Objective: To assess the knowledge of and attitudes towards dementia among Shanghai residents. Methods: A 10-item optional questionnaire relating to dementia was developed for the project. Questionnaires were randomly distributed to 1806 families, each family had one respondent. Results: A total of 1531 questionnaires were available. Among them, 45% considered ‘dementia is a normal part of ageing’ and 29–41% correctly identified the symptoms of mild dementia. Of the respondents, 43% indicated that they would not be ashamed of having a demented relative, and 45% did not think that medical care benefited those with dementia. Subgroups analyses showed there was a wider agreement on the concept ‘dementia is a normal part of ageing’ in the elderly or the females with primary school education background than the counterpart. According to the educational level, the sequence (from the highest to the lowest) of the proportion of respondents who considered a demented relative to be shameful was as follows: middle school group (60.5%) > primary school group (41.3%) > university group (25.2%); according to age group: adult group (59.8%) > elderly group (37.3%) > youth group (30.2%). There was a higher identification rate of the symptoms of mild dementia in women than in men (P primary school group > middle school group; according to age group: elderly group > youth group > adult group. There was a significant difference among groups (P < 0.01). Multivariate regression results suggested that the sex, educational level and age had an influence on the concept of ‘dementia is part of normal ageing’; the feeling of shame of having demented relatives was influenced by the educational level and age. Conclusion: Lack of correct knowledge about dementia and discrimination of dementia are highly prevalent among urban residents in Shanghai.

Alzheimer’s disease (AD) is the most common form of dementia in elderly people. It is an irreversible and progressive brain disease. In this paper, we utilized diffusion-weighted imaging (DWI) to detect abnormal topological organization of white matter (WM) structural networks. We compared the differences between WM connectivity characteristics at global, regional, and local levels in 26 patients with probable AD and 16 normal control (NC) elderly subjects, using connectivity networks constructed with the diffusion tensor imaging (DTI) model and the high angular resolution diffusion imaging (HARDI) model, respectively. At the global level, we found that the WM structural networks of both AD and NC groups had a small-world topology; however, the AD group showed a significant decrease in both global and local efficiency, but an increase in clustering coefficient and the average shortest path length. We further found that the AD patients had significantly decreased nodal efficiency at the regional level, as well as weaker connections in multiple local cortical and subcortical regions, such as precuneus, temporal lobe, hippocampus, and thalamus. The HARDI model was found to be more advantageous than the DTI model, as it was more sensitive to the deficiencies in AD at all of the three levels.

Tofu is a soy product which is commonly consumed in Asian countries, such as China and Indonesia. Several studies found negative associations of high tofu consumption with cognitive function in older Asian populations. However, the effect of tofu on cognitive function remains disputed as it was not found in Western populations. In the present study, the effect of weekly tofu intake on cognitive performance was investigated in an observational cross sectional study of 517 Chinese elderly from Shanghai. Similar to earlier studies, results showed that a higher weekly intake of tofu was associated with worse memory performance using the Hopkins Verbal Learning Test (β = -0.10, p = 0.01) after controlling for age, gender, education, being vegetarian, and weekly intake of fruit/juice, green vegetables, and orange/red vegetables. Furthermore, among older elderly (≥68 years of age), high tofu intake increased the risk of cognitive impairment indicative of dementia (OR = 1.27, 95% CI = 0.99-1.64, p = 0.04), after adjusting for all covariates. Consumption of meat and green vegetables independently also reduced risk of dementia. To conclude, high intake of tofu was negatively related to cognitive performance among community-dwelling elderly in China. Similar findings were reported in Indonesia and in Japanese Americans in the US. These findings suggest that the effect of tofu on cognition in elderly should be further investigated.

International audience; BACKGROUND: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.Methods/design: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress. DISCUSSION: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.

Saccadic impairment in Alzheimer's disease (AD) was found in horizontal saccades. The present study extends investigation to vertical saccades in a large number of subjects, including AD and amnestic mild cognitive impairment (aMCI). We examined both horizontal and vertical saccades in 30 healthy elderly, 18 aMCI, and 25 AD. Two tasks were used: gap (fixation target extinguishes prior to target onset) and overlap (fixation stays on after target onset). Eye movements were recorded with the Eyeseecam system. (1) Robust gap effect (shorter latencies in gap than in overlap) exists for AD and aMCI patients as for healthy elderly; (2) abnormal long latency of saccades in gap and overlap tasks for AD relative to healthy elderly and aMCI patients; (3) longer latency for aMCI patients than for healthy elderly for the overlap task; (4) significant correlation between scores of Mini-Mental State Examination (MMSE) and latencies of saccades considering the AD group only; (5) higher coefficient of variation in latency for AD patients than for healthy elderly and for aMCI patients; (6) variability of accuracy and speed is abnormally higher in AD patients than in aMCI and healthy elderly. Abnormalities of latency and latency-accuracy-speed variability reflect deficits of cerebral areas involved in the triggering and execution of saccades; latency of saccades can be used as follow-up test for aMCI and AD patients with its significant correlation with the changes of MMSE scores.

Background:To assess the reliability, validity, and diagnostic utility of the Chinese version of General Practitioner Assessment of Cognition (GPCOG-C). The GPCOG, which is specifically designed for use in primary care to screen for cognitive impairment, consists of a patient section testing cognition, and an informant section asking about decline in cognitive and functional abilities.Methods:The English version of GPCOG was translated, back-translated, and subsequently revised to determine the final GPCOG-C. Our sample comprised 253 community-dwelling volunteers with memory concerns aged 50 years and over and 103 outpatients of a psychogeriatric clinic with memory complaints. Participants were assessed by one of the four general practitioners or six psychogeriatricians. The Mini-Mental State Examination (MMSE), the Hasegawa's Dementia Scale (HDS), and the GPCOG-C were compared against the DSM-IV-defined dementia diagnosis.Results:The internal consistency (Cronbach's α) was 0.68 for the GPCOG patient section. The test–retest was 0.98 for the GPCOG-C total. The sequential administration of both components of GPCOG-C had a sensitivity of 97% and a specificity of 89%, with a positive predictive value of 72% and a negative predictive value of 99%. Both the GPCOG-C total and sequential two-stage scoring methods performed at least well as the MMSE and HDS in detecting dementia. The administration time for the two-stage approach was 4.3 ± 2.4 min.Conclusions:The GPCOG-C is a valid, time efficient instrument for dementia screening in China.

Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China.We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year.The mean age at diagnosis was 72.0 ± 10.0 years (range 38-96 years), and the mean age at onset of AD was 69.8 ± 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ± 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11-2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09-3.06).Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset.