The MoCA-BC is a reliable cognitive screening test across all education levels in Chinese elderly adults, with high acceptance and good reliability.
Background Reduced 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) brain metabolism was recognized as a biomarker of neurodegeneration in the recently proposed ATN framework for Alzheimer’s disease (AD) biological definition. However, accumulating evidence suggested it is an independent biomarker, which is denoted as “F” in the very study. Methods A total of 551 A+T+ individuals from the Alzheimer’s Disease Neuroimaging Initiative database were recruited and then further divided into four groups based on the biomarker positivity as 132 A+T+N−F−, 102 A+T+N−F+, 113 A+T+N+F−, and 204 A+T+N+F+. Frequency distributions of the groups were compared, as well as the clinical progression [measured by the longitudinal changes in cognition and brain structure, and mild cognitive impairment (MCI) to AD dementia conversion] between every pair of F+ and F− groups. Results The prevalence of A+T+N+F+ profile was 66.24% in clinically diagnosed AD dementia patients; similarly, the majority of individuals with reduced FDG-PET were AD dementia subjects. Among the 551 individuals that included, 537 had at least one follow-up (varied from 1 to 8 years). Individuals in F+ groups performed worse and dropped faster in Mini-Mental State Examination scale and had faster shrinking middle temporal lobe than those in F− groups (all p < 0.05). Moreover, in MCI patients, reduced FDG-PET exerted 2.47 to 4.08-fold risk of AD dementia progression compared with those without significantly impaired FDG-PET (both p < 0.001). Conclusions Based on the analyses, separating FDG-PET from “N” biomarker to build the ATN(F) system is necessary and well-founded. The analysis from this study could be a complement to the original ATN framework for AD’s biological definition. Electronic supplementary material The online version of this article (10.1186/s13195-019-0512-1) contains supplementary material, which is available to authorized users.
SignificanceAlzheimer’s disease (AD) is an age-related neurodegenerative disease. Genome-wide association studies predominately focusing on Caucasian populations have identified risk loci and genes associated with AD; the majority of these variants reside in noncoding regions with unclear functions. Here, we report a whole-genome sequencing study for AD in the Chinese population. Other than the APOE locus, we identified common variants in GCH1 and KCNJ15 that show suggestive associations with AD. For these two risk variants, an association with AD or advanced onset of disease can be observed in non-Asian AD cohorts. An association study of risk variants with expression data revealed their modulatory effects on immune signatures, linking the potential roles of these genes with immune-related pathways during AD pathogenesis.
The anterior temporal lobes (ATL) have become a key brain region of interest in cognitive neuroscience founded upon neuropsychological investigations of semantic dementia (SD). The purposes of this investigation are to generate a single unified model that captures the known cognitive-behavioural variations in SD and map these to the patients' distribution of frontotemporal atrophy. Here we show that the degree of generalised semantic impairment is related to the patients' total, bilateral ATL atrophy. Verbal production ability is related to total ATL atrophy as well as to the balance of left > right ATL atrophy. Apathy is found to relate positively to the degree of orbitofrontal atrophy. Disinhibition is related to right ATL and orbitofrontal atrophy, and face recognition to right ATL volumes. Rather than positing mutually-exclusive sub-categories, the data-driven model repositions semantics, language, social behaviour and face recognition into a continuous frontotemporal neurocognitive space.
Previous studies demonstrated that plasma neurofilament light chain (NFL) played important predictive roles in disease progression and neurodegeneration in the preclinical phase of familial Alzheimer’s disease (AD). However, whether plasma NFL has the same predictive roles in sporadic AD is still unclear. In this study, 243 cognitively normal (CN) participants from the ADNI database were divided into two subgroups (CN- and CN+) according to CSF Aβ or AV45-PET. Associations of baseline plasma NFL concentrations or rate of change in plasma NFL with longitudinal data on other biomarkers were tested by multivariate linear mixed effects models (LMEMs). Results showed that plasma NFL concentration and its rate of change were already abnormally high in the preclinical phase of AD. Plasma NFL was associated with three core AD-related biomarkers in preclinical phase. Baseline plasma NFL, but not its rate of change, played predictive roles in both cognitive decline (β = -0.0349, p = 0.0274) and hippocampal atrophy (β = -0.0351, p = 0.0088), especially for preclinical AD participants. In summary, these results indicated that baseline plasma NFL, but not its rate of change, may be a valuable noninvasive tool to assess neurodegeneration and predict longitudinal disease progression in preclinical AD individuals.
ObjectivesTo find out whether the Chinese version of Montreal Cognitive Assessment Basic (MoCA-BC) and its subtests could be applied in discrimination among cognitively normal controls (NC), mild cognitive impairment (MCI), mild and moderate Alzheimer’s Disease (AD), and furthermore, to determine the optimal cutoffs most sensitive to distinguish between them.DesignA cross-sectional validation study.SettingHuashan Hospital, Shanghai, China.ParticipantsThere was a total of 1,969 participants: individuals with MCI (n=663), mild (n=345), moderate (n=441) AD, and cognitively NC (n=520) were recruited from the Memory Clinic, Huashan Hospital, Shanghai, China.MeasurementsBaseline MoCA-BC scores were collected from firsthand data. Two subtests were calculated from MoCA-BC: the Memory Index Score of MoCA-BC (MoCA-BC-MIS) and the Non-memory Index Score of MoCA-BC (MoCA-BC-NM).ResultsMoCA-BC was an effective cognitive tool to discriminate among NC, MCI, mild and moderate AD in the Chinese elderly across all education groups, implying that it was efficient not only for detecting MCI, but for different severities of AD as well. For MCI screening, the total score of MoCA-BC (MoCA-BC-T) and MoCA-BC-MIS had similar high sensitivity and specificity. For discrimination among MCI, mild and moderate AD, the MoCA-BC-T and MoCA-BC-NM had similar performance.ConclusionMoCA-BC is an effective cognitive test to distinguish between NC, MCI, mild and moderate AD among the Chinese elderly with various levels of education.
Eight rare pyrrole‐based cytochalasans, termed armochaetoglobins K–R (1–8), along with three known analogues (9–11), were isolated from the solid culture broth of Chaetomium globosum TW1‐1, a symbiotic fungus derived from the medicinal terrestrial arthropod Armadillidium vulgare. Their structures were elucidated using a combination of spectroscopic analysis, a single‐crystal X‐ray diffraction experiment, and an electronic circular dichroism (ECD) calculation. Compounds 4–8 represent the first examples of chaetoglobosin‐type cytochalasans with an sp3 methine carbon at C‐18. All of the isolates were evaluated for their anti‐HIV activities in vitro, and compounds 2–4, 7, 8, and 10 showed significant anti‐HIV activities, with EC50 values ranging from 0.11 to 0.55 μM, and selectivity index (SI) values ranging from 12.33 to 75.42. A plausible biosynthetic pathway was proposed to explain the origin of the pyrrole ring.
Given that extensive cerebral regions are co-atrophic in semantic dementia (SD), it is not yet known which critical regions (SD-semantic-critical regions) are really responsible for the semantic deficits of SD. To identify the SD-semantic-critical regions, we explored the relationship between the degree of cerebral atrophy in the whole brain and the severity of semantic deficits in 19 individuals with SD. We found that the gray matter volumes (GMVs) of two regions [left fusiform gyrus (lFFG) and left parahippocampal gyrus (lPHG)] significantly correlated with the semantic scores of patients with SD. Importantly, the effects of the lFFG remained significant after controlling for the GMVs of the lPHG. Moreover, the effects of the region could not be accounted for by the total GMV, general cognitive ability, laterality of brain atrophy, or control task performance. We further observed that each atrophic portion of the lFFG along the anterior–posterior axis might dedicate to the loss of semantic functions in SD. These results reveal that the lFFG could be a critical region contributing to the semantic deficits of SD.
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