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Introduction: This study investigated the potential link between serum klotho levels and cognitive function in patients with non-alcoholic fatty liver disease (NAFLD). Materials and Methods: Utilizing NHANES data from 2011 to 2014, the research included 356 eligible participants. NAFLD was identified with the United States Fatty Liver Index (US-FLI), and cognition was measured by various tests including the Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), Immediate Recall Test (IRT), and Delayed Recall Test (DRT). Weighted logistic regression and restricted cubic splines were employed to analyze the relationship between klotho levels and cognitive scores. Results: A significant nonlinear association was observed between klotho levels and the performance in DSST and Delayed Recall Test (DRT). After controlling for confounding factors, the study found a positive association between higher serum klotho levels and improved cognitive performance in both AFT and DSST. However, there was no significant relationship between klotho levels and the IRT or DRT, regardless of whether the natural logarithm or quartile was considered. Discussion: The findings suggest that a higher serum klotho level may be positively correlated with better cognitive performance in NAFLD patients. [ABSTRACT FROM AUTHOR]

Introduction: This study investigated the potential link between serum klotho levels and cognitive function in patients with non-alcoholic fatty liver disease (NAFLD). Materials and Methods: Utilizing NHANES data from 2011 to 2014, the research included 356 eligible participants. NAFLD was identified with the United States Fatty Liver Index (US-FLI), and cognition was measured by various tests including the Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), Immediate Recall Test (IRT), and Delayed Recall Test (DRT). Weighted logistic regression and restricted cubic splines were employed to analyze the relationship between klotho levels and cognitive scores. Results: A significant nonlinear association was observed between klotho levels and the performance in DSST and Delayed Recall Test (DRT). After controlling for confounding factors, the study found a positive association between higher serum klotho levels and improved cognitive performance in both AFT and DSST. However, there was no significant relationship between klotho levels and the IRT or DRT, regardless of whether the natural logarithm or quartile was considered. Discussion: The findings suggest that a higher serum klotho level may be positively correlated with better cognitive performance in NAFLD patients. [ABSTRACT FROM AUTHOR]

Young onset breast cancer (YOBC) is an increasing demographic with unique biology, limited screening, and poor outcomes. Further, women with postpartum breast cancers (PPBCs), cancers occurring up to 10 years after childbirth, have worse outcomes than other young breast cancer patients matched for tumor stage and subtype. Early-stage detection of YOBC is critical for improving outcomes. However, most young women (under 45) do not meet current age guidelines for routine mammographic screening and are thus an underserved population. Other challenges to early detection in this population include reduced performance of standard of care mammography and reduced awareness. Women often face significant barriers in accessing health care during the postpartum period and disadvantaged communities face compounding barriers due to systemic health care inequities. Blood tests and liquid biopsies targeting early detection may provide an attractive option to help address these challenges. Test development in this area includes understanding of the unique biology involved in YOBC and in particular PPBCs that tend to be more aggressive and deadly. In this review, we will present the status of breast cancer screening and detection in young women, provide a summary of some unique biological features of YOBC, and discuss the potential for blood tests and liquid biopsy platforms to address current shortcomings in timely, equitable detection. [ABSTRACT FROM AUTHOR]

Introduction: Estradiol is a sex steroid hormone, which has been implicated in the pathogenesis of Alzheimer's disease and cognitive impairment. This crosssectional study aimed to examine the relationship between serum estradiol levels and cognitive performance in older American women. Methods: Data were obtained from the National Health and Nutrition Examination Survey 2013-2014. A total of 731 women aged =60 years who met the inclusion criteria were included in this study. Serum estradiol levels were measured using the isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) method developed by the Centers for Disease Control and Prevention for routine analysis. All measured serum levels were further divided into three parts: T1, <3.68 pg./mL; T2, 3.68-7.49 pg./mL; T3, >7.49 pg./mL, and analyzed. Participants' cognitive abilities were tested using the Vocabulary Learning Subtest (CERAD), Animal Fluency Test (AFS), and digital symbol substitution test (DSST). Scores for each test were calculated based on the sample mean and standard deviation (SD). To examine the relationship between serum estradiol level tertiles and cognitive scores, multiple linear regression models were developed, controlling for race/ethnicity, education level, hypertension, diabetes, and insomnia. Results: The mean age of the participants was 69.57 ± 6.68 years. The non-Hispanic whites were 78.95%, and those who had completed at least some college-level education were 60.62%. The mean BMI of the participants was 29.30 ± 6.79, and 10.85% had a history of smoking. Further, 73.41% did not have a history of alcohol consumption, and 63.03% had hypertension (63.03%). In addition, 81.81 and 88.3% did not have a history of diabetes mellitus and did not have sleep disorders, respectively. The mean serum estradiol level was 8.48 ± 0.77 pg./mL. Multivariate linear regression of the reference group consisting of participants in tertiles of serum estradiol levels revealed that one unit increase in serum estradiol levels increased DSST scores by 0.61 (0.87, 6.34) in the T3 group. However, no significant correlation was found in the CERAD and AFS tests. Conclusion: Participants with higher estradiol levels had higher DSST scores and better processing speed, sustained attention, and working memory, suggesting that serum estradiol may serve as a biomarker for cognitive decline in older women. [ABSTRACT FROM AUTHOR]

Background: Currently, there are no disease-modifying pharmacological treatment options for dementia with Lewy bodies (DLB). The hallmark of DLB is pathological alpha-synuclein (aS) deposition. There are growing amounts of data suggesting that reduced aS clearance is caused by failure in endolysosomal and authophagic pathways, as well as and glucocerebrosidase (GCase) dysfunction and mutations in the GCase gene (GBA). The population’s studies demonstrated that the incidence of GBA mutations is higher among Parkinson’s disease (PD) patients, and carriers of such mutations have a higher risk of developing PD. The incidence of GBA mutations is even higher in DLB and a genome-wide association study (GWAS) confirmed the correlation between GBA mutations and DLB. In vivo experiments have shown that ambroxol (ABX) may increase GCase activity and GCase levels and therefore enhance aS autophagy-lysosome degradation pathways. Moreover, there is an emerging hypothesis that ABX may have an effect as a DLB modifying drug. The aims of the study “Ambroxol in new and early Dementia with Lewy Bodies (ANeED) are to investigate the tolerability, safety and effects of ABX in patients with DLB. Methods: This is a multicentre, phase IIa, double-blinded, randomised and placebo-controlled clinical trial, using a parallel arm design for 18 months’ followup. The allocation ratio is 1:1 (treatment:placebo). Discussion: The ANeED study is an ongoing clinical drug trial with ABX. The unique, but not fully understood mechanism of ABX on the enhancement of lysosomal aS clearance may be promising as a possible modifying treatment in Trial Registration: The clinical trial is registered in the international trials register – clinicaltrials.com (NCT0458825) and nationally at the Current Research Information System in Norway (CRISTIN 2235504). [ABSTRACT FROM AUTHOR]

Introduction: In this study, we investigated the relationship between serum lead levels and cognitive functioning in a sample of older adults in the US. Method: Using the National Health and Nutrition Examination Survey (NHANES) 2011--2013, a total of 768 older adults aged ≥60 years were included in the analysis. Lead concentrations in the whole blood samples were assessed using mass spectrometry. We used the immediate and delayed memory portions of the Consortium to Establish a Registry for Alzheimer's Disease Word Learning Subtest (CERAD-WL), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST) to assess the participants' cognitive performance. Using sample averages and standard deviations (SDs), we computed test-specific and global cognition z-scores. To assess the relationships between the quartiles of serum lead levels and cognitive performance, we built multiple linear regression models and adjusted for covariates, including age, sex, race/ethnicity, education, depressive symptoms, alcohol usage, and body mass index. Results: The average age of the participants was 69.6 (SD 6.6) years. Approximately half of the participants were women (52.6%), non-Hispanic white (52.0%), and had completed at least some college education (51.8%). The average serum lead concentration was 1.8 g/dL (SD 1.6) for these participants. The results of multiple linear regression using individuals in the lowest serum lead quantile as a reference group revealed that the serum lead level was not associated with test-specific (CERAD-WL, AFT, and DSST) or global cognitive z-scores. Conclusions: In older adults, concurrent serum lead concentration is not related to cognitive performance. Early or continuous lead exposure may exert a greater effect on the etiology of accelerated cognitive decline with old age. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a multifactorial disorder diagnosed through the assessment of amyloid-beta (Aß) and tau protein depositions. Filamin A (FLNA) could be a key partner of both Aß and tau pathological processes and may be an important contributor to AD progression. The main aim of this study was to describe the differences in FLNA levels across clinicopathologic groups. Methods: From parietal cortex samples of 57 individuals (19 with no cognitive impairment (NCI), 19 mild cognitively impaired (MCI) and 19 with dementia) from the Religious Orders Study (ROS), we quantified total tau, phosphorylated tau (pTau), FLNA, synaptophysin, vesicular acetylcholine transporters (VAChT) and choline acetyltransferase (ChAT) by Western blot. Aß42 and neuritic plaques (NP) were quantified by ELISA and Bielschowsky silver impregnation, respectively. AD staging was determined using ABC method combining Thal, Braak and the CERAD staging. From this, clinicopathologic stages of AD were established by subdividing subjects with neuropathological AD between preclinical AD, prodromal AD and AD dementia (ADD). Receiver operating characteristics analyses were performed to predict AD neuropathology from FLNA quantifications. Results: Insoluble FLNA was significantly and positively correlated with Aß42, NP, Thal stages, ABC scores and AD clinicopathologic stages (p < 0.05 False discovery rate-corrected). No correlation of FLNA with tau measures was found. Insoluble FLNA levels were significantly higher in the prodromal AD, ADD and intermediate ABC groups. This was consistent with significantly lower levels of soluble FLNA specifically in prodromal AD. Insoluble (AUC: 0.830) and soluble FLNA levels (AUC: 0.830) as well as the ratio of soluble over insoluble FLNA (AUC: 0.852), were excellent predictors of prodromal AD among subjects with MCI from the ROS cohort. Discussion: We observed opposite level changes between insoluble and soluble FLNA in prodromal AD. As this stage coincides with the appearance of cognitive symptoms, this may be a key event in the transition from preclinical to prodromal AD. Insoluble FLNA could be useful to identify prodromal AD among subjects with an MCI, indicating that it might be a hallmark of prodromal AD. [ABSTRACT FROM AUTHOR]

Introduction: Secondhand smoke (SHS) is common in older adults; however, its cognitive effect is unclear. We aimed to examine the association between serum cotinine level and cognitive functioning among non-smoking older adults. Materials and methods: A total of 2,703 older adults aged 60 and above from the National Health and Nutrition Examination (NHANES) Survey 2011-2014 were included. Serum cotinine level was analyzed in the laboratory. A level ≤10 ng/ml and a response of "no" to the question "Do you currently smoke?" were used to select non-smokers. Cognitive functioning was measured using the Consortium to Establish a Registry for Alzheimer's disease Word Learning subtest (CERAD-WL) immediate and delayed recall tests, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Multivariable linear regression models were constructed to examine the association between serum cotinine level quartile and test-specific and global cognition z scores adjusting for age, race/ethnicity, education, depressive symptoms, body mass index, alcohol use, smoking history, prevalent coronary heart disease (CHD), stroke, and systolic blood pressure. Results: About half of the participants (mean age 70.5 years) were female (53.6%), non-Hispanic White (48.3%), and completed some college and above (50.2%). Multivariate linear regressions with a reference group being those in the 1st quantile (lowest) showed that participants in the 4th quartile (highest) of serum cotinine level had lower immediate recall [β = -0.16, 95% confidence interval (CI) = -0.29, -0.03], AFT (β = -0.19, 95% CI = -0.33, -0.05), DSST (β = -0.27, 95% CI = -0.39, -0.15), and global cognition (β = -0.26, 95% CI = -0.39, -0.14) z scores. Participants in the 3rd quartile had lower immediate recall (β = -0.16, 95% CI = -0.30, -0.02) and global cognition (β = -0.16, 95% CI = -0.29, -0.02) z scores. Participants in the 2nd quartile had lower delayed recall z scores (β = -0.16, 95% CI = -0.29, -0.02). Conclusion: Higher serum cotinine level was associated with worse cognitive functioning in non-smoking older adults. Prevention and reduction of SHS in older adults may help protect their cognitive functioning. [ABSTRACT FROM AUTHOR]

Objective: Brain tissue changes dynamically during aging. The purpose of this study was to use synthetic magnetic resonance imaging (syMRI) to evaluate the changes in relaxation values in different brain regions during brain aging and to construct a brain age prediction model. Materials and methods: Quantitative MRI was performed on 1,000 healthy people ≥ 18 years old) from September 2020 to October 2021. T1, T2 and proton density (PD) values were simultaneously measured in 17 regions of interest (the cerebellar hemispheric cortex, pons, amygdala, hippocampal head, hippocampal tail, temporal lobe, occipital lobe, frontal lobe, caudate nucleus, lentiform nucleus, dorsal thalamus, centrum semiovale, parietal lobe, precentral gyrus, postcentral gyrus, substantia nigra, and red nucleus). The relationship between the relaxation values and age was investigated. In addition, we analyzed the relationship between brain tissue values and sex. Finally, the participants were divided into two age groups: < 60 years old and ≥ 60 years old. Logistic regression analysis was carried out on the two groups of data. According to the weight of related factors, a brain age prediction model was established and verified. Results: We obtained the specific reference value range of different brain regions of individuals in different age groups and found that there were differences in relaxation values in brain tissue between different sexes in the same age group. Moreover, the relaxation values of most brain regions in males were slightly higher than those in females. In the study of age and brain relaxation, it was found that brain relaxation values were correlated with age. The T1 values of the centrum semiovale increased with age, the PD values of the centrum semiovale increased with age, while the T2 values of the caudate nucleus and lentiform nucleus decreased with age. Seven brain age prediction models were constructed with high sensitivity and specificity, among which the combined T1, T2 and PD values showed the best prediction efficiency. In the training set, the area under the curve (AUC), specificity and sensitivity were 0.959 [95% confidence interval (CI): 0.945-0.974], 91.51% and 89.36%, respectively. In the test cohort, the above indicators were 0.916 (95% CI: 0.882-0.951), 89.24% and 80.33%, respectively. Conclusion: Our study provides specific reference ranges of T1, T2, and PD values in different brain regions from healthy adults of different ages. In addition, there are differences in brain relaxation values in some brain regions between different sexes, which help to provide new ideas for brain diseases that differ according to sex. The brain age model based on synthetic MRI is helpful to determine brain age. [ABSTRACT FROM AUTHOR]

Dietary carbohydrate consumption was related to cognitive function. Whereas, there was no study investigate the association of dietary carbohydrate consumption with cognitive function modification by daily fasting duration. This study aims to examine the association between dietary carbohydrate consumption and cognitive function among participants with different daily fasting duration. In this cross-sectional study, 2485 adults aged over 60 years from the nationally representative data of the National Health and Nutrition Examination Survey (NHANES, 2011-2014) were enrolled. Percentage energy from carbohydrates was present in both quartiles and continuous forms. Daily fasting duration = 24 - (timing for dinner - breakfast). Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer's Disease Word List Learning (CERAD-WL), CERAD Word List Delayed Recall (CERAD-DR), Animal Fluency (AF), and Digit Symbol Substitution (DSST) Test. Multiple logistic regression and linear regression models were developed to examine the association of dietary carbohydrates with cognitive function among participants with different daily fasting duration. Restricted cubic spline models were also applied. Compared with the lowest quartile of percentage energy from carbohydrates, the highest quartile had higher ORs of poor cognitive performance among total participants [(ORCERAD-WL 1.84 95% CI 1.25-2.71); (ORCERAD-DR 1.45 95% CI 1.10-1.91)] and participants with daily fasting duration fewer than 16 h [(ORCERAD-WL 2.14 95% CI 1.29-3.55); (ORCERAD-DR 1.51 95% CI 1.05-2.17)] but not in participants with daily fasting duration of more than 16 h. Further, the negative associations between percentage energy from carbohydrates and CERAD-WL score were still significant in addition to participants whose daily fasting duration was more than 16 h. Additionally, dose-response associations were detected between dietary carbohydrates and cognitive decline, while "U" curves were observed among participants whose daily fasting duration was more than 16 h. This study indicated that dietary carbohydrates consumption was associated with poor cognitive performance, but not in participants whose daily fasting duration was more than 16 h among US older adults. The current analysis provides evidence that a longer daily fasting duration may improve the harmful effect of dietary carbohydrates on cognitive function. [ABSTRACT FROM AUTHOR]

Introduction: Oral consumption of probiotics can alter Gut Microbiota by causing changes in the production of probiotic derivatives. Therefore, by utilizing Gut-Brain-Axis (GBA), probiotics could provide an opportunity for central nervous system (CNS) modulation, including cognitive function. Tempeh is a traditional Indonesian food rich in probiotics and beneficial for cognitive function. However, the type of probiotics that play a role in cognitive improvement and the number of probiotics needed for the benefits of increasing cognitive function was unknown. Method: This experimental study involved a total of 93 subjects, divided into 3 groups: A, B and C/control (n: 33, 32, and 28), who were provided with probiotic supplementation isolated from tempeh for 12 weeks intervention. Inclusion criteria were age > 60 years, and memory impairment with the third repetition value of Word List Memory Immediate Recall (WLMIR) < 7. Subjects with diabetes were excluded. Cognitive function examinations were carried out before and after treatment. The tempeh-derived probiotics were prepared trough several processes. Genomic isolation, detection of GABA-encoding genes, and species identification using the 16S-rRNA gene encoding were performed. Results: The probiotics isolate used in the intervention was identified as Limosilactobacillus fermentum. We assigned this isolate as L. fermentum A2.8. The presence of the gene encoding GABA was found on this isolate. There was an increase in the cognitive domains of memory, learning process, and verbal fluency (p < 0.05) in group A (probiotics at concentration of 108 CFU/mL). Memory function, visuospatial, and verbal fluency improved (p < 0.05) in group B (probiotics at concentration of 107 CFU/mL). Only an increase in the memory domain was observed in the control group. Improvement of the learning process occurred only in group A (p = 0.006). Conclusion: Administration of probiotics derived from L. fermentum A2.8 increased the cognitive domains of memory, language and visuospatial function. However, probiotic supplementation at a concentration of 108 CFU/mL was better in improving the learning process. This study succeeded in detecting Lactic Acid Bacterial isolates L. fermentum A2.8 that enclosed gene encoding glutamate decarboxylase (gad) which is involved in the synthesis of -aminobutyric acid (GABA), a neurotransmitter vital for cognitive function. [ABSTRACT FROM AUTHOR]

A major type of serious mood disorder, depression is currently a widespread and easily overlooked psychological illness. With the low side effects of natural products in the treatment of diseases becoming the pursuit of new antidepressants, natural Chinese medicine products have been paid more and more attention for their unique efficacy in improving depression. In a view from the current study, the positive antidepressant effects of berberine are encouraging. There is a lot of work that needs to be done to accurately elucidate the efficacy and mechanism of berberine in depression. In this review, the relevant literature reports on the treatment of depression and anxiety by berberine are updated, and the potential pharmacological mechanism of berberine in relieving depression has also been discussed. [ABSTRACT FROM AUTHOR]

Objective: Current evidence on the association between serum testosterone and cognitive performance has been inconsistent, especially in older adults. To investigate the associations between serum testosterone and cognitive performance in a nationally representative sample of older men and women. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. 1,303 men and 1,349 women aged 60 years or older were included in the study. Serum total testosterone was preformed via isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) method. Free testosterone was calculated by Vermeulen's formula. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, Animal Fluency test, and Digit Symbol Substitution Test (DSST). Binary logistic regression and restricted cubic spline models were applied to evaluate the association of testosterone and cognitive performance. Results: In men, higher concentrations of total testosterone were associated with better performance on CERAD test (OR = 0.51; 95%CI = 0.27–0.95) and DSST (OR = 0.54; 95%CI = 0.30–0.99) in adjusted group. Similarly, higher concentrations of free testosterone were associated with better performance on CERAD test (OR = 0.32; 95%CI = 0.17–0.61) and DSST (OR = 0.41; 95%CI = 0.17–0.96) in men. These associations were not seen in women. Conclusion: Serum testosterone concentrations were inversely associated with cognitive performance in older men but not women in the United States. [ABSTRACT FROM AUTHOR]

Aging is accompanied by unisensory decline. To compensate for this, two complementary strategies are potentially relied upon increasingly: first, older adults integrate more information from different sensory organs. Second, according to the predictive coding (PC) model, we form "templates" (internal models or "priors") of the environment through our experiences. It is through increased life experience that older adults may rely more on these templates compared to younger adults. Multisensory integration and predictive coding would be effective strategies for the perception of near-threshold stimuli, which may however come at the cost of integrating irrelevant information. Both strategies can be studied in multisensory illusions because these require the integration of different sensory information, as well as an internal model of the world that can take precedence over sensory input. Here, we elicited a classic multisensory illusion, the sound-induced flash illusion, in younger (mean: 27 years, N = 25) and older (mean: 67 years, N = 28) adult participants while recording the magnetoencephalogram. Older adults perceived more illusions than younger adults. Older adults had increased pre-stimulus beta-band activity compared to younger adults as predicted by microcircuit theories of predictive coding, which suggest priors and predictions are linked to beta-band activity. Transfer entropy analysis and dynamic causal modeling of pre-stimulus magnetoencephalography data revealed a stronger illusion-related modulation of cross-modal connectivity from auditory to visual cortices in older compared to younger adults. We interpret this as the neural correlate of increased reliance on a cross-modal predictive template in older adults leading to the illusory percept. [ABSTRACT FROM AUTHOR]

Background: Small noncoding microRNA (miRNA) have regulatory functions in polycystic ovary syndrome (PCOS) that differ to those in women without PCOS. However, little is known about miRNA expression in women with PCOS who are not insulin resistant (IR). Methods: Circulating miRNAs were measured using quantitative polymerase chain reaction (qPCR) in 24 non-obese BMI and age matched women with PCOS and 24 control women. A miRNA data set was used to determine miRNA levels. Results: Women with PCOS showed a higher free androgen index (FAI) and anti-mullerian hormone (AMH) but IR did not differ. Four miRNAs (miR-1260a, miR-18b-5p, miR-424-5p, and miR let-7b-3p) differed between control and PCOS women that passed the false discovery rate (FDR) out of a total of 177 circulating miRNAs that were detected. MiRNA let-7b-3p correlated with AMH in PCOS (p < 0.05). When the groups were combined, miR-1260a correlated with FAI and let-7b-3p correlated with body mass index (BMI) (p < 0.05). There was no correlation to androgen levels. Ingenuity pathway analysis showed that nine of the top 10 miRNAs reported were associated with inflammatory pathways. Conclusion: When IR did not differ between PCOS and control women, only four miRNA differed significantly suggesting that IR may be a driver for many of the miRNA changes reported. Let-7b-3p was related to AMH in PCOS, and to BMI as a group, whilst miR-1260a correlated with FAI. Androgen levels, however, had no effect upon circulating miRNA profiles. The expressed miRNAs were associated with the inflammatory pathway involving TNF and IL6. [ABSTRACT FROM AUTHOR]

A variety of anatomical alterations have been reported in the hippocampal formation of patients with Alzheimer's Disease (AD) and these alterations have been correlated with cognitive symptoms in the early stages of the disease. Major hallmarks in AD are the presence of paired helical filaments of tau protein (PHFTau) within neurons, also known as neurofibrillary tangles (NFTs), and aggregates of amyloid-β protein (Aβ) which form plaques in the extracellular space. Nevertheless, how the density of plaques and NFTs relate to the severity of cell loss and cognitive decline is not yet clear. The aim of the present study was to further examine the possible relationship of both Aβ plaques and NFTs with neuronal loss in several hippocampal fields (DG, CA3, CA1, and subiculum) of 11 demented AD patients. For this purpose, using stereological techniques, we compared neuronal densities (Nissl-stained, and immunoreactive neurons for NeuN) with: (i) numbers of neurons immunostained for two isoforms of PHFTau (PHFTau-AT8 and PHFTau-pS396); and (ii) number of Aβ plaques. We found that CA1 showed the highest number of NFTs and Aβ plaques, whereas DG and CA3 displayed the lowest number of these markers. Furthermore, AD patients showed a variable neuronal loss in CA1 due to tangle-related cell death, which seems to correlate with the presence of extracellular tangles. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases share the fact that they derive from altered proteins that undergo an unfolding process followed by formation of β-structures and a pathological tendency to self-aggregate in neuronal cells. This is a characteristic of tau protein in Alzheimer's disease and several tauopathies associated with tau unfolding, α-synuclein in Parkinson's disease, and huntingtin in Huntington disease. Usually, the self-aggregation products are toxic to these cells, and toxicity spreads all over different brain areas. We have postulated that these protein unfolding events are the molecular alterations that trigger several neurodegenerative disorders. Most interestingly, these events occur as a result of neuroinflammatory cascades involving alterations in the cross-talks between glial cells and neurons as a consequence of the activation of microglia and astrocytes. The model we have hypothesized for Alzheimer's disease involves damage signals that promote glial activation, followed by nuclear factor NF-kβ activation, synthesis, and release of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, and IL-12 that affect neuronal receptors with an overactivation of protein kinases. These patterns of pathological events can be applied to several neurodegenerative disorders. In this context, the involvement of innate immunity seems to be a major paradigm in the pathogenesis of these diseases. This is an important element for the search for potential therapeutic approaches for all these brain disorders. [ABSTRACT FROM AUTHOR]

Informatics increases the yield from neuroscience due to improved data. Data sharing and accessibility enable joint efforts between different research groups, as well as replication studies, pivotal for progress in the field. Research data archiving solutions are evolving rapidly to address these necessities, however, distributed data integration is still difficult because of the need of explicit agreements for disparate data models. To address these problems, ontologies are widely used in biomedical research to obtain common vocabularies and logical descriptions, but its application may suffer from scalability issues, domain bias, and loss of low-level data access. With the aim of improving the application of semantic models in biobanking systems, an incremental semantic framework that takes advantage of the latest advances in biomedical ontologies and the XNAT platform is designed and implemented. We follow a layered architecture that allows the alignment of multi-domain biomedical ontologies to manage data at different levels of abstraction. To illustrate this approach, the development is integrated in the JPND (EU Joint Program for Neurodegenerative Disease) APGeM project, focused on finding early biomarkers for Alzheimer's and other dementia related diseases. [ABSTRACT FROM AUTHOR]

Introduction: Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer's disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer's disease. However, the relationship between CSF Aβ43 and established imaging biomarkers of Alzheimer's disease has never been assessed. Materials and Methods: In this observational study, CSF Aβ43 was measured with ELISA in 89 subjects; 34 with subjective cognitive decline (SCD), 51 with MCI, and four with resolution of previous cognitive complaints. All subjects underwent structural MRI; 40 subjects on a 3T and 50 on a 1.5T scanner. Forty subjects, including 24 with SCD and 12 with MCI, underwent 18F-Flutemetamol PET. Seventy-eight subjects were assessed with 18F-fluorodeoxyglucose PET (21 SCD/7 MCI and 11 SCD/39 MCI on two different scanners). Ten subjects with SCD and 39 with MCI also underwent diffusion tensor imaging. Results: Cerebrospinal fluid Abβ3 was both alone and together with p-tau a significant predictor of the distinction between SCD and MCI. There was a marked difference in CSF Aβ43 between subjects with 18F-Flutemetamol PET scans visually interpreted as negative (37 pg/ml, n = 27) and positive (15 pg/ml, n = 9), p < 0.001. Both CSF Aβ43 and Aβ42 were negatively correlated with standardized uptake value ratios for all analyzed regions; CSF Aβ43 average rho -0.73, Aβ42 -0.74. Both CSF Aβ peptides correlated significantly with hippocampal volume, inferior parietal and frontal cortical thickness and axial diffusivity in the corticospinal tract. There was a trend toward CSF Aβ42 being better correlated with cortical glucose metabolism. None of the studied correlations between CSF Aβ43/42 and imaging biomarkers were significantly different for the two Aβ peptides when controlling for multiple testing. Conclusion: Cerebrospinal fluid Aβ43 appears to be strongly correlated with cerebral amyloid deposits in the same way as Aβ42, even in non-demented patients with only subjective cognitive complaints. Regarding imaging biomarkers, there is no evidence from the present study that CSF Aβ43 performs better than the classical CSF biomarker Aβ42 for distinguishing SCD and MCI. [ABSTRACT FROM AUTHOR]