bluuebunny/crossref_metadata_2025 huggingface dataset:
Blending as a sample preparation protocol for mitigating intra- and inter-fruit heterogeneity in sensory analysis of sweetness and acidity in tomatoes
Authors: Casals Joan , Romero del Castillo Roser
Published: November 2024

Tomato sensory analysis typically involves assessing different fruits, and the inherent intra- and inter-fruit variability poses experimental challenges. To address this, blending emerges as a sampling protocol to minimize panelist experimental error. This study delves into intra-(locule/pericarp) and inter-fruit heterogeneity, examining the efficacy of blended samples in assessing sweetness and acidity. Results reveal a higher acidity (22.2%) and sweetness perception (10.3%) in locular tissue, influenced by elevated titratable acids (TA) and soluble solids (TSS). The observed locular-to-fruit weight ratios (6–31%) might impact overall taste intensity. Fruit-to-fruit variation was high among the 16 varieties studied for TA, TSS, and dry matter. The use of blending to construct an “average” sample, increased sweetness (23%) and acidity perception (17%) without affecting sample ordering. Our results underscore the need to integrate locular relative weight into tomato phenotyping protocols and highlight the potential of blended samples in sensory analysis of traits related to the non-volatile fraction.
Same same but different: Introduction of a classification system in calcar-guided short-stem total hip arthroplasty
Authors: Kutzner Karl P
Published: November 2024

Background:

The concept of calcar-guided short-stem THA (ssTHA) has largely emerged over the last decade, especially in Europe, and today modern calcar-guided short stems are among the most successful primary femoral implants in terms of complications and revision rates as indicated by multiple registry data. The philosophy originally comprised an individualised reconstruction of the hip anatomy by following the calcar of the femoral neck providing bone- and soft-tissue-sparing characteristics. However, as the stem design allows either metaphyseal fixation alone or additional diaphyseal anchoring, depending on the stem alignment and indication, distinct knowledge is required regarding the implantation technique, the broad variation of positioning and fixation and its potential clinical consequences.

Aim:

To report on and highlight the characteristics of different ways of performing calcar-guided ssTHA as well as to introduce a classification in order to systematically account for the variety of strategies and the respective implications on the type of fixation.

Surgical technique:

Already when templating preoperatively, surgeons need to weigh up the different fixation types taking into account a number of patient-related factors. Intraoperatively, by individually controlling the level of osteotomy, the intended type of anchorage can be implemented. Intraoperative radiography to confirm the result, is mandatory.

Results:

Despite numerous options of stem alignment, depending on the patient’s anatomy, the bone quality or the indication for operation, a total of 4 categories were identified to characterise different fixation strategies in calcar-guided ssTHA.

Conclusions:

The classification system should be used for the preoperative determination of the intended type of anchorage. Whenever a short-stem philosophy with metaphyseal fixation (Type I (M)) is possible, it should be pursued.
Portfolio career formation in Australia: Implications for higher music education
Authors: Carroll Christine , Latukefu Lotte
Published: November 2024

This article reports findings from a qualitative study undertaken to explore the career trajectories of Australian portfolio musicians including their interactions and engagement with formal, non-formal, and informal modes of music education. Semi-structured interviews were undertaken with 18 musicians, selected with a desire to represent musical, cultural, social, and gender diversity. The participants exhibited composite or “portfolio” careers, consisting of work across multiple domains. The investigation revealed that such career formation happens in an episodic rather than linear fashion, as opportunity and adversity lead to portfolio diversification. Ongoing theorisation of the data identified ways in which musicians’ portfolio diversification is enabled by knowledge and skill connections, and, by a keen awareness of intra- and inter-personal values, beliefs, and personal qualities. By observing the ways that musicians construct and then draw upon their epistemic and social foundations laid down both in and outside of formal education, higher music education providers may be able to better plan and enact meaningful curriculum reform for the future.
Exploring personality correlates of falsification of COVID-19 lateral flow tests through vignettes
Authors: Ray Devashish , Dhami Raenhha , Mukherjee Aritra , Lecouturier Jan , McGowan Laura J , Vlaev Ivo , Kelly Michael P , Sniehotta Falko F
Published: November 2024

Regular testing using rapid antigen lateral flow tests (LFTs) was an important prevention strategy during the COVID-19 pandemic. However, falsification of home LFTs was a concern. Using a large quota-representative sample of adults ( n = 1295) in England, we conducted a vignette survey consisting of four hypothetical scenarios of LFT falsification behaviours (FBs) to examine whether prosocial personality traits were associated with attitudes towards and intentions for falsifying home LFTs during the pandemic. Results show that higher levels of affective empathy for people vulnerable to COVID-19 and Honesty-Humility from the HEXACO model of Personality are associated with non-acceptability of LFT FBs and intentions to not engage with them. However, affective empathy explained more of the variation compared to the facet-level measures of Honesty-Humility for both attitude and intention. Public health communications aimed at encouraging personal protective behaviours should consider the role of empathy and prosocial messages.
Are health protective behaviors promoted by anticipated regret?
Authors: Xiong Lise C , Caparos Serge , Gueraud Sabine , Augusto Chrystelle , Habib Marianne
Published: November 2024

Several factors influence the adoption of health-protective behaviors, including anticipatory affective reactions like regret. The ability to anticipate regret matures with age, allowing individuals to make increasingly risk-averse decisions. This study examined the relationship between age and the adoption of health-protective behaviors to limit the spread of a virus from adolescence to adulthood, and the mediating effect of anticipated regret. A total of 410 French participants, aged 14–58, reported their compliance with health-protective behaviors (e.g., using surgical masks, handwashing, social distancing), along with their anticipated regret in the event of non-adherence to such behaviors leading to the contamination of themselves or others. The findings revealed that both the adoption of these behaviors and anticipated regret increased with age. Moreover, anticipated regret mediated the effect of age on health-protective behavior, encouraging higher compliance with preventive measures and reducing risk-taking.
Methods to reduce fraudulent participation and highlight autistic voices in research
Authors: Carey Meghan E , McLean Kiley J , Chvasta Kyle , de Marchena Ashley , Roux Anne M
Published: November 2024

Alongside the rise in online qualitative research, fraudulent representation of research participants is increasing, and current strategies to address this issue within studies of non-neurodiverse samples may exclude autistic voices. Seeking to reduce fraudulent or “scammer” participation in our focus group study, and increase data validity and expenditure efficiency, we implemented strategies suggested in the literature and tested additional strategies. This research adds to the growing conversation around best practices for reducing scammers in autism research using online methods by (1) providing data evaluating the utility of existing strategies; (2) testing emerging strategies; and (3) discussing ethical dilemmas involved in addressing scammers in studies. We received over 200 expressions of interest and the established strategies suggested in the literature plus emerging strategies proved critical for mitigating the enrollment of scammers in focus groups. Protecting the integrity of data about human subjects from fraud is essential for rigorous autism research; trustworthy conclusions cannot be otherwise drawn from analysis. However, the strategies inherently require subjective decision-making that could systematically exclude participants with more limited or atypical communication and result in unfair subject selection. Procedures we recommend incur resources and are time consuming but are beneficial to ensure data integrity and inclusivity.

Lay abstract

Over the last decade, especially since the pandemic, more research has been happening online. Conducting research online can create opportunities to include autistic people across the world and make our studies more diverse. However, conducting research online had led to scammers, or people pretending to be autistic, participating in autism research studies. Strategies to stop scammers may accidentally leave out autistic people who have difficulty with processing time and open-ended questions. We tried out documented strategies to stop scammers from participating in autism research. We also tested new strategies to understand how helpful they are. Using these strategies, we suspected over 100 people who wanted to participate were scammers and did not invite them to participate. As researchers, we must ensure we stop scammers from participating in our studies. It’s important to highlight autistic voices and guarantee we get accurate results. However, the strategies to identify scammers may also leave out autistic people who have communication differences. This is unfair and could also make our results less reliable. The existing and new strategies to stop scammers take a lot of time and resources but they’re worth it to make sure our data are reliable, and include only autistic voices.
Out-of-plane shear behavior of BFRP-reinforced geopolymer concrete one-way slabs: Experimental and numerical investigations
Authors: Huang Jun-Qi , Kumar Sushil , Guo Dong , Dai Jian-Guo
Published: November 2024

Sustainability and durability in construction are vital considerations that involve using environmentally friendly materials and implementing efficient design and construction techniques to minimize the environmental impact. This research study investigated the structural behavior of one-way solid slabs incorporating basalt fiber-reinforced polymer (BFRP) reinforcement and geopolymer concrete to develop an environmentally sustainable and durable structural member. Six full-scale BFRP-reinforced geopolymer concrete one-way slab specimens were prepared and subjected to four-point loading tests to assess their out-of-plane shear performances. The considered experimental parameters were compressive strength of concrete (i.e., 30, 40 and 50 MPa) and longitudinal tensile reinforcement ratios (i.e., 1.20% and 2.18%). The structural performance of the slabs was carefully investigated in terms of crack patterns, failure modes, load-deflection relationships and load-strain relationships. The obtained shear resistances from tests were compared with predicted results from the Codes of Practice and design guidelines. A two-dimensional (2D) finite element (FE) analysis was conducted, considering the bond-slip relationship between BFRP rebar and geopolymer concrete. It was found that all tested specimens were governed by shear failure and had similar shear resistance for the chosen values of considered parameters. The JSCE shear design method provided the closest prediction of shear resistance of BFRP-reinforced geopolymer concrete one-way slab. The developed FE models predicted the out-of-plane shear performance with reasonable accuracy and revealed that the slip distribution of the BFRP rebar presents a sawtooth shape owing to concrete cracking.
A genetic programming Rician noise reduction and explainable deep learning model for Alzheimer's diseases severity prediction
Authors: Khan Sajid Ullah , Albanyan Abdullah , Bilal Mohsin , Ullah Shahid
Published: November 2024

Background:

Degradation of magnetic resonance imaging (MRI) remains a challenging issue, with noise being a key damaging component introduced due to a variety of environmental and mechanical factors.

Objective:

The aim of this research work is to addresses the issue of noise reduction and to predict Alzheimer's disease detection efficiently.

Methods:

First, we present a genetic programming (GP) technique for reducing Rician noise in MRI images to pre-process the dataset. To effectively reduce Rician noise, this GP approach combines a Feature Extraction component, GP Optimal Expression, and an Optimum Removal Estimation component. In the second phase, we design and develop an explainable Deep Learning framework. This framework uses a local data-driven interpretation technique based on SHAP values to investigate the relationship between the neural network's estimated AD diagnosis and the input MRI images. In addition, we handle class distribution by combining an oversampling strategy with a minority approach. Several assessment metrics are used to analyze the performance of our proposed model.

Results:

The proposed method is tested on a variety of medical samples, and the results are compared to those obtained using other comparable approaches. We also test and compare our model to three cutting-edge models: DenseNet169, VGGNet15, and Inceptionv3.

Conclusions:

The empirical results show that our proposed model outperforms others, particularly in handling basic structures with limited spectral features, lower computational complexity, and less overfitting. This research worked addressed Rician noise issue in MRI images and predict AD severity prediction using explainable deep learning framework.
Association between selective serotonin reuptake inhibitors and mortality following COVID-19 among patients with Alzheimer's disease
Authors: Gao Zhenxiang , Dorney Ian , Davis Pamela B , Kaelber David C , Xu Rong
Published: November 2024

Background:

Recent research suggests that selective serotonin reuptake inhibitors (SSRIs) may reduce mortality in COVID-19 patients; however, research into their benefits for elderly Alzheimer's disease (AD) patients remains limited.

Objective:

To investigate the relationship between SSRIs therapy and the mortality risk after COVID-19 infection in elderly patients with and without AD.

Methods:

This retrospective cohort study leveraged a large database containing over 100 million electronic health records in the US from the TriNetX platform to compare the hazard rates of mortality after COVID-19 infection in elderly AD patients prescribed SSRIs versus propensity-score matched individuals prescribed other antidepressants. This study was also conducted in separate cohorts of patients without AD to compare the findings.

Results:

When compared with non-SSRI antidepressants, SSRIs were associated with lower risk for mortality after COVID-19 infection in elderly patients without AD over early, middle, and later stages of the pandemic with HRs of 0.84 (95% CI: 0.75–0.93), 0.86 (95% CI: 0.79–0.93), and 0.77 (95% CI: 0.71–0.33), respectively. When comparing SSRIs with non-SSRI antidepressants for mortality risk following COVID-19 among patients with AD, HRs of 0.95 (95% CI: 0.71–1.27), 0.80 (95% CI: 0.61–1.06), and 0.99 (95% CI: 0.75–1.32), were found respectively.

Conclusions:

Our findings suggest that the use of SSRIs is significantly associated with reduced mortality risk following COVID-19 in elderly patients without AD compared to other antidepressants. While a lower mortality risk was also observed among AD patients, the association was not statistically significant.
Neutrophil percentage-to-albumin ratio is associated with cognitive function in adults aged over 60 years: An analysis of data from the NHANES 2011–2014
Authors: Fan Di , Wang Tingfan , Xiang Jinxian , Bai Yiping , Zhang Liling , Wang Xiaobin
Published: November 2024

Background:

The aging global population is increasing the attention to cognitive decline in older individuals.

Objective:

This study sought to examine the potential link between the neutrophil percentage-to-albumin ratio (NPAR) and cognitive function.

Methods:

We analyzed data from the National Health and Nutrition Examination Survey 2011–2014 using multivariate logistic regression and smooth curve fitting, to investigate the correlation between NPAR and cognitive performance. Restricted cubic spline analysis assessed the linear relationship with high-risk cognitive dysfunction, while piecewise linear regression identified thresholds. Subgroup analyses confirmed the consistency and reliability of our findings.

Results:

Our study included data from 2759 individuals aged >60 years. NPAR showed a significant correlation with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word learning score, CERAD delayed recall score, total z-score and a high risk of cognitive dysfunction. Furthermore, there were statistically significant trends in the changes in CERAD word learning, digit symbol substitution test, and CERAD delayed recall scores as the NPAR quartile increased, these trends were inverted U-shaped. When the NPAR exceeded 14.57, there was a positive association with the likelihood of a high risk of cognitive impairment. The link between NPAR and cognitive performance was notably stronger in individuals with moderate body mass index and those aged 73–80 years.

Conclusions:

A strong link was observed between the NPAR and cognitive function. NPAR may serve as a tool to identify individuals at increased risk of cognitive decline.
Early Alzheimer's disease diagnosis via handwriting with self-attention mechanisms
Authors: Kang Lei , Zhang Xiaolei , Guan Jitian , Huang Kai , Wu Renhua
Published: November 2024

Background

The neurodegenerative diseases like Alzheimer's disease (AD) can result in progressive decline in both cognitive functions and motor skills, which have critical need for accurate early diagnosis. However, current diagnosis approaches primarily rely on timely clinical magnetic resonance imaging (MRI) scans, which impede widely application for potential patients. Leveraging handwriting as a diagnostic tool offers significant potential for identifying AD in its early stages.

Objective

This study aims to develop an efficient, rapid, and accurate method for early diagnosis of AD by utilizing handwriting analysis, a promising avenue due to its association with compromised motor skills in neurodegenerative diseases.

Methods

We propose a novel methodology that leverages self-attention mechanisms for the early diagnosis of AD. Our approach integrates data from 25 distinct handwriting tasks available in the DARWIN (Diagnosis AlzheimeR WIth haNdwriting) dataset.

Results

The Self-Attention model achieved an accuracy of 94.3% and an F1-score of 94.5%, outperforming other state-of-the-art models, including traditional machine learning and deep learning approaches. Specially, the Self-Attention model surpassed the previous best model, the convolutional neural networks, by approximately 4% in both accuracy and F1-score. Additionally, the model demonstrated superior precision (94.7%), sensitivity (94.5%), and specificity (94.1%), indicating high reliability and excellent identification of true positive and true negative cases, which is crucial in medical diagnostics.

Conclusions

Handwriting analysis, powered by self-attention mechanisms, offers significant potential as a diagnostic tool for identifying AD in its early stages, providing an effective alternative to traditional MRI-based diagnosis.
Influence of APOE4 genotype on PCSK9-lipids association in cerebrospinal fluid and serum of patients in the Alzheimer's disease continuum
Authors: Papotti Bianca , Palumbo Marcella , Adorni Maria Pia , Elviri Lisa , Chiari Annalisa , Tondelli Manuela , Bedin Roberta , Baldelli Enrica , Lancellotti Giulia , Lupo Maria Giovanna , Ferri Nicola , Bertolotti Marco , Bernini Franco , Mussi Chiara , Zimetti Francesca
Published: November 2024

Background

Alterations in factors involved in cholesterol homeostasis are critical in Alzheimer's disease (AD), but the stage of occurrence, their specific association, and a possible relationship with the APOE4 genotype are not clarified.

Objective

We aimed to quantify and correlate specific lipid factors in patients with different degrees of cognitive decline, namely patients with AD and patients with mild cognitive impairment due to AD (MCI-AD), carriers or non-carriers of the APOE4 genotype.

Methods

We evaluated Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), cholesterol and the oxidative metabolites 24-, 25-, 27-hydroxycholesterol (HC) in the cerebrospinal fluid (CSF) and serum of AD (n = 28) and MCI-AD (n = 27) patients.

Results

CSF and serum PCSK9 and lipids were similar, except for higher serum PCSK9 and triglycerides in MCI-AD compared to AD. In CSF, AD APOE4 carriers showed higher PCSK9 and 24-HC (+61.3%, p = 0.027 and +32.7%, p = 0.037), compared to non-carriers. There was a negative association between CSF PCSK9 and 27-HC in AD (r = −0.444, p = 0.049) and, exclusively among AD APOE4 carriers, a negative association between CSF PCSK9 and 24-HC (r = −0.786, p = 0.028). A positive correlation was observed between CSF and serum PCSK9 in AD (r = 0.520, p = 0.004), driven by APOE4 carriers (r = 0.544, p = 0.038), suggesting PCSK9 exchange between brain and periphery. A positive correlation was detected between serum and CSF 27-HC (r = 0.465, p = 0.039) in AD. None of these results were found in MCI-AD patients.

Conclusions

PCSK9 and 24-HC might be specific markers of ApoE4-associated lipid alterations in AD, possibly contributing to clinical progression in the AD continuum.
Is KIBRA polymorphism associated with memory performance and cognitive impairment in Alzheimer's disease?
Authors: Jurasova Vanesa , Andel Ross , Katonova Alzbeta , Nolan Raena , Lacinova Zuzana , Kolarova Tereza , Matoska Vaclav , Vyhnalek Martin , Hort Jakub
Published: November 2024

Background:

Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD).

Objective:

We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered.

Methods:

Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory.

Results:

KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p = 0.027).

Conclusions:

Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.
Frontiers and hotspots evolution between air pollution and Alzheimer's disease: A bibliometric analysis from 2013 to 2023
Authors: Liu Zhirong , Hu BingShuang , Tang Ju , Liu XinLian , Cheng BaoJing , Jia Cui , Zhang LuShun
Published: November 2024

In recent years, the study of air pollution has received increasing attention from researchers, but a summary of Alzheimer's disease (AD) and air pollution is missed. Through combing the documents in the core dataset of Web of Science, this study analyzes current research based on specific keywords. CiteSpace and VOSviewer perform statistical analysis of measurement metrics to visualize a network of relevant content elements. The research devotes discussion to the relationship between air pollution and AD. Keyword hotspots include AD, children, oxidative stress, and system inflammation. Overall, 304 documents on air pollution and AD from 2013 to 2023 were retrieved from Web of Science. One hundred twenty-two journals published relevant articles, and the number of articles has increased gradually since the past decade. Research and development in AD and air pollution are progressing rapidly, but there is still a need for more connections with multidisciplinary technologies to explore cutting-edge hotspots.
Performance of the Benton Judgment of Line Orientation test across patients with different types of dementia
Authors: Chen Huifeng , Wang Lijun , Chen Feifan , Sun Wenhao , Wang Siqi , Zhang Nan
Published: November 2024

Background

The Benton Judgment of Line Orientation (JLO) test is one of the most frequently used tests for assessing visuospatial function.

Objective

This study aimed to determine the diagnostic and differential performance of JLO for different types of dementia.

Methods

A total of 258 participants, including 68 patients with Alzheimer's disease (AD), 86 with subcortical ischemic vascular dementia (SIVD), 30 with frontotemporal lobar degeneration (FTLD), 22 with Lewy body dementia (LBD), and 52 cognitively unimpaired (CU) controls, were enrolled from a memory clinic. The total scores and error types in the JLO test were compared between groups. Receiver operating characteristic curve analyses were used to estimate the diagnostic and differential abilities of the JLO test for patients with different types of dementia.

Results

We found that the JLO score was significantly lower in patients with AD, SIVD, FTLD, or LBD than in CU controls (12.90 ± 8.72 versus 17.06 ± 6.14 versus 15.47 ± 8.39 versus 9.23 ± 8.96 versus 21.69 ± 3.72, respectively; all p < 0.05). In particular, for patients with LBD, the JLO score was significantly lower than that for patients in the other groups (all p < 0.05) and showed excellent performance in distinguishing LBD patients from CU controls, with an AUC of 0.888 (sensitivity 72.73% and specificity 94.23%) at a cutoff value of 16. Intraquadrant oblique error was the most common type of error in dementia patients.

Conclusions

The JLO test is an effective tool for evaluating visuospatial function in patients with dementia, particularly for identifying LBD patients.
Sensitive written hedgehog PICture Naming and Immediate Recall (PICNIR) as a valid and brief test of semantic and short-term episodic memory for very mild cognitive impairment
Authors: Bartos Ales , Diondet Sofie
Published: November 2024

Background

Semantic and short-term episodic memory are impaired in some brain disorders including Alzheimer's disease.

Objective

Development and validation of an almost self-administered, but cognitively demanding four-minute test identifying very mild cognitive impairment (vMCI).

Methods

The innovative hedgehog PICture Naming and Immediate Recall ( PICNIR) consisted of two parts. The first task was to write down the names of 20 black-and-white pictures to evaluate long-term semantic memory and language. The second task involves immediate recall and writing the names of as many previously named pictures as possible in one minute. The PICNIR is assessed using the number of naming errors (NE) and correctly recalled picture names (PICR). The PICNIR and a neuropsychological battery were administered to 190 elderly individuals living independently in the community. They were divided into those with vMCI (n = 43 with Montreal Cognitive Assessment (MoCA) 24 ± 3 points) and sociodemographically matched cognitively normal (CN) individuals (n = 147 with MoCA 26 ± 3). Both subgroups had predicted mean Mini-Mental State Examination scores of 28–29 points.

Results

Compared to CN, vMCI participants made more NE (0.3 ± 0.6 versus 0.6 ± 0.9; p = 0.02) and recalled fewer PICR (8.9 ± 2.2 versus 6.8 ± 2.2; p < 0.000001). Discriminative validity was satisfactory using the area under the ROC curve (AUC): 0.76 for PICR, 0.74 for MoCA, 0.67 for MoCA-five-word recall, and 0.59 for NE. The AUCs of PICR and MoCA were comparable and larger than those of MoCA five-point recall or NE. Logical Memory scores, RAVLT scores, Digit symbol, and animal fluency correlated with PICR.

Conclusions

The picture-based PICNIR is an ultra-brief, sensitive cognitive test valid for assessing very mild cognitive impairment. Its effectiveness should be validated for other languages and cultures.
Reporting of comorbidities and health status of participants in clinical trials testing amyloid- and tau-targeting monoclonal antibodies for Alzheimer's disease: A systematic review
Authors: Canevelli Marco , Ancidoni Antonio , Valletta Martina , Toccaceli Blasi Marco , Alfano Alba Rosa , Buscarnera Simona , Salzillo Martina , Nuti Filippo , Zambri Francesca , Di Nolfi Annachiara , Lacorte Eleonora , Grande Giulia , Vanacore Nicola , Bruno Giuseppe
Published: November 2024

Background

Controversies exist around the external validity of clinical trials on disease-modifying treatments for Alzheimer's disease (AD). Detailed information on the clinical characteristics of research participants is lacking, hampering the understanding of their representativeness.

Objective

This study aimed to systematically review the baseline comorbidities and health status of patients with AD enrolled in clinical trials.

Methods

A systematic review of scientific and gray literature was conducted. Randomized controlled trials, enrolling participants in the AD continuum, and testing amyloid- and tau-targeting monoclonal antibodies were selected. Data on the type of study and intervention and the baseline clinical characteristics of participants were extracted. The proportion of studies reporting information on comorbidities, integrative measures of health (e.g., number of chronic diseases and multimorbidity, frailty, and gait speed), and non-neurological concomitant therapies of participants was calculated.

Results

Thirty-six articles, referring to 41 studies (21,952 participants) were included. None of the retained trials provided information on the comorbidities or other integrative measures reflecting the baseline health status of participants. Only three studies reported data on non-neurological concomitant therapies. Five documents providing relevant information were identified through gray literature searches covering the websites of regulatory agencies and pharmaceutical manufacturers.

Conclusions

The health characteristics of patients with AD included in randomized controlled trials are poorly reported. Therefore, the external validity of the study findings cannot be fully appreciated.
The phospho-tau cascade, basal forebrain neurodegeneration, and dementia in Alzheimer's disease: Anti-neurodegenerative benefits of acetylcholinesterase inhibitors
Authors: Moss Donald E , Perez Ruth G
Published: November 2024

A conundrum in Alzheimer's disease (AD) is why the long-term use of acetylcholinesterase (AChE) inhibitors, intended for treatment of dementia, results in slowing neurodegeneration in the cholinergic basal forebrain, hippocampus, and cortex. The phospho-tau cascade hypothesis presented here attempts to answer that question by unifying three hallmark features of AD into a specific sequence of events. It is proposed that the hyperphosphorylation of tau protein leads to the AD-associated deficit of nerve growth factor (NGF), then to atrophy of the cholinergic basal forebrain and dementia. Because the release of pro-nerve growth factor (pro-NGF) is activity-dependent and is controlled by basal forebrain projections to the hippocampus and cortex, our hypothesis is that AChE inhibitors act by increasing acetylcholine-dependent pro-NGF release and, thus, augmenting the availability of mature NGF and improving basal forebrain survival. If correct, improved central nervous system-selective AChE inhibitor therapy started prophylactically, before AD-associated basal forebrain atrophy and cognitive impairment onset, has the potential to delay not only the onset of dementia but also its rate of advancement. The phospho-tau hypothesis thus suggests that preventing hyperphosphorylation of tau protein, early should be a high priority as a strategy to help reduce dementia and its associated widespread social and economic suffering.
Valuing the importance of sex differences in prodromal Alzheimer's disease based on structural magnetic resonance imaging
Authors: Ren Chao , Wang Wen-Qian , Li Hui-Hua , Li Bing-Yu , Shi Ke-Ning , Yang Li-Na , Guan Li-Na , Kong Min , Ba Mao-Wen ,   for the Alzheimer’s Disease Neuroimaging Initiative **
Published: November 2024

Background

Alzheimer's disease (AD) can be optimally managed from a healthcare point of view if detected at a prodromal stage. Amnestic mild cognitive impairment (MCI) is known as prodromal AD, has attracted extensive attention and research.

Objective

To identify the differences in cognitive function and structural magnetic resonance imaging (MRI) features between men and women with MCI on the basis of A/T/N classification system (“A” means amyloid-β biomarker, “T” means tau biomarker, and “N” means neurodegeneration biomarker as determined by clinical imaging (e.g., positron emission tomography, magnetic resonance imaging (MRI)) or by the measurement of total tau protein (T-tau) in the cerebrospinal fluid (CSF)) and to further explore the correlation between them.

Methods

406 MCI subjects were selected from the Alzheimer's Disease Neuroimaging Initiative database and divided into male and female MCI groups. Differences in demographic characteristics, biomarkers, cognitive assessment performance, and regions of interest (ROIs) of structural MRI were compared between the two groups. The correlations between brain structural changes quantified by MRI and cognitive abilities were investigated through linear regression models.

Results

Compared with male MCI subjects, females had significantly higher T-tau concentration in CSF. There were significant differences in ROIs between the sex groups. In the male MCI group, the average cortical thicknesses of the right posterior cingulate, right anterior cingulate and right supramarginal gyrus were more closely correlated with cognitive function. In the female MCI group, the volume of the right rostral anterior cingulate, and the surface area and average cortical thickness of the right isthmus of the cingulate gyrus were more closely correlated with cognitive function.

Conclusions

Based on A/T/N classification system, the structural MRI data analysis was closely correlated with the difference of cognitive function from patients with prodromal AD in a sex-dependent manner.
Exploring heterogeneity in mild cognitive impairment
Authors: Goodman Zachary T , Llabre Maria M , Kaur Sonya , Banerjee Nikhil , McInerney Katalina , Sun Xiaoyan , Saporta Anita Seixas Dias , Levin Bonnie E
Published: November 2024

Background

Mild cognitive impairment (MCI) is a heterogeneous diagnostic entity, without a clear prognosis, often accompanied by psychiatric symptomatology and physical frailty.

Objective

Understanding the heterogeneity within MCI is a critical step in improving the early detection of cognitive decline and developing effective interventions.

Methods

Cross-sectional multivariate latent mixture analyses of data from patients evaluated between 2015 and 2019, who were routinely entered into a multidisciplinary database for research purposes. A sample of 538 community-dwelling older adults drawn from a large academic medical center, referred from within the Department of Neurology (63.7% Female, Mage = 67.8, SDage = 10.6). Participants completed comprehensive neuropsychological assessments, psychiatric symptom measures, and frailty evaluations.

Results

Latent profile analyses supported five profiles of cognitive impairment: At-Risk, Pre-MCI, Amnestic MCI, Multiple Domain MCI, and Major Cognitive Impairment. The inclusion of concomitant psychiatric symptoms and frailty criteria revealed two additional profiles: Psychiatric/Frail, without cognitive impairments, and Multiple Cognitive Domains/Psychiatric/Frail. Critically, 55% of those classified as Healthy based on cognitive data alone were reclassified. Significant profile-wise differences emerged across auxiliary variables of brief cognitive screening, sociodemographics, and medical and psychosocial risk.

Conclusions

Results highlight heterogeneity represented by neurologic patients referred for neuropsychological evaluation that include key physical and emotional symptoms known to increase the risk of cognitive decline. Findings are in alignment with more recent research suggesting that the traditional paradigm cognitive impairment may need to be expanded to improve diagnostic accuracy and to develop more tailored, precision-driven interventions.
Memory consolidation, temporal and parietal atrophy, and metabolism in amyloid-β positive and negative mild cognitive impairment
Authors: Keith Cierra M , Haut Marc W , Vieira Ligo Teixeira Camila , Mehta Rashi I. , Phelps Holly , Ward Melanie , Miller Mark , Navia R Osvaldo , Coleman Michelle M , Marano Gary , Wang Xiaofei , Pockl Stephanie , Rajabalee Nafiisah , Scarisbrick David M , McCuddy William T , D’Haese Pierre-François , Rezai Ali , Wilhelmsen Kirk
Published: November 2024

Background

Alzheimer's disease (AD) is classically characterized by alterations in memory consolidation. With the advent of diagnostic biomarkers, some patients clinically diagnosed with AD display biomarkers inconsistent with the diagnosis.

Objective

We aimed to explore differences in memory consolidation and neurodegeneration of the temporal and parietal lobes as a function of amyloid-β status in amnestic mild cognitive impairment (aMCI).

Methods

We examined differences in memory consolidation and neurodegeneration between patients diagnosed with amyloid-β positive aMCI (Aβ+ N = 78), amyloid-β negative aMCI (Aβ− N = 48), and healthy participants (HP; N = 41), within a well-characterized clinical cohort.

Results

Aβ+ exhibited more pronounced consolidation impairments compared to Aβ−, while Aβ− faced more consolidation challenges than HP. Both Aβ+ and Aβ− were similar in hippocampal volume and entorhinal thickness, but Aβ+ had thinner inferior parietal cortex than Aβ−. Using 18F-fluoro-deoxyglucose-positron emission tomography, metabolism in both temporal and parietal regions was lower in Aβ+ relative to Aβ−.

Conclusions

These findings suggest pathologies other than AD likely contribute to memory consolidation difficulties in aMCI, and neurodegeneration of the parietal cortex in combination with hypometabolism may contribute to more pronounced consolidation problems in Aβ+.
Functional connectivity changes in two cortico-hippocampal networks of Alzheimer's disease continuum and their correlations with cognition: A SILCODE study
Authors: Shao Kai , Chen Xiao , Yu Xianfeng , Yang Jie , Wei Min , Zhang Mingkai , Li Ruixian , Wang Xuanqian , Wei Yongzhe , Chao-Gan Yan for the SILCODE study group , Han Ying
Published: November 2024

Background

The anterior-temporal (AT) and posterior-medial (PM) networks have been proposed to play pivotal roles in the memory processing associated with Alzheimer's disease (AD). Nevertheless, these two networks’ intrinsic functional coupling characteristics are still vague in different AD stages.

Objective

To explore the functional connectivity (FC) alterations within and across the AT&PM networks in patients with dementia of the Alzheimer's type (DAT), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and normal controls (NC).

Methods

A total of 368 participants over 50 years old from the SILCODE study were recruited, including 99 NC, 134 SCD, 67 MCI, and 68 DAT patients. All the participants underwent a resting-state functional magnetic resonance imaging scan and a battery of neuropsychological tests. The 56 regions-of-interest of the AT&PM networks were defined broadly following existing literature. The FCs were calculated using DPABINet and compared among these four groups. Correlation analyses were performed on FCs and cognitive tests.

Results

Analysis of variance of all four groups showed significant alteration, mainly in the PM networks. Compared to NC, globally decreased FCs regarding AT&PM networks were observed in DAT and MCI patients, while globally increased FCs regarding AT&PM networks were observed in SCD. The decreased FCs in DAT were significantly correlated with the neuropsychological test on the memory domain.

Conclusions

The FC alteration showed different patterns across the AD continuum, especially in individuals with SCD. The elevated FCs in the AT&PM networks of SCD may implicate certain compensating processes in the early stage of AD.
Single step capture and assessment of multiple plasma extracellular vesicle biomarkers in Alzheimer's disease detection
Authors: Lewis Jean M , Harris Dorathy-Ann , Kosmatka Janell , Mikrut Emily , Evenson Jack , Balcer Heath I , Dhani Harmeet , Hinestrosa Juan Pablo , Rissman Robert , Billings Paul R
Published: November 2024

Background

Blood tests for Alzheimer's disease (AD) that measure biomarkers related to neuropathology have demonstrated to be useful, minimally-invasive ways to identify patients for screening into clinical trials. While some AD biomarkers can be detected in plasma, greater sensitivity is needed to make plasma AD tests more effective. Extracellular vesicles (EVs) in plasma carry AD-related biomarkers from the brain and could offer a concentrated source of brain-related biomarkers, though the methodological complexities involved in isolating plasma EVs have hampered its validation for clinical use.

Objective

To explore the feasibility and effectiveness of developing blood tests for AD utilizing extracellular vesicle-bound protein biomarkers.

Methods

We developed a simplified method for isolating EVs directly from plasma using an alternating current electrokinetic (ACE) microchip. No sample pretreatment steps were needed. Protein biomarkers on the EVs were detected by adding fluorescent antibodies to the plasma samples before capture by the chip. This allowed measurement of EV biomarker levels directly on the chip.

Results

AD or non-AD control plasma was measured for ten different AD-related biomarkers. EV-associated NCAM1, pTau231, α-synuclein, and TDP-43 levels were able to distinguish a group of 10 AD, 10 mild cognitive impairment (MCI), and 10 non-AD subjects. pTau231 was different between AD and non-AD (p = 0.0300) and α-synuclein differentiated AD from MCI (p = 0.0148).

Conclusions

This study shows how ACE microfluidic chip technology can help differentiate AD and MCI patients from non-AD controls with clinical relevance. This work also highlights the important diagnostic role of plasma EV biomarkers in neurodegenerative disease.
A systematic review of lifestyle-based interventions for managing Alzheimer's disease: Insights from randomized controlled trials
Authors: Martínez-López Sara , Tabone Mariangela , Clemente-Velasco Sara , González-Soltero Maria del Rocío , Bailén María , de Lucas Beatriz , Bressa Carlo , Domínguez-Balmaseda Diego , Marín-Muñoz Juan , Antúnez Carmen , Gálvez Beatriz G , Larrosa Mar
Published: November 2024

Background

Alzheimer's disease (AD) presents a significant challenge in healthcare, prompting exploration into non-pharmacological interventions to complement traditional treatments.

Objective

This systematic review explores the efficacy of lifestyle-based interventions in managing AD.

Methods

A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus between 2018 and 2023, selecting randomized controlled trials examining factors such as exercise, diet, stress, and cognitive training in AD patients.

Results

The review revealed physical exercise as the predominant non-pharmacological intervention, accompanied by dietary modifications, cognitive training, and therapies such as mindfulness and music. While exercise demonstrated improvements in quality of life, its cognitive benefits were limited. Modified diets, such as Atkins and ketogenic, displayed inconsistent effects on cognitive function but influenced other health-related parameters. Additionally, probiotic therapy and novel cognitive training technologies were explored.

Conclusions

Despite some interventions showing promise in enhancing cognitive function and slowing disease progression, uncertainties remain regarding the dose-response relationship, underlying mechanisms, and potential synergistic effects. Moreover, consideration of genetic and sex-based disparities is warranted. This synthesis underscores the need for further research to elucidate the nuances of non-pharmacological interventions in managing AD effectively.

PROSPERO registration number

CRD42023432823
Identification of key neutrophil extracellular trap genes in Alzheimer's disease
Authors: Pan Hengming , Wang Ge , Bi Zhichao , Lai Chao , Wang Min
Published: November 2024

Background

Alzheimer's disease (AD) is a neurodegenerative disorder that is associated with neuroinflammation. Neutrophil extracellular traps (NETs) are web-like structures that cause inflammation, but its involvement in AD pathogenesis is unclear.

Objective

This study aimed to identify key NETs related genes associated with AD.

Methods

A total of 180 samples from the GSE122063 and GSE36980 dataset were obtained from the GEO repository. The representative genes were obtained, and its diagnostic performance was evaluated by analyzing operating characteristic curves. Consensus clustering and principal component analysis were performed to cluster AD samples. Gene ontology, KEGG pathway enrichment, and protein interaction network were analyzed. Peripheral blood samples were collected from 5 AD patients and 5 healthy donors to determine the expression of representative proteins or genes using WB, ELISA, and RT-qPCR.

Results

A total of 297 differentially expressed genes (DEGs) were associated with AD, 18 NETs genes showed potential diagnostic value. NETs genes expression effectively distinguished AD patients into 2 subgroups. The AD1 cluster showed higher abundance of activated dendritic cells, monocytes, and neutrophils, the AD2 cluster showed higher levels of naive B cells, eosinophils, and activated NK cells. We randomly selected and measured the levels representative genes in AD patients. The levels of NETs and CCL2, TLR2 expressions were significantly increased, whereas the level of BDNF was significantly decreased in AD patients comparing with healthy controls.

Conclusions

This study identified key NET genes including BDNF, CCL2, and TLR2 to be associated with AD pathogenesis and classification.