bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.