bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of tau on global graph measures from high‐density EEG in preclinical and prodromal stage of Alzheimer disease
Authors: Spruyt Laure , Mlinarič Tjaša , Reinartz Mariska , Hulle Marc Van , Laere Koen Van , Dupont Patrick , Vandenberghe Rik 
Published: January 2025

AbstractBackgroundIn Alzheimer disease (AD) changes in the small world network have been described, which can be considered as the balance between local connectivity, exhibited with the “clustering coefficient”, and global integration, investigated by “characteristic path length”. With high‐density EEG, we examined the effect of early spread of tau aggregates on these global graph measures.MethodThis study includes 47 participants who underwent a 100‐minute dynamic 18F‐MK6240 PET‐scan and a five‐minutes eyes closed 128‐channel resting‐state EEG. The total group consisted of 24 cognitively normal amyloid‐negative individuals (CN_N), 10 cognitively normal amyloid‐positive individuals (asymptomatic AD) (CN_P) and 13 patients with prodromal AD (Table 1). We calculated in the alpha frequency band the average undirected weighted Phase‐Lag‐Index and used this as weights for the graph and analyzed the global graph measures characteristic path length and clustering coefficient in sensor‐space. For both the whole group as for the constituent subgroups, we examined the Spearman correlation between these global graph measures and tau‐PET load in an a priori defined early‐metaVOI, comprised of the entorhinal and perirhinal cortex, hippocampus, parahippocampus and fusiform cortex. To investigate the difference between tau‐PET load, clustering coefficient and path length in the 3 subgroups, we applied a Kruskal‐Wallis test.ResultThere was a significant correlation of tau‐PET load with the characteristic path length (r=0.33; p=0.03) and also with the global clustering coefficient (r=‐0.39; p=0.007) in the whole group analysis. When considering the asymptomatic AD group separately, there was also a significant correlation of tau‐PET load with the characteristic path length (r=0.77; p=0.01) and with the global clustering coefficient (r=‐0.82; p=0.007). There was no significant correlation within the CN_N subgroup (path length r=‐0.03; p=0.91; clustering coefficient (r=‐0.06; p=0.80)), neither in the prodromal AD subgroup (path length r=‐0.13; p=0.67; clustering coefficient (r=‐0.03; p=0.92)) (Figure 1). There was a significant difference in tau‐PET load between the subgroups CN_N and prodromal AD (p<0.025) and in clustering coefficient and path length between the CN_N and the CN_P group versus the prodromal AD subgroup (p<0.025).ConclusionIn the asymptomatic stage of AD, focal tau‐PET load in medial temporal cortex is associated with global electrophysiological measures of network disintegration.
Comparing the short‐term and long‐term impact of primary and secondary prevention strategies on population‐level dementia burden: A microsimulation modelling study
Authors: van Rosmalen Lynn , Brück Chiara C. , Wolters Frank J. , Handels Ron , de Kok Inge M.C.M. 
Published: January 2025

AbstractBackgroundDementia prevention can be achieved through modification of risk factors (primary prevention) or targeted therapy against pathophysiological hallmarks of disease (e.g., amyloid‐lowering medication (secondary prevention)). To compare the effectiveness of primary and secondary prevention approaches on population dementia burden over time, we used a microsimulation approach.MethodWe used the microsimulation model MISCAN‐Dementia to simulate 10 million people born between 1910‐1989, in absence and presence of dementia prevention (Figure 1). For primary prevention, we assumed it is effective if there is no brain pathology, and dementia was attributable to risk factors. We assumed that primary prevention delays the presymptomatic stage by 12 months. For secondary prevention, we assumed patients are eligible for amyloid‐lowering treatment if they are in MCI or early dementia stage and are amyloid positive. We assumed that treatment increases MCI and mild dementia stage durations by 10%. To simulate these primary and secondary interventions, we incorporated a presymptomatic dementia stage (pathology present, no cognitive decline), amyloid status, and risk factor status in the model. Both interventions are initiated in 2025. We calculated the number of life years lived with dementia per 100.000 persons <85 years by disease stage.ResultBenefits of primary prevention accrued slowly over time, from no benefit at 5 years post initiation, to around 8‐9% reduction in the number of life years with moderate‐severe dementia at 25 years after initiation. After 5 years, secondary prevention showed a 4.8% decrease in years lived with moderate dementia and 2.6% with severe dementia. This reduction increases to 5‐6% in 25 years (Figure 2). In case both interventions are applied, the effect is 0.5‐1% weaker than additive. The two modes of prevention are equally effective 19 years after initiation.ConclusionCompared to secondary prevention, primary preventive strategies can yield a larger reduction in life years with dementia, but benefits take a much longer time to accrue. These findings underline the need for combined primary and secondary prevention initiatives and sustained, long‐term efforts to achieve the full potential of dementia prevention in the population. Sensitivity analyses to examine the robustness of the findings need to be complemented.
Optimizing blood biomarkers collection for Alzheimer’s disease among older adults in rural Kenya
Authors: Ndetei David , Nyamai Pascalyne , Musyimi Christine W. , Kasomo Diana , Mutiso Victoria 
Published: January 2025

AbstractBackgroundPlasma/serum measurements, which stand as the clinical gold standard biomarkers for Alzheimer’s disease (AD) are minimally invasive, facilitating easy collection and processing particularly in low‐resource settings. Often, both laboratory and non‐laboratory medical personnel find themselves collecting these blood biomarker samples in remote hospitals characterized by a high influx of patients, leaving them with limited time and resources (e.g. freezers) for immediate sample processing, transport, and storage. This abstract describes blood biomarker sample collection and storage for AD research among older adults in Makueni County, Kenya.MethodsIn optimizing blood biomarkers collection for AD research among hard‐to‐reach older adults, a multidisciplinary team is crucial. Blood was collected into three Ethylenediamine tetraacetic acid (EDTA) of 10mls each. To ensure the preservation of biomarker integrity, we focused on refining sample handling processes, and maintained the required temperature for sample transportation.ResultsFollowing sample collection, one of the three EDTA blood tubes was immediately stored in dry ice (‐80 degrees) for Deoxyribonucleic acid (DNA) extraction. A volume of 0.5ml whole blood was taken from one of the remaining two EDTA tubes. The rest was centrifuged at 3400 rpm for 10 minutes and plasma aliquots obtained and put into the barcoded storage vials prelabeled. To preserve the integrity of the blood biomarkers, the collection and transportation process necessitated the use of dry ice (‐80 degrees) with continuous monitoring. This not only ensured the retention of blood biomarkers but also the importance of stability in these biomarkers. Subsequently, during storage, temperature monitoring becomes imperative. The options ranged from manual temperature monitors, albeit with inherent limitations, to more reliable yet costly data loggers. This monitoring was crucial to guarantee the integrity of the stored samples and maintain the accuracy of biomarker analysis.ConclusionThe transportation of blood samples from the rural hospital to centralized facilities with adequate freezers demands meticulous cold chain maintenance. Clear guidelines encompassing sample collection, transport, processing, and storage, in hard‐to‐reach older adults should be delineated for future biomarker research in AD research.
Brazilian Subjective Cognitive Decline (BRASCODE) Cohort: baseline sociodemographic and clinical data
Authors: de Albuquerque Ana Letícia Amorim , Giordani Manuella Edler Zandoná , Souza Victória Tizeli , da Mota Simone Sieben , De Marchi Bruno De Olive , Rivas Gabriela Raquel Paz , Carvalho Guilherme Da Silva , De Souza Haniel Bispo , Beltrami Lucas Bastos , Santos Rhaná Carolina , Borelli Wyllians Vendramini , Carello‐Collar Giovanna , Chaves Marcia L Fagundes , Zimmer Eduardo R. 
Published: January 2025

AbstractBackgroundSubjective cognitive decline (SCD) is the self‐perceived impairment of cognitive function and has been studied as a risk factor for objective cognitive impairment. Monitoring patients with SCD can aid in understanding the risk factors for dementia in low‐ and middle‐income countries. We aimed to describe the baseline sociodemographic and clinical data of the Brazilian Subjective Cognitive Decline (BRASCODE)MethodsBRASCODE is an observational, prospective cohort study of cognitively unimpaired individuals with > 65 years‐old with cognitive complaints conducted at the Hospital de Clínicas de Porto Alegre, Brazil. The baseline evaluation was performed from March 2022 to January 2024. Exclusion criteria were previous diagnosis of dementia or cerebrovascular disease and uncontrolled neuropsychiatric/clinical illness. Sociodemographic, memory complaint scale (MCS), Mini‐Mental State Examination (MMSE), Clinical Dementia Rating (CDR) Scale and Cognitive Reserve Scale (CRS) were collected. Blood, cerebrospinal fluid, and imaging Alzheimer’s disease (AD) biomarkers were also performed.ResultsA total of 144 patients were included, with 72.2% being female. The majority were of white ethnicity (92.1%), belonging to middle‐class socioeconomic status (B and C ‐ 79.9%). The median age was 69 years, and the median education level was 15 years. The most prevalent comorbidities were arterial hypertension (46.5%), diabetes mellitus (14.6%), and smoking (6.9%). The median score on the MMSE was 29 [27, 30] points. Regarding the CDR scale, 109 patients (75.7%) had a CDR of 0, and 35 (24.3%) had a CDR of 0.5. CRS scores exhibited a positive correlation with MMSE (rho = 0.304; p = 0.0002) and years of formal education (rho = 0.408; p<0.0001). Age correlated negatively with MMSE (rho = ‐0.188; p = 0.024) and MCS (rho = ‐0.245; p = 0.003). MCS score of the subject and informant also correlated (rho = 0.305; p = 0.0002) and exhibited no correlation with CRS scores and MMSE.ConclusionsOur results show an association between the patient’s cognitive reserve and education and formal cognitive testing (MMSE). The future availability of AD biomarkers and follow‐up data will provide additional information about cognitive progression of the SCD participants.
Abdominal Obesity (Waist‐to‐Hip Ratio) is Superior to Body Mass Index as an Indicator of Cognitive Health in Older African Americans
Authors: Niraula Sophee , Fausto Bernadette A. , Osiecka Zuzanna , Gluck Mark A. 
Published: January 2025

AbstractBackgroundRecent studies suggest that body mass index (BMI) may overestimate obesity and related cognitive health consequences in some populations due to racial differences in body shape and composition. Conversely, waist‐to‐hip‐ratio (WHR) may better capture cognitive health, because this measure accounts for where body fat accumulates. However, few studies have compared the influence of BMI vs. WHR on cognitive function in older African Americans. As such, this study aimed to identify the relative contributions of BMI and WHR to cognitive function in older African Americans.Method122 older African American participants (mean age = 72.19; SD = ±6.65) from the Pathways to Healthy Aging in African Americans study completed demographic and mood questionnaires, cognitive assessments of attention, memory, executive function, and language, and anthropometric measurements (height, weight, waist and hip circumference). Participants were categorized into four BMI groups per established cut offs (normal weight = 18.5 to 24.9 kg/m2; overweight = 25 to 29.9 kg/m2; class 1 obese = 30.0 to 34.9 kg/m2; class 2 obese or greater = > 35.0 kg/m2). We also used the World Health Organization’s proposed cutoffs for WHR to classify participants with and without abdominal obesity (men ≥ 0.90 cm; women ≥ 0.85 cm). ANCOVA was employed to investigate the main effects of BMI and WHR groups while controlling for age, sex, education, depressive symptomatology, and APOE‐e4 carrier status.ResultThe WHR group with abdominal obesity had significantly poorer attention and executive function performance via the Digit Span test, F(1, 75) = 7.37, p = 0.01, η2
p = .09). There were no significant differences in cognitive test performance across the BMI groups when controlling for WHR, F(3, 75) = 54.10, p = .12, η2
p = .07.ConclusionAbdominal obesity (WHR) is superior to BMI as an indicator of cognitive health in older African Americans. The lack of independent association between BMI and cognition highlights the importance of considering more nuanced measures of body weight such as WHR and abdominal obesity in older African Americans
Association of Pesticide Use with Cognition in Aging Community‐Dwelling Rural Adults in South India
Authors: Panchawagh Suhrud , Mitra Sumedha , Sundarakumar Jonas S. 
Published: January 2025

AbstractBackgroundEmerging evidence suggests environmental factors, such as chronic pesticide exposure, may influence cognitive functioning, yet research in this area remains limited, particularly in rural Indian settings. Our objective was to investigate the potential link between pesticide exposure and cognitive performance in an aging population from rural India.MethodThis cross‐sectional analysis included 4320 participants from the Srinivasapura Aging NeuroSenescence and COGnition (SANSCOG) cohort. They are predominantly farmers, recruited from the rural areas of Srinivaspura in southern India. Pesticide exposure was assessed based on self‐reporting of usage. Cognitive performance was evaluated using a comprehensive, culturally adapted, computerized neurocognitive battery (COGNITO), which encompasses various domains of cognitive function, such as attention (reaction time, visual attention, auditory attention), memory (immediate and delayed episodic memory, implicit memory, name‐face recognition), language (reading & comprehension, phoneme comprehension, phonemic fluency, semantic associations, vocabulary), visuospatial ability (visuospatial span and visuospatial construction), and executive function (form matching, fluid intelligence, semantic fluency). We used multivariate regression models, adjusting for potential confounders such as age, gender, education, diabetes mellitus, and hypertension to test the association between pesticide use and cognition. Multiple comparisons were handled using the Bonferroni correction.ResultIn our study, 3661/4320 participants (85%) were involved in agriculture, of which 1136/3661 (31%) used pesticides. (Table 1) The median duration of pesticide usage was 10 years (IQR: 5, 15). Our study did not find a statistically significant association between high pesticide use and cognitive performance scores in any domain after adjusting for multiple comparisons. (Figure 1)ConclusionOur analysis reports that moderate‐term pesticide use did not significantly impact cognitive function in this population of aging rural Indian adults. However, the cross‐sectional nature, lack of objective information on the severity of exposure, and potential confounders suggest caution in interpretation. We intend to follow up these participants with periodic cognitive monitoring to examine if long‐term pesticide exposure could be linked to accelerated cognitive decline and increased risk for dementia.
A new class of neurodegenerative disease‐fighting drugs: morADC (Morphomer®‐ antibody drug conjugates)
Authors: Nampally Sreenivasachary , Adolfsson Oskar , Martin Camille , Ollier Romain , Menant Sebastien , Tsika Elpida , Fenyi Alexis , Ait‐Bouziad Nadine , Aeschbach Lorene , Pautet Sylvain , Fuchs Aline , Ribas David , Derouazi Madiha , Pfeifer Andrea , Kosco‐Vilbois Marie 
Published: January 2025

AbstractBackgroundAntibody‐drug conjugates (ADCs) represent a major advancement in oncology to deliver selectively cytotoxic drug to tumor cells while reducing their exposure to normal tissues. Each ADC consists of a monoclonal antibody (mAb) selective to a tumor specific/overexpressed surface antigen conjugated to the cytotoxic agent. In this study, we are investigating the potential of an ADC approach in neurodegenerative diseases (NDD) to increase the exposure of therapeutic mAbs in the brain using small molecules known to be brain penetrant.MethodSeveral ADCs were engineered by conjugating mAbs and small molecules (SME) derived from our Morphomer® platforms, resulting in molecules called morADC. The properties of those morADCs incorporating each different mAbs, morphomers and various linkers were assessed in an in vitro blood‐brain‐barrier (BBB) permeability, a primary neuron seeding and Thioflavin T (ThT) aggregation assays. In the latter, the aggregates were also analyzed by electron microscopy. The most promising molecules were injected in mice to monitor brain exposure and pharmacokinetic compared to the parental mAb.ResultOver 30 morADCs were produced to target pathological proteins, e.g., Abeta, Tau and alpha‐synuclein. Drug‐to‐antibody ratios (DAR) from 2.5 to 4.5 were achieved exhibiting excellent purity and plasma stability. The morADC molecules demonstrated in vitro a synergistic effect quantified by isobologram analysis with 2 log higher potency in various seeding assays. When assessed in vitro for brain permeability, morADCs showed 3‐6‐fold enhanced BBB penetration as compared to parental mAb, dependent on the conjugated morphomer and the linker. Increased brain exposure of the morADC compared to the parental mAb was confirmed in mice: 3‐fold increase in vitro in the BBB permeability assay translated in 2.5‐fold increase of the mAb exposure in the mice parenchyma. The initial pharmacokinetic results indicate similar plasma concentration and stability of the morADC as the parental mAb.ConclusionBioconjugating functionally active mAbs and SMEs provides therapeutic morADCs as a new treatment modality with synergistic potential to target NDD pathology. More work is ongoing to better characterize the unexpected synergistic effect observed as well as proof‐of‐concept studies in relevant model pathological models. Nevertheless, our morADC platform represents a promising breakthrough approach in NDDs.
Gender Differences in the Predictive Efficacy of Mayo‐PACC for Alzheimer's Disease Biomarkers: Results from a South American Cohort
Authors: Keller Greta , Mendez Patricio Chrem , Corvalan Nicolas , Clas Giulia Solange , Álvarez María Florencia , Pertierra Lucia , Allegri Ricardo , Sevlever Gustavo , Crivelli Lucia , Surace Ezequiel Ignacio 
Published: January 2025

AbstractBackgroundWith the increase in life expectancy and the rising prevalence of Alzheimer's Disease (AD), the integration of biomarkers for early diagnosis is crucial. The Mayo Preclinical Alzheimer's Cognitive Composite (Mayo‐PACC), encompassing the Rey‐Auditory Verbal Learning Test (RAVLT), Trail Making Test ‐ B (TMT B), and semantic fluency, is designed to detect cognitive changes in preclinical AD. This study investigates gender‐based differences in the predictive efficacy of Mayo‐PACC for AD biomarkers following the ATN (Amyloid, Tau, Neurodegeneration) criteria.MethodThe study included 112 patients diagnosed with Mild Cognitive Impairment (MCI), comprising 38% women and 61% men, matched by age (mean ± SD: 68.73 ± 10.70 years), education (14.21 ± 3.56 years), and cognitive performance (Mayo‐PACC p= 0.76). Neuropsychological assessments were conducted using the Mayo‐PACC, and cerebrospinal fluid biomarkers (amyloid β1–42, total tau, and phosphorylated tau at threonine 181) were quantified by ELISA (Fujirebio, Japan). Biomarkers were dichotomized using cutoff values previously determined in our laboratory.ResultRandom Forest models indicated an overall area under the curve (AUC) of 0.67 for the Mayo‐PACC. In gender‐specific analyses, women showed a lower predictive capacity (AUC: 0.43), with TMT B (35.42%), RAVLT (32.84%), and semantic fluency (31.74%) as key predictors. For men, a higher AUC of 0.90 was observed, with TMT B (35.49%) and semantic fluency (34.91%) being the most influential. When examining individual ATN biomarkers, women showed an AUC of 0.25 for Aβ1‐42, 0.54 for N, and 0.40 for T, with RAVLT (40.51%) as a prominent feature. Men exhibited AUCs of 0.63 for Aβ1‐42, 0.83 for N, and 0.48 for T, with semantic fluency (33.95%), and RAVLT (33.12%) being significant predictors.ConclusionThe study highlights notable gender differences in the predictive performance of neuropsychological composites for AD biomarkers. Biomarker prediction was more accurate in men. These findings suggest the importance of gender‐specific approaches in predictive modeling for AD diagnosis, underscoring the potential to enhance diagnostic precision in clinical practice.
Association between hippocampal volume and visual classification of hippocampal atrophy: an MRI study
Authors: Garrafiel Fabricio Nery , Vidaletti Vitor Verlindo , Soder Ricardo Benardi , Paganin Ricardo Pessini , da Silva Maria Rosa Alves , Aguzzoli Cristiano Schaffer , Schilling Lucas Porcello 
Published: January 2025

AbstractBackgroundHippocampus has a key role in the memory and cognitive functions and its volume tends to decrease during aging and is severely affected in neurodegenerative disorders such as Alzheimer’s disease (AD). The hippocampal atrophy can be assessed by quantitative volumetry or classified by the Mesial Temporal Atrophy Score (MTA). Here, we perform a comparison between the values of automatic hippocampal volumetry and the MTA score, to analyze possible variations through a correlation curve and their impacts on quantitative and qualitative measures.MethodWe analyzed 100 cranial Magnetic Resonance Imaging (MRI) images, T1‐weighted from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The hippocampal volume was obtained by Freesurfer analysis. All images were classified using MTA score by two experienced neuroradiologists. In the statistical analysis, a correlation curve was created, and the Pearson correlation coefficient was obtained between the volumetry and the degree of atrophy and between the interpretations of both radiologists.ResultThe hippocampus volumetric mean size was 2963.83 mm³ (standard deviation 495.16 mm³). As expected, the data exhibited a consistent inverse relationship between hippocampal volume and the MTA score (Figure 1A, B). The Pearson correlation showed a negative correlation between MTA score and hippocampal volume of ‐0.75 for one radiologist and ‐0.76 for the second radiologist and 0.89 between radiologists. However, we observed a variation ≥ 1 predominantly in higher MTA scores in 17 individuals when comparing the MTA scores between radiologists (Figure 2).ConclusionThe results showed an inverse correlation between MTA score and hippocampal volume, but also indicates discrepancies in visual interpretation of data. Our findings highlight that in some situations the MTA classification has an important mismatch compared to volumetry, and future analysis could clarify in which situations MTA is less accurate and should be complementary to other analysis.