bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual Cognitive Assessment Test (VCAT): Utility in detecting early dementia in diverse language cohorts
Authors: Ng Kok Pin , Ong Gwen Cui Fann , Yeoh Odelia Huai‐En , Raghu Rema , Rosa‐Neto Pedro , Gauthier Serge , Liu Yidan , Li Xiaofeng , Baek Min Jae , Kim SangYun , Kandiah Nagaendran 
Published: December 2023

AbstractBackgroundCognitive tests play a crucial role in evaluating mild cognitive impairment (MCI) and dementia. As most tests are originally developed in English‐speaking cohorts, their application in multilingual populations will need to be translated and may affect the test psychometrics. Therefore, the VCAT was developed as a language‐neutral visual‐based assessment to mitigate this issue. Although the VCAT has been validated in Southeast Asian countries, its performance in wider language cohorts remains unclear. Here, we aim to compare the utility of VCAT with established screening tests, Montreal Cognitive Assessment (MoCA) and Mini‐Mental State Examination (MMSE), in distinguishing MCI and dementia from cognitively normal (CN) individuals in a multinational study.MethodThis collaboration between Canada, China, India, Korea and Singapore recruited 614 participants (306 CN, 212 MCI, 94 Dementia). The administration of the cognitive tests were standardized across all study sites. Participants underwent the MMSE, MoCA, and VCAT on the same day, with their scores and demographic data (age, gender, years of education, ethnicity, primary written and spoken language) collected in the centers respectively. The performance of VCAT in distinguishing MCI and dementia from CN were assessed within each sites using the area under the curve (AUC).ResultBaseline demographics of the participants in each site were summarized in Table 1. The mean (SD) MMSE, MoCA and VCAT scores in each diagnostic group across all countries were summarized in Table 2. The mean (SD) VCAT scores across all countries for CN, MCI and dementia were 25.91 (3.14); 21.00 (5.36) and 11.91 (4.79) respectively. Corresponding scores for MoCA were 26.09 (2.76); 22.62 (4.43); 14.02 (5.17) and corresponding scores for MMSE were 28.34 (1.79); 26.55 (2.90); 18.91 (4.81). The AUC of VCAT in detecting cognitive impairment (MCI+Dementia) was found to be 0.83 (95%CI 0.80 to 0.86), which is comparable to the MoCA 0.82 (95%CI 0.78 to 0.85) and the MMSE 0.78 (95%CI 0.74 to 0.81).ConclusionVCAT was comparable to the MoCA and MMSE in distinguishing cognitive impairment from CN in a multinational, multilingual population. Further studies with wider language populations are needed to further validate the utility of VCAT globally.
Physically demanding work and cognitive impairment in late life
Authors: Barbosa Matheus Ghossain , Rabelo Wendell Lima , Bertola Laiss , Lima‐Costa Maria Fernanda , Ferri Cleusa P 
Published: December 2023

AbstractBackgroundCognitive decline is increasing in prevalence worldwide and poses a heavy burden on society. Sociodemographic factors and health behaviors associated with cognitive decline have been described. While physical exercise has been reported as a protective factor, less education acts as a risk factor. Conversely, work activities associated with lower educational levels are frequently more physically demanding. Few studies have analyzed the impact of work activities on cognition.MethodWe used data from the Brazilian Longitudinal Study of Aging, with a sample of 8,336 complete cases. Linear regression was performed to assess the impact of physical demand at work on cognitive performance, as measured by a global cognitive score composed of temporal orientation, verbal fluency, and memory tests. Work activities were classified by the question “How would you describe physical demand of the job you had most of your life?”, with the following possible answers: “mostly sitting”, “mostly standing or walking”, “some physical effort” and “intense physical effort”. Age, sex, marital status, educational level, household income per capita, number of comorbidities, smoking and alcohol consumption, and level of physical activity were used as covariates.ResultWhen compared to a “mostly sitting” type of work (e.g., office job), a “mostly standing or walking” (e.g., security worker) job did not show any difference in cognitive performance (β = ‐0.03, p = 0.089). On the other hand, a “some physical effort” job (carrying weights or using tools, such as nurse or carpenter) and an “intense physical effort” job (carrying heavy weights, such as miner or construction worker) showed an increasingly worse cognitive performance (respectively, β = ‐0.09, p = 0.000 and β = ‐0.11, p = 0.000).ConclusionAlthough sedentarism has been shown to be associated with a worse cognitive performance and increased dementia risk, physically demanding jobs do not appear to be beneficial. Meanwhile, work stress associated with these activities might exert a negative effect on cognition independent of educational level and physical exercise unrelated to work. Some data suggest mentally demanding jobs, on the contrary, can be beneficial. With development of new technologies, moving from physical work into mental work can potentially reduce dementia risk.
The therapeutic potential of ellagic acid loaded in nanocarriers for the treatment of the Alzheimer’s disease
Authors: Maisto Nunzia , Mango Dalila , Barbato Gaetano , Marianecci Carlotta , Carafa Maria , Rinaldi Federica , Nisticò Robert 
Published: December 2023

AbstractBackgroundEllagic acid (EA) has been shown to have protective effects on Alzheimer’s disease, but it shows poor pharmacokinetic profile. A valid approach is delivering the drug in non‐ionic surfactant vesicles (NBVs) through the nose to brain (N2B) route coupled to focused ultrasound (FUS) improving brain targeting. Several niosomal formulations composed by specific surfactants (potentially enhance neuroprotective effect) have been characterized. The contrast agent was loaded inside the nanocarriers which was subsequently characterized using FUS in vitro technique. The EA will be loaded inside the vesicles and the neuroprotective effect of NBVs and EA‐NBVs will be explored using electrophysiological recordings (field and whole cell patch clamp) of hippocampal synaptic transmission and plasticity in ex‐vivo Alzheimer model.MethodEmpty and loaded NBVs were prepared and deeply characterized. In vitro FUS analysis were performed to evaluate the ability of FUS to induce a stable and prolonged release of probe‐drug loaded. The electrophysiological experiments were conducted using C57BL6/J mice of both sexes aged between 30 and 40 days. We performed electrophysiological recordings in area CA1‐CA3. Paired pulse facilitation was assessed at inter‐stimulus intervals ranging from 50 to 500 ms. An additional recording of baseline was evaluated before inducing Long‐Term Potentiation (LTP) by theta‐burst stimulation. Responses (fEPSP) were recorded for 1 hour after tetanization. In vitro Alzheimer model was obtained applying Aβ1‐42 oligomers (200 nM). As a control, we tested the effect of Aβ1‐42 with a scrambled sequence applied in the same condition of Aβ1‐42. Empty and loaded NBVs were used in presence and not of Aβ1‐42 and of Aβ1‐42 scrambled.ResultPreliminary results of empty and loaded NBVs present an optimal range of size for N2B delivery and in vitro FUS release shows a stable and controlled release profile of loaded drug. Slices incubated in presence of Aβ1‐42 showed an impairment of LTP, while this effect didn’t occur after incubation of slices with Aβ1‐42 scrambled. Preliminary results show that NBVs formulations didn’t compromise LTP suggesting the possibility of using them as drug carriers in Alzheimer’s disease.ConclusionA better brain delivery of EA could be a valid approach in pathologies characterized by synaptic dysfunction.
Tau Protein in the Retina
Authors: Kayabasi Umur A. 
Published: December 2023

AbstractBackgroundCurrently there is no definite cure for Alzheimer’s therefore early detection is critical. Undetected Alzheimer’s Disease (AD) can lead to severe accidents, neglecting to take essential medications, injury to oneself or others, and/or financial problems. Currently, biomarkers are the most promising way to detect Alzheimer’s early on. Biomarkers such as beta‐amyloid and tau levels taken through invasive mehods or brain scans that involve radiation are among them.As the retina is an extension of the brain and the brain structure, it is possible to detect misfolded proteins via retinal examination non‐invasively. The aim of this study was to discover the binding property of curcumin to both Tau and AB in the retina as a potential biomarker for AD.MethodIn this study, 20 patients were invited with mild AD who had undergone retinal examination within the past 2 years. All the patients had retinal imaging with curcumin which revealed misfolded proteins during the examination and then they were advised to take daily curcumin. The mean age of the patients was 71, and the patients were instructed to take Curcumin Meriva in 500 mg supplements once daily after their prior examinations. All patients had tests repeated with FAF and Heidelberg Spectralis OCT device. The regions with abnormal lesions on FAF were detected and the layer of the defect was scanned by OCT plus compared with the previous imaging of the patients. The images were examined in a masked fashion by 2 specialists.ResultThe images disclosed hyperfluorescent lesions on FAF and OCT revealed accumulations in the inner layers of the retina. Some accumulations had dot shapes and others had fibril‐tangle shapes. Some lesions were present in prior exams, but they were more pronounced and shinier after curcumin use. Their size and shape were in concordance with misfolded proteins in the brain (Figure).ConclusionRetinal examination with curcumin revealed AB plaques in the retina in prior studies. Our study is the first that may demonstrate an easy way to detect the culprit plaque Tau inside the retina of live patients.
Renal function, Alzheimer’s plasma biomarker, and cognitive phenotypes among rural older adults in China: a population‐based study
Authors: Wang Nan , Liang Xiaoyan , Fa Wenxin , Ma Yixun , Tian Xunyao , Liu Cuicui , Zhu Min , Tian Na , Liu Keke , Tang Shi , Song Lin , Cong Lin , Wang Yongxiang , Hou Tingting , Du Yifeng , Qiu Chengxuan 
Published: December 2023

AbstractBackgroundEmerging evidence has linked impaired renal function with dementia, but the neuropathological mechanisms underlying the association remains poorly understood. We sought to examine the relationships of renal function, Alzheimer’s plasma biomarker, and cognitive phenotypes among rural Chinese older adults.MethodThis population‐based cross‐sectional study included 5715 participants (age ≥60 years; 57.15% women; 40.49% illiteracy) in the Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND‐China). We calculated the estimate glomerular filtration rate (eGFR) using serum creatinine and the simplified modification of diet in renal disease equation specifically for individuals from China, and impaired renal function was defined as eGFR <60 mL/min/1.73 m2. Dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) were diagnosed following the international criteria. Plasma amyloid‐β (Aβ) 40, Aβ42, total tau, and neurofilament light chain (NfL) concentrations were measured using the SIMOA platform in a subsample (n = 1446). Data were analyzed using logistic, the general linear regression, and mediation models.ResultOf the 5715 participants, 283 (4.95%) were detected with renal function impairment, and 326 (5.70%) were diagnosed with dementia (195 with AD and 10 with VaD). The multivariable‐adjusted odds ratios of eGFR <60 mL/min/1.73 m2 (vs. >90mL/min/1.73 m2) were 2.43 (95% confidence interval [CI] 1.56‐3.72) for all‐cause dementia, 2.74 (1.64‐4.49) for AD, and 1.30 (0.50‐2.98) for VaD. In the plasma biomarkers subsample, controlling for demographic factors, impaired renal function was significantly associated with higher levels of plasma Aβ40 (demographic‐adjusted β‐coefficient = 59.06; 95%CI 46.93‐71.19), Aβ42 (3.41; 2.62‐4.20), NfL (14.57; 9.08‐20.05), and total tau (0.74; 0.48‐1.01), and the observed associations remained significant even in the multivariable‐adjusted model (P<0.001). The mediation analysis showed that total tau mediated 12.77% of the association between impaired renal function and AD.ConclusionImpaired renal function is associated with an increased risk of dementia and AD. Plasma total tau may partly underlie the association of renal function with Alzheimer’s dementia.
Amyloid beta and tau pathology compared within different Alzheimer’s disease mouse models after inoculation with Alzheimer’s disease brain tissue
Authors: Turnbull Catherine , Purro Silvia , Collinge John 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD), the leading cause of dementia worldwide, is associated with two proteins known as amyloid beta (Aβ) and tau. Both proteins are thought to have prion‐like properties, resulting in the seeded propagation and spread of disease‐related assemblies. We have investigated three different AD knock‐in mouse models containing humanised versions of Aβ and tau to further our understanding of how AD progresses after the inoculation of Aβ/tau assemblies or seeds. These transmissions would also aid in deciphering the prion‐like properties of both Aβ and tau. These included the APPNL‐F/NL‐F model, which contains a Swedish and Iberian mutation (NL‐F) in the amyloid precursor protein (APP), expressing elevated levels of human Aβ42, and the human (h)TauKI/KI model, which contains all six human isoforms of human tau. Moreover, the AppNL‐F/NL‐F/hTauKI/KI mouse model expresses both human tau and human Aβ42, allowing a side‐to‐side comparison of all three models to provide an informative insight into the best model to study Aβ and tau pathology after inoculation with AD cases.MethodWe previously characterised three AD cases for prion‐like properties, in terms of protease resistance and conformational stability, and inoculated each of the cases into the different AD mouse models. Aβ and tau seeding was determined via histological and western blot analysis, via probing for 82E1 and AT8, to determine the presence of human Aβ and phosphorylated tau respectively.ResultUsing transmission studies, significant differences were seen for Aβ and tau seeding within the APPNL‐F/NL‐F, human (h)TauKI/KI and AppNL‐F/NL‐F/hTauKI/KI mouse models. We show that the AppNL‐F/NL‐F/hTauKI/KI mouse model demonstrates both Aβ and tau seeding from the inoculation of AD cases at earlier time points compared to its retrospective APPNL‐F/NL‐F and hTauKI/KI mouse models in vivo.ConclusionAfter comparing the three different mouse models, our data suggests that the AppNL‐F/NL‐F/hTauKI/KI mouse model may be a superior model for studying prion‐like behaviour and the role of Aβ and tau assemblies within AD. With regards to future characterisation of possible Aβ and tau strains, we anticipate that this model will be able to distinguish any potential strains indicated from serial passages in vivo using the AppNL‐F/NL‐F/hTauKI/KI model.
Shared and unique effects of ApoEε4 and pathogenic gene mutation on cognition and imaging in preclinical familial Alzheimer’s disease
Authors: Quan Meina , Wang Qi , Qin Wei , Jia Longfei , Jia Jianping 
Published: December 2023

AbstractBackgroundNeuropsychology and imaging changes have been reported in the preclinical stage of familial Alzheimer’s disease (FAD). This study investigated the effects of APOEε4 and known pathogenic gene mutation on different cognitive domains and circuit imaging markers in preclinical FAD.Method139 asymptomatic subjects in FAD families, including 26 APOEε4 carriers, 17 APP and 20 PS1 mutation carriers, and 76 control subjects, went through a series of neuropsychological tests and MRI scanning. Test scores and imaging measures including volumes, diffusion indices and functional connectivity (FC) of frontostriatal and hippocampus to posterior cingulate cortex pathways were compared between groups, and analyzed for correlation.ResultCompared with controls, APOEε4 group showed increased hippocampal volume and decreased FC of fronto‐caudate pathway (figure 1). APP group showed increased recall scores in auditory verbal learning test, decreased fiber number, increased radial diffusivity and FC of frontostriatal pathway (figure 1 & 2). All three genetic groups showed decreased fractional anisotropy of hippocampus to posterior cingulate cortex pathway (figure 1). These neuropsychological and imaging measures were able to discriminate genetic groups from controls, with areas under the curve from 0.733 to 0.837 (figure 3). Circuit imaging measures are differentially associated with scores in various cognitive scales in control and genetic groups.ConclusionThere are neuropsychological and imaging changes in the preclinical stage of FAD, some of which are shared by APOEε4 and known pathogenic gene mutation, while some are unique to different genetic groups. These findings are helpful for the early identification of Alzheimer’s disease, and for developing generalized and individualized prevention and intervention strategies.
Manual Motor Function as a Classifier for Alzheimer’s Disease
Authors: Koppelmans Vincent , Ruitenberg Marit F. L. , Tasdizen Togla , Duff Kevin 
Published: December 2023

AbstractBackgroundIn contrast to numerous reports of gross motor problems in Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD), fine motor function has been relatively understudied. We examined if performance on manual motor tasks can distinguish between cognitively normal (CN) subjects, and individuals with MCI or AD, and which fine motor features are most informative.Method47 CN, 25 MCI, and 16 AD participants completed computerized tests of unimanual (dominant and non‐dominant hand) tapping, synchronous bimanual tapping, and alternate bimanual tapping. Outcome measures included initial reaction time, tapping speed, and variance. We used imbalanced random forest learning for classification modeling. The model was trained on 70% of the data and tested on the remaining 30% using 5‐fold cross‐validation. To investigate the contribution of individual variables to the classification model, we conducted permutation feature importance analysis.ResultThe overall classification accuracy of the training data was 56%, while the overall classification accuracy of the test data was 70%. The group‐specific accuracy, defined as the proportion of subjects predicted to belong to a certain group who are truly a member of that group, was 76% for CN, 33% of amnestic MCI, and 86% for AD. In 50% of the cases amnestic MCI subjects were classified as control subjects, and in 17% of the cases as AD subjects. The group‐specific precision, defined as the proportion of subjects who received a certain group label who truly belonged to that group (i.e., ‘true positives’) was 76% for controls, 100% for amnestic MCI, and 45% for AD. The three most important features that were used for classification of the test hold‐out data were 1) variance in tapping speed during dominant hand finger tapping; 2) the number of dual tapping trials without gaps or onset delays; and 3) initial reaction time for non‐dominant hand finger tapping.ConclusionSupervised machine learning can discriminate CN and AD subjects based on finger tapping performance features, but is less effective for distinguishing MCI subjects from CN and AD subjects. Finger tapping performance could be a cost‐effective tool for augmenting existing AD biomarkers.
High School and Beyond: Cohort Data for Studying the Effects of Education on Midlife Cognition
Authors: Brickman Adam M. , Grodsky Eric , Manly Jennifer J. , Muller Chandra , Warren John Robert 
Published: December 2023

AbstractBackgroundThe objective of our presentation is to describe the utility of data from the High School and Beyond (HSB) cohort for studying the impact of early life circumstances and experiences—especially related to education—on risk of midlife cognitive impairment. HSB is a cohort study of a large (n∼25,500), diverse, nationally‐representative probability sample of American high school students in 1980. Participants were surveyed in 1980, 1982, 1984, 1986, 1992, and 2014/2015 with high rates of response; teachers and school administrators were also surveyed, and transcripts provide information about secondary and postsecondary course taking. HSB data from 1980 through 1992 include detailed information about educational contexts, opportunities, and outcomes as well as about family circumstances, labor force activities, and other early life factors.MethodA 2021/2022 follow‐up survey with surviving cohort members featured lengthy interviews; a home health visit that included blood and saliva collection and anthropometric measures; and linkages to administrative records (e.g., mortality records, prescription records). Interviews included immediate and delayed recall tasks; a phonemic fluency task; a semantic fluency task; working memory tasks; self‐reported memory complaints; and detailed information about health conditions.ResultOf the ∼24,330 surviving HSB panelists, ∼13,900 completed surveys in 2021/2022. Of the ∼13,900 sample members completing surveys, ∼4,880 completed a home health visit; an additional ∼1,560 mailed back saliva kits. HSB ultimately received ∼4,430 blood samples by the time fieldwork concluded in late 2022. Blood collected in 2022 is being used to construct (1) measures that define the main pathological features of ADRD (e.g., Aβ42, Aβ40, p‐tau 181, total tau, NFL, and gFAP); (2) measures that reflect cognition‐relevant pathologies (e.g., hemoglobin A1c, inflammatory markers, markers of endothelial function, markers of blood‐brain barrier disfunction, and blood lead levels); and (3) measures of biological aging (e.g., the GrimAge clock, DunedinPACE pace of aging, the Hannum clock).ConclusionHSB is now an extraordinary resource for studying—using a large, diverse national sample—the effects of educational contexts, opportunities, and outcomes on midlife cognitive functioning and biological markers of ADRD risk.