bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prevalence of Alzheimer disease in Odesa region
Authors: Vorokhta Yurii , Khubetova Iryna 
Published: January 2025

AbstractBackgroundThe prevalence of dementia in people aged 65 and over in the world is approximately 6‐10%, two‐thirds of these cases are due to Alzheimer disease The frequency of deaths from Alzheimer disease in Ukraine is 0.3 per 100,000 population, while in Great Britain this indicator is 112 per 100,000 people, USA – 82, France – 76, Germany – 51 [1, 2].The purpose of the study was to estimate the prevalence of Alzheimer’s disease in the Odesa region.MethodRetrospective analysis of the medical records about the registered cases of Alzheimer disease were received from Odesa Regional Mental Health Center for the years 2016‐2022. These data were analysed by the frequency and variance for indices of prevalence, age and gender structure.ResultAccording to the retrospective data of the Odesa Regional Mental Health Center for the years 2016‐2022, a constant increase in the number of detected patients with Alzheimer disease was noted ‐ from 4.9 cases per 100,000 population in 2016 to 6.3 cases in 2022. The gender balance throughout the analyzed period was stable, with a slight predominance (60%) of women in the structure of patients.The average age of men was 72.8±0.3 years, women – 78.6±0.3 years. Statistically significant differences (p<0.05) could be explained by longer life expectancy in women.ConclusionThe prevalence of neurodegenerative diseases in the Odesa region, according to medical records, is significantly lower than the European average, which indicates underdiagnosis.References:1. 2023 Alzheimer’s disease facts and figures. Alzheimers Dement. 2023 Apr;19(4):1598‐1695. https://doi.org/10.1002/alz.13016. Epub 2023 Mar 14. PMID: 36918389.2. Федотова М. С., Панфілова Г. Л., Цурікова О. В., Блажієвська О.М. Дослідження епідеміології деменції та хвороби Альцгеймера в Україні. [Research on the epidemiology of dementia and Alzheimer’s disease in Ukraine] Вісник фармації. 2021. 2(102) 50‐58 [Ukr]
A machine learning approach to predict tau positivity using clinical features in amyloid‐positive individuals
Authors: Arnold Daniel , Borelli Wyllians Vendramini , Machado Luiza Santos , Rahmouni Nesrine , Therriault Joseph , Servaes Stijn , Stevenson Jenna , Macedo Arthur C. , Schumacher‐Schuh Artur Francisco , Mattjie Christian , Barros Rodrigo C. , de Bastiani Marco Antônio , Lussier Firoza Z , Chamoun Mira , Bezgin Gleb , Benedet Andrea L. , Pascoal Tharick , Rosa‐Neto Pedro , Zimmer Eduardo R. ,   Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: January 2025

AbstractBackgroundAnti‐amyloid therapy appears to have an increased effect on reducing cognitive decline in amyloid‐ and tau‐positive individuals. However, clinical trials inclusion criteria require solely amyloid positivity. Herein, we developed a machine‐learning prediction model to identify tau positivity in amyloid‐positive individuals using clinical variables.MethodWe selected 1191 amyloid‐positive participants and tau status from ADNI, TRIAD, PPMI databases. Commonly shared clinical features selected between datasets were age, total MOCA scores, clinical diagnosis, sex, education, BMI, heart disease, stroke, hyperlipidemia and diabetes. Amyloid positivity was defined by amyloid‐PET (PIB‐PET, FBB‐PET or AZD4694‐PET) or CSF AB42 and Tau positivity defined by Tau‐PET (MK6240‐PET or AV1451‐PET) or CSF p‐tau181. The dataset was split into training (49%), validation (21%), and testing datasets (30%). A XGBoost model was tuned, and then used to predict the tau status outcome in the testing dataset.ResultA total of 647 men and 544 women were included with mean age 66.1 ± 10.4 (mean ± SD) years, MOCA 25.1 ± 4.1 scores and education 16.1 ± 3.2 years (Table). The population consisted of 794 controls, 271 MCI and 126 dementia individuals. Tau status was negative for 854 individuals and positive for 337. The receiver‐operator characteristic (ROC) analysis showed that the area under the curve (AUC) was 0.81 for discriminating tau‐negative vs. tau‐positive, with 0.76 as sensitivity, specificity as 0.86, and accuracy as 0.83. The top 3 most impactful features were found to be age, diagnosis‐CN and MOCA score through a SHAP value analysis (Figure).ConclusionPredicting tau positivity with clinical and cognitive variables may improve the selection of individuals for AD trials. A two‐step workflow using this approach may significantly reduce the need for tau‐PET exams in trials by screening individuals using clinical variables. The following steps should include adding more individuals and other clinical variables through different cohorts to optimize the model applicability and test their performance in outcomes of clinical trials.
Vascular risk, WMH, pTau 181 and NfL, but not ApoE or Aβbeta 42/40, are associated with cognitive impairment in Latinos from the SOL‐INCA‐MRI study
Authors: Decarli Charles , Sapkota Shraddha , Márquez Freddie , Tarraf Wassim , Isasi Carmen R , Lipton Richard B. , Gallo Linda C , Talavera Gregory A , Daviglus Martha L , Testai Fernando Daniel , Ramos Alberto R , Rundek Tatjana , Thyagarajan Bharat , Gonzalez Hector M 
Published: January 2025

AbstractBackgroundSerum AD biomarkers are becoming useful to the early and accurate diagnosis of neurodegenerative disease, but much of this work has been done with clinic‐based studies of mostly non‐Hispanic Whites. For this study, we examined relations between plasma biomarkers Aβ 42/40, pTau 181, NfL, GFAP, ApoE genotype and cognitive state in the SOL‐INCA‐MRI study. Given that prior work in SOL‐INCA found vascular risk to be associated with mild cognitive impairment1, we included vascular risk measured by the Framingham CVD risk score2 and white matter hyperintensity (WMH) burden from MRI as additional predictors.Method2288 individuals enriched for cognitive impairment (29%), mean age 64.5 ± 6.8 years of which 69% were female and 60% had at least a high school education were studied. All subjects had MRI as well as plasma measures of Aβ 42/40, pTau 181, GFAP and NfL and a diagnosis of normal (71%), questionable (16%), or mild cognitive impairment (13%). Multi‐variate linear regression adjusted for age, sex, heritage, and education was used to build models of associations between each of the measures and cognition. Finaly, structural equation modeling was used to assess the structural relationship between measured variables.ResultHigher serum pTau181 and Nfl concentrations were significantly associated with diagnosis (Table 1). PTau181, NfL and GFAP were also associated with MRI measures, particularly WMH (Table 2). CVD risk also was significantly associated with pTau181 (β=1.23 ± 0.34, p <0.0001) and NfL (β=25.4 ± 2.8, p <0.0001). In a final model (Table 3), sex, CVD risk, WMH and pTau181 remained significantly associated with cognition. Best fit SEM summarizes the relationship of these measures to each other and cognition (Figure). ApoE4 genotype and Abeta 42/40 ratio were not associated with diagnosis in this group.ConclusionIn a group of Latinos, enriched for cognitive impairment, vascular risk, WMH and pTau181 were significantly associated with diagnosis. The lack of association with serum Abeta 42/40 ratio suggest that vascular disease and not AD pathology are most strongly associated with cognition. The relationship between CVD risk, WMH, and pTau181is consistent with emerging evidence relating tau phosphorylation to vascular disease3, 4.
Midlife Periodontal Disease and Cognitive Functioning: Evidence from High School and Beyond
Authors: Warren John Robert , Demmer Ryan , Grodsky Eric , Muller Chandra 
Published: January 2025

AbstractBackgroundPeriodontal disease is a prevalent, preventable, and highly treatable oral infection that is (1) stratified by sociodemographic, educational, and spatial factors and (2) is believed to impact cognitive impairment and ADRD risk. However, there is very little information from community‐based, population‐representative, longitudinal studies about the association between periodontal disease and midlife cognitive functioning net of early life confounders.MethodWe use data from the U.S. High School and Beyond (HSB) cohort study, which has followed a nationally representative sample of ∼25,500 people from high school in 1980 through midlife in 2021‐22. HSB data from the 1980s includes rich information about educational contexts, opportunities, and outcomes; early life socioeconomic and family circumstances; spatial location; and demographic group memberships. HSB data from 2021‐22 include indicators of periodontal disease diagnosis and multiple measures of cognitive functioning.ResultPeople who have been diagnosed with periodontal disease score worse on measures of memory, executive function, and other domains of cognitive functioning at midlife. These associations are only partly attributable to early life confounders. Some ─ but not all ─ of the association can be attributed to the mediating role of diabetes and CVD.ConclusionPeriodontal disease is a preventable and treatable risk factor for subsequent cognitive impairment. Because risk of periodontal disease is stratified by demographic, educational, and other social factors, periodontal disease may also be important in shaping sociodemographic gradients in midlife cognitive functioning. This is the first population‐representative study using data from a community‐based cohort that has been followed from adolescence through midlife. As such, this work provides important evidence about the role of periodontal disease in stratifying cognitive outcomes.
Olfaction and blood‐based biomarkers of Alzheimer’s disease pathology and neurodegeneration in the ARIC Study
Authors: Shrestha Srishti , Zhu Xiaoqian , Sullivan Kevin J. , Palta Priya , Deal Jennifer A. , Schneider Andrea L.C. , Chen Honglei , Gottesman Rebecca F. , Thyagarajan Bharat , Windham B Gwen , Mosley Thomas H. , Griswold Michael E. , Kamath Vidyulata 
Published: January 2025

AbstractBackgroundOlfactory impairment appears early in the course of Alzheimer’s Disease (AD) and may serve as a non‐invasive early marker of AD. Few studies have examined the association between olfaction and blood biomarkers of AD neuropathology in large, diverse, community‐based populations. Blood levels of amyloid‐beta (Aβ42 and Aβ40), phosphorylated‐tau (p‐tau) forms, glial fibrillary acidic protein (GFAP), and neurofilament‐light chain (NfL) appear to reliably reflect corresponding brain neuropathologies and neurodegeneration. Investigation of olfaction in relation to these biomarkers could provide insights into its utility in the early identification of individuals at high risk of progressing to AD.MethodsWe investigated cross‐sectional associations of olfaction (measured by a 12‐item odor identification test) with blood Aβ42/Aβ40 ratio, GFAP, NfL, p‐tau181, and p‐tau181/Aβ42 ratio (measured using Quanterix ultrasensitive single‐molecule array assays) in 1,565 Black and White participants from the community‐based ARIC Study and whether these associations differed by race and APOE ε4 genotype. Both olfaction and blood biomarkers were obtained at ARIC visit 5 (2011‐2013). Separate linear regression models were used to examine the association of continuous olfaction score and olfaction categories (anosmia: score ≤6; hyposmia: score 7‐8; moderate olfaction: score 9‐10, normal olfaction: score 11‐12) with each biomarker (all biomarkers were log‐transformed and measured in pg/mL), adjusting for relevant covariates (See Table).ResultsAmong 1,565 participants (mean ± SD age:76±5 years, 60% women, 27% self‐reported Black), the mean ± SD olfaction score was 9.2±2.3; 14% had anosmia. Consistent with our hypotheses, higher olfaction score (i.e., better olfactory function) was significantly associated with lower levels of NfL, GFAP, p‐tau181, and p‐tau181/Aβ42, and higher Aβ42/Aβ40 ratio (See Table). Compared to normal olfaction, anosmia (i.e., poor olfaction) was significantly associated with higher NfL, GFAP, p‐tau181, and p‐tau181/Aβ42 ratio and lower (although not statistically significant) Aβ42/Aβ40 ratio. Associations of hyposmia and moderate olfaction with these biomarkers were not statistically significant. The associations did not differ by APOE ε4 status or race.ConclusionOur findings suggest that poor olfaction is associated with concurrent blood biomarkers of AD and neurodegeneration. Future analyses will examine associations of olfaction with prospective changes in these biomarkers and if these associations are explained by relevant neuroimaging markers.
An Imaging Marker for MCI to AD Conversion: Functional Dysconnectivity between Primary Olfactory Cortex to Default Mode Network
Authors: Pang Ran , Wang Jianli , Karunanayaka Prasanna , Kanekar Sangam , Eslinger Paul , Will Jens , Kalra Deepak , Ahmed Biyar , Elyan Rommy , Yang Qing 
Published: January 2025

AbstractBackgroundResting‐state functional MRI (rs‐fMRI) has been widely used for assessing disease progression in AD. It becomes, however, notoriously variable at disease’s prodromal stage when the cognitive functions are fluctuating while declining at the same time during this transitional period, which reduces its sensitivity in AD detection. Olfactory deficit has been shown to be an early sign of AD when the cognition decline is indistinguishable from normal aging. In this study, we investigated our hypothesis that functional connectivity (FC) between olfactory network and default mode network (DMN) will be disrupted in early AD.MethodLongitudinal rs‐fMRI data of 42 clinically diagnosed MCI were collected at 1st‐time point from ADNI database (Table 1). The piriform cortex was manually segmented as the seed of POC (Figure 1A). The FC between POC and DMN was evaluated and analyzed within and between MCI‐AD converters and non‐converters.ResultCompared to MCI non‐converters, AD patients’ FC between POC and DMN was significantly weaker (p<0.05, Table 1 and Figures 1‐2), while there was no significant difference in regards of POC‐DMN FC between MCI‐AD converters and non‐converters at the baseline (p>0.05). When the disease was progressed to AD, the FC between right piriform cortex and precuneus/PCC was significantly reduced (p=0.04). The FC of POC to DMN in MCI non‐converters was significantly correlated with cognitive score CDR‐cog, but not in MCI‐AD converters (Figure 2).ConclusionThe FC between POC and DMN was disrupted in early AD. The observed disruption established a mechanistic link between olfactory deficits and cognition decline in AD. The functional dysconnectivity between POC and DMN could be an objective imaging marker for MCI conversion to AD.
Restoring Cognitive functions: Unveiling the Procognitive and Neurotrophic Impact of Chronic Administration of a Selective A5‐GABAA Receptor Positive Allosteric Modulator in Mouse Models of Amyloid Load and Tau Phosphorylation
Authors: Prevot Thomas D , Bernardo Ashley D , Wong Kayla D , Pina‐Leblanc Celeste , Marcotte Michael D , Sharmin Dishary , Mondal Prithu , Cook James M , Sibille Etienne 
Published: January 2025

AbstractBackgroundDysregulated GABA/somatostatin (SST) signaling has been implicated in psychiatric and neurodegenerative disorders. The inhibition of excitatory neurons by SST+ interneurons, particularly through α5‐containing GABAA receptors (α5‐GABAAR), plays a crucial role in mitigating cognitive functions. Previous research demonstrated that an α5‐positive allosteric modulator (α5‐PAM) mitigates working memory deficits and reverses neuronal atrophy in aged mice. Subsequently, we explored the behavioral and neurotrophic effects of this α5‐PAM in animal models reflecting β‐amyloid load and tau phosphorylation, hallmarks of Alzheimer’s disease progression.MethodTwo studies were conducted with approximately 12 mice per group, including 50% females: 1) 5xFAD transgenic mice exhibiting progressive amyloid‐related cognitive decline; 2) PS19 transgenic mice displaying progressive tau‐tangle‐cognitive decline. Chronic administration of GL‐II‐73 (30mg/kg, p.o, for 4 weeks) was employed to assess its efficacy in rescuing cognitive deficits across three domains. Working memory, spatial memory, and cognitive flexibility were evaluated through an alternation task, water maze, and set‐shifting assay, respectively. Golgi‐Cox staining of brains (n = 4brain/group; 8cell/brain) facilitated the quantification of dendritic length and spine density in the prefrontal cortex and hippocampus using NeuroLucida. In the 5xFAD cohort, the impact of treatment on spine maturation steps was also examined.ResultChronic treatment in both models reversed cognitive deficits across domains (ps<0.01), demonstrating a robust effect on working memory. Furthermore, it significantly mitigated amyloid‐induced and tau‐related dendritic shrinkage and reduction of spine density at apical and basal dendrites (p<0.001 in PFC and CA1). Notably, this effect extended to all maturation steps in the 5xFAD model.ConclusionThe findings collectively indicate that selectively targeting α5‐GABAA receptors overcomes amyloid‐ or tau‐related cognitive deficits and neuronal morphology detriments. This marks the first intervention addressing the GABAergic system with both symptomatic and disease‐modifying therapeutic potential across various disorders. This breakthrough suggests a promising avenue for clinical development, offering hope to patients grappling with cognitive deficits across a spectrum of brain disorders.
Dysphagia‐Related Burden in Caregivers of Persons with Early‐Stage Dementia: Impact of Disease Stage and Diet Level
Authors: Todd Marissa , Mackowicz‐Torres Meredith , Gustafson Sara , Shune Samantha , Namasivayam‐MacDonald Ashwini , Rogus‐Pulia Nicole M. 
Published: January 2025

AbstractBackgroundCaregiver burden, or the impact of caregiving, commonly occurs in caregivers of persons with dementia (PWD); however, prior research focused on caregiver burden in this population has not considered the impact of dysphagia. Therefore, the purpose of this study was to measure dysphagia‐specific burden in caregivers of PWD and examine its relationship to general caregiver burden, as well as the PWD’s current diet level and dementia severity.MethodData were collected from PWD‐caregiver dyads participating in a prospective, dysphagia‐focused clinical trial at the initial study visit. The Clinical Dementia Rating (CDR) scale was administered to dyads to determine dementia severity. The Zarit Burden Interview (Zarit) and Caregiver Analysis of Reported Experiences with Swallowing Disorders (CARES) were administered to caregivers. Functional Oral Intake Scale (FOIS) scores were recorded for the PWD.ResultTwenty‐nine dyads were included. Caregivers were 93% female with a mean age of 65 years. PWD were 21% female with a mean age of 80 years. The mean CARES score was 2.86 (range = 0‐26; SD = 3.43) and the mean Zarit score was 28.1 (range = 5‐65; SD = 16.64). The median FOIS score for PWD was 7 (range = 5‐7). The highest CARES values were reported for the following experiences: being worried about the future, fear of their care recipient choking, and feeling “anxious.” A one‐way analysis of variance revealed no differences in CARES scores based on CDR stage. A Kendall tau rank correlation coefficient revealed a significant moderate, negative association between FOIS and CARES scores (r = ‐0.52; p<.002); while the moderate, positive association Pearson correlation between CARES and Zarit scores (r = .40; p = .03) was also significant.ConclusionFindings revealed that dysphagia‐associated caregiver burden may trend similarly as general burden (Zarit) but is generally low in earlier stages of dementia. However, the more restrictive the PWD’s diet (lower FOIS scores), the greater the dysphagia‐related burden reported by caregivers. Higher ratings on specific CARES items can guide clinical decision‐making regarding support needed by caregivers of PWD with early‐stage disease. The relationship between dysphagia‐related burden and general burden may change with disease progression, warranting continued investigation.
Construction and Validation of the modified visual index of parietal atrophy by brain magnetic resonance imaging in Alzheimer's Disease in a memory clinic
Authors: Aguilar‐Navarro Sara Gloria , Martínez Daniel Herrera , Ortega Jhonatan Ruvalcaba , Putoy Michelle Gonzalez , Mejía Ivonne Uscanga , Jiménez Irvin Abharca , Mimenza Alberto Jose 
Published: January 2025

AbstractBackgroundMagnetic resonance imaging (MRI) has been very useful in evaluating brain atrophy related to Alzheimer's Disease (AD), so it is important to have scales that allow objective evaluation specifically of parietal atrophy. The objective of this study was to develop and validate a modified visual scale for the assessment of parietal atrophy (APM Scale) by brain MRI in a single slice (axial T2‐FLAIR), with focus on the measurement of the posterior cingulate sulcus to differentiate between Mild Cognitive Impairment (MCI), AD and other forms of dementia (OD not AD).Methodretrospective validation study carried out in a memory clinic of a tertiary hospital in Mexico City, in a period from March 2015 to June 2023. Patients with a complete clinical and cognitive evaluation were included, including: MMSE, MoCA, brain MRI, Comprehensive Geriatric Evaluation, who met the diagnostic criteria for AD and other dementias and who, according to the evaluation carried out by the group of specialists, were classified into the following groups: Cognitively Healthy (CS), MCI, AD and OD non‐AD. A descriptive statistical analysis to characterize the population, normality tests, ANOVA for continuous variables and chi‐square tests for categorical variables. To demonstrate interobserver agreement, Cohen's Kappa test and the construction of ROC curves were used to determine the sensitivity and specificity of the APM Scale, as well as a logistic regression model to search for its association according to the Gold standard for AD.Results400 files were reviewed, 238 were excluded due to lack of data. The average age was 77 SD: 3.2 years, 55.6% were women. Diagnoses by groups included: 12.9% CS, 22.6% MCI, 50% AD dementia and 15.4% other non‐AD dementias. The interobserver agreement for the APM Scale was 0.880 for observer 1 and observer 2, 0.73 for observer 1 and observer 3 and 0.60 for observer 1 and observer 4 (p < 0.001). The AUC for EA was 0.748, with a sensitivity of 72% and a specificity of 71%. (p< 0.001).ConclusionThis study demonstrates that the APM Scale based on MRI in axial T2 FLAIR sequence is a useful and valid tool to support the diagnosis of AD.