bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicentre validation of the dementia with Lewy bodies‐related metabolic brain pattern
Authors: Perovnik Matej , Simončič Urban , Kos Hana , Jamšek Jan , Kramberger Milica G , Brendel Matthias , Camacho Valle , Vandenberghe Rik , Garibotto Valentina , Ochoa‐Figueroa Miguel A , Padovani Alessandro , Morbelli Silvia , Ferreira Daniel , Trošt Maja ,   Alzheimer's Disease Neuroimaging Initiative
Published: January 2025

AbstractBackgroundDementia with Lewy bodies (DLB) is a an α‐synucleinopathy characterized by dementia and a combination of parkinsonism, visual hallucinations, fluctuating cognition or REM sleep behaviour disorder. Specific biomarkers for DLB are lacking. DLB‐related pattern (DLBRP) is a metabolic network imaging biomarker which expression can be quantified on a single patient basis. DLBRP has been identified in few different cohorts but lacks a multicentric validation.MethodsFDG PET scans from 259 DLB patients and 176 normal controls (NC) were obtained from eight centres from European DLB Consortium (EDLB, 180 patients), Alzheimer’s disease Neuroimaging Initiative (ADNI, 135 NC) and local dataset from Ljubljana (LJU, 79 patients and 41 NC). FDG PET scans were pre‐processed and we used topographic profile rating to calculate the DLBRP expression (i.e. subject scores). Subject scores were compared between groups using t tests and ANOVA and correlated with clinical parameters using Pearson’s correlation coefficient.ResultsPatients from different centres differed in MMSE (p < 0.001), proportion of patients with parkinsonism (p < 0.001) and visual hallucinations (p < 0.001), but not in age (p = 0.15) or sex distribution (p = 0.13). DLB patients from all centres had significantly higher DLBRP expression than NCs (all p < 0.001). We could accurately distinguish between DLB and NC (AUC = 0.983) based on DLBRP expression. We observed a negative correlation between DLBRP expression and MMSE (r = –0.30, p < 0.001). The expression of DLBRP differed among centres, post hoc analysis showed that only patients from Barcelona had significantly lower DLBRP subject scores in comparison to other groups but they were also less cognitively impaired. Patients with visual hallucinations (p < 0.001) had significantly higher DLBRP expression than those without hallucinations and patients with abnormal Datscan™ (p = 0.02) had higher DLBRP expression than those with normal Datscan™. Other core features, levodopa or antidementives did not affect the DLBRP expression.ConclusionsWe showed that DLBRP can accurately distinguish between DLB and NC from multiple centres and different scanners. The DLBRP expression correlated with measurements of cognitive impairment. This validation study confirms that the DLBRP is a robust metabolic imaging biomarker of DLB.
Empowering Communities: Culturally Competent Dementia Awareness Education for Older Adults in Miami‐Dade County
Authors: Madan Krisstina , Brown Ellen L , Gordon Vanessa 
Published: January 2025

AbstractBackgroundThe purpose of this Doctor of Nursing Practice Project (DNP) was to explore community stakeholders' perspectives on a newly developed Dementia Awareness Educational Video (DAEV) within a culturally diverse community. Dementia is a global public health concern, with far‐reaching implications affecting millions of individuals, families, and communities. Raising awareness and delivering effective education is paramount, especially within culturally diverse communities.MethodThis qualitative study explored the potential effectiveness of the DAEV. A virtual focus group was conducted. Half (n = 3) of the participants were White and 2 (33%) were Black or African America (one participant was identified as “other”). Most participants were of Hispanic descent (n = 4, 66%). All of participants were highly educated including 2 (33%) participants having a Doctoral degree, 3 (50%) master’s degrees, and 1 (16.7%) bachelor’s degree. A semi‐structured format allowed for exploration of participant perspective on the clarity of the message in the DAEV, overall reaction, and recommendations for community dissemination.ResultTwo main areas of improvement were identified: enhancing message clarity and areas to disseminate the video. To enhance the clarity of the message suggestions included incorporating more images, addressing language accessibility, and ensuring that each video concludes with a clear and concise call to action. Regarding dissemination of the DAEV physician offices, waiting rooms, online platforms, social media and community partners and stakeholder websites were all suggestions.ConclusionIn the future, these findings will inform the enhancement of the DAEV, ensuring it serves as an effective tool for raising dementia awareness within culturally diverse communities. The collaborative effort among stakeholders, guided by the insights gathered from this focus group, reinforces the commitment to fostering a more dementia‐informed society, where diverse communities receive the support and information, they need to face this critical healthcare issue.
Comprehensive nutrient biomarker assessment in older adults at risk for dementia: Pre‐analytical and intra‐individual stability over 2‐4 years in the Nutrition and Brain Aging Study
Authors: Bowman Gene L. , Duskin Jonathan A , Haber Juliana A , Mattek Nora , Shrestha Hira , Corthésy John , Dodge Hiroko H , Silbert Lisa C , Quinn Joseph F , Kaye Jeffrey A 
Published: January 2025

AbstractBackgroundNutrient biomarkers (NBs) may serve as more accurate and precise indicators of dietary intake, particularly in older adults who often have subtle episodic memory recall and digestive/microbiome issues that alter the nutritional substrate readily available to the brain. NBs also allow insight into modes of action and metabolic changes that are actionable targets for modification through nutritional means in hopes of disease prevention and treatment. Prior to broad investment and deployment, the pre‐analytical and intra‐individual temporal variation over time should be documented to design and interpret clinical and epidemiological studies properly. We quantified 155 NBs and calculated their intra‐individual stability over time as selection criterion for future research to establish nutritional requirements for brain health and dementia prevention.MethodBlood samples from three time points, spanning a 2‐4 years, were obtained from older adults participating in the NIA‐Layton Oregon Alzheimer’s Disease Research Center’s Nutrition and Brain Aging Study (NBAS). Blood samples were batched randomly across time points for quantification of blood amino acids, minerals, hydro‐and‐liposoluble micronutrients, lipids, 1‐carbon, and kynurenine pathway metabolites using a variety of state‐of‐the‐art methods including, inductively coupled mass spectrometry. Pre‐analytical coefficients of variation (CV) and intraclass correlation coefficients (ICC) were calculated for each NB to evaluate the intra‐individual stability in a subset of NBAS cohort (n = 315).ResultThe mean analytic sample (n = 137) baseline age was 85.6 (±8.3, 57‐101 years), and mean MMSE was 28.3 (±1.78) with all having Clinical Dementia Rating of 0.5 or less. Seventy‐three percent were female and 19% carried the apoEe4 allele. The pre‐analytical CVs range from 0.9 to 55.0% and the ICC from 0 to 0.87 (25%‐tile/median/75%‐tile 0.41/0.54/0.66). Twenty four percent had ICC< 0.40, 66% had ICC 0.40‐0.75 and 10% had ICC>0.75.ConclusionThe pre‐analytical and intraindividual variation of NBs ranges widely in older adults. Most can reasonably estimate average blood concentrations over a 4‐year period using a single measurement (ICC≥0.40). NBs with ICC above 0.40 can be used for measurement error correction and those with ICC< 0.40 require repeat sampling and further investigation into the methodological/biological source of variation over time in older adults at risk of dementia.
Posturographic findings and reports of falls in elderly people with mild cognitive impairment: a comparative study
Authors: Anselmo Michele da Rocha , Novaes Juliana de Sá , Engelmann Gabriela Tomé Oliveira , Viana Bernardo M , Bicalho Maria Aparecida Camargos , Labanca Ludimila , de Oliveira Ana Julia Delfim 
Published: January 2025

AbstractBackgroundChanges in the connections between the cortical regions responsible for integrating balance are observed in individuals with MCI, however, studies that clarify the association of these changes and the risk of falling due to body imbalance are still rare. The present study aims to compare the posturography response of individuals diagnosed with MCI in relation to individuals in a control group without MCI.MethodsThis research project was approved by the local ethics committee. The sample was composed of 64 elderly people, of which 32 participants were from the MCI group and 32 from the control group. Participants underwent medical and neuropsychological evaluation where the characterization of general health and cognitive diagnosis designation was determined. Furthermore, an anamnesis composed of questions regarding the presence of complaints of dizziness, reports of fall episodes in the last year and the presence of other associated comorbidities was applied. The Timed‐Up and Go scale was used and static posturography was performed to determine the postural profile of the sample. To evaluate posturography, two tests were performed: stability limit test and sensory integration test. The data from the present study were tabulated in Microsoft Excel® version 10.0 and analyzed using SPPS® version 20 software.ResultsParticipants were comparable in terms of age, body weight, gender and education. The CCL group showed increased TUG time compared to the control group (p = 0.001) indicating decreased mobility. The occurrence of 53% of reports of falls in the last year was observed in the CCL group, with this presentation being higher than that observed in the control group (p = 0.001). In the posturography results, impairment was found in the CCL group in relation to the control at the limit of stability (p≤0.001), general balance index (p≤0.001), visual index (0.002) and vestibular index (<0.001).ConclusionsElderly people diagnosed with MCI may be more susceptible to balance disorders, increasing their risk of falling compared to healthy elderly people.
Establishing a Remote Patient Monitoring Infrastructure with Starlink in Indonesia for the Aging Population to Improve Alzheimer’s and Dementia Care
Authors: Kresnasandi Ida Bagus , Johnson Brian B 
Published: January 2025

AbstractBackgroundModernizing the remote patient monitoring (RPM) infrastructure in Indonesia has historically been limited by the unmet need of access to internet connectivity. New advancements made possible by Starlink and the internet of things (IoT) for RPM present new opportunities to connect people separated by geography and diverse cultural variations which includes over 700 languages and dialects. Alzheimer’s disease has increased by 87% from 2019 to 2022 and similar challenges in the United States apply to Indonesia; the cost of care, nurse shortage, and large aging population. Clinicians, scientists, and engineers now have the potential to solve the unmet need of insufficient aging care by leapfrogging previous technologies with the latest in artificial intelligence (AI) and digital health (DH).MethodEstablishing internet connection across the 16,771 islands is the first step to creating a communication network that provides the aging population in Indonesia access to the benefits of modern healthcare. With consistent and reliable access to internet access through Starlink satellite broadband internet a constellation of devices can be utilized in urban and remote areas such as the 12,000 villages that have no 4G internet access. For example WhatsApp is currently being tested to connect patients to clinicians because this application does not need a cellular plan. A pilot study conducted by Udayana University, Bali, could test the feasibility of delivering a RPM system to rural areas such as Batur village and the island of Nusa Penida.ResultSolving the problem of lack of access to internet connectivity in Indonesia creates tremendous opportunity to deliver state of the art AI and DH tools to clinicians for Alzheimer’s, dementia care and healthcare overall, reducing health disparities on a national level.ConclusionExporting the latest innovations from the top biomedical research institutions in the US to Indonesia could benefit the aging population by increasing their quality of life. Starlink is a key component of establishing access to communication infrastructure by allowing Indonesia’s public health insurance system, BPJS, to reach people in remote places.
The associations between air pollution and hippocampal volume: The Betula Project
Authors: Sindi Shireen , Andersson Micael , Stiernstedt Mikael , Oudin Anna , Nyberg Lars 
Published: January 2025

AbstractBackgroundLong‐term exposure to ambient air pollution has recently been highlighted as a modifiable risk factor for dementia. However, the mechanisms underlying these associations still remain unclear. The goal of this study was to investigate the associations between air pollution and neuroimaging correlates in a sample of middle‐aged and older adults.MethodsThis study used data from the Betula Project, which is a longitudinal study on aging, memory and dementia in Umeå, Northen Sweden. Participants were aged 50‐81 years old. For air pollution measures, data were available for local and total fine ambient particulate matter (PM2.5, PM10) and black carbon (BC) from vehicle exhaust and wood‐smoke. Participants were scanned in a 3T Discovery 750 (General Electric) MR‐scanner. All T1‐images were processed through a longitudinal pipeline in Freesurfer ver 7.11. MRI outcomes included total grey volume, cortex thickness, ventricle volume, and hippocampus volume. After removing participants due to incorrect hippocampus segmentation or missing values in air pollution or nuisance regressors 249 participants were included in the analyses. Partial correlations were performed, adjusting for age, sex and education. Additional analyses were conducted, stratifying by APOE4 status and sex.ResultsThe analyses showed that smaller hippocampal volume was associated with higher levels of all three air pollution measures (PM2.5 (r = ‐0.159, p = 0.012), PM10 (r = ‐0.125, p = 0.048), and BC (r = ‐0.148, p = 0.019)). In the APOE4 non‐carrier group, smaller hippocampal volume was associated with higher PM2.5 (r = ‐159, p = 0.034), whereas this association was not significant among the APOE4 carriers (r = ‐0.161, p = 0.178). The association between smaller hippocampal volume and PM2.5 was more pronounced among women (r = ‐0.168, p = 0.052) compared to men (r = ‐0.150, p = 0.112)ConclusionThis study shows that ambient air pollution is associated with smaller hippocampal volume, and this association appears to be more pronounced among APOE4 non‐carriers and women. These results shed light on the mechanism through which air pollution may increase the risk for cognitive decline and dementia, with important implications for risk reduction initiatives.
Mapping healthcare utilization of people with Alzheimer’s Disease and Related Dementias to identify priority areas in the State of South Carolina
Authors: Knox Sara , Dooley Mary , Johnson Jada , Simpson Kit 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease and related dementias (ADRD) are a critical healthcare crisis in the State of South Carolina (SC), with over 115,000 individuals diagnosed with ADRD accounting for 11% of South Carolinians aged 65 or over and 52% of South Carolinians aged 85 or over. Exorbitant resources are used to care for these individuals, including $650 million in Medicaid dollars and over 300 million hours of unpaid caregiver time. SC has enacted a statewide plan to address ADRD with the mission of promoting “a comprehensive approach to risk reduction, early detection and diagnosis, high‐quality dementia services, and a coordinated and equitable continuum of care across…” Yet, ADRD does not present uniformly across SC. Heat mapping healthcare utilization of individuals with ADRD across SC provides an opportunity to better understand where resources should be directed to support individuals and caregivers currently coping with ADRD as well as inform future research aimed at risk reduction and disease prevention.MethodWe used the South Carolina All‐Payer (Hospital and Emergency Department Admissions) Encounter data from the South Carolina Revenue and Fiscal Affairs Office to map the occurrence of Alzheimer’s disease and related dementias at the county level between 2018‐2020. Counties were grouped into five recognized regions of SC, 1) Upstate, 2) Midlands, 3) Coastal, 4) Pee Dee, and 5) Low Country. The Chronic Conditions Warehouse algorithm for ADRD was used to identify ICD‐10 codes for ADRD. Rates per 10,000 were reported.ResultThe prevalence of ADRD was concentrated in two regions of the state, the Pee Dee region and the Upstate region. The Pee Dee region had the highest rates, with 9 of it’s 11 counties having rates of greater than 500/10,000. The eleven counties in the Upstate region had rates greater than 400/10,000. In the other three regions, counties typically had rates between 170‐ 300/10,000.ConclusionThe findings from this study provide clear evidence that there is a greater need for resources to support SC residents with ADRD and their caregivers in the Pee Dee and Upstate regions. Future studies should examine environmental, sociodemographic, and economic factors of these regions that may contribute to increased disease prevalence.
Mid‐life occupational hazardous exposures is associated with late‐life dementia risk in the Wisconsin Longitudinal Study
Authors: Williams Victoria J. , Sicinski Kamil , Trane Ralph , Herd Pamela , Asthana Sanjay 
Published: January 2025

AbstractBackgroundExposures to environmental toxicants and pollutants occur at various points along the life course, with mounting evidence that late‐life pollution exposure increases risk for neurological disease, including dementia. Although occupational hazards constitute a primary source of modifiable environmental exposure during the working years, there is little research examining the protracted effects of mid‐life occupational exposure on late‐life dementia risk.MethodThis study leveraged life course data from the Wisconsin Longitudinal Study (WLS) to evaluate the effects of mid‐life occupational hazardous exposures on late‐life dementia outcomes. The WLS is a randomly selected population‐based cohort of 1/3 of all 1957 Wisconsin high school graduates and a selected sibling. Occupational hazardous exposures (to solvents and chemicals, pesticides, or airborne particulate matter) was prospectively collected in mid‐life (age ∼54). Dementia status was determined by a clinician consensus‐based approach using comprehensive medical and cognitive date collected in late‐life (age ∼81). Binary logistic regression was used to determine whether midlife occupational exposure predicted late‐life dementia risk, covarying for the effects of age, sex, education, adolescent IQ, ApoE‐4 status, systemic disease burden (hypertension, diabetes, stroke, heart disease), comprehensive smoking history, and occupational education and earnings scores.Result3811 WLS participants were included in the analysis, with 523 (13.7%) reporting history of midlife occupational hazardous exposure, and 322 (8.4%) receiving a research diagnosis of dementia. The full binary logistic regression model was statistically significant (Chi2(13) = 177.55, p<0.001), accounting for 10.4% of the overall variance in dementia outcome. Midlife occupational exposure significantly predicted dementia risk, such that history of occupational exposure conferred 47.8% increased odds of dementia in late‐life (OR = 1.478 [95%CI: 1.082‐2.020]).ConclusionReported history of mid‐life hazardous occupational exposures significantly increased the odds of all‐cause dementia in the WLS cohort, even after accounting for key confounders including job characteristics that may independently influence dementia risk. Because dementia pathologies often begin accumulating in the brain 20‐30 years prior to the onset of the clinical syndrome, midlife offers a key window for addressing modifiable risk factors to prevent disease. Public policy regulating occupational hazardous exposures in the workplace constitutes a promising strategy to reduce dementia in the general population.
Discovery of novel small molecule Asparaginyl endopeptidase inhibitors via dual approach‐based virtual screening and molecular simulation studies
Authors: SINGH MEENAKSHI , Xavier Joyal , Tamhankar Sampada P , Amin Raj 
Published: January 2025

AbstractBackgroundNeurological disorders are at epidemic levels in the world today. Various proteins are being targeted for the development of novel molecular therapeutics; however, no small‐molecule inhibitors have been discovered. Recent studies suggest that there are few molecules in clinical trials for various secretase (α, β, and γ), caspase, and calpain inhibitors. However, recently an emerging target was highlighted i.e. asparaginyl endopeptidase (AEP). This lysosomal cysteine protease cleaves the glycine‐rich C‐terminal to form an asparagine residue. In addition, the highly conserved and spatially close catalytic triad (Oδ1ASN42‐Nε2HIS148 ̴ 3.0Å) active site residue is Asn 42, His 148‐spacer‐Cys 189, which is responsible for proteolytic activity are also impacted by the cleavage of the C‐terminal region of AEP. Therefore, the current study focuses on screening, available small molecule databases for potential interactions with the active binding sites within the AEP binding pocket for inhibiting its proteolytic activity and restoring neuronal damage.MethodVarious online available CNS‐focused databases were screened to find small molecule inhibitors using an in‐silico structure‐based virtual screening method and molecular dynamics simulation. Further selected small molecules were assayed on overexpressed AEP stable cell line (HMC‐3) with exiting peptide and compound 11ResultThere is no small molecule inhibitor for the AEP yet, and the screened small molecule could be a potential hit for drug discovery. In addition, we have observed that AEP is involved in various proteinopathies which leads to neuroinflammation and can be reversed. Moreover, we found that our in‐silico screened molecules are more potent than the compound 11 and peptide. Further assays on a stable AEP immortal HMC‐3 cell line also line up with the in‐silico results.ConclusionThe selected small molecule presented a potential non‐covalent interaction (hydrogen bonds, ionic bonds, and pi‐pi interaction) within the catalytic binding sites with high binding energies and stable complex during simulation when compared to exiting compound 11 and peptide. The findings from the current study will help identify the critical subgroups needed for the development of our lead AEP inhibitory molecule.