bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daily care hours among older emergency department patients with dementia and undiagnosed cognitive impairment: a cross‐sectional study
Authors: Galske James , Chera Tonya , Hwang Ula , Monin Joan , Venkatesh Arjun , Lam Kenneth , Leggett Amanda N , Gettel Cameron 
Published: January 2025

AbstractBackgroundOver 15 million informal caregivers provide assistance to persons living with dementia. Despite increasing emergency department (ED) use within the population, little is known regarding the support required of older adults seeking acute care with varying degrees of cognitive impairment. Our objectives were to quantify the daily care hours that informal caregivers provide to older ED patients with diagnosed dementia, undiagnosed cognitive impairment, and intact cognition.MethodsWe conducted a cross‐sectional analysis of caregivers of community‐dwelling older adults aged 65+ years seeking emergency care. The caregiver‐completedAD8 (cAD8) was administered to screen for cognitive impairment among caregivers of older ED patients without a diagnosis of dementia indicated in the electronic health record. Based on the caregiver’s response, older adults were categorized into groups of: diagnosed dementia, undiagnosed cognitive impairment (cAD8 score of 2+), and cognitively intact (cAD8 score of <2). The primary outcome was mean self‐reported hours of care per day provided by the caregiver assessed using the Mann‐Whitney U test.ResultsOur analytic sample included caregivers of 439 older ED patients; 58 had diagnosed dementia, 69 had undiagnosed cognitive impairment, and 312 had intact cognition. Hours of care per day provided by caregivers were significantly greater for older adults with diagnosed dementia (13.8 hours, P<0.0001) and undiagnosed cognitive impairment (9.9 hours, P<0.0001) compared to those with intact cognition (1.7 hours).ConclusionsDementia and cognitive impairment, whether diagnosed or undiagnosed by the health system, were associated with increased daily care hours among caregivers of older adults seeking emergency care. Older adults with undiagnosed cognitive impairment required nearly ten hours of care daily, suggesting that improved diagnostic screening capabilities may optimize resource allocation to support caregivers.
Low‐Dose Radiation Therapy in Alzheimer’s disease: An Interim Neurocognitive Analysis from a Multicenter Phase II Clinical Trial
Authors: Kim Byoung Hyuck , Kim Keun You , Park Woo‐Yoon , Kim Aryun , Hong Eun‐Hee , Kim Ji Young , Cho Seong‐Jun , Rhee Hak Young , Chung Weon Kuu 
Published: January 2025

AbstractBackgroundRecent preclinical studies have revealed a significant reduction in amyloid‐β plaques and pro‐inflammatory cytokines in Alzheimer’s disease (AD) mouse models following low‐dose radiation therapy (LDRT). This phase II, multicenter, prospective, single‐blinded, randomized controlled trial (NCT05635968, funding from Korea Hydro & Nuclear Power: Grant No. A21IP11) aims to investigate the efficacy and safety of whole‐brain LDRT in patients with AD.MethodProbable AD dementia patients (MMSE 13‐24 & CDR 0.5‐1) with evidence of amyloid pathology (confirmed by a positive 18F‐flutemetamol PET scan) were randomly assigned to one of three groups. They received a total of six fractions of LDRT: Group A with total 0 cGy (sham irradiation), Group B with 24 cGy, and Group C with 300 cGy. The effectiveness of LDRT was assessed through 18F‐flutemetamol PET, brain MRI and neurocognitive function tests at baseline, and at 6 and 12 months post‐LDRT. The primary endpoint was the change in the ADAS‐K‐cog score. The secondary endpoints included the changes in 18F‐flutemetamol PET, brain MRI, and scores of K‐MMSE, CDR, CGA‐NPI and K‐iADL.ResultA total of 15 patients (5 in each group) who completed 6 months post‐LDRT follow‐up were analyzed in this interim analysis. Baseline ADAS‐K‐cog (mean values in the order of group A, B, and C: 40.8 vs. 30.2 vs. 37.4, p = 0.111), CDR (1.0 vs 0.7 vs. 0.8, p = 0.141), K‐MMSE (19.6 vs. 22.4 vs. 19.2, p = 0.125) scores were not statistically different across the three groups. After 6 months, mean differences in cognitive test scores compared to baseline were 3.4 vs. 0.2 vs 0.4 (ADAS‐K‐cog, p = 0.369), 0.6 vs 0.0 vs 0.0 (CDR, p = 0.089), and ‐1.8 vs. 0.8 vs. 1.2 (K‐MMSE, p = 0.081). Compared to Group A, more subjects in experimental groups (B+C) showed improvement in K‐iADL (0/5 in Group A vs. 4/10 in Group B+C) and CGA‐NPI (0/5 in Group A vs. 5/10 in Group B+C). LDRT was well‐tolerated in all patients without any adverse events.ConclusionWhole‐brain LDRT for patients with AD was tolerable and demonstrated potential benefits in neurocognitive function tests. Quantitative imaging analysis will follow, and final results with the planned follow‐up are awaited.
Digital biomarker co‐design with patients and caregivers
Authors: Köhler Stefanie , König Alexandra , Linz Nicklas , Altenstein Slawek , Butryn Michaela , Glanz Wenzel , Jessen Frank , Munk Matthias H. J. , Osterrath Antje , Schott Björn H. , Spottke Annika , Teipel Stefan 
Published: January 2025

AbstractBackgroundUsing artificial intelligence approaches enable automated assessment and analysis of speech biomarkers for Alzheimer’s disease, for example using chatbot technology. However, current chatbots often are unsuitable for people with cognitive impairment. Here, we implemented a user‐centred‐design approach to evaluate and improve usability of a chatbot system for automated speech assessments for people with preclinical, prodromal and early dementia.MethodParticipants (n = 221 by January 2024, 300 planned, see Figure 1) of the PROSPECT‐AD study were automatically called for six times every three months by our chatbot “Mili”. In each call three cognitive tasks (Wordlist, Semantic Verbal Fluency, Story Telling) are offered. We applied the System Usability Scale (SUS) in all participants and conducted additional semi‐structured interviews in a subgroup to gain in‐depth information for improving Mili and adapting it to the users’ needs. During the interviews, we focus on affinity for technology and Mili’s usability.ResultWe collected usability data at M3 by the SUS from 163 participants (12 missings, ØAge: 73.2 years, SD: 6.6 years, see Figure 2) after their second call. The results indicated a good usability of Mili (ØSUS: 70.4/100, SD: 22.2). Within semi‐structured interviews we asked 22 participants (ØAge: 73.0 years, 12 female, ØMMST: 29.3, range 24‐30, medium tech‐savvy) for their ideas to improve the Mili system. We analysed the interviews using qualitative content analysis. Participants wished for an intelligent chatbot and a feedback system after each call about participants’ cognitive performance. In the event that the performance would indicate cognitive decline, Mili should provide information on local services for dementia, and give recommendations for prevention and advises for the user’s physician for medication. Seventeen interviewees (2 undecided, 3 negative) would like to use Mili regularly if they would receive a feedback on their cognitive performance.ConclusionOur results revealed a high usability and feasibility of the automated phone calls by Mili. Eligible feedback solutions would increase the usefulness and usage of remote testing if a they provide individual advises for prevention and contact persons. Unrealistic expectations on Mili regarding the recommendation of medication must be discussed with the users.
The effectiveness of dementia prevention programs: A systematic review and Meta analysis for 61,457 patients
Authors: Al‐Shammary Ali Saad , WSSAWI AMEER FADHIL ABBAS AL , Hashim Hashim Talib , fadhel Fdel 
Published: January 2025

AbstractBackgroundPrevention programs for dementia are gaining increasing attention as the global population ages. These initiatives aim to reduce the risk of developing dementia by promoting brain health and implementing lifestyle changes. Through strategies such as regular physical exercise, a balanced diet, cognitive stimulation, and managing chronic health conditions, these programs strive to protect cognitive function and delay the onset of dementia. With the growing prevalence of this debilitating condition, investing in dementia prevention has become a crucial public health priority.Method884 records were screened based on our search strategy on main database (Pubmed/ MIDLINE, Scopus, WOS, Cochrane). After remove the duplicate and meticulous assess for eligibility 38 RCT included in our review.Result38 RCTs and qualitative studies were included. 61,457 patients were included in all the studies. The ages were ranging from 60 years and above. We found that the most effective programs are ACTIVE diet and FINGER diet. ACTIVE program affecting mainly the reasoning and memory interventions primarily and secondarily the HRQoL, mobility and health services use. While FINGER program affecting global cognition and daily functioning in older people.Conclusionprevention programs for dementia play a pivotal role in promoting cognitive health and enhancing the quality of life for individuals as they age. These programs encompass lifestyle modifications, cognitive training, and early detection efforts that empower individuals to take proactive steps in reducing their risk of dementia.
Longitudinal associations of cardiovascular health and vascular events with incident dementia
Authors: Ou Ya‐nan , Tan Lan , Yu Jin‐Tai 
Published: January 2025

AbstractBackgroundEvidence supporting cardiovascular diseases could increase the risk of dementia remains fragmented. A comprehensive study to illuminate the distinctive associations across different dementia types is still lacking. This study is sought to: 1) determine the clinical validity of Framingham General Cardiovascular Risk Score (FGCRS) for dementia assessment; 2) examine the associations between cardiovascular diseases and the risk of dementia.MethodA total of 432079 dementia‐free individuals at baseline from UK Biobank were included. Score points of FGCRS were assigned to corresponding risk factors, including age, sex, smoking status, blood pressure measurements, medication for hypertension, diabetes mellitus, total cholesterol, high‐density lipoprotein cholesterol to compose a rating scale. Participants were further categorized into groups of low, intermediate and high. The date and source of cardiovascular traits via self‐report, primary care, hospital in‐patient admission and death registry were collected under the circulatory system disorders category of the UK Biobank. Multivariable Cox proportional hazard models were used to investigate the prospective associations for FGCRS and a series of cardiovascular diseases with all‐cause dementia (ACD) and its major component, Alzheimer’s disease (AD) and vascular dementia (VaD).ResultDuring a median follow‐up of 110.1 months, 4711 individuals were diagnosed with dementia. FGCRS was associated with increased risks across the dementia spectrum. In stratification analysis, high‐risk groups have demonstrated the greatest dementia burdens, particularly to VaD. Over 74 traits, 9 adverse associations, such as chronic ischemic heart disease (ACD: HR = 1.354; AD: HR = 1.269; VaD: HR = 1.768), atrioventricular block (ACD: HR = 1.562; AD: HR = 1.556; VaD: HR = 2.069), heart failure (ACD: HR = 1.639; AD: HR = 1.543; VaD: HR = 2.141), and hypotension (ACD: HR = 2.912; AD: HR = 2.361; VaD: HR = 3.315) were observed. Several distinctions were also found, which atrial fibrillation, and cerebral infarction, and hemorrhage only associated with greater risks of ACD and VaD.ConclusionBy identifying distinctive associations between cardiovascular diseases and dementia, this study has established a comprehensive “mapping” that may untangle the long‐standing discrepancy. FGCRS has demonstrated its predictivity beyond cardiovascular diseases burdens, suggesting potential opportunities for implantation.
Decoding Complexity: Readability Analysis of Public Online Health Information on Common Neurological Diagnoses
Authors: Punukollu Manvi , Venkatesan Archana 
Published: January 2025

AbstractBackgroundAlzheimer’s disease poses significant global health challenges, particularly as people increasingly turn to online platforms for health information in the digital era. Given the intricate nature of Alzheimer’s, it is imperative to evaluate the readability of online content. This study aims to assess the readability of information related to Alzheimer’s disease on reputable health websites.MethodWe carefully selected websites based on authority and prevalence through Google, the most popular search engine. Utilizing the neutral term “Alzheimer’s” ensured a broader sample of websites. We identified common domains within the top ten search results and meticulously sorted and saved them. Texts were then extracted and cleaned using Microsoft Office Excel. To evaluate readability, we employed various readability formulas using Python. The Flesch Reading Ease Score (FRES), Flesch–Kincaid grade level (FKGL), Simple Measure of Gobbledygook (SMOG), Gunning Fog (GFOG), Coleman–Liau score (CL), automated readability index (ARI), and Linsear Write (LW) were utilized.ResultWhen comparing our readability results to the sixth‐grade level recommended by the American Medical Association and the National Institute of Health, we observed that the scores exceeded the recommended level. Findings from widely used internet resources revealed variations in readability scores across different websites. Notably, publicly accessible data related to Alzheimer’s disease tends to be presented at a higher reading level than recommended for general comprehension, carrying critical implications for patient education and health literacy within the Alzheimer’s context.ConclusionAssessing the readability of online health information for Alzheimer’s disease is crucial to ensure accessibility and comprehension for diverse audiences. This study provides valuable insights into the readability landscape of reputable health websites, uncovering a potential gap between the complexity of information and the general public’s reading ability in the context of Alzheimer’s disease. Recognizing and addressing this gap is essential for enhancing patient education and empowerment, ultimately contributing to improved health outcomes in the realm of Alzheimer’s.
Identifying feature relevance for transition from Questionable‐ to Low‐ AD using Interpretable‐AI
Authors: Beerapalli Sai Sanhitha 
Published: January 2025

AbstractBackgroundIn the face of increasing Mild Cognitive Impairment(MCI) and Dementia rates among aging populations, understanding the factors shaping the non‐normal cognitive decline is crucial. Leveraging the Clinical Dementia Rating (CDR) data, this study has a dual focus. (1) It utilizes CDR to aid early MCI diagnosis by investigating factors contributing to transition from Questionable‐ to Low‐ AD. (2) It undertakes a comparative analysis between Indian and Caucasian populations, acknowledging cultural influences on cognitive health.MethodSHAP analysis (Lundberg et al, 2017), a game‐theory based explainable‐AI technique, performed on classifier accurately classifying Questionable‐ and Low‐AD subjects of Indian population (LASI‐DAD study) and Caucasian population(ADNI‐CDR study) to identify relevance of features for transition from Questionable‐ to Low‐AD. In extension, scatter Index analysis of SHAP values help identify the distribution of influence along with the the pivotal features that played significant role in the classification.ResultBalanced datasets comprising 472 subjects of Caucasian population and 188 subjects of Indian population have been examined. SHAP analysis of logistic regression model with classification accuracy of 98%‐ADNI and 97%‐LASI yielded highest mean absolute value for Community domain (0.13) in ADNI data and Orientation domain (0.14) in LASI‐DAD data. Scatter Index of SHAP values resulted in scatter index deviation of 14.8% for Questionable‐AD and 26.8% for Low‐AD in Caucasian population; and 13.9% for Questionable‐AD and 13.6% for Low‐AD in Indian population. The analysis revealed that for ADNI data the distribution of feature importance is highly skewed to Community Affairs and for LASI data the feature importance is highly skewed to Orientation skills.ConclusionPerformance of individuals in Orientation domain is the most important feature affecting the transition from Questionable‐AD to Low‐AD in the Indian population, while Community affairs is the most important in Caucasian population. Worsening of the performance in those particular domains is the biggest key factor in conversion to Low MCI. Although CDR is heavily dependent on Memory scores, while analyzing the transition from Questionable‐AD to Low‐AD in particular, it is not the most important factor.
Human restricted CHRFAM7A mediates neuronal and innate immune gain of function
Authors: Szigeti Kinga , Ihnatovych Ivanna , Dorn Ryu , Rosas Nicolas , Gomez Eduardo Cortes , Wilding Gregory , Jianmin Wang 
Published: January 2025

AbstractBackgroundUnderstanding the fundamental differences between the human and pre‐human brain is a prerequisite for designing meaningful models and therapies for AD. Expressed CHRFAM7A, a human restricted gene with carrier frequency of 75% in the human population predicts profound translational significance.MethodThe physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples (ROSMAP). The emerging pathways are tested and validated in an isogenic hiPSC model of CHRFAM7A knock‐in neurons and monocytes. In vivo validation is performed in a double blind pharmacogenetic study on the effect of nicotinic acetyl‐choline esterase inhibitor therapy. The effect of CHRFAM7A carrier status was assessed in two paradigms: response to drug initiation and disease modifying therapy (DMT) effect over an 8 year observation period. Fitted general linear model independent variables included age, sex, and medication regimen at the time of the first MMSE, APOE4 carrier status (0, 1 or 2 alleles as categorical variables) and CHRFAM7A genotype.ResultCHRFAM7A is identified as a modulator of intracellular calcium dynamics and an upstream regulator of Rac1. Rac1 activation re‐designs the actin cytoskeleton leading to dynamic actin driven remodeling of membrane protrusion and a switch from filopodia to lamellipodia. Phenotypic readouts in both the neuronal and monocytic lineages confirm actin cytoskeleton gain of function. The actin cytoskeleton reorganization shifts dendritic spine differentiation from filopodia towards spines with increased head area to stem diameter ratio resulting in increased synapse clustering (“high quality wellcro”) in neurons. In monocytes, the reorganized actin cytoskeleton leads to increased invasion, phagocytosis and cytokine release. These data suggest a shift from neurodegenerative to neuroinflammatory mechanism in 75% of AD patients. From the cholinergic treatment perspective incorporation into the a7 nAChR pentamer results in a hypomorphic receptor, which has diminished response to pharmacological modulation. Proof of principle pharmacogenetic study found a CHRFAM7A effect on treatment response both in the acute response and DMT paradigms.ConclusionHuman restricted CHRFAM7A defines the biological background for AD pathology by shifting neurodegeneration to neuroinflammation in a 25‐75% split. Introducing a CHRFAM7A model into the target selection workflow may increase clinical trial success.
Immediate post‐diagnostic support for people with dementia and thier care partners: Scoping literature review
Authors: Pavkovic Sladana , Goldberg Lyn R. , Alty Jane E , Abela Melissa , Low Lee‐Fay 
Published: January 2025

AbstractBackgroundTimely post‐diagnostic support is necessary to assist people living with dementia and their families to preserve their independence and to facilitate emotional and practical adaptation to dementia diagnosis and life after diagnosis. However, there is a noticeable scarcity of evidence concerning support following dementia diagnosis.Our objective was to examine the following aspects: the nature and type of evidence pertaining to post‐diagnostic support within the initial two years of diagnosis; the conceptualization of post‐diagnostic support; and the existing gaps in the literature concerning this essential support.MethodWe conducted a comprehensive scoping literature review following the systematic process outlined by the Joanna Briggs Institute (JBI), employing the Population‐Who, Concept‐What, Context‐With What Qualifiers (PCC) protocol. All relevant keywords and index terms were systematically searched across PubMed, Scopus, CINAHL, and PsychInfo databases. The review encompassed evidence spanning from 2005 to 2023. The screening process is visually represented in the PRISMA diagram. Subsequently, two authors independently applied critical appraisal to the studies using the Mixed Method Appraisal Tool.ResultFor eligibility, a total of 506 articles were assessed, leading to the inclusion of 29 papers derived from 26 studies characterized by high methodological quality. Notably, the majority of these articles (n = 14, from 12 studies) were authored by researchers based in the UK. High methodological quality was reflected in various types of evidence, encompassing reviews (n = 2), mixed studies (n = 8), quantitative studies (n = 9), and qualitative studies (n = 7).Specialist memory clinic support emerged as the most prevalent form of assistance during the initial two years following a dementia diagnosis. This support varied in its implementation, with some studies indicating support provided in (n = 12) or by (n = 5) memory clinics. Additionally, other studies presented post‐diagnostic support through diverse avenues, including day centres, on‐going support workers; home support programs, and community or non‐government organization initiatives.ConclusionA notable literature gap exists in immediate post‐diagnostic support for people with dementia and care partners. However, it remains unclear whether this gap is confined to the literature alone or extends to actual practice. Further research is imperative to delve into the support programs following dementia diagnosis, with a specific emphasis on settings beyond memory clinics.