bluuebunny/crossref_metadata_2025_split huggingface dataset:
More than burden: the relationship between caregivers and people with dementia unmet needs
Authors: Bertola Laiss , da Mata Fabiana A F , Ramos Ari Alex , Godoy Carolina , Júnior Haliton Alves de Oliveira , Ferri Cleusa P 
Published: January 2025

AbstractBackgroundPeople with dementia (PWD) have several unmet needs during the syndrome progression. More unmet needs are related to worse outcomes, such as hospitalizations, injuries, and death. The caregiving burden has been related to more PWD unmet needs. However, looking beyond the burden to a broader impact of caring activities on the carer’s life is necessary. This study aims to verify if caregivers' unmet needs predict PWD unmet needs beyond the burden.MethodIn‐home interviews of a nationally distributed sample of 140 dyads (caregiver and PWD) assessed the care needs of both using the Johns Hopkins Dementia Care Needs Assessment (JHDCNA 2.0). We considered each item as 0 ‐ not needed or needed and fully met, or 1 – needed and partially met or unmet. Beyond the care assessment, the interview included several measures, including sociodemographic, caregiver burden (Zarit Burden Scale), mental health, quality of life, and information about dementia care. We conducted regression models to verify which information of the dyad best predicted more PWD unmet needs. Additionally, we performed a mediation analysis to confirm if the caregiver’s burden impacts the PWD unmet needs by its effects on the caregiver’s unmet needs.ResultPWD had at least two unmet needs of 44 (M = 18,1; SD = 6,9), the caregiver had a mean of 11,4 (SD = 3,8) unmet needs, and 71.4% reported burden (Table 1). The PWD being male, having less education, and having more neuropsychiatric symptoms, combined with the caregiver being male, having fewer years as the primary caregiver, and having more unmet needs were associated with more PWD unmet needs (Table 2). Mediation results indicate that the burden only indirectly affects the PWD’s unmet needs through the unmet needs of the caregiver (Table 3).ConclusionUnmet needs are a reality for the dyad. Considering that family members predominantly provide care in low‐ and middle‐income countries, supporting caregivers is essential for their health and for them to be able to reduce the unmet needs of PWD. The impact of the caregiving burden extends beyond mental health, operating in a complex environment of unmet needs.
Hispanic/Latino ethnicity moderates the plasma P‐tau217 and memory relationship in older adults across the cognitive continuum
Authors: Lee Shannon Y. , Emanuel Olivia M , Matusz Emily F , Bove Jessica , Fiala Jacob , Arias Franchesca , Levy Shellie‐Anne , Marsiske Michael , Rosselli Monica , Curiel Rosie E , Loewenstein David A. , Duara Ranjan , Velez‐Uribe Idaly , Barker Warren W , Vaillancourt David , Armstrong Melissa J , Smith Glenn E. , Asken Breton M. 
Published: January 2025

AbstractBackgroundPlasma P‐tau217 demonstrates strong sensitivity and specificity for Alzheimer’s disease (AD) neuropathological change, but existing studies are often ethnically homogeneous. Assumptions about how well plasma P‐tau217 relates to key AD‐related cognitive outcomes like memory may not generalize. We assessed whether the association between plasma P‐tau217 and memory depended on ethnicity in a sample of Hispanic/Latino and non‐Hispanic/Latino White older adults.MethodWe studied 273 1Florida ADRC participants with normal cognition, mild cognitive impairment (MCI), or dementia (Table 1). All participants had plasma samples analyzed for P‐tau217 (ALZPath) and neuropsychological assessments. Using Pearson’s correlations, we first evaluated the bivariate association between P‐tau217, Craft Story verbatim recall (verbal memory), and Benson Figure recall scores (visual memory) overall and stratified by ethnicity. To determine whether ethnicity moderated the effects of P‐tau217 on memory, we used multiple linear regression to assess the interaction of P‐tau217 and ethnicity (Hispanic/Latino vs. non‐Hispanic/Latino) controlling for age, sex, education, and testing language. Post hoc sensitivity analyses separately evaluated individuals below and above internal Aβ PET‐derived P‐tau217 cutoffs for “AD positive” concentration.ResultHigher P‐tau217 was significantly associated with worse verbal (r= ‐0.38, p < 0.001) and visual memory (r= ‐0.31, p < 0.001) overall and separately in Hispanic/Latino (r= ‐0.56, r= ‐0.57; p’s <.001) and non‐Hispanic/Latino White participants (r= ‐0.30, r = ‐0.34; p’s < 0.001). Ethnicity significantly moderated P‐tau217 associations with verbal (β= ‐0.38, p= 0.001) and visual memory (β = ‐0.38, p= 0.001). The negative relationship between P‐tau217 and memory was significantly stronger for Hispanic/Latino than non‐Hispanic/Latino participants. P‐tau217 and demographic covariates explained more variance in verbal (R2= 0.39) and visual memory (R2= 0.37) for Hispanic/Latino than non‐Hispanic/Latino Whites (R2= 0.16 and R2= 0.19, respectively). Post hoc analyses suggested these findings were driven by individuals on the AD continuum.ConclusionAD pathology, measured via plasma P‐tau217, may more strongly relate to memory function in Hispanic/Latino than non‐Hispanic/Latino Whites. Findings have implications for the potential roles of co‐pathology or unexplored risk factors in explaining memory loss beyond AD across demographic subgroups. Ethnically representative studies will improve translation of AD biomarkers and inform anticipated AD‐directed treatment effects.
Predicting Alzheimer’s Diseases and Related Dementias in 3‐year timeframe with AI Foundation Model on Electronic Health Records
Authors: Zhu Weicheng , Tang Huanze , Rajamohan Haresh Rengaraj , Madaan Divyam , Chaudhari Ankush , Huang Shih‐Lun , Ma Xinyue , Chopra Sumit , Dodson John , Brody Abraham A. , Masurkar Arjun V. , Razavian Narges 
Published: January 2025

AbstractBackgroundAs disease‐modifying interventions advance, there is a critical need to detect Alzheimer’s disease and related dementias (ADRD) at the earlier, pre‐symptomatic stages. Transformer is a powerful model used to understand high‐dimensional data like images and languages. In this study, we propose a transformer‐based algorithm for predicting mild cognitive impairment (MCI) and ADRD 12 to 36 months in advance based on electronic health records (EHR).MethodOur study analyzed EHR from NYU Langone between Jan 1 2014 and Jun 29 2022. The patient records were analyzed with sliding windows (Figure 1b): For every index date with at least one‐year lead‐time to onset, records from one preceding year were used as features, and the MCI/ADRD onset within 1‐3 years after the index date served as outcome labels. Patients with MCI/ADRD records in the feature and gap window are excluded to avoid data leakage.Our prediction framework included two stages ‐ pretraining and finetuning (Figure 1a, c, d). First, we pretrained a foundation Transformer‐based model (EHR‐BERT) using the full cohort, which enabled the model to understand the semantic meanings of variables in EHR. Then we finetuned the pretrained model with the MCI/ADRD outcome labels to identify the potential MCI/ADRD patients. Final predictive performance was evaluated on a fully held‐out validation cohort.ResultPretraining used EHRs from 1.98M patients; 947K records from 366K patients over 60, without preexisting MCI/ADRD, were used for finetuning in the downstream prediction task. The demographics are shown in Table 1. We evaluated the prediction performance on a held‐out validation set, consisting of 118,516 records from 46,082 patients. The model obtained AUROC at 0.761 [0.760, 0.762] for prediction in 0‐3 years and 0.740 [0.739, 0.742] in 1‐3 years. Figure 2 shows that EHR‐BERT performed better than existing algorithms in PPVs at the same sensitivity level.ConclusionIn this study, our transformer‐based AI foundation model, trained on large‐scale electronic health records, demonstrated strong capability in predicting MCI/ADRD up to three years in advance. This algorithm will allow us to advance the current recruitment of dementia screening.
Enhancing Community Engagement for Dementia Research in Africa: The Integral role of Community Advisory Boards in Recruitment and Retention
Authors: Farombi Temitope Hannah , Arulogun Oyedunni , Nichols Michelle , Olorunsogbon Olorunyomi F , Kumolu Timilehin , Ogunronbi Mayowa , Sanni Taofeek Adedayo , Mutiso Victoria , Uthman Muhammed , Sule Abdullateef , Assey Emmanuel , Mwombeki Innocent , Onoria Joy , Onunka Godspower Chibuke , Tagoe Benedict , Melkamu Selem K , Adigwe Ifeoma , Ogunyemi Adedoyin O , Gyabaah Solomon , Byrd Goldie S. , Ogunniyi Adesola , Pericak‐Vance Margaret A. , Akinyemi Rufus O. ,   Africa Dementia Consortium
Published: January 2025

AbstractBackgroundHistorically, efforts to engage under‐represented communities in health research have encountered limited success, attributable to inadequate community participation, acceptability, and ownership. Globally, an innovative strategy to foster community involvement in research is the establishment of Community Advisory Boards (CABs). These boards consist of stakeholders from the target community, providing partnership and support throughout all phases of the research, from conception to implementation and evaluation. In pursuit of effective recruitment and retention into the Recruitment and Retention of Alzheimer’s Disease Diversity Genetic Cohorts‐ Alzheimer’s disease Sequencing Project (READD – ADSP) Study, each participating site within the African Dementia Consortium (AfDC) constituted a Community Advisory Board.MethodA comprehensive standard operating procedure outlining the group’s activities and delineating the composition and role of the CAB within the READD_ADSP project was developed. Eligible members received letters of invitation, and those who agreed were convened for an inaugural meeting to discuss project aims, objectives, and other pertinent details using the SOP as template.ResultAbout 14 CAB with 120 members have been established across the nine African sites. Each board comprised a diverse mix of geriatricians, public health leaders, community and religious leaders, retiree organizations, dementia caregivers, NGO dedicated to person living with dementia, media organizations, legal experts, and communication experts. Inaugural meetings at each site demonstrated a high level of interest and motivation to collaborate with the research team for the promotion of recruitment, retention, and advocacy. Using culturally appropriate names for dementia, case identification and referral system, lack of awareness and skilled personnel were among many concerns raised at the cab meetings. There is ongoing to continue to address these concerned raised for effective recruitment at the community.ConclusionThe strategic partnership with community stakeholders, facilitated through the Community Advisory Boards, proved effective in achieving recruitment and retention goals for dementia research.
The new landscape of APOE genotyping in the Alzheimer’s Clinic: Harnessing genetic counseling experience to create digital tools to support patients considering anti‐amyloid therapies
Authors: Wood Elisabeth , Cacioppo Cara , Weinberg Michelle , Dratch Laynie , Azage Meron , Mim Rajia , Ofidis Demetrios , Milinski Sarah , Langlois Carolyn , Harkins Kristin , Erickson Claire M , Egleston Brian L , Karlawish Jason , Langbaum Jessica B. , Bradbury Angela R. 
Published: January 2025

AbstractBackgroundWith the advent of FDA approved anti‐amyloid therapy and recognition of increased side effects in APOE e4 carriers, APOE testing is now recommended for patients considering anti‐amyloid therapies such as lecanemab. Given the therapeutic implications and anticipated volume of eligible patients, the traditional model of in‐person, pre‐ and post‐test genetic counseling is not feasible to incorporate in clinical pathways. Alternative delivery models, including digital tools and telehealth, will be key in providing APOE genetic counseling support.MethodsThe Penn Telegenetics Program provided APOE genotype disclosure to cognitively intact participants across the United States in two Alzheimer’s prevention studies (API Generation Studies 1 and 2). An ancillary, multi‐site randomized study (CONNECT 4 APOE) evaluated the relative advantages of real time videoconference over telephone for disclosure of APOE genotype results within the API Generation Program. Outcomes of these studies informed the development of digital tools to support genetic counseling and educational needs specific to this patient population. Standard user and usability testing as well as rapid cycle testing were used in the development of digital tools.ResultsOver 2600 API Generation Program participants received APOE genotype disclosure via the Penn Telegenetics Program, and over 600 participants enrolled in the ancillary CONNECT 4 APOE protocol. This work informed the development of clinical chatbots for patients undergoing APOE testing for anti‐amyloid therapy. These chats include an education chat for patients prior to receiving APOE results and an APOE result specific chat to provide support to patients after receipt of results. Chatbot development and results of rapid cycle testing with patients will be described. Additionally, experiences with initial implementation of these digital tools and requests for genetic counseling among patients and their relatives will be reported.ConclusionsHarnessing the experiences and outcomes from the described studies provides a unique opportunity to better understand use of telehealth modalities for APOE genotype disclosure and launch the development of digital tools that can further support the genetic counseling needs of this patient population. As indications for APOE testing rapidly increase, alternative delivery models will be critical to maximizing benefits and limiting harms.
Biomarker Differences in Post‐acute Sequelae of COVID‐19 Patients Compared to Controls
Authors: Boutajangout Allal , Frontera Jennifer A. , Masurkar Arjun V. , Debure Ludovic , Ahmed Wajiha , Vedvyas Alok , Links Jon , Jiang Li , Thawani Sujata , Sun Zhe , Ghuman Mobeena , Pirraglia Elizabeth , Betensky Rebecca A , Shao Yongzhao , Ge Yulin , Wisniewski Thomas 
Published: January 2025

AbstractBackgroundCognitive impairment is a major symptom among patients with post‐acute sequelae of COVID‐19; the underlying pathogenesis is unknown. This impairment may be associated with changes in the level of plasma biomarkers of neurodegeneration and neuroinflammation.MethodPlasma samples were collected from COVID‐19 patients (Covpos, median 724 days from index SARS‐CoV‐2 infection), and from non‐COVID‐19 controls (Covneg; no history of SARS‐CoV‐2 infection and negative SARS‐CoV‐2 nucleocapsid antibody). All patients underwent neuropsychological testing using the Uniform Data Set Version‐3 Cognitive Battery. Patients were coded as having cognitive impairment (Cogabnormal) based on neuropsychological testing (≥1 abnormal test result) or cognitively normal (Cognormal) (normal performance). Plasma biomarker assays Aβ40, Aβ42, NFL, and GFAP were measured using an N4PE kit. pTau181 V2 was measured on the pTau181 kit, using Simoa HD‐X technology that employs sensitive immunoassays with a limit of detection under 100 fg/ml. Multiple linear regression models were fit for each biomarker, with covariates of binary cognitive status and COVID‐19 and their interaction, and age, sex and education. If the interaction term was not statistically significant (p<0.05), it was removed from the model. No adjustments were made for multiple comparisons in this exploratory analysis.ResultsA total of 131 subjects were enrolled: Covpos / Cognormal (n=61), Covpos/Cogabnormal (n=46), Covneg/Cognormal (n=11), and Covneg/Cogabnormal (n=13). The Cog‐Covid interaction terms were significant for Aβ42 and pTau181/Aβ42 ratio. The mean levels of Aβ42 in Covpos/Cogabnormal is significantly lower than in Covpos/Cognormal (‐1.05, 95%CI[‐1.74,‐0.36], p=0.003), and trending lower in Covneg/Cogabnormal (‐1.12, 95%CI [‐2.26,0.01], p=0.05), and not significantly different in Covneg/Cognormal. Older subjects had a higher pTau181/Aβ42 ratio (0.05, 95%CI[0.03,0.07], p<0.001). The levels of pTau181/Aβ42 ratio in Covpos/Cogabnormal were significantly higher than in Covneg/Cogabnormal (1.68, 95%CI [0.60,2.76], p=0.003), and in Covpos/Cognormal (0.92, 95%CI[0.27,1.58], p=0.007) and not significantly different in Covneg/Cognormal. Other biomarkers showed no significant differences between any of the groups.ConclusionBiomarker levels of Aβ42 and pTau181/Aβ42 ratio in COVID‐19 plasma samples were significantly different in COVID‐19 patients with cognitive impairment compared to COVID‐19 patients with normal cognition. Additionally, among all patients with cognitive impairment, those with COVID‐19 had significantly higher ptau181/Aβ42, suggestive of an Alzheimer’s‐type neurodegenerative process.
Impact of Grey Matter Volume and White Matter Hyperintensities on Functional Capacity for Activities of Daily Living: A Study in the Alzheimer's Disease Continuum
Authors: Campo Cecilia Gonzalez , Henriquez Fernando , Contreras Patricio Riquelme , Lillo Patricia , Martínez‐Pernía David , Thumala Daniela , Aboitiz Francisco , Chonchol Andrea Slachevsky , Henriquez Rodrigo 
Published: January 2025

AbstractBackgroundThe Alzheimer's disease (AD) continuum is composed of the stages of Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI), and Alzheimer's Disease Dementia (ADD). The decrease in gray matter volume (GMV) secondary to cortical atrophy, commonly seen in this continuum, is related to cognitive and activities of daily living (ADL) impairment. Additionally, White Matter Hyperintensities (WMH), MRI abnormalities frequently observed in older adults and patients with dementia, are also associated with cognitive and ADL performance. This study aimed to evaluate the relationship of GMV and WMH on ADL performance across the AD continuum.MethodWe conducted a cross‐sectional study of 77 SCD, 30 MCI, and 23 ADD subjects, matched for age, sex, and education. ADL was assessed using the Technology‐Activities of Daily Living Questionnaire (T‐ADLQ). Total GMV was calculated via voxel‐based morphometry analysis in SPM12. Total (tWMH), periventricular (pWMH), and subcortical (sWMH) WMH lesions were calculated with the lesion prediction algorithm (LST) and the ALVIN mask (Figure 1a). Spearman correlation analysis was used to test associations among GMV, WMH, and ADL. A linear regression model was employed to assess the relative effect of GMV and WMH on ADL scores.ResultADD patients performed worse on ADL and showed decreased GMV and higher pWMH burden in comparison with all the other AD continuum groups (Table 1). Within the whole sample, worse ADL scores correlated significantly with decreased GMV and higher pWMH load (Figure 1b and 1c, respectively). In addition, lower GMV was correlated with greater pWMH load (Figure 1d). The linear regression model (R2= 0.183, F = 13.890, p = 0.000) showed that only GMV had a significant impact (Beta = ‐0.338, p = 0.000), while pWMH load did not significantly influence ADL performance (Beta = 0.164, p = 0.064).ConclusionLower GMV and higher pWMH load are associated with worse ADL performance. These features differentially contribute to explain ADL performance across the AD continuum, with a more pronounced effect of GMV over pWMH. Widespread GM atrophy and pWMH burden are distinctive features of ADD, strongly suggesting a fundamental detrimental role of these structural brain abnormalities along the AD continuum.
Amyloidogenic biomarkers in Down syndrome
Authors: Bram Jessyka Maria de França , Cordeiro Augusto Magno Tranquezi , Sarno Tamires Alves , Talib Leda Leme , Gattaz Wagner Farid , Forlenza Orestes Vicente 
Published: January 2025

AbstractBackgroundDue to the genetic characteristics of Down syndrome (DS), it is directly associated with a group of clinical manifestations resulting from premature aging and may present patterns of Alzheimer’s disease (AD). Thus, this study aimed to investigate AD biological markers in peripheral blood samples from adults and elderly individuals with DS and compare them with individuals with normal karyotype.MethodsThe DS group was subclassified into 55 SD without evidence of cognitive decline (DSNC) and 27 DS with cognitive decline (SDAD). Two comparative groups composed of euploid individuals were constituted, 23 elderly with AD (AD) and 76 adults and elderly with normal cognition (Control). AD biomarkers were determined in platelets and plasma, including the Amyloid Precursor Protein ratio (APPr) between secreted 130‐ and 110kDA peptides, the protein expression of ADAM10, BACE1 and PSEN1, as well as levels of Aβ40, Aβ42 and between Aβ42/Aβ40 ratio.ResultsResults demonstrated increased APPr for both DS groups compared to euploids. Lower expression of the APP130 and 110kDa fragments was observed in both DSNC and DSAD, and both fragments showed levels between 6 and 7 times lower in DSAD compared to DSNC. A reduction in the expression of ADAM10, BACE1 and PSEN1 was observed in individuals with DS compared to euploids, with no difference between DSNC and DSAD. AD subgroup had higher levels of BACE1 when compared to the Control. A higher plasma level of Aβ40 and a lower Aβ42/Aβ40 ratio were identified for both DSNC and DSAD groups, in relation to the Control. Using CART model, the combination of APP130kDa biomarkers and the Aβ42/Aβ40 ratio proved to be relevant for separating groups in terms of cognitive impairment, through the classification APP130kDa < 0.9, Aβ42/Aβ40 ≥ 0.409 and APP130 ≥ 0.77 or APP130kDa < 0.9, Aβ42/Aβ40 < 0.409, with a diagnostic accuracy of 79.9% (sensitivity: 30.6%; specificity: 98.5%; Kappa concordance coefficient: 0.365).ConclusionThe results of this study demonstrate that people with DS can show different patterns of expression of the proteins involved in the amyloid cascade, detectable even in the absence of cognitive decline, suggesting DS as a good predictive model of AD.