bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel approach to optimization of Alzheimer’s vaccine configuration for maximal targeting of toxic amyloid‐beta oligomers
Authors: Kaplan Johanne , Gibbs Ebrima , Napper Scott , Scruten Erin , Coutts Juliane , Cashman Neil R 
Published: January 2025

AbstractBackgroundA large body of evidence now indicates that the most pathogenic species of Aß in Alzheimer’s disease (AD) consist of soluble toxic oligomers (AßO) as opposed to insoluble fibrils and monomers. Using our computational platform, we identified 4 different AßO‐restricted conformational B cell epitopes (300, 301, 303, 305) that were tested as vaccines for their ability to induce an antibody response that selectively targets toxic AßO, without inducing potentially detrimental B or T cell responses against plaque or normal Aß. A novel ex vivo approach was then used to select an optimal vaccine configuration amongst the 15 possible combinations of the 4 epitopes to provide maximal binding to a toxic oligomer‐enriched low molecular weight (LMW) fraction of soluble AD brain extracts.MethodMice were vaccinated with four different AßO‐restricted conformational B cell epitopes conjugated to KLH to provide T cell help and formulated with QS‐21 adjuvant. Serum IgG titers against the peptide epitopes were measured by ELISA and T helper cell responses by ELISPOT. The reactivity of serum antibodies with AßO versus monomers was evaluated by SPR, and plaque binding by immunohistochemistry.ResultAll 4 epitopes elicited robust antibody responses when administered either individually or together as part of a quadrivalent vaccine. ELISPOT analysis showed a T cell response to KLH and not the AßO B cell epitopes. Serum antibodies elicited by the monovalent and quadrivalent vaccines all showed the desired selectivity and reacted with AßO only, not monomers nor plaque. Comparison of the SPR binding responses to the toxic AßO‐enriched LMW fraction of AD brain extract by equivalent amounts of IgG from immune serum of monovalent vaccines vs mixtures of 2, 3 or 4 sera was used to rank vaccine configurations. Interestingly, maximal reactivity was observed with immune IgG against the monovalent vaccine containing epitope 301, the target of PMN310, our clinical‐stage monoclonal antibody. There was no advantage of additional epitopes beyond 301 alone.ConclusionVaccination with AßO‐restricted conformational B cell epitopes conjugated to KLH produced strong antibody responses with no measurable pro‐inflammatory T cell responses against Aß. Immunization with epitope 301 alone was sufficient to produce maximal reactivity against brain AßO.
Implementation of the meaningful activity for managing behavioral symptoms of distress (MAC‐4‐BSD) intervention in assisted living
Authors: Scherr Susan 
Published: January 2025

AbstractBackgroundMost assisted living (AL) settings organize and provide opportunities for residents to participate in activities (e.g., exercise, music, arts and craft, cognitive activities, religious services, community outings). Despite the known benefits of activity participation, it is widely reported that there is a lack of activities that are considered meaningful for residents and thus many residents spend much of their time during the day disengaged. Further, there are numerous challenges to engaging assisted living (AL) residents with dementia in meaningful activity at the resident and community level. Resident challenges include acute medical events, advanced age, comorbidities, physical and cognitive abilities, lack of motivation, cultural expectations, pain, and behavioral symptoms of distress (BSD). Community level challenges include environments and policies that limit opportunities for meaningful activities and limited resources.MethodTo overcome these challenges and optimize engagement in meaningful activity for residents with dementia, the Meaningful Activity for Managing Behavioral Symptoms of Distress (MAC‐4‐BSD) intervention was developed. MAC‐4‐BSD is theoretically based using the Social Ecological Model and Social Cognitive Theory and includes four components: 1. Assessment of the environment and policies; 2. Education of staff; 3. Assessment of resident preferences and goals for meaningful activity; 4. Mentoring and motivating staff and residents. The overall aim of MAC‐4‐BSD is to reduce BSD, increase engagement in meaningful activity, and improve quality of life for residents by modifying the environment and empowering staff to facilitate and engage residents with dementia in AL settings. The MAC‐4‐BSD intervention is implemented by a Research Facilitator working with a facility champion and monthly meetings take place with a facility stakeholder team to provide updates on successful strategies and brainstorm challenges encountered.ResultsTo date, a total of 5 AL settings and 71 residents with dementia have participated in the study. Based on content analysis of field notes we will describe stakeholder goals established, barriers to implementation, and facilitators to meet goals in the participating settings.ConclusionsKey findings include the influence of administrative or leadership support, level of engagement among direct care staff, interdisciplinary collaboration, and access to resources and supplies in the environment to facilitate meaningful activity for residents with dementia.
Cross‐sectional evaluation of early childhood experiences and AD biomarkers in older adults
Authors: Streitz Marissa L , Bui Quoc , Xiong Chengjie , Moulder Krista L. , Morris John C. 
Published: January 2025

AbstractBackgroundCalculating an individual’s risk for preclinical and symptomatic Alzheimer disease (AD) involves considering their experiences across the lifespan. This includes assessment of childhood experiences as risk factors for dementing disorders in later life.MethodThe Knight Alzheimer Disease Research Center (ADRC) examined the relationship of well‐established AD biomarkers with childhood experiences as reported by research participants. ANCOVA was used to model biomarker outcomes as a function of childhood events, adjusting for covariates such as age, education, cognitive status, presence of APOE e4, race, sex, and fasting status (for plasma only). Amyloid‐β (Aβ) and tau biomarkers (Aβ42, Aβ40, p‐tau181, p‐tau217) were measured in the cerebrospinal fluid (CSF) and plasma, cerebral amyloid and tau uptakes with positron emission tomography (PET) scans, and MRI scans assessed hippocampal and cortical volumes.ResultThere were 656 participants; 314 were female (56%) and 80 (14%) self‐identified as Black. The mean age was 75.2 ± 8.9 years, and 90% of the participants were cognitively unimpaired (CDR® 0). Those who reported attending a segregated school during childhood demonstrated lower hippocampal volume (p = 0.0005) and cortical thickness (p = 0.0028), as well as higher plasma tau181 (p = 0.037). Participants who attended a private school had lower levels of tauopathy as measured by tau PET compared to those who attended public school (p = 0.036). Frequently experiencing food insecurity throughout early life was related to higher levels of CSF p‐tau181 (p< 0.0001), total tau (p<0.0001), and PET tauopathy (p = 0.03) as well as lower levels of CSF Aβ42/Aβ40 (p = 0.002). Higher levels of CSF total tau (p = 0.0003) and p‐tau181 (p = 0.0015) were found for those who experienced an intensely frightening event as a child. Participants who reported frequent physical punishments showed a trend toward lower hippocampal volumes (p = 0.077). Lower levels of CSF p‐tau181 (p = 0.037) and plasma tau217 (p = 0.029) were found among those who frequently felt special, loved, supported, protected, and close to their families during adolescence. All findings remained significant after adjustment for covariates except for the biomarkers for segregated school attendance.ConclusionEarly life experiences, both positive and negative, may be associated with the development and presence of AD biomarkers in later life.
Evaluation of the therapeutic potential of nucerin, an oral TGR5 agonist HY209, in a murine model of alzheimer’s disease
Authors: Kim Siwon , Islam Jahirul , Kim Juyong , Koh Youngjae , Hwang Jungjoong , Kim Hyoung Tae , Seong Seung‐Yong 
Published: January 2025

AbstractBackgroundPreviously, we demonstrated therapeutic benefits following intraperitoneal delivery of the TGR5 agonist HY209 in 5xFAD, a transgenic mouse model of Alzheimer’s Disease (AD). Given the desirability of a more acceptable administration route for prolonged AD treatment, we assessed the efficacy of HY209 via oral delivery. This study aims to elucidate the therapeutic potential of NuCerin, an oral formulation of HY209, in the aforementioned AD model, while simultaneously identifying potential blood biomarkers indicative of NuCerin’s therapeutic action.MethodIn both non‐Tg and 5xFAD mouse models, NuCerin (or its vehicle control) was orally administered for a duration of 12 weeks (30 mg/kg, b.i.d.). Subsequent cognitive assessment was undertaken using the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. Amyloid plaque deposition in the cortical regions was measured after Thioflavin‐S staining. NeuN immunostaining was conducted to quantify mature neuronal population. LC‐MS/MS was employed on serum samples to identify potential protein biomarkers indicative of NuCerin’s efficacy.ResultThe MWM and NOR tests indicated that oral delivery of NuCerin ameliorated cognitive impairment observed in 5xFAD murine models. Furthermore, a marked reduction in amyloid plaque deposition was observed in the NuCerin‐treated 5xFAD group. There was also an attenuation in the decline of NeuN‐positive neuronal populations in the NuCerin‐treated 5xFAD group as compared to the vehicle‐treated counterparts. Proteomic assessment highlighted an elevation in biomarker H levels in 5xFAD mice relative to non‐Tg mice; this increase, however, was mitigated in the NuCerin‐treated 5xFAD group.ConclusionOur findings indicate that oral delivery of NuCerin attenuates the progression of Alzheimer’s disease, positioning NuCerin as a potential oral therapeutic for AD. Concurrently, we identified biomarker H as a potential biomarker to gauge NuCerin’s efficacy
Specialized infrastructure in a tertiary hospital to administer disease modifying treatments in Alzheimer’s disease
Authors: Nathan Talya , Ash Elissa , Shir Dror , Trabulus Noa , Bar‐David Aya , Wolpe Galia , Shiner Tamara , Bregman Noa 
Published: January 2025

AbstractIntroductionLecanemab (LEQEMBI®), a humanized monoclonal antibody targeting Amyloid‐beta (Aβ) protofibrils, received full FDA approval in July 2023 for treating early‐stage Alzheimer’s disease (AD). This abstract highlights Tel Aviv Medical Center’s (TLVMC) specialized infrastructure for early AD diagnosis and treatment and includes presenting baseline characteristics of initial patients opting for LEQEMBI®.MethodsOutlining our clinics' operational experience in establishing the Center for advanced treatments for AD, treatment protocol, and a descriptive analysis of baseline assessment data including demographics, baseline Magnetic‐Resonance‐Imaging (MRI), Cerebrospinal‐fluid (CSF)/PET biomarkers, pre‐treatment cognitive evaluations (Mini‐Mental‐State‐Examination (MMSE)/Montreal‐Cognitive‐Assessment (MoCA)), and Apolipoprotein‐E (APOE) status.ResultsRigorous screening and specialist approval were prerequisites for candidate selection, adhering with published appropriate use recommendations. All patients, diagnosed with Mild‐Cognitive‐Impairment (MCI)/mild dementia due to AD confirmed by biomarkers, underwent APOE testing.Lecanemab Administration commenced in Israel in November 2023, with 31 patients (F = 15, mean age = 72) initiating treatment by year‐end. 22 underwent neurological evaluation within a year of symptom onset. Mean MMSE = 24 (n = 27, SD = 3) mean MoCA = 23 (n = 4, SD = 2). CSF testing (27 patients), showed mean levels (pg/ml) of total‐Tau = 585 (SD = 251), phosphorylated‐Tau = 121 (SD = 38) and Aβ = 261 (SD = 172). APOE Ɛ4 polymorphism was present in 55%, with 18% showing 1‐2 micro‐hemorrhages on baseline MRI, compared to 8% of non‐carriers.ConclusionThe evolving landscape of AD treatments necessitates complex screening and comprehensive clinical‐radiological follow‐up. Establishing specialized medical infrastructures is crucial to enable the wide and safe administration of new treatments, reflecting the ongoing paradigm shift in AD management.
Investigating remote assessments and interventions for multilingual people living with dementia and their caregivers
Authors: Taiebine Mohamed , Keegan Louise 
Published: January 2025

AbstractBackgroundGiven the widespread of tele‐assessment and tele‐rehabilitation in speech language pathology and clinical neuropsychology for monolingual English‐speaking patients with acquired neurogenic language and cognitive disorders, there is an urgent need to implement a culturally and linguistically tailored telepractice for multilingual people living with dementia (MPLWD), for whom there is no consensus on a standard model. This study aims to investigate the delivery model of remote assessment and intervention for this population.MethodA systematic scoping review was conducted in December 2023 following frameworks described by Arksey and O’Malley (2007). A literature search was conducted for articles published in English that addressed telepractice services MPLWD in the field of speech language pathology and clinical neuropsychology. Factors that contributed to the successful delivery of telepractice sessions were described in terms of technological medium, modality of intervention (assessment vs rehabilitation), as well as target population (patients, caregivers or both).ResultA total of 53 articles were identified through search engines and 12 duplicates were excluded. After title and abstract screening, another 32 studies were removed. Finally, a total of 9 full‐text studies were selected. This review has demonstrated a need for setting up tele‐rehabilitation for the benefit of MPLWDs. Despite the paucity of studies addressing multilingual considerations and needs of patients with dementia and their caregivers, the focus on caregivers was reported in 7 studies using different remote services (web‐based intervention, mobile, draw‐care), while 2 studies reflected on gender and health disparities stemming from Latino, Korean, American and Australian contexts. MPLWDs may experience a mild or severe loss of one or more of their acquired languages as a result of the neurodegenerative trajectory of their disease. They may also present cognitive, communicative, and socio‐professional impairments impeding their daily life functioning.ConclusionThe scarcity of studies reflects a need for future research of MPLWD. More inclusive model of telepractice is the leitmotiv for cross‐linguistic studies in ethnically diverse population with dementia. The underrepresentation of multilingual telepractice should be taken into consideration and technological advances should be made accessible to diverse MPLWDs in different cultures and languages through equity and digital inclusion.
Semi‐passive monitoring of game play detects learning curves distinctive to subjective cognitive decline (SCD) and mild cognitive impairment (MCI)/mild‐stage dementia
Authors: Wu Chao‐Yi , Galler Jake A , Schwab Nadine A , Rashid Barnaly , Young Cathrine , Yang Liuqing , Gerber Jessica A. , Dodge Hiroko H , Arnold Steven E. 
Published: January 2025

AbstractBackgroundThe ability to monitor cognitive trajectories over the course of trials can provide valuable insights into treatment efficacy. However, existing trial methods are limited in monitoring cognition in real‐time and at high frequencies. Gameplay‐based assessments hold promise as complementary cognitive tools. In this study, we investigated the learning curves of gameplay features linked to cognitive impairment.MethodMIND GamePack is an iOS‐based system that includes a set of four games: Memory Match (Card matching), Word Scramble (Boggle), FreeCell (Solitaire), and Block Drop (Tetris). Sixty participants included 26 older adults with intact cognition, 11 with subjective cognitive decline (SCD) and 23 with mild cognitive impairment (MCI)/mild‐stage dementia. Participants were asked to play each game for at least five minutes/day and five days/week for four months. Latent trajectory models were used to detect learning curves distinctive to persons with SCD and MCI/mild‐stage dementia as compared with normal.ResultFor Memory Match, the latent trajectory model identified two learning curves for card matching accuracy. Participants with MCI/mild‐stage dementia were more likely to belong to a group where their accuracy exhibited a slight improvement but remained consistently below‐average throughout the monitoring period (odds ratio [OR] = 3.17, p<.001). Two learning curves were identified for the self‐chosen game level. Participants with MCI/mild‐stage dementia were more likely to belong to the flat curve group that chose the same game level throughout the monitoring period (OR = 1.98, p = .01). For Word Scramble, two learning curves were identified for word discovery rate and word repetition rate, respectively. Participants with MCI/mild‐stage dementia were more likely to belong to the group that demonstrated a decrease in the word discovery rate and an increase in word repetition rate throughout the monitoring period (OR = 2.91, p = .001; OR = 3.17, p<.001). For FreeCell, two learning curves were identified for the percentage of incorrect moves. Those with SCD and MCI/mild‐stage dementia were more likely to belong to the group that showed a higher percentage of incorrect moves at the beginning but gradually decreased throughout the monitoring period (OR = 2.01‐2.62, p = 0.03‐0.003).ConclusionLearning curves of game features associated with memory and language can distinguish cognitive severities. Changes in gameplay learning patterns could serve as additional evidence of potential treatment effects.
An automated method for quantifying syntactic complexity of spontaneous speech in Primary Progressive Aphasia
Authors: Agmon Galit , Cho Sunghye , Ash Sharon , Cousins Katheryn A Q , Pradhan Sameer , Kim Yoon Duk , Liberman Mark Y , Irwin David J , Nevler Naomi 
Published: January 2025

AbstractBackgroundReduced syntactic complexity is the predominant linguistic impairment unique to the nonfluent agrammatic variant of PPA (naPPA).Reliable, objective and automatic methods for assessing syntactic complexity are currently lacking. Here, we introduce an automatic method for quantifying syntactic complexity in speech. We show that this method differentiates naPPA from other subtypes and monitors disease progression and severity.MethodWe analyzed speech samples of picture descriptions that were collected from PPA patients and healthy controls (HC) at the University of Pennsylvania during 2000‐2021, including a subset of patients with longitudinal data. Ten syntactic features were automatically extracted from the speech samples and combined into a composite score, using principal component analysis, to represent syntactic complexity. Regression models compared syntactic complexity between PPA phenotypes, covarying for age, sex, education and MMSE. Linear mixed‐effects models tested change in syntactic complexity over time. The correlation of syntactic complexity with neurofilament light chain (NfL) levels in the cerebrospinal fluid (CSF) was tested in naPPA and svPPA patients.ResultWe examined a total of 136 participants: HC (n=36, 31% males, age 69±8y, MMSE 29±1), naPPA (n=31, 51% males, age 71±8y, MMSE 24±5), lvPPA (n=32, 50% males, age 68±9y, MMSE 22±6) and svPPA (n=37, 49% males, age 64±7y, MMSE 22±7). Z‐scored syntactic complexity scores showed significant group differences, with naPPA scoring lower than HC (β=1.08, p=.004), lvPPA (β=1.19, p=.001) and svPPA (β=.93, p=.008) [Fig‐1]. Sensitivity to disease progression and severity was found only within the naPPA group. The syntactic score of naPPA significantly decreased over time (‐.5 per year, p=.005), significantly different from the 0 decrease in lvPPA (p=.001) or the .1 decrease in svPPA (p=.001) [Fig‐2]. naPPA patients had a significant inverse correlation of syntactic complexity score and CSF NfL levels (r=‐.58, p=.03), while svPPA patients did not (r=.39, p=.9) [Fig‐3].ConclusionWe introduce a novel measure of syntactic complexity which can be extracted automatically from brief naturalistic speech samples. We validated this measure by relating it to naPPA and its biological underpinning. We provided objective evaluation of syntax, which has great potential as a non‐invasive biomarker in the dementia research and clinic.
Prevalence of Subjective Cognitive Decline by Social Determinants of Health and Health‐Related Social Needs — 15 States, 2022
Authors: Eugene DaJuandra Y 
Published: January 2025

AbstractBackgroundDementia is a critical public health issue with known health disparities. Social determinants of health (SDOH) and health‐related social needs (HRSN) may influence differences across various health outcomes, including cognitive functioning. We describe the association between subjective cognitive decline (SCD), an early indicator of possible future dementia, and select adverse SDOH‐HRSN.MethodWe used 2022 data (n = 80,943) from 15 states that administered both the Cognitive Decline and Social Determinants and Health Equity modules in the Behavioral Risk Factor Surveillance System. Prevalence of SCD was estimated among adults aged ≥45 years by 6 adverse SDOH measures (i.e., loss of employment, food stamp use, food insecurity, housing insecurity, inconsistent home utility, lack of transportation) and 3 HRSN measures (i.e., lack of social emotional support, social isolation, stress). Pairwise t‐tests were used to identify significant differences (P <.05).ResultOverall, prevalence of SCD was 11.1% (95% CI: 10.4‐11.8), and SCD was significantly higher among adults reporting each adverse SDOH‐HRSN (e.g., housing insecurity = 27.4%; 95% CI: 23.6‐31.1 vs no housing insecurity = 9.5%; 95% CI: 8.8‐10.1). For adverse SDOH, prevalence of SCD ranged from 19.3% (95% CI: 15.6‐23.1) among those with loss of employment to 32.6% (95% CI: 27.5‐37.8) among those with lack of transportation. For HRSN, prevalence of SCD ranged from 20.3% (95% CI: 18.2‐22.4) among those with lack of social or emotional support to 33.2% (95% CI: 29.7‐36.7) among those with stress.ConclusionIn 2022, differences in the prevalence of SCD were identified between adults with and without each adverse SDOH‐HRSN examined. Addressing these key drivers of inequities (e.g., transportation), which may lead to barriers in accessing care and services, is essential to help reduce potential disparities in dementia and to support early detection and cognitive health.