bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortical correlations of CSF Neurogranin, VILIP‐1, Alpha‐Synuclein and NFL in SCD and MCI according to amyloid status
Authors: Guimarães Emanuel R. , de Campos Brunno , Ribeiro Isadora Cristina , Aventurato Ítalo Karmann , da SIlva Marjorie Cristina Rocha , Rizzi Liara , Balthazar Marcio 
Published: January 2025

AbstractBackgroundAlzheimer's disease (AD) pathophysiology is complex and not completely known. Emerging new biomarkers that evaluate synaptic function (VILIP‐1, neurogranin), co‐pathology (alpha‐synuclein), and neurodegeneration (NFL) are potential candidates to be incorporated into the early AD diagnosis. To better understand the relevance of these biomarkers, we evaluated the correlations between their CSF concentrations with whole‐brain grey matter volumes in SCD and MCI, according to their amyloid status (A‐ or A+).Method75 participants diagnosed with SCD or MCI were included, 30 A‐ and 45 A+. They all underwent comprehensive neuropsychological assessment, CSF analyses (Roche Elecsys), and volumetric 3T MRI (Philips Achieva). Voxel‐based morphometry was used to quantify brain volumes through CAT12 running on MATLAB 2019b. Partial correlation analysis between CSF biomarkers and cortical volumes was performed with SPSS 22, adjusting for age and sex.ResultSignificant correlations were found in the A‐ but not in the A+ group. NFL and hippocampus (r=0.40, p =0.028); VILIP‐1 and superior temporal gyrus (r= ‐0.38, p=0.035), and superior frontal gyrus (r=‐0.40, p=0.025); alpha‐synuclein and hippocampus (r= ‐0.39, p=0.036), middle frontal gyrus (r=‐0.375, p=0.049), and superior temporal gyrus (r=‐0.478, p=0.01).ConclusionWe found different patterns of correlations between brain anatomy and emerging biomarkers, according to amyloid status, in the very early stage of the neurodegenerative process. Interestingly, these correlations were found only in the amyloid‐negative group, which might suggest that different pathological processes involving synaptic function, neurodegeneration, and co‐pathology occur in suspected non‐Alzheimer pathophysiology cases.
Considerations for implementation of Alzheimer’s disease blood‐based biomarkers in clinical care based on recently updated NIA‐AA criteria
Authors: Mielke Michelle M. 
Published: January 2025

AbstractBackgroundThe National Institute on Aging (NIA) and the Alzheimer’s Association (AA) recently updated their 2018 recommendations for the diagnosis and characterization of Alzheimer’s disease (AD), which include the use of blood‐based biomarkers (BBMs) for the differential diagnosis of AD. BBMs of amyloid‐beta, phosphorylated tau, neurodegeneration, inflammation, and alpha‐synuclein were defined, with a highlighted need for blood biomarkers of vascular brain injury. Many questions remain regarding how to implement these biomarkers for clinical care including diagnosis and to assess eligibility for disease modifying treatments (DMT).MethodUsing examples from published and unpublished studies, the barriers to implementation of the use of AD BBMs will be synthesized. Additional discussion will focus on the current status and future discovery and implementation of non‐AD BBMs for vascular injury, inflammation, and alpha‐synuclein.ResultThere are unique barriers and facilitators for the use of BBMs in primary and secondary care to diagnosis AD and assess DMT eligibility. Many questions remain regarding how to utilize the BBMs for disease staging in clinical care as compared to the research setting, which BBMs to use and when, as well as how to implement the BBMs at the population level.ConclusionAdvancing technology has led to the clinical use of BBMs to diagnose AD and assess treatment eligibility. Several considerations and steps are needed before these blood biomarkers can be implemented for use at the population level.
Optimizing Mealtime (OPTIMAL): A Pilot Trial of a Person‐Centered Care Program in Nursing Home Care Staff and Residents with ADRD
Authors: Liu Wen , Suh Heather , Williams Kristine N , Galik Elizabeth , Resnick Barbara , Buckwalter Kathleen , VanHaitsma Kimberly S , Rakel Barbara 
Published: January 2025

AbstractBackgroundNursing home (NH) residents with dementia commonly experience mealtime behaviors that negatively impact nutrition and function. Residents do not receive person‐centered mealtime care (PCMC) due to multilevel factors one prioritized modifiable factor is lack of effective PCMC programs. This study aimed to develop a PCMC program and test its feasibility, acceptability, usefulness and preliminary efficacy.MethodWe developed Optimizing Mealtime (OPTIMAL), a multifaceted, evidence‐based, theoretically grounded PCMC program with five components: community stakeholder engagement, environment/policy assessment/modifications, staff education, individualized care planning, and ongoing motivation. A mixed methods design (single‐group repeated measures design followed by stakeholders’ interviews) was used. Repeated measures (resident mealtime resistive behaviors, mealtime functional impairments, eating independence, and food intake amount) were collected at baseline (T1), and at 6‐week (T2) and 12‐week (T3) post baseline.ResultOPTIMAL was delivered in one NH, where 95 direct care staff received education (age = 45±12.1 years, 13% male, 15% non‐white, 19% Hispanic, 89% experienced challenges with mealtime care), and 17 residents with moderate‐to‐severe dementia were observed (age = 74±7.9 years, 88% male, 12% non‐white, 6% Hispanic). We achieved high recruitment (74%, 77%) and retention (94%, 99%) rates for residents and staff. Stakeholders felt OPTIMAL was useful for staff who provide care to residents, with and without ADRD, who need assistance and/or experience behavioral symptoms at mealtime. Further, videotaped observations of dyadic mealtime interactions (N = 265) at three time points supported preliminary efficacy of OPTIMAL: 1) resident mealtime resistive behaviors and functional impairments decreased from T1 to T2 and T3; 2) resident eating independence showed slight decline over time; and 3) resident food intake amount (grams/meal) increased from T1 to T2 and T3.ConclusionFindings supported feasibility, acceptability, and usefulness of OPTIMAL in NH staff and residents with dementia. OPTIMAL shows preliminary efficacy
in decreasing resident mealtime resistive behaviors and functional impairments, preserving eating independence, and increasing food intake amount in NH residents with moderate‐to‐severe dementia – a vulnerable population that typically experience deteriorations as their cognition declines. Future large‐scale trials are needed to test the efficacy of OPTIMAL in residential care settings.
Investigating Spatial Characteristics of Brain Atrophy in Alzheimer’s and LATE neuropathology
Authors: Saifullah Khalid , Ridwan Abdur Raquib , Bennett David A. , Schneider Julie A. , Arfanakis Konstantinos 
Published: January 2025

AbstractBackgroundAlzheimer’s disease neuropathologic change (AD‐NC) and limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) are common in older adults and have been associated with brain atrophy, cognitive decline, and dementia. Since AD‐NC and LATE‐NC are often comorbid and due to the fact that LATE‐NC can only be detected at autopsy, in this work, we combined deformation‐based morphometry (DBM) on ex‐vivo brain MRI and detailed neuropathological evaluation in a large number of community‐based older adults to investigate the difference in brain atrophy patterns associated with AD‐NC and LATE‐NC.MethodCerebral hemispheres from 912 older adults participating in four longitudinal, clinical‐pathologic cohort studies of aging were included in this work: MAP, ROS, MARS, and AA Core of the Rush Alzheimer’s Disease Research Center (Rush ADRC) (Figure 1). All hemispheres were imaged ex‐vivo on 3T clinical MRI scanners approximately 1‐month postmortem while immersed in 4% formaldehyde solution. T2‐weighted images of all hemispheres were non‐linearly registered and logarithm of the Jacobian determinant (LogJ) of the deformation field was calculated in each voxel. Following ex‐vivo MRI, the pathologies that were assessed were AD‐NC, LATE‐NC, Lewy bodies, gross infarcts, microscopic infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy. AD‐NC‐pos was defined as moderate or severe AD‐NC according to the NIA‐AA criteria, and LATE‐NC‐pos was defined as LATE‐NC stages 2 or 3.Voxel‐wise linear regression was used to test the association of the deformations observed in the smoothed log Jacobian maps with the four different groups, controlling for all other neuropathologies, demographics, postmortem intervals, and scanner. We used 5000 permutations, and statistical significance was set at p<0.05 after family wise error (FWE) correction.ResultBoth the AD‐NC‐pos LATE‐NC‐neg group (Figure 2a) as well as the AD‐NC‐neg LATE‐NC‐pos group (Figure 2b) were associated with lower tissue volume mainly in medial temporal lobe structures. The AD‐NC‐pos LATE‐NC‐pos group (Figure 2c) showed substantially lower volume in the temporal, frontal, and parietal lobes. Interestingly, the AD‐NC‐neg LATE‐NC‐pos group showed lower volume in the anterior portion of the hippocampus than the AD‐NC‐pos LATE‐NC‐neg group (Figure 2d).ConclusionThe findings suggest that in the presence of LATE‐NC, the volume of the hippocampus cannot serve as a marker of AD‐NC.
Efforts to increase the racial and ethnic and socioeconomic diversity of the Adult Changes in Thought study cohort
Authors: Gatto Nicole M , LaCroix Andrea Z. , Tom Sarah E. , Ralston James , Crane Paul K. , Muiruri Roxanne , Sankaran Sundary , Shaw Pamela A. , Gibbons Laura E. , McEvoy Linda K. 
Published: January 2025

AbstractBackgroundThe Adult Changes in Thought (ACT) study is an ongoing population‐based prospective cohort study that began in 1994 and aims to identify risk and preventive factors for dementia. ACT randomly selects and enrolls Kaiser Permanente Washington (KPWA) health plan members age ≥ 65 years. Historically, the cohort make up has been 88% non‐Hispanic White participants. A core aim of the ACT U19 is to expand enrollment with a specific emphasis on increasing racial, ethnic, and socioeconomic diversity of study participants. A set target is to enroll 600 new members from historically minoritized groups by April 2026, including Asian, Black and Hispanic participants, such that these groups represent > 20% of the active sample (n = 3,000).MethodTo meet our target, we implemented a series of changes to our recruitment processes including revising recruitment materials to improve their informativeness, oversampling racial and ethnic groups, and locating a second ACT research clinic site in the socioeconomically diverse southeastern region of Seattle to expand our catchment area. We will examine how our newly enrolled cohort members compare to the KPWA population with respect to age, sex, area deprivation index (ADI) and health status.ResultFor the one year‐period spanning December 2022 through December 2023 when modifications to recruitment began to be rolled out and participant visits were restarted after COVID‐19, we enrolled 320 new participants with a racial and ethnic distribution of 25% Asian, 12% Black, 16% Hispanic, 2% Pacific Islander or Native American and 49% White.ConclusionBroader representation of diverse participants within ACT will make study findings more generalizable to the KPWA source population.
Preliminary Validation of the Malayalam‐version of the Cognitive Change Index
Authors: Stimmel Marnina B , Emmeline Ayers , Verghese Joe , Weiss Erica , Rabin Laura 
Published: January 2025

AbstractBackgroundWith the worldwide geriatric population steadily increasing, identifying older adults in need of treatment for cognitive difficulties is imperative. Limited specialty resources makes it particularly important to identify which individuals would most benefit from further evaluation and treatment, including in countries where dementia care is limited, such as India. Self‐report measures are timely and cost effective tools that can assist providers in identifying individuals at risk of cognitive decline. The Cognitive Change Index (CCI), a 20‐item measure of self‐perceived cognitive functioning, has been validated in English and Spanish. In the present study, we present preliminary findings on the translated, Malayalam‐version of the CCI.Method500 Malayalam‐speaking older adults (mean age = 68.8[SD = 5.4]; 62% male; mean education = 9.6 years[SD = 3.5]) completed the CCI, Addenbrooke’s Cognitive Examination‐III (ACE‐III) and Geriatric Depression Scale‐30 item (GDS‐30) as part of the Kerala Einstein Study, an ongoing longitudinal community‐based study of pre‐dementia syndromes in Kerala India. The CCI was translated and back‐translated for accuracy. Means and SDs were calculated for various baseline demographics. Pearson correlation and t‐tests (and cohen’s d for effect size) were used to compare the CCI to demographic variable and to GDS‐30 and ACE‐III performances.ResultHigher endorsement on the CCI was strongly correlated with lower ACE‐III performances (r(498) = ‐.66, p <.001), and weakly correlated with higher GDS‐30 scores (r(498) = .33, p <.001). The CCI was not correlated with age or education. While men endorsed significantly higher CCI scores (mean = 37.7; SD = 16.9) compared to women (mean = 34.8; SD = 15.3), t(498) = ‐1.925, p = .027, the effect size was small (Cohen’s d = ‐.178) and the difference not clinically meaningful. When gender and GDS‐30 were controlled, the correlation between CCI and ACE‐III remained strong (r(498) = ‐.66, p <.001).ConclusionPreliminary data showed confirmatory performance of the Malayalam‐version of the CCI in identifying individuals at risk for cognitive impairment (i.e., lower performances on a cognitive screener), and was not meaningfully influenced by age, gender, or education. Although additional validation is needed, this preliminary analysis suggests that the CCI could be a useful self‐report measure for providers to use with Malayalam speaking older adults to ascertain possible cognitive impairment.
Developing a predictive model for deterioration in long‐term care level among Japanese older adults with mild cognitive impairment and dementia: NCGG‐STORIES
Authors: Uchida Kazuaki , Sugimoto Taiki , Jin Xueying , Nakagawa Takeshi , Ogata Soshiro , Kiyoshige Eri , Fujita Kosuke , Kuroda Yujiro , Sakurai Takashi , Saito Tami 
Published: January 2025

AbstractBackgroundTo enhance the well‐being of individuals with dementia, it is crucial to minimize the risk of deterioration in long‐term care needs. This study aimed to identify factors and construct predictive models for deterioration in long‐term care (LTC) levels in Japanese older adults with Mild Cognitive Impairment (MCI) and dementia.MethodThis retrospective cohort study utilized the data from a memory clinic‐based cohort study (NCGG‐STORIES) and individual LTC insurance data provided by three municipalities. We included older adults aged ≥ 65 with MCI or dementia who had LTC levels ≤1 and resided in these municipalities at the initial visit. We used the certified LTC levels of the LTC insurance (seven care levels based on the severity of their physical and cognitive disability), and the outcome was the number of days from the initial visit to the new occurrence of LTC level ≥ 2, approximately equating to any care needs in basic activities of daily living (BADL). Demographic, lifestyle, functional, behavioral, and psychological factors assessed at the initial visit were included as potential predictors. The selection of predictors involved a backward stepwise Cox regression model, and the predictive model was formulated using a regression coefficient‐based scoring approach. Discrimination and calibration were assessed via Harrell’s C‐statistic and a calibration plot, respectively.ResultWe analyzed 605 patients (mean age, 79.1 years; 57.7% women). During a mean follow‐up of 3.4 years, 329 older adults were newly certified LTC Level ≥ 2. Among possible sociodemographic and clinical variables, age, BADL, behavioral and psychological symptoms of dementia (BPSD), care burden, and history of fall were selected according to the analysis. The resulting predictive model exhibited good discrimination and calibration (Harrell’s C‐statistic [standard error] = 0.748 [0.013]).ConclusionThis study clarified some modifiable factors with deterioration in long‐term care needs, such as BPSD, care burden, and history of fall. Furthermore, the developed predictive model may have an effective discriminative ability for the new occurrence of LTC level ≥ 2 and holds potential for implementation in individuals with MCI and dementia referred to a memory clinic in Japan.
Basic Performance of highly sensitive Chemiluminescent Enzyme Immunoassay for β‐Amyloid 1‐40 and β‐Amyloid 1‐42
Authors: Nakazawa Takuya , Sakurai Yuji , Shima Yoko , Imai Yuka , Aoyagi Katsumi , Nojima Hisashi 
Published: January 2025

AbstractBackgroundAlzheimer's disease (AD) is the most common cause of a decline in cognitive ability. The pathogenesis of AD involves the deposition of β‐amyloid (Aβ) plaques and the formation of neurotoxic oligomers of Aβ protein. This leads to neurofibrillary tangles composed of phosphorylated Tau proteins, neuroinflammation, loss of nerve cells and synapses, and ultimately dementia. Recent research suggests that the Aβ1‐42/Aβ1‐40 ratio in plasma can predict amyloid deposition in the brain. However, the small difference between amyloid‐positive and ‐negative subjects results in a very low total allowable error. Therefore, the assay system with high reproducibility is required. Here, we improved Aβ1‐40 and Aβ1‐42 assays in Lumipulse and report the basic performance.MethodThe Lumipulse system is a fully automated chemiluminescent enzyme immunoassay platform that processes samples in approximately 30 minutes. This assay uses two monoclonal antibodies to capture and detect Aβ1‐40 or Aβ1‐42. Baseline performance was analyzed in a limited set of characterized patient samples. The analytical study included a series of plasma samples (K2EDTA) at various concentration levels, and each analyte was tested in multiple replicates, sized to suit the various parameters tested.ResultAs shown previously on other LUMIPULSE assays, variability (within‐ and between‐run) was found to be low. An acceptable Limit of Quantification or functional sensitivity was obtained based on the evaluation of low Aβ1‐40 and Aβ1‐42 concentrated serum samples. No cross reactivity toward other Aβ fragments was observed. In the frozen‐thawed samples, no effect was observed for several times.ConclusionThese studies showed promising performance with less variability, suggesting that these Aβ assays could be useful in screening appropriate patients for AD therapy.
Adverse childhood experiences and subjective cognitive decline among transgender adults
Authors: Chiow Jobina , Cicero Ethan C. 
Published: January 2025

AbstractBackgroundAdverse childhood experiences (ACEs) are associated with an increased risk of developing chronic health conditions later in life, including Alzheimer’s disease and related dementias (ADRD) and subjective cognitive decline (SCD), a self‐reported confusion and memory loss and one of the first clinical manifestations of ADRD. While ACEs and SCD have both been individually studied in transgender and nonbinary (TGN) adults, no study has examined the relationship between ACEs and SCD among this population. This study sought to establish the prevalence of ACEs and their association with SCD among TGN adults.Method2019‐2021 Behavioral Risk Factor Surveillance System (BRFSS) data, representing 16 U.S. states that assessed ACEs, SCD (confusion/memory loss happening more often/getting work over previous 12months), and self‐reported gender identity were used to determine the association between ACEs and SCD among TGN adults aged 45+ (N = 206). Pearson’s chi‐squared/Fisher’s exact tests assessed the association between ACEs (individual, categorical, sum score) and SCD. Crude and adjusted odds ratios (aOR) along with 95% confidence intervals (CI) were calculated to investigate the associations between ACEs (individual, categorical, sum score) and SCD.Result18% (n = 38) of TGN adults in the sample reported SCD, 60% (n = 120) experienced any ACE, 20% (n = 41) 1 ACE, and 18% (n = 37) experienced ≥4 ACEs. Nearly 50% experienced childhood abuse (n = 94) or household dysfunction (n = 92); the most prevalent ACE was verbal abuse by parent/adult in the home. Among those endorsing SCD, 34% (n = 13) reported ≥4 ACEs, 73% (n = 26) childhood abuse or household dysfunction (n = 27). Most ACES were significantly associated with and increased the risk of SCD, even after adjusting for BRFSS year, age, race, education, and employment. The odds of SCD increased 40% as the number of ACEs increased (aOR = 1.4, 95% CI:1.2‐1.6, p<0.0001). The odds of SCD were significantly higher with childhood abuse (aOR = 4.3, 95% CI: 1.88‐10.02, p<0.01) or household dysfunction (aOR = 4.7, 95% CI: 2.00‐11.07, p<0.01).ConclusionA lifecourse perspective is needed when examining the brain health of TGN adults. Childhood abuse and household dysfunction are risk factors for SCD. ACE screening/interventions for TGN youth are needed to help reduce the risk of SCD and cognitive impairment later in life.
Drug Substitution as a Potential Unintended Consequence of Antipsychotic Deprescribing in Long‐Term Care: A Retrospective Cohort Study in Ontario, Canada
Authors: Kirkham Julia G , Harris Daniel A , Nguyen Paul , Bronskill Susan E , Maxwell Colleen J , Iaboni Andrea , Chowdhury Mohammad Z I , Seitz Dallas 
Published: January 2025

AbstractBackgroundThe overuse of antipsychotics in persons with dementia in long‐term care (LTC) has been a source of clinical concern, public attention, and policy intervention for over 30 years. Targeted quality improvement, broader awareness of risks, and other initiatives have resulted in substantial reductions in antipsychotic use in LTC settings in North America and elsewhere. Limited evidence suggests that reductions in antipsychotic use may be resulting in unintended consequences, such as substitution with alternate, but similarly harmful, psychotropic medications.MethodsWe used a retrospective, matched cohort study design using linked population‐based health care databases held at ICES. LTC residents 66 years or older with dementia who were prescribed an inappropriate (i.e., without an indication aligning with the definition of appropriate antipsychotic use in LTC, including schizophrenia, Huntington’s disorder, hallucinations, delusions, or end‐of‐life care) antipsychotic medication with at least 6‐months of continuous use were identified over a 10‐year period (2008‐18). Antipsychotic users who subsequently discontinued an antipsychotic medication were matched 1:1 to persistent users on key variables and followed for up to 1‐year following antipsychotic discontinuation for new prescriptions of one or more psychotropic medications and clinical outcomes.ResultsAmong 26,092 LTC residents with dementia (mean age of 84 years) who were prescribed an inappropriate antipsychotic medication, 5,854 (22%) discontinued during the follow‐up period. After adjusting for key variables, new psychotropic medication prescription was not more common among antipsychotic discontinuers in the 6‐months following antipsychotic discontinuation compared to those who continued an antipsychotic medication (hazard ratio (HR) 0.90; 95% CI, 0.70‐1.15). Mortality was similar between the two groups (HR 1.01; 95% CI 0.90‐1.15) at up to 1‐year following antipsychotic discontinuation.ConclusionAntipsychotic discontinuation in this study was not associated with medication substitution. These results supports other studies indicating that antipsychotic discontinuation in dementia can be safe but has questionable effect on mortality. While medication use trends in LTC have shown increases in other psychotropic medication use alongside antipsychotic reductions, this study suggests that this may be driven by factors other than substitution, such as increasing complexity of LTC residents, including higher prevalence of mental health disorders other than dementia.