bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of Blood GFAP Concentration to Evaluate KDS2010 (MAO‐B Inhibitor) Drug in APP/PS1 Mice Using a Magnetic Bead‐based Electrochemical Sensor
Authors: Cho Hana , Park Sang‐Heon , Jeong Yeeun , Park Jong‐Hyun , Lee Soo Hyun 
Published: January 2025

AbstractBackgroundBlood GFAP levels have the potential to reflect and predict worsening disability in individuals with degenerative diseases such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). Recently published research suggests that blood GFAP levels can be used to detect even subtle damage to the degenerative disease. In this study, we evaluated the effectiveness of the KDS2010 (MAO‐B inhibitor) drug targeting AD by measuring blood glial fibrillary acidic protein (GFAP) levels in APP/PS1 mice using a magnetic bead‐based electrochemical sensor.MethodMagnetic beads were coated with a primary antibody that was specifically bound to the antigen. Subsequently, the magnetic beads were incubated with 3 blood different samples from: 1) wild‐type (control, WT), 2) APP/PS1 model (TG), and 3) APP/PS1 + KDS2010 drug (TGD). The magnetic beads coated with the samples were measured using a nano‐gap based electrochemical sensor.ResultThe TG sample exhibited much lower impedance values compared to the WT sample due to the high concentration of GFAP in the blood. On the other hand, the TGD samples showed a value (‐8.1%) similar to that (‐5.6%) of the WT samples, as shown in Figure 1. This result means that KDS 2010 (MAO‐B inhibitor) plays a good role in suppressing the reactivity of astrocytes. And then, blood GFAP levels can be lower after KDS 2010 treatment.ConclusionWe validated the effectiveness of the KDS2010 in APP/PS1 mice with a magnetic bead‐based electrochemical sensor. Successful validation of a point‐of‐care platform for blood GFAP could increase the diagnostic reliability of AD, which could have a significant economic impact on the dementia diagnostics market.
Initial evaluation rate invariance for Alzheimer’s Disease drug trials after first appointment modification
Authors: Lee Ralph , Huoh Yu‐Jay , Martinez Brenda , Lee Elly 
Published: January 2025

AbstractBackgroundRecruiting large numbers of study participants for Alzheimer’s Disease (AD) drug trials remains a significant challenge in need of more effective approaches. Advertising can be an effective way to reach large numbers of prospective participants, but can suffer from low attendance rates. This study examined the relationship between the initial behaviors of prospective AD trial participants who did not attend their first scheduled appointment and their overall likelihood of eventually attending an in‐person consultation.MethodIn 2023, 4,043 potential participants were identified through online advertising and scheduled for 5,561 appointments for an in‐person pre‐screen at a commercial research site. Only 45.0% attended their first scheduled appointment. In lieu of attending their first scheduled appointment, 32.3% (n = 1,307) called in to the clinic to modify (i.e. cancel or reschedule) their first scheduled appointment and the remaining 22.7% (n = 915) simply did not attend their first scheduled appointment. Recruiters attempted to reschedule the latter group for another appointment.ResultOf the 4,043 potential participants who were ever scheduled for an in‐person pre‐screen, 55.8% of these participants eventually attended an appointment, whether during the first or subsequently scheduled appointments.Of the 1,307 potential participants who called in to modify their first scheduled appointment, 506 of these potential participants were scheduled for a subsequent appointment, with 57.3% of these persons eventually attending. This deviation from the 55.8% overall attendance rate is not statistically significant (p = 0.50).However, of the 915 potential participants who simply did not attend their first scheduled appointment, 352 were scheduled for a subsequent appointment. Of these 352, only 43.5% eventually attended an appointment. This deviation from both the overall attendance rate and the attendance rate for those who modified their first appointment were highly significant (p < 1e‐4 for both).ConclusionPotential AD trial participants who modify their first appointment are adequately engaged in the process, and so not attending their first appointment does not adversely affect their chances of attending a pre‐screen. In contrast, potential participants who simply do not show up are much less likely to ever attend any appointment (almost 25% relative, >13% absolute).
Is the residual approach reliable to estimate resilience to Alzheimer’s disease pathology? Comparison among different methods
Authors: Mutel Sophie , Quattrocchi Lara , Altomare Daniele , Scheffler Max , Chicherio Christian , Blennow Kaj , Zetterberg Henrik , Garibotto Valentina , Ashton Nicholas J. , Frisoni Giovanni B , Ribaldi Federica 
Published: January 2025

AbstractBackgroundResilience, the ability to maintain normal cognition (cognitive resilience, CR) or brain integrity (brain resilience, BR) despite neuropathological burden, is often quantified using the residual approach. This method calculates residuals from a linear regression where the dependent variable is brain volume or cognition, and the independent variable is neuropathology. Residuals can be corrected to render them independent from the dependent variable, but comparative analyses of residual correction methods within memory clinic populations are scarce. Our study aims to bridge this gap by comparing non‐corrected and corrected residual approaches.Methods112 MCI patients from the Geneva Memory Center who underwent amyloid‐PET (A), tau‐PET (T), MRI (N), and clinical and neuropsychological assessments were included. Standardized residuals were extracted from linear regression models between hippocampal volume and AT (BR) or MMSE scores and ATN (CR). We compared: (i) non‐corrected residuals (nBR and nCR); (ii) residuals corrected by regressing the dependent variable out of the residuals (cBR and cCR); (iii) non‐corrected residuals with the dependent variable included as covariate (covBR and covCR). Associations between CR or BR and demographic, clinical, cognitive, and biomarker variables were investigated. Linear mixed models explored the impact of CR and BR on cognitive trajectories over time. Results were compared with non‐residual based statistical models.ResultsCorrected and non‐corrected approaches yielded significantly different results. Several factors were associated with nBR, but not with cBR or covBR, such as age (nBR: β = ‐0.399, p < 0.001; cBR: β = ‐0.048, p = 0.641; covBR: β = ‐0.012, p = 0.614). Conversely, several factors were associated with cBR and covBR, bur not nBR, such as female sex (nBR: β = ‐0.102, p = 0.619; cBR: β = ‐0.506, p = 0.012; covBR: β = ‐0.108, p = 0.013). Similar results were observed with CR. Longitudinal assessments also indicated differences in the relationship between corrected/non‐corrected resilience and cognitive trajectories. For example, there was a significant interaction of time x cBR on MMSE scores (p < 0.001), but not of time x nBR (p = 0.226)ConclusionResearchers should be aware that the choice of residual correction method significantly influences study conclusions. Our findings emphasize the necessity of adopting sophisticated modeling approaches to accurately capture resilience.
Translation and Cultural Adaptation of Tools to Assess Diverse Asian American and Asian Canadian Populations: The Asian Cohort for Alzheimer’s Disease Study
Authors: Lee Haeok , Tzuang Marian , Chow Tiffany W , Kang Younhee , Tee Boon Lead , Li Clara , Ho Pei‐Chuan , Gu Yian , Lu Anna T. , Choi Yun‐Beom , Jun Gyungah R , Wang Li‐San , Yu Haung (Ho) , Park Van Ta ,   The Asian Cohort for Alzheimer’s Disease Study
Published: January 2025

AbstractBackgroundSocio‐cultural and language‐appropriate study materials and instruments are critical for accurate assessment of cognitive function in people from diverse backgrounds. Most research uses cognitive tests based on Western, industrialized, English‐speaking cultures and may not reflect global experiences. The purpose of this study was to describe the translations of study materials and cultural adaptations that were developed for the Asian Cohort for Alzheimer’s Disease (ACAD).MethodsMulti‐lingual researchers, clinicians, and community leaders with extensive practical translation experience created materials and instruments in accordance with World Health Organization (WHO) guidelines, using a translation process that consisted of preparing materials, translating materials, conducting a committee review, conducting a pretest (as appropriate), and conducting necessary revisions. The ACAD study population speaks Chinese (Simplified and Traditional), Korean, or Vietnamese. The majority of instruments in the protocol harmonize with the National Alzheimer’s Coordinating Center purposefully, warranting both literal and conceptually cultural‐appropriate translations for our older Asian American and Asian Canadian participants.ResultsWe have developed Asian language versions of the ACAD informed consent, data collection packet, and community outreach materials for all our target groups. Many cognitive tools had been previously translated into Asian languages and made minor modifications. Some items required cultural adaptations to reflect the socio‐cultural background of the targeted Asian languages, e.g., the types of physical activities or dietary choices surveyed.ConclusionThis multi‐stage translation process accounts for the distinctive socio‐cultural and language backgrounds of each Asian population. Alzheimer’s disease and related dementias researchers interested in engaging with these populations may apply this translation process to reduce health disparities in these underrepresented populations. To ensure fidelity across different languages, ACAD will continue to engage in this comprehensive translation process with our diverse community stakeholders.
Results from a Phase 2a Proof‐of‐Concept Double‐Blind, Randomized, Placebo‐Controlled Trial of Lomecel‐BTM in Mild Alzheimer’s Disease Dementia
Authors: Ramdas Kevin N. , Agafonova Nataliya , Hare Joshua M. , Naioti Eric , Kopcho Steven , Cummings Jeffrey L. , Carballosa Raul , Patel Paayal , Brody Mark , Herskowitz Brad , Fuquay Ana , Rodriguez Savannah , Botbyl Jeffrey , Rash Brian , Oliva Anthony A. 
Published: January 2025

AbstractBackgroundLomecel‐B is a novel cell‐based therapy with potential to demonstrate clinical benefit on Alzheimer’s disease (AD) and its progression. Here we present the results of a phase 2a proof‐of‐concept trial (n = 49) to further define the potential of Lomecel‐B in patients with mild AD dementia.MethodsThis double‐blind, randomized, placebo‐controlled 45‐week trial (ClinicalTrials.gov: NCT05233774) enrolled patients (60‐85 yrs.) with mild AD dementia (MMSE score 18‐24); with evidence of amyloid on positron‐emission tomography (PET) and brain MRI consistent with AD. There were 4 study arms of Lomecel‐B intravenous infusion: 25 million (25M) cells once followed by 3 infusions of placebo (N = 13); 25 million (25M) cells (N = 13) or 100 million (100M) cells (N = 11) monthly for 4 months; 4 IV infusions of Placebo (N = 12). The primary endpoint was safety, secondary endpoint was change from baseline to Week 39 in Composite AD Score (CADS) that equally incorporated z‐scores of CDR‐SB, ADAS‐Cog‐13, ADCS‐ADL, and left hippocampal volume.ResultsThe trial achieved its primary endpoint of safety and tolerability (no infusion‐related reactions, ARIA or death). One SAE occurred within 30 days post‐infusion for each Lomecel‐B group with none for placebo. Lomecel‐B 25Mx1 demonstrated a trend toward slowing of disease progression relative to placebo on the CADS score (0.38 [‐0.06, 0.82], p = 0.091 (pre‐specified level of significance for CADS is p = 0.1)). While CADS declined by ‐0.25 [95% CI, ‐0.56, 0.07] in placebo, no decline occurred in the individual or pooled Lomecel‐B treatment groups. Regarding cognitive function, MoCA improved vs placebo (25Mx1: (4.90 [95% CI, 1.26, 8.55], p = 0.009) and (pooled: 3.74 [95% CI, 0.73, 6.75] p = 0.015). ADRQL and QOL‐AD were numerically improved in Lomecel‐B treatments; with significant improvement observed in the ADCS‐ADL for the 100M×1 (10.74 [95% CI, 0.50, 20.98] p = 0.040) and pooled group at Week 39 p = 0.047). Lomecel‐B slowed whole brain volume loss by 49% (100Mx4 (8.31 [95% CI, 0.12, 16.50] p = 0.034) with significant preservation of left hippocampal volume (pooled: 0.0253 [95% CI, 0.0015, 0.0492] p = 0.038), Week 39 compared to placebo.ConclusionTogether, the study achieved proof‐of‐concept in a small sample size. Accordingly, these findings support further development of Lomecel‐B in a larger dose‐finding study.
Attributable fractions of risk factors for cognitive impairment in the ELSA‐Brasil cohort
Authors: Castilhos Raphael Machado , Leotti Vanessa Bielenfeldt , Feter Natan , Duncan Bruce , Schmidt Maria Inês 
Published: January 2025

AbstractBackgroundAttributable fractions (AFs) of the modifiable risk factors of dementia are usually calculated using population‐based samples. Nevertheless, assessing AF within cohorts offers a more nuanced perspective on the impact of these factors. We aimed to estimate the relative risks (RRs) for cognitive impairment (CI) for eight risk factors for dementia and their respective AF in the Longitudinal Study of Adult Health (ELSA‐Brasil).MethodsA global cognitive function score was established by averaging Z scores from six standardized tests. Risk factors and sociodemographic variables were collected between 2008 and 2010, while CI (defined as < ‐1.5 SD on the global cognition Z score) was assessed approximately 10 years later. Participants with CI in the baseline were excluded. We calculated the RR for CI of eight risk factors (physical inactivity, depression, tobacco use, excessive alcohol consumption, obesity, low education, diabetes and hypertension) using a robust Poisson model. AFs were computed using the average attributable fraction method.ResultsOf the 15,105 individuals of the ELSA‐Brasil, 10,058 were included in this analysis. At baseline, the median (IQR) age was 50 (44‐56) years and 56.7% (5,704) were women. The incidence of CI was 5.5% (n = 549). RRs for CI were significant for low education (4.37, 3.61‐5.29), hypertension (1.43, 1.21‐1.7), smoking (1.37, 1.09‐1.71), diabetes (1.27, 1.05‐1.54), in addition to male sex (1.31, 1.11‐1.55) and older age (1.07, 1.06‐1.08). Adjusted risks for depression, physical inactivity, excessive alcohol consumption and obesity were not significant. Low education had the highest AF (CI 95%), 14.3% (10.8‐17.7), followed by hypertension, 13.1% (6.8‐19.4), diabetes, 4.3% (0.4‐8.1) and smoking 3.3% (0.5‐6.1). The total AF for CI was 35% (28‐42).ConclusionsThis is the first assessment of AF of the modifiable dementia risk factors in a Brazilian cohort, with RR calculated directly from the sample. In the ELSA‐Brasil, assuming causality, around one‐third of cognitive impairment cases could be prevented if these four risk factors were eliminated.
The Relationship between Cancer Diagnosis Timing and Cognition in Older Adults in the National Health and Nutrition Examination Survey
Authors: Chen Annie , Bowles Erin J Aiello , Chubak Jessica , Cosentino Stephanie , Genkinger Jeanine M , Levine Deborah A , Tehranifar Parisa , Wolfova Katrin , Tom Sarah E. 
Published: January 2025

AbstractBackgroundCancer diagnosis is related to poor short‐term cognition, reflecting the condition, stress, and management. Less is known about long‐term relationships between time since cancer diagnosis and cognition. We evaluated the association between recency of cancer diagnosis and cognition.MethodThe National Health and Nutrition Examination Survey is a nationally representative, cross‐sectional survey of community‐dwelling people in the United States. In 2011‐2012 and 2013‐2014, the study included questions on the timing of cancer diagnosis. Participants age ≥ 60 years completed the Digit Symbol Substitution Test and the Consortium to Establish a Registry for Alzheimer’s Disease Total Learning Test and Recall Test. Our analytic sample included individuals age ≥ 60 years who reported a cancer diagnosis and completed all cognitive tests. We calculated z‐scores for each cognitive test and a global score (sum across individual z‐scores). We used linear regression to assess the relationship between time since cancer diagnosis (current ‐5 years, >5 years) and cognition. We estimated an age and sex‐adjusted model and included potential confounders in a series of nested models, with each step adding: race and ethnicity, education level, marital status, and health insurance status. Analyses were weighted such that results represent the US community‐dwelling population.ResultThe analysis sample included 477 participants who ever had a cancer diagnosis, excluding unknown and non‐melanoma skin cancers, corresponding to an implied population of 9,027,595 (including 11% melanoma skin, 23% breast, 16% prostate) with a mean age of 71.2 years (SD = 6.6). A total of 31% of participants reported a cancer diagnosis within the past five years. Demographic characteristics were similar based on cancer diagnosis timing. Adjusting for age and sex, participants greater than five years from cancer diagnosis had a higher cognition level, compared to those with a cancer diagnosis within five years (coefficient = 0.22, 95% CI = 0.05, 0.39). Results were similar when adjusting for additional covariates.ConclusionAmong older adults who ever had a cancer diagnosis, a diagnosis that occurred more than 5 years ago was related to better cognition. Future studies should investigate the roles of cancer site, treatments, and stage at diagnosis in this relationship.
Risk Factors and Brain Substrates of Motoric Cognitive Risk Syndrome in Rural and Urban Residents: Results from the Kerala‐Einstein Study
Authors: Emmeline Ayers , Blumen Helena M , Delpratt Natalie A , Adhikari Dristi , Verghese Joe 
Published: January 2025

AbstractBackgroundRural populations are under‐represented in cognitive studies worldwide. The few extant studies report differences in risk profiles for pre‐dementia and dementia syndromes among urban and rural residents. We compared risk factors and brain substrates of Motoric Cognitive Risk (MCR) syndrome, a pre‐dementia syndrome identified by slow gait speed and subjective cognitive concerns, in urban and rural participants in the Kerala‐Einstein study.MethodParticipants (aged 60+) are recruited from rural and urban sites in Kozhikode district, Kerala, India. Participants with possible dementia were excluded (score ≤4 on the Picture‐Memory Impairment Screen). Logistic regression was used to identify risk factors of MCR in rural and urban residents. Multivariate general linear models were used to examine the relationship between MCR and brain structures as a function of residency.Result334 rural (M age = 68.7±5.1; 64% male, 20% high school graduates) and 299 urban (M age = 68.7±6.1; 60% male, 25% high school graduates) participants without dementia were examined. MCR prevalence was similar in rural (10%) and urban (9%) settings. Individuals with MCR in both samples reported more depressive symptoms and fewer years of education. Urban MCR participants were more likely to use a hearing aid, have apathy, and have occupations that involved manual labor. Modeled simultaneously, hearing aids (p = 0.05) and manual labor (p = 0.027) were associated with MCR in urban settings, and education years (p = 0.010) in the rural setting. In a subset of participants with MRI (N = 213; 145 Urban; 68 rural; 15% MCR), significant interactions between MCR and residency were observed for the right frontal cortical thickness (p = 0.005) and left hippocampal volume (p = 0.018) such that a significant association was only observed in the urban residents – after adjusting for age, sex, education, overall white matter lesion burden, total intracranial volume, and depressive symptoms. After adjusting for apathy, only the association between MCR and left hippocampal volume remained significant.ConclusionThe risk factors and the brain substrates associated with MCR differ in urban and rural residents from Kerala, India, and have implications for designing interventions and understanding the pathophysiology of MCR.
Event‐based modeling of T‐N mismatch reveals distinct spatio‐temporal trajectories of subtypes with likely co‐pathology in Alzheimer’s disease
Authors: Lyu Xueying , Yushkevich Paul A. , Hrybouski Stanislau , Li Yue , Duong Michael Tran , Xie Long , Wisse Laura E.M. , de Flores Robin , Irwin David J , Dickerson Bradford C. , Nasrallah Ilya M. , Das Sandhitsu R. , Wolk David A 
Published: January 2025

AbstractBackgroundThe heterogeneity of Alzheimer’s disease (AD) and lack of well‐validated markers of co‐pathologies present a substantial challenge for therapeutics. We previously found phenotypes defined by Tau (T) ‐ Neurodegeneration (N) discordance linked to non‐Alzheimer’s pathologies (e.g. TDP‐43, vascular disease). In this work, we aim to leverage T‐N mismatch for identifying distinct spatial‐temporal progression patterns of non‐AD pathologies.MethodWe performed T‐N regression on 1040 scan pairs (n=722 individuals) from ADNI, using cortical thickness (N) and 18F‐Flortaucipir uptake (T) in 20 bilateral cortical regions of interest. As in previous work, residuals were identified as canonical (T∼N), vulnerable (N>T) and resilient (N<T). Here, we apply SuStaIn, a phenotype discovery and stage inference algorithm, to standardized T‐N residuals in canonical and vulnerable cases (n=608), expecting the latter would reflect co‐pathologies.ResultBesides the "canonical" subtype (S0), SuStaIn identified three subtypes with distinct T‐N mismatch (N>T) progression profiles (Figure 1). Two exhibited different but progressively diffuse spatial patterns of T‐N mismatch — the anterior subtype (S1) starting from frontal, and the posterior subtype (S2) initiating from occipital/temporal regions. The third subtype (S3) exhibited temporal‐limbic mismatch patterns, with spreading to anterior limbic regions.The three mismatch subtypes had worse cognition, greater age and larger rate of amyloid positivity than canonical subtype (Table 1). SuStaIn‐identified stage was associated with age and worse cognition but not tau severity (Figure 2A‐C), indicating the stages do not represent AD progression. The anterior subtype had the largest white matter hyperintensity (WMH) volume, increasing with higher stages (Figure 2D), suggesting an association with vascular disease. The temporal‐limbic subtype demonstrated poorest memory performance (Figure 2E) and may be associated with TDP‐43 pathology, as suggested in our prior work. 90.1% with longitudinal scans did not change subtype or transitioned from canonical to mismatch subtypes (Figure 2F), supporting the stability of classifications.ConclusionWe identified distinct T‐N mismatch progression trajectories in AD, potentially reflecting progression of co‐pathologies. It is important to better define these groups in the context of anti‐amyloid therapies to better understand their effectiveness in populations with likely co‐pathology and whether these mismatch trajectories driven by non‐AD factors would continue independent of treatment.