bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Psychosocial Analyzation of Alzheimer’s Disease and other Dementia among Black Ohioans
Authors: Harris Camren J 
Published: January 2025

AbstractBackgroundOlder Black Americans are twice as likely to have Alzheimer’s Disease or another dementia, and 65% of Black Americans say that they know somebody with Alzheimer’s or dementia. More locally, according to Ohio county level estimates, 11.3% of Ohioans aged 65 are currently living with Alzheimer’s Disease. Higher than the national average 10.7%MethodA small sample size of Black Ohioans from different counties took a questionnaire pertaining to information as it relates to Alzheimer’s Disease and other dementia in the Black Communities in Ohio.Result82% of Black Ohioans surveyed know someone who has been diagnosed with Alzheimer’s Disease or related dementia. 64% of Black Ohioans do not believe cognitive decline issues are a part of normal aging. Only 35% of Black Ohioans surveyed say they are very knowledgeable about dementia. 87% of Black Ohioans surveyed are concerned about developing Alzheimer’s. 94% of Black Ohioans surveyed believe that the lack of access to resources is a reason why Black Americans are more likely to be diagnosed with Alzheimer’s Disease. 62% of Black Ohioans surveyed say they would consider participating in clinical trial concerning Alzheimer’s and/or related dementias if provided more information. 94% recorded that they have not (in the last 6 months) become aware of any elected officials creating or advocating for any legislation concerning cognitive care or dementia support and treatment. 52% believe dementia care, support and treatment should be a priority for elected officials.ConclusionBlack Ohioans are concerned about the rising prevalence of Alzheimer’s Disease, however social barriers that prevent equitable access to care, support and treatment is of overwhelming concern. Additionally, Black Ohioans are interested in participating in clinical trials but due to the lack of resourceful information presented and/or provided concerning clinical trials to Black communities, further creates reluctance to participate. Lastly, more than half of the Black Ohioans surveyed are simply unaware of the public policy issues and priorities concerning cognitive decline, but would like for elected officials (federal, state and local) to be more intentional about utilizing public policy to build a better dementia infrastructure for those affected by Alzheimer’s Disease and other dementias.
Early Alterations of White Matter Neuroinflammation in Autosomal Dominant Alzheimer's Disease
Authors: Wang Qing , Jiang Meng , Cohen Kayle , Flores Shaney , Keefe Sarah J. , Patel Aakash , Chen Gengsheng , Millar Peter R , Schindler Suzanne E. , Cruchaga Carlos , Gordon Brian A. , Morris John C. , Bateman Randall J. , McDade Eric , Wang Yong , Benzinger Tammie L.S. ,   Dominantly Inherited Alzheimer Network
Published: January 2025

AbstractBackgroundAutosomal Dominant Alzheimer's Disease (ADAD) is a rare and early‐onset form of Alzheimer's disease with a familial pattern of inheritance. While the pathological features of ADAD, such as amyloid plaques and neurofibrillary tangles, have been extensively studied, the involvement of white matter (WM) neuroinflammation is not well‐explored. In sporadic AD, the hindered ratio (HR) derived from diffusion basis spectrum imaging (DBSI) has been used to study neuroinflammation in WM. This study aims to investigate the potential role of WM neuroinflammation as an early driver in the progression of ADAD using DBSI.MethodThis study included 104 participants from the Dominantly Inherited Alzheimer Network (DIAN) Observational Study. 60 participants were identified as mutation carriers of pathologic variants in PSEN1, PSEN2, or APP. Estimated years until symptom onset (EYO) were calculated for each participant based on previous methods (1). Participants’ demographics are summarized in Table 1. Diffusion MRI was acquired using a multi‐b value scheme (bmax =2000 s/mm2 and 28 directions) (2). The DBSI‐HR was quantified and obtained from the JHU white matter tracts. Non‐parametric Kruskal‐Wallis and Chi‐square tests were employed to compare demographic variables. The DBSI‐HR on each WM tract as a function of EYO was explored using generalized additive mixed models. All statistical tests were conducted in R4.2.2 (R Core Team). Age, sex, education, and APOE ε4 carrier status were adjusted as covariates.ResultDemographic data are summarized in Table 1. Mutation carriers had an elevated averaged DBSI‐HR for total WM tracts compared to non‐carriers (Figure 1). Mutation carriers displayed divergent trends from non‐carriers prior to the expected symptom onset for the posterior thalamic radiation (‐5.87 EYO, Figure 2), tapetum (‐2.9 EYO), and sagittal stratum (‐1.20 EYO).ConclusionDBSI‐HR measurements indicate increased WM neuroinflammation in the posterior thalamic radiation, tapetum, and sagittal stratum prior to symptom onset in ADAD. We have recently identified these three WM tracts as having the earliest change in DBSI‐HR in sporadic AD. Together, these findings suggest that WM neuroinflammation occurs prior to onset of AD symptoms.
Associations between imaging biomarkers and sleep quality in the U.S. POINTER study baseline cohort
Authors: Winer Joseph R. , Ward Tyler J. , Scales Margaret , Taggett Jacinda , Howard Marjorie , Stone Katie L , Lockhart Samuel N. , Baker Laura D , Hayden Kathleen M. , Landau Susan M. , Harrison Theresa M. ,   The U.S. POINTER Study Group
Published: January 2025

AbstractBackgroundWorse sleep is associated with a greater risk of Alzheimer’s disease (AD). However, few studies have linked objective sleep with neuroimaging outcomes, limiting our understanding of how poor sleep impacts the brain. The U.S. POINTER trial, which has enrolled a heterogeneous cohort of older adults at elevated risk for cognitive decline, is a unique sample differing from prior investigations of sleep, aging, and brain health. Here we investigate how actigraphy‐assessed sleep duration and efficiency are cross‐sectionally associated with baseline neuroimaging measures of brain structure and AD pathology.MethodParticipants underwent neuroimaging (MRI, 18F‐florbetaben amyloid PET, and 18F‐MK6240 tau PET), cognitive testing, and wristwatch actigraphy, which assessed sleep duration and sleep efficiency averaged across six nights. Imaging analyses focused on bilateral entorhinal tau PET, cortical amyloid PET, hippocampal volume, white matter hyperintensity (WMH) volume, and diffusion free water. Based on prior literature suggesting short and long sleep duration are disadvantageous, quadratic models were fit for sleep duration predicting neuroimaging and cognitive measures, with age, sex, years of education, body mass index, and self‐identified racial ethnic category as covariates. Linear models were fit for sleep efficiency with the same covariates.ResultAcross 454 participants (Table 1), sleep measures were not related to cognition. Hippocampal volume, WMH volume, and free water showed U‐shaped relationships with sleep duration such that average sleep durations shorter and longer than approximately 6‐7 hours were associated with worse brain health outcomes (Figure 1). There were no associations between tau or amyloid PET and sleep duration. When stratified by amyloid status, associations between sleep duration and brain structure were significant in only the amyloid negative group. Unexpectedly, there were no associations between neuroimaging measures and sleep efficiency except for a significant positive relationship with entorhinal tau PET uptake.ConclusionIn the largest and most heterogeneous sample to date of older adults with actigraphy and neuroimaging measures, sleep duration was associated with multiple measures of brain structure but not AD pathology. These relationships may reflect heterogeneity and selection characteristics of the at‐risk POINTER cohort, which differ from previous studies of sleep and AD biomarkers.
Blood‐based biomarkers of Alzheimer’s disease and 15‐year rate of olfactory decline in an elderly population
Authors: Ekström Ingrid , Vetrano Davide Liborio , Ruane Robert , Grande Giulia , Valletta Martina , Larsson Maria , Fredolini Claudia , Winblad Bengt , Fratiglioni Laura , Laukka Erika J 
Published: January 2025

AbstractBackgroundOlfactory impairment has been observed as an early sensory marker of cognitive decline and dementia, but its association with biomarkers of Alzheimer’s disease (AD) pathology remains understudied, particularly in the context of blood‐based biomarkers.MethodHere, we examine six common biomarkers of AD, tau phosphorylated at threonine 181 (P‐tau181), total tau (T‐tau), amyloid‐β ratio (Aβ42/Aβ40), P‐tau181/Aβ42 ratio, neurofilament light (Nfl), and glial fibrillary acidic protein (GFAP), derived from serum at the baseline assessment of the population‐based Swedish National Study on Aging and Care in Kungsholmen (SNAC‐K; n = 1933, mean age at baseline = 71 years). Participants were free from dementia and neurodegenerative disorders at baseline. Linear mixed modeling examined the association between blood‐biomarker levels and Sniffin’ Sticks odor identification performance at baseline, and changes in performance over 15 years. Missing olfactory values during follow‐up were imputed by the maximum likelihood method.ResultIn multi‐adjusted models, controlling for demographic (age, sex, education), health (cerebrovascular disease, cardiovascular disease, chronic kidney disease, anemia, obesity) and cognitive (vocabulary) factors, higher levels of P‐tau181 (β = ‐0.087, 95% CI: ‐0.121 to ‐0.053), P‐tau181/Aβ42 ratio (β = ‐0.030, 95% CI: ‐0.054 to ‐0.006), Nfl (β = ‐0.055, 95% CI: ‐0.082 to ‐0.028), and GFAP (β = ‐0.026, 95% CI: ‐0.048 to ‐0.005) were associated with steeper olfactory decline over follow‐up. No significant associations with olfactory decline were observed for T‐tau or Aβ42/Aβ40. However, higher T‐tau levels were associated with lower olfactory baseline ability (β = ‐0.118, 95% CI: ‐0.234 to ‐0.007). Follow‐up analyses explored interactions for age, sex, and Apolipoprotein (APOE) ԑ4‐carrier‐status.ConclusionIn sum, this study shows higher concentrations of blood‐based biomarkers of AD to be associated with faster rates of olfactory decline in community‐dwelling older adults. Our results support the validity of olfactory identification performance as a marker sensitive to underlying AD‐pathology. As such olfactory assessment could be of particular utility in settings where physiological biomarkers of pathology are unavailable, and olfactory performance may aid in determining which patients likely to benefit from further assessments.
Synergistic effects of GFAP and Aβ42 on clinical outcomes: Implications for white matter microstructure and verbal memory
Authors: Bettcher Brianne M , Paniagua Dan Lopez , Wang Yue , McConnell Brice , Coughlan Christina M , Carlisle Tara C , Thaker Ashesh A , Lippitt William , Filley Christopher M. , Pelak Victoria S , Potter Huntington , Solano D. Adriana , Boyd Jada , Carlson Nichole E 
Published: January 2025

AbstractBackgroundPlasma GFAP, a biomarker of astrogliosis, has previously been linked with Alzheimer’s disease clinical status, amyloid levels, and memory performance in older adults. The neuroanatomical pathways by which GFAP might impact cognitive outcomes remains unclear. We evaluated whether fornix structure, which is critically involved in AD‐associated cholinergic pathways, is associated with interactive effects of plasma GFAP and amyloid levels. We also appraised whether fornix structure mediates associations between GFAP and verbal memory.MethodIn a cohort of both asymptomatic and symptomatic older adults (total n=90), we assessed GFAP, AD‐related proteins, and vascular markers in plasma, and we conducted comprehensive memory testing. Tractography‐based methods were used to assess structure of the fornix, and whole brain diffusion metrics were also ascertained to control for diffuse alterations in white matter.ResultIn individuals whose blood levels of Aβ42 were in the lowest tertile, higher GFAP levels were associated with lower fractional anisotropy (FA; p=0.007), higher mean diffusivity (MD; p<0.001), higher radial diffusivity (RD; p <0.001), and higher axial diffusivity (AD; p=0.001) in the left fornix. These associations were independent of APOE gene status, plasma levels of total tau and neurofilament light, plasma vascular biomarkers, and whole brain diffusion metrics. Fornix structure partially mediated the association between higher GFAP levels and lower verbal memory performance in participants with lower plasma Aβ42.ConclusionResults suggest that in the setting of greater amyloid deposition, higher levels of blood GFAP are associated with altered fornix microstructure. We also expanded on our prior GFAP‐verbal memory findings, demonstrating that in the subset of participants with lower blood Aβ42 levels, left fornix integrity may be a primary white matter pathway for the negative associations between GFAP and verbal memory performance. Overall, these findings suggest that GFAP may play an early, pivotal role in AD pathogenesis, and further demonstrate that the combination of blood GFAP and Aβ42 may have a particularly negative role in forniceal‐memory pathways.
Feasibility and refinement of a culturally tailored intervention to reduce financial strain among Latino caregivers using AI
Authors: Meyer Kylie , Dorai Chitra , Perales Jaime , Puga Frank , Zauszniewski Jaclene A , Benton Donna Marie 
Published: January 2025

AbstractBackgroundFamily caregivers to persons living with dementia are at risk of financial strain from the high out‐of‐pocket costs of care and reduced employment opportunities. Financial strain disproportionately affects U.S. Latino caregivers, who experience higher care costs proportionate to household incomes than non‐Latinos. In 2022, the authors presented the preliminary results of a pilot study to test a culturally tailored psychoeducational intervention (CONFIDENCE) to reduce financial strain; we summarize the results of this study and describe planned intervention refinements.MethodWe conducted a pilot study to test the feasibility of the CONFIDENCE intervention from May 2021 to September 2023. CONFIDENCE is a 5‐week group intervention delivered by Zoom by a community‐based organization in Los Angeles, CA. Caregivers could register to participate in CONFIDENCE, and, if eligible, enroll in an optional pre‐ and post‐test trial. Those in the trial completed a self‐administered online survey before the first session, post‐intervention, and 2‐ months post‐intervention. Surveys measured financial strain, and anticipated mechanisms (resourcefulness and self‐efficacy). Scores were compared using paired t‐tests.Result136 caregivers registered to attend CONFIDENCE, among whom 69 attended at least one session (51%). On average, the 69 attendees participated in 3.13 of 5 sessions (SD = 0.17). The 21 attendees who completed the satisfaction survey indicated they would recommend CONFIDENCE (Figure 1). Moreover, the 20 caregivers who enrolled in the optional trial reported lower levels of financial strain after participating in CONFIDENCE (p‐value = 0.013), as well as increased resourcefulness and self‐efficacy two months post‐intervention (p‐value = 0.015 and <0.001, respectively; Figure 2).ConclusionAssessed with Bowen et al.’s (2009) feasibility model, CONFIDENCE demonstrated high acceptability, adequate demand from end‐users, preliminary efficacy, and the ability to be implemented in a community setting. However, low attendance suggests the intervention may not be practical for end‐users to attend. CONFIDENCE is being modified to improve feasibility by consolidating sessions from 5 to 4 and integrating a digital application. This app, provided in partnership with Amicus Brian Innovations, includes text message reminders and access to interactive AI digital assistance (Figure 3). A second pilot is being conducted to examine the ongoing feasibility of the refined intervention.
Lateral Ventricle Volumes Predict Hippocampal Volume and Cognition
Authors: Chen Gengsheng , Doering Stephanie , Joseph‐Mathurin Nelly , Massoumzadeh Parinaz , Liu Jingxia , Wang Qing , Gordon Brian A. , Morris John C. , Benzinger Tammie L.S. 
Published: January 2025

AbstractBackgroundThe use of biomarkers for early detection of Alzheimer disease (AD) is crucial for developing potential treatments. As neurons die, brain structures, including the hippocampus, shrink and the cerebrospinal fluid spaces ventricles expand. However, due to its small size, hippocampal volumes can be challenging to measure. The lateral ventricles are larger and easier to reproducibly segment, even in low resolution scans. In this study, we investigated whether baseline and longitudinal changes in lateral ventricle volume could predict baseline and longitudinal changes in hippocampal volume and in cognition, assessed by the clinical dementia rating (CDR®) sum of boxes.MethodWe evaluated 518 participants enrolled in longitudinal studies at the Knight ADRC at Washington University in St. Louis (See Table 1). MRI and clinical data were obtained through OASIS (www.oasis‐brains.org). Lateral ventricular and hippocampal volumes were extracted and corrected for intracranial volume using FreeSurfer. Linear regression models were used to assess whether the baseline lateral ventricle volumes predict the baseline CDR sum of boxes or baseline hippocampal volume. A two‐step random coefficient model was used to assess whether the rate of change in lateral ventricle volume predicts the rate of change in the CDR sum of boxes or the rate of change in hippocampal volume.ResultWe found that larger baseline lateral ventricle volumes predict smaller baseline hippocampal volumes (estimate β =‐0.04, p<0.0001, Table 2, Figure 1A) and worse baseline CDR sum of boxes (estimate β =0.000007, p=0.0024, Table 2, Figure 1C). Additionally, the rate of change in lateral ventricle volumes predicts the rate of change in hippocampal volume (estimates β =‐0.0221, p<0.0001, Table 2, Figure 1B) and rate of change in CDR sum of boxes (estimates β =0.0001, p<0.0001, Table 2, Figure 1D).ConclusionLarger baseline lateral ventricles volumes predict smaller baseline hippocampal volumes and worse baseline CDR sum of boxes in an AD cohort. In addition, increased rates of enlargement of lateral ventricle volumes predict increased atrophy rates of the hippocampus and worsening CDR sum of boxes. Baseline and longitudinal lateral ventricle volumes could potentially be used to evaluate risk for AD in clinical populations.
Gamma‐secretase modulation: from bench to clinic
Authors: Gerlach Irene , Tortelli R. , Mueggler T. , Müller L. , Lindemann L. , Croney R. , Piosik P. , DeBuck S. , Vardar5 T. , Baumann K. 
Published: January 2025

AbstractAmyloid β (Aβ) has been confirmed as a therapeutic target in AD by recent findings in Phase 3 trials with anti‐Aβ antibodies. Modulators of γ‐secretase (GSMs) are an emerging complementary approach to target amyloid. GSMs “modulate” the interaction between γ‐secretase and amyloid precursor protein (APP), leading to a reduced production of long, amyloidogenic Aβ42 and Aβ40 and to concomitantly increased levels of the shorter, non amyloidogenic Aβ37 and Aβ38. This change in processivity of γ‐secretase results in a reduced formation of soluble and insoluble Aβ aggregates and plaque deposits. Unlike inhibitors of γ‐secretase or BACE1, GSMs do not inhibit the activity of γ‐secretase and thus do not block the processing of APP and of other substrates. In addition, non‐clinical studies showed that GSMs may have beneficial effects on synaptic integrity and Aβ‐associated neuro‐inflammation.The clinical relevance of higher Aβ37 and Aβ38 ‐levels for a reduced risk of cognitive decline have been described in observational cohorts (vonKienlin et al. 2018; Cullen et al. 2022). Nevertheless, to date the effects of GSMs on brain function and course of disease in people living with AD have not been investigated. Our novel orally available GSM RG6289 has completed the Phase 1 study in healthy young and elderly volunteers. Safety, pharmacokinetic and pharmacodynamic data from this study support the further clinical development of the molecule. The Phase 2 study in individuals with AD is expected to start this year. Challenges of developing in clinic a new mechanism of action, as well as considerations regarding how to best position this molecule for AD will be discussed in this presentation.
Structural Mechanism of γ‐secretase Cleavage and Regulation
Authors: Zhou Rui 
Published: January 2025

AbstractAlzheimer’s Disease (AD) is characterized by the amyloid plaques in patient brain. The plaques are formed by β‐amyloid peptides (Aβs) that derive from the cleavage by γ‐secretase. Over 300 AD pathogenic mutations have been identified in presenilin1/2 (PS1/PS2), the catalytic subunit of γ‐secretase. Therefore, γ‐secretase serves as a potential drug target of AD. But inhibition of γ‐secretase suffers from severe side effect in clinical trials, which is thought to derive from unspecific inhibition towards its other substrates such as Notch. So, what is the molecular basis of γ‐secretase cleavage and how does the activity of γ‐secretase is regulated, especially in a substrate‐selective way?To unravel the mechanism of substrate cleavage, we determined the cryo‐EM structures of γ‐secretase in complex with APP/Notch fragment, respectively. These structures reveal contrasting features of different substrates binding, thus providing valuable information for modulation of γ‐secretase cleavage in a substrate‐selective way. In addition, we solved structures of γ‐secretase bound to a number of inhibitors and modulator. Structural analysis reveals a set of shared themes and variations for inhibitor and modulator recognition that will guide development of the next‐generation substrate‐selective inhibitors. All these works lay the foundation for a better understanding towards the working mechanism of γ‐secretase and may facilitate related therapeutic intervention.