bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating segregated school attendance as a mediator of geographic inequities in late‐life cognitive function: evidence from the Study of Healthy Aging in African Americans (STAR)
Authors: Gutierrez Sirena , Whitmer Rachel A. , Lor Yi , George Kristen M. , Barnes Lisa L. , Mayeda Elizabeth Rose , Allen Isabel Elaine , Glymour M. Maria , Torres Jacqueline M , Gilsanz Paola 
Published: January 2025

AbstractBackgroundBeing born in the Southern US is associated with poorer cognitive health and related cardiovascular outcomes in late life, especially among Black Americans. Geographic disparities in brain aging may be mediated by school segregation; school segregation has been disproportionately high in the South given historical and contemporary policies and practices.MethodThis study included 727 Black adults ages 50+ (mean 68.8 (8.8±SD) years) living in Northern California from the Study of Healthy Aging in African Americans (2018). We employed linear regression models to estimate associations between Southern US birth and domain‐specific cognitive function z‐scores, adjusting for early‐life covariates. Utilizing mediation analysis, we decomposed the total effect of Southern birth into natural direct effects and natural indirect effects via self‐reported ever attending a segregated school at grade 1, 6, 9, or 12.ResultThe 38% of participants born in the South averaged older age (74.9 vs. 65.0 years), had less educated parents (38.4% vs. 15.4% with less than high school), and were more likely to have attended segregated schools (71.7% vs. 18.1%) compared to those born in other regions. Southern birth was associated with lower late‐life executive function (β[95% CI] = ‐0.18 [‐0.33, ‐0.03]) and semantic memory (‐0.36 [‐0.52, ‐0.20]); estimates were imprecise for verbal episodic memory (‐0.07 [‐0.23, 0.09]). Under the assumptions for mediation analyses, the estimated direct effect of Southern birth, not mediated by attending a segregated school, was ‐0.12 [‐0.29, 0.05] for executive function, ‐0.19 [‐0.39, 0.00] for semantic memory, ‐0.11 [‐0.27, 0.05] for verbal episodic memory. Attending a segregated school mediated 38% and 47% of the total effect of Southern birth on executive function (indirect effect: ‐0.07 [‐0.17, 0.03]) and semantic memory function (indirect effect: ‐0.17 [‐0.28, ‐0.06]).ConclusionSchool segregation may be an important mechanism underlying geographic inequities in late‐life health in the US. Interventions to reduce persistent de facto school segregation may help ameliorate these inequities. Future research should consider other mechanisms related to the schooling environment (e.g. resources, quality) that may be additional targets of intervention.
Longitudinal multicenter head‐to‐head harmonization of tau‐PET tracers: an overview of the HEAD study cohort
Authors: Lussier Firoza Z , Povala Guilherme , Bauer‐Negrini Guilherme , Amaral Livia , Cehula Juli , Fine Devin J , Lemaire Peter , Bloomquist Madeleine , Pascual Belen , Gordon Brian A. , Lowe Val J. , Oh Hwamee , soleimani‐meigooni David N. , Rosa‐Neto Pedro , Tudorascu Dana , Jagust William J. , Klunk William E , Baker Suzanne L. , Pascoal Tharick Ali 
Published: January 2025

AbstractBackgroundStandardizing tau pathology quantification in vivo is challenged by differences in binding characteristics between tau‐PET tracers. The HEAD study aims to generate a leading, longitudinal head‐to‐head dataset of MK‐6240, Flortaucipir, RO948, and PI‐2620 tau‐PET to harmonize these tracers' outcomes and develop tools allowing for the generalization of findings across large studies and trials. Here, we present current advancements in building the HEAD study cohort and dataset.MethodsThe HEAD study is managed at the University of Pittsburgh. HEAD comprises several sites across the US and Canada in which 620 subjects (young, cognitively unimpaired, mild cognitive impairment, and Alzheimer’s disease (AD)) will undergo tau‐PET with at least two tracers, amyloid‐PET with PiB or NAV4694, MRI, blood collection, and standardized neuropsychological testing at baseline and at 18‐month follow‐up. PET and MRI acquisition parameters are based on ADNI4 protocols and neuropsychological testing employs the NACC Uniform Data Set. The National Centralized Repository for AD serves as the biorepository for blood samples and the Laboratory of Neuroimaging provides a centralized database for imaging and neuropsychological archiving. PET data is reconstructed to maximize cross‐scanner harmonization and is processed uniformly similarly to ADNI4 PET.ResultsIn one year of active enrollment (Jan 2023‐Jan 2024), 362 participants were enrolled at six active sites; over 80% of participants completed neuropsychological testing and MRI, and over 70% completed Flortaucipir, MK‐6240, and amyloid‐PET, with a mean tau‐PET acquisition window of 29.1 days. RO948 and PI‐2620 tau‐PET are additionally acquired in a subset currently including 41 participants (Figure 1). Current HEAD cohort demographics including age, sex, underrepresented populations, and group distributions, APOEε4 carrier status, and amyloid positivity are shown in Figure 2. A case of a subject with AD with all 4 tau‐PET tracers acquired head‐to‐head within 49 days is shown in Figure 3.ConclusionThe HEAD study represents a continued effort in the optimization of AD imaging biomarkers. Baseline data collection is projected to be completed in 2024; results being generated by multiple groups from this dataset will provide novel and crucial guidance on the use of tau‐PET tracers in research, clinical trials, and prospectively in clinical practice.
Cross‐sectional study of the impact of psychosocial factors on cognitive and behavioral symptoms in patients at the University Hospital of Buenos Aires
Authors: Dunovits Cynthia , Brusco Luis Ignacio , Olivar Natividad , Germani Sandra 
Published: January 2025

AbstractBackgroundIncreasing evidence points to the possible risk roles of psychosocial factors (lack of education, active social participation, physical exercise and mentally stimulating activity, economic instability, traumatic life events) in the pathogenic process and clinical manifestation of dementia disorders.In recent years in our country, in the context of a complex inflationary process, there has been an increase in all indicators of vulnerability and poverty, exceeding 40% of the population below the poverty line in 2023 and around 9% below the indigence line.MethodIn the context of International Alzheimer’s Day, the Alzheimer’s Disease Awareness Week was held at the Hospital de Clínicas of Buenos Aires. In it, spontaneous attention was provided to 100 patients between 60 and 85 years old with cognitive complaints, evaluating education, occupation, socio‐environmental variables along with anxiety scales (GAD); affective (PHQ), minimental and NPI.ResultIn our sample of one hundred patients, a clear prevalence of women in the consultation with a medium educational level was observed. An increase in the incidence of anxious symptoms (40%) and depressive symptoms (40%) was evident; followed by irritability (30%); sleep disturbances (35%); apathy (20%).ConclusionPsychosocial factors play a fundamental role in the incidence, onset and progression of cognitive conditions, which is why they should be a priority in dementia prevention policies. The prevalence of women’s consultations and their earlier access in a preventive modality also shows their more fluid contact and circulation in the health system and particularly in primary care.
Amyloid Plaque Reduction as a Surrogate Marker of Efficacy: Assessment of Amyloid PET and Change in CDR‐SB Utilizing Semi‐Mechanistic Model
Authors: Willis Brian A. , Bhagunde Pratik , Bell Robert , Penner Natasha , Charil Arnaud , Irizarry Michael C. , Hersch Steven , Reyderman Larisa 
Published: January 2025

AbstractBackgroundLecanemab is a humanized IgG1 monoclonal antibody binding with high affinity to protofibrils of amyloid‐beta (Aβ) protein. In clinical studies, lecanemab has been shown to reduce markers of amyloid in early symptomatic Alzheimer’s disease (AD) and slow decline on clinical endpoints of cognition and function. Herein, a modeling approach was used to correlate amyloid reduction with change in rate of AD progression. This model was then utilized to evaluate amyloid PET as a surrogate marker of efficacy and to assess long‐term effect of lecanemab treatment on CDR‐SB.MethodNonlinear mixed‐effects modeling assessed the correlation between amyloid PET and change in CDR‐SB. Data from the lecanemab phase 2 study (Study 201) and Clarity AD (Study 301) were pooled, and CDR‐SB scores were used with beta regression to fit a Richard’s function parameterized in terms of baseline CDR‐SB, intrinsic rate of disease progression, shape, and precision of the beta distribution. Inter‐subject variability was included on baseline CDR‐SB and intrinsic rate. Data from placebo‐treated subjects was used to establish a disease‐progression model; the effect of amyloid reduction on disease progression was defined using data from lecanemab‐treated subjects. Other baseline factors influencing disease progression were explored. Simulations were conducted to evaluate the impact of lecanemab treatment over 4 years.ResultRichard’s model well‐described AD progression. Baseline CDR‐SB was predicted by diagnosis and baseline mini‐mental state examination (MMSE) score. Intrinsic rate of disease progression was predicted by baseline amyloid PET and baseline MMSE score. Change in amyloid PET was a better predictor of drug effect than lecanemab exposure, demonstrating amyloid reduction as a surrogate marker of clinical efficacy. Simulations projected that the difference in CDR‐SB between lecanemab and placebo treated subjects continued increasing over the entire simulation period. Patients with low amyloid at baseline and less severe disease were projected to have slower disease progression than patients with higher amyloid or more severe disease at start of treatment.ConclusionAmyloid reduction was shown to be predictive of slowing of AD progression. Individuals with less advanced disease and lower amyloid baseline were projected to have better outcomes with lecanemab treatment than more advanced patients.
Improving Black/African American Recruitment in ADRD Observational Studies: Black Women Inflammation and Tau Study
Authors: Stradford Joy , Heyworth Nadine , Jackson Michelle , Norman Marc , Thames April , Banks Sarah , Sundermann Erin E. 
Published: January 2025

AbstractBackgroundBlack/African American women are the most at‐risk demographic group for developing Alzheimer’s disease and related dementias (ADRD). Unfortunately, Black Americans are underrepresented in research, accounting for just 8% of clinical trial participants in the USA. Restrictive study exclusion criteria and medical mistrust are pervasive barriers to research participation in minoritized communities and are often disregarded during the development of a research study. The Black Women Inflammation and Tau Study (BWITS) is an observational study aiming to identify biopsychosocial risk factors for ADRD in Black women to improve health outcomes. Study development was informed by Community‐Based Participatory Research (CBPR) and National Institute on Minority Health and Health Disparities (NIMHD) Research Frameworks to address common participation challenges in minoritized groups.MethodBWITS is utilizing the CBPR and NIMHD frameworks to design the study and develop culturally informed and effective recruitment strategies. Recruitment is expected to begin in spring, 2024.ResultMultidisciplinary Team. The study has established a diverse multidisciplinary research team including Black neuropsychologists, neuroscientists, nurse practitioners, and scholars working together to address participants needs.Community Reciprocity & Partnerships. BWITS strives to establish community reciprocity by providing education outreach to the community and communicating procedures, results, and providing health data to participants. The study team is actively working to build trust through community partnerships with Black community organizations and through routine consultation with a representative Community Advisory Board.Reducing Barriers. BWITS will use minimally invasive blood draws to study ADRD biomarkers. To minimize time and transportation burden and increase accessibility, BWITS study visits will take place in convenient locations within predominantly Black communities of San Diego and Los Angeles with transportation options offered.Acknowledging Health Determinants in Minoritized Groups. Diabetes affects 12.1% of Black American adults; however, individuals with diabetes are often ineligible from participating in ADRD studies resulting in disproportionate exclusion. BWITS has adopted broader eligibility criteria to combat this systemic problem.ConclusionUnderstanding and incorporating the lived experiences of special populations should inform the foundation of any research study. The results of study enrollment will illustrate the significance of establishing a thoughtful recruitment plan for Black women research participants.
"Paradoxical” Cerebral Volume Changes in Anti‐Amyloid Immunotherapy Trials
Authors: Fox Nick C , Charil Arnaud , Sachdev Pallavi , Niu Hongmei , Irizarry Michael C. , Hersch Steven , Reyderman Larisa 
Published: January 2025

AbstractBackgroundLecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils. In two clinical study evaluations of lecanemab, Clarity AD (NCT03887455) and lecanemab phase 2 study (Study 201, NCT01767311), the drug showed statistically significant reduction in disease progression during 18 months of treatment relative to placebo. Anti‐amyloid immunotherapy can result in higher rates of “pseudo‐atrophy” (ie, whole brain volume loss or ventricular enlargement) relative to disease progression observed in placebo‐treated subjects. Herein, we evaluated volumetric MRI changes associated with lecanemab treatment to assess the neurological impact.MethodVolumetric MRI changes over the duration of the Clarity AD study was compared between placebo and lecanemab‐treated participants (n = 1311). In addition, the association between pseudo‐atrophy and longitudinal changes in tau and amyloid PET were evaluated regionally in a subset of participants in the Clarity AD PET sub‐study (n = 342). The association between volume changes and fluid biomarkers was also investigated.ResultVolumetric MRI results were inconsistent, with slowing of hippocampal atrophy but greater whole brain volume loss on lecanemab relative to placebo. Volume loss was not associated with worsening in any neurodegenerative biomarkers (plasma NfL, CSF NfL, and t‐tau) or clinical outcomes (CDR‐SB, ADAS‐Cog14, ADCS MCI‐ADL). With disease progression (placebo group), regional atrophy was associated with regional tau accumulation, but was not associated with regional amyloid accumulation. With lecanemab treatment, regional pseudo‐atrophy was associated with amyloid clearance and was not associated with regional tau levels or neuronal loss.ConclusionGreater volume loss may be related to reduced amyloid plaques and associated dystrophic neurites as well as inflammation/gliosis. Volume changes are not accompanied with worsening in any neurodegeneration biomarkers and likely do not represent neuronal loss.
Targeting Lrig1 on the surface of Treg cell in the periphery alleviates the symptoms of Alzheimer’s Disease in vivo
Authors: Lee Sang‐Kyou 
Published: January 2025

AbstractBackgroundNeurodegenerative diseases, including Alzheimer’s disease (AD), have been long thought to be independent of the peripheral immune system, but their pathogenesis status is functionally influenced by various T cell subsets in the periphery. Especially Treg cells are emerging as an important dynamic population in the brain, but the detailed immunological molecular and cellular processes are poorly characterizedMethodWe reported that the cell surface protein Lrig1 is enriched in Treg cells and is an essential regulator of the functions of Treg cells in vitro and in vivo. To evaluate the functional importance of Treg cells in AD pathogenesis, the modulating mAb specific to Lrig1 (GTC 310‐01) via intravenous injection route was administered into 5xFAD or 6xTg mice, the genetic mouse model of AD, and the various AD symptoms were investigated.ResultGTC 310‐01 significantly improved the cognitive ability of the AD mice, which were analyzed using three different methods (Y‐maze test, passive avoidance test and NOR test). And the level of Ab42 and tau aggregates in AD mice’s hippocampus and cortex areas were substantially reduced by GTC 310‐01 treatment. When the immunological and functional status of T cell subsets in the periphery of the treated animal was evaluated, GTC 310‐01 treatment inhibited the functions of Treg cell. It enhanced gIFN secretion, which increased the permeability of choroid plexus and other BBBs. Thereby, the monocytes in the periphery migrated into the brain and differentiated into active microglial cells and macrophages responsible for clearing the Ab42 and tau aggregates in the brain. After the initial pro‐inflammatory phase after GTC 310‐01 treatment, the number of Treg cells in the brain increased and created the anti‐inflammatory environment to resolve the inflammatory insults.ConclusionIn conclusion, functional modulation of Treg cells using GTC 310‐01 mAb specific to Lrig1 in the periphery could be a novel therapeutics for treating AD conditions without BBB penetration.
Conditionally Automated Vehicles and Cognitive Challenges: Assessing the Safety of Conditionally Automated Vehicles for Older Adults with Cognitive Challenges
Authors: Hajian Gelareh , Ye Bing , Haghzare Shabnam , Campos Jennifer L. , Mihailidis Alex 
Published: January 2025

AbstractBackgroundDriving cessation among people with cognitive impairments (e.g., Mild Cognitive Impairment; MCI) significantly impacts their independence and overall well‐being. Conditionally Automated Vehicles (CAVs) have emerged as a promising solution, potentially extending the safe driving years of at‐risk drivers. However, the safety of using CAVs for individuals with cognitive impairment remains underexplored. Individuals with Subjective Cognitive Decline (SCD; a potential early biomarker for later clinical decline), may also be at‐risk for difficulties managing complex behaviours such as driving. Therefore, this study aims to evaluate the driving performance of older adults with normal cognition, SCD, and MCI to assess their ability to safely transition between automated and manual driving modes using a simulated CAV.MethodPreliminary data from 17 cognitively healthy older adults, 2 with SCD, and 1 with MCI have been collected. Participants performed conditionally automated driving tasks using a high‐fidelity driving simulator under varied environmental conditions (daytime, nighttime), road geometries (straight, curved), with varying speed limits. A detailed analysis of driving safety, focusing on key metrics such as takeover reaction time and quality (lane centering, steering variation, and acceleration variability) was conducted. A performance baseline was established from the healthy group, segregating them into ‘safe’ and ‘less safe’ categories using a clustering method. The driving performance of participants with SCD and MCI was compared to the control group. By calculating Euclidean distances from cluster centroids we identified the most representative cluster for each individual.ResultThe clustering technique successfully distinguished between ‘safe’ and ‘less safe’ drivers within the cognitively healthy group, outperforming traditional manual methods. This baseline then enabled a comparative assessment for participants with MCI and SCD, demonstrating the ability of our approach to assess whether individuals with SCD and MCI were able to safely perform takeover requests.ConclusionThis study provides valuable insights into the safety of individuals with cognitive challenges to use CAVs. Our ongoing research aims to expand the participant sample, further explore the relationship between cognitive abilities and driving performance in CAVs, and ultimately develop a methodology to assess and predict the safety of using CAVs for older adults with cognitive impairment.
Analyses of Progressive Supranuclear Palsy Quality of Life in Frontotemporal Lobar Degeneration: Findings from the ALLFTD Consortium
Authors: Nelson Kevin M , Syrjanen Jeremy A. , Forsberg Leah K. , Heuer Hilary W. , Boxer Adam L. , Rosen Howard J. , Boeve Brad F. 
Published: January 2025

AbstractBackgroundThe Progressive Supranuclear Palsy Quality of Life (PSP‐QoL) scale is a 45‐question participant‐completed questionnaire used to evaluate physical and cognitive task difficulties. Participants enrolled in the ALLFTD research program are asked to complete this questionnaire annually during their study visits.MethodPSP‐QoL responses were analyzed at baseline visits. Our analysis focused on responses to the overall satisfaction of life (range 0‐100, with 0 being extremely dissatisfied and 100 being extremely satisfied) relative to disease severity (CDR®+NACC‐FTLD global scores) and as a function of clinical phenotypes. A Kruskal‐Wallis test was used to compare overall satisfaction ratings against CDR®+NACC‐FTLD global score.Result788 PSP‐QoL survey responses were analyzed (participant mean age 55.3 ±15 years, 50.5% female). Analysis included responses from 372 (47.2%) asymptomatic participants (CN; CDR®+NACC‐FTLD = 0), 140 prodromal (17.8%) CDR®+NACC‐FTLD = 0.5, 160 (20.3%) CDR®+NACC‐FTLD = 1, 106 (13.5%) CDR®+NACC‐FTLD 2, and 10 (1.3%) CDR®+NACC‐FTLD = 3. All symptomatic groups were similar in PSP‐QOL overall satisfaction of life rating: (mean overall satisfaction CDR®+NACC‐FTLD = 0.5: 74.5 (SD 22.5); CDR®+NACC‐FTLD = 1: 74.1 (SD 24.7) and CDR®+NACC‐FTLD = 2/3: 74.1 (SD 25.8)), but these differed from asymptomatic (cognitively normal): (mean 83.7, (SD 14.6); p<0.0001). Similarly, when including the CN group and symptomatic phenotype groups, a statistically significant difference in ratings was seen: mean overall satisfaction CN = 83.7 (SD 14.7), MCI = 78.3 (SD 16.6), PPA = 71.6 (SD 26.9), PSP = 66.3 (SD 28.2), bvFTD = 76.8 (SD 23.8), and other = 70.6 (SD 23.2). However, even after removing the CN group, a difference amongst symptomatic phenotypes remained (p = 0.036).ConclusionMean overall life satisfaction as measured by the PSP QoL questionnaire was lower in all symptomatic compared to clinically normal participants, regardless of disease severity or phenotype. Further longitudinal analyses are needed to better understand how clinical progression impacts overall satisfaction of life.