bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data‐driven analysis of 10,361 amyloid‐PET scans from the IDEAS study reveals two primary axes of variation
Authors: Giorgio Joseph , Mundada Nidhi S , Blazhenets Ganna , Mejía‐Perez Jhony Alejandro , Schonhaut Daniel R. , Carrillo Maria C. , Hanna Lucy , Gatsonis Constantine , March Andrew , Apgar Charles , Siegel Barry A. , Hillner Bruce E , Whitmer Rachel A. , Jagust William J. , Rabinovici Gil D. , Joie Renaud La 
Published: January 2025

AbstractBackgroundThe variability in the regional distribution of Aβ‐PET signal and its relation to clinical features is debated. We used data‐driven approaches to uncover heterogeneity in cortical Aβ‐PET signal from a large representative sample collected through the IDEAS study.MethodsWe analysed cross‐sectional Aβ‐PET collected from 10,361 patients with MCI or mild dementia scanned in 295 PET facilities using one of the 3 FDA‐approved tracers. Central image processing resulted in template‐space SUVR images (reference: whole cerebellum) and centiloid (CL) values. Spatial independent component analysis was used to decompose SUVR volumes into 40 independent components. After excluding noise components, participants’ scores were extracted for each of the remaining 11 grey matter (GM) components describing cortical and subcortical binding. K‐means clustering was used on these GM component scores to assign each participant to different Aβ‐PET clusters based on GM binding (Figure 1).ResultsThree informative clusters of PET binding were estimated. Cluster 1: Aβ‐(n=4729, CL mean=2±23) with low GM binding, and two Aβ+ clusters; Cluster 2(n=2484, CL mean=76±34) and Cluster 3(n=3148, CL mean=86±32). Subtracting average SUVR of Clusters 2 and 3 showed they differed along a posterior‐anterior gradient with Cluster 2 showing an occipital predominant pattern. Principal component analysis conducted on the GM scores confirmed two dominant axes of variation separated the clusters, a Aβ‐ to Aβ+ axis and, an anterior‐posterior axis (Figure 2). Statistically significant but weak differences were observed between the two Aβ+ Clusters (2 vs. 3); Visual Read (positive: 95% vs. 92%); Clinical Stage (dementia: 47% vs. 41%); Age (76.9±6.4 vs. 75.9±6.2), however, most clinical variables showed no differences (Figure 3a). 48 ADNI participants with Aβ‐PET and post‐mortem neuropathology data (11 Female, Age mean=79.7±7.4, PET‐Death mean=2.3±1.7years; Aβ‐CL mean=71.2±55.5; APOE4(0/1/2)=22/21/5; Diagnosis(CN/MCI/AD)=6/8/32) were applied to the model fit on IDEAS data. Qualitatively, no differences in neuropathology were observed between the two Aβ+ Clusters (Figure 3b).ConclusionData driven classification of Aβ‐PET reveals two primary axes reflecting Aβ load and anterior‐posterior binding, with the later not clearly related to clinical or pathological variation. Future work will apply new data to this model and investigate if this spatial variation in Aβ‐PET is related to longitudinal changes in pathology.
Assessing Alzheimer’s Disease and Related Dementia risk in American Samoa using the Talanoa research framework
Authors: Tofaeono Vaatausili 
Published: January 2025

AbstractBackgroundThe American Samoa population has high prevalence for Alzheimer’s Disease and Related Dementia (ADRD) risk factors (e.g. tobacco use, obesity, hypertension, and diabetes), however ADRD risk has not been defined or assessed. The Puipui Malu Manutu (PMM) Study (RF1AG075904) is accomplishing this by assessing knowledge, health literacy, readiness, and resiliency and vulnerability factors using culturally adapted instruments in a sample of 1098 adults aged 50 and above. Additionally, Indigenous populations have unique worldview perspectives and epistemologies that have not been widely accepted in mainstream academia. Therefore, we decolonized Westernized research approaches by incorporating the Talanoa framework into the discussion and decision making of the ADRD risk profile each participant. The Talanoa framework is rooted in Samoan cultural norms to eliminate power, building trusting relationships, and is conducted face‐to‐face in individual or group settings. Talanoa is culturally grounded in four unique perspectives: alofa (love between the participant and researcher), fa’aaloalo (respect), tautau (service to the community), and malamalama (knowledge gained for the community).MethodWe established a Consensus Group comprised of the PMM Multiple Principal Investigators, a Samoan Nurse Practitioner, a Samoan clinical Psychologies, and a Samoan Medical Doctor to define the ADRD risk The Talanoa framework guided the Consensus Group, with the PMM study staff and ADRD risk definition, to openly discuss and decide ADRD risk in participants in a culturally safe manner.ResultFirst, a definition of ADRD risk using cut offs and ranges of subjective and objective data gathered by various cognitive assessment tools was created. Second, preliminary results of 26 participants have shown 61.5% are at high risk. Diet and lack of physical activity are contributing risk factors. Further results will be made available at the time of presentation for the AAIC.ConclusionDetermining ADRD risk will assist public health programs to prioritize risk factors in education and awareness efforts. Decolonizing concepts and paradigms of ADRD research is a first step to ensuring Indigenous values are recognized to achieve a culturally safe environment and build trust for research in our community.
Modifiable risk factors for age‐at‐onset of Alzheimer’s disease through genetic determinants
Authors: Li Yi‐Ju , La Jong ok , Fan Qiao , Martin Eden R. 
Published: January 2025

AbstractBackgroundAge and genetic predisposition are well‐known, non‐modifiable risk factors for Alzheimer’s disease (AD). Epidemiological studies have linked several modifiable risk factors to AD, but less is known about their influence on the age‐at‐onset (AAO) of AD. With an increase of genome‐wide association studies (GWASs) and advanced genetic analysis developed, we sought to identify modifiable risk factors for AAO of AD and evaluate their causal effects.MethodFor AAO of AD, we utilized pooled genome‐wide imputed genotype data from 9,219 AD cases and 10,345 controls from 20 cohorts of the Alzheimer Disease Genetics Consortium (ADGC) and our own GWAS summary statistics for AAO of AD (Li et al. 2023). Thirty‐eight exposure factors related to comorbidity, lifestyle, and psychosocial risk factors were screened. The GWAS summary statistics of these exposures were from results released by individual publications or IEU OpenGWAS projects. PRSice‐2 was used to construct polygenic scores (PGS) for each exposure in ADGC subjects. Linear mixed models (LMM) were used to test for association of the exposure‐PGS with AAO, adjusting for sex, APOE‐E4, 10 PCs, and a random intercept by cohort. Exposures meeting p< 0.005 were considered significant risk factors, and they were then evaluated for the causal effect on AAO of AD by a two‐sample Mendelian Randomization (MR) using GWAS summary statistics of exposures (exposure‐GWAS) and AAO of AD. Instrumental variables were selected based on variants meeting p< 5×10−8 and p<5×10−6, respectively, from the exposure‐GWAS. We evaluated causal effects by the MR inverse variance weighted method and then followed by sensitivity analyses using weighted median and MR‐Egger.ResultSeven genetically inferred exposures via PGS were significantly associated with AAO of AD (p < 0.005), including higher education attainment and relative fat intake delaying AD onset and type 2 diabetes, cardiovascular disease (CVD), hypertension, and smoking leading to earlier AAO. MR analysis showed lower education, T2D, CVD, and hypertension with significant causal effects on shifting AAO earlier (p<0.007).ConclusionThe seven modifiable risk factors, particularly, the four causal factors for AAO of AD, will facilitate the early intervention and provide targets to delay AD onset.
Associations of positive and negative social connections with brain health in UK Biobank data
Authors: Samtani Suraj , Mahalingam Gowsaly , Wen Wei , Brodaty Henry , Sachdev Perminder S. 
Published: January 2025

AbstractBackgroundSocial connections are linked to brain health. Studies to date have ignored negative social connections and the association between social connections and white matter health. We explored the relationship between positive and negative social connections and brain imaging including white matter health. We hypothesized that positive and negative social connections would be related to better and worse brain health, respectively.MethodWe analysed UK Biobank data from 5704 adults aged 40+ (Mage = 54.12, 51.19%) who had brain scans at waves 2 and 3. We examined baseline social connections which were positive (household size, friend/family visits, community group engagement, having a confidante) and negative (loneliness, belittling or violence in romantic relationships). Outcome variables were total grey and white matter, amygdala and hippocampus volumes, white matter integrity and hyperintensities, and peak width of skeletonized mean diffusivity (PSMD; a marker of microstructural white matter changes) at waves 2 and 3. We ran linear mixed models controlling for age, sex and scanner (partially adjusted) and additionally for intracranial volumes (for brain volumes), education, physical activity, BMI, depression, hearing loss, alcohol use, smoking, hypertension, CVD, and air pollution (fully adjusted).ResultIn fully adjusted models, having a larger social network was associated with less decline from wave 2 to 3 in total grey matter (B = 671.61, 95%CI: 226.96,1,115.85), white matter (B = 511.72, 95%CI: 52.33,971.82), and right hippocampus volumes (B = 8.99, 95%CI: 1.44,16.54). Living with more people (B = 0.00049, 95%CI: 0.00021, 0.00077) and having a larger network size (B = 0.00035, 95%CI: 0.00024, 0.00045) were associated with less decline in white matter integrity. Experiencing romantic partner violence was associated with a greater increase in PSMD (B = 0.000079, 95%CI: 0.000016, 0.00014). Loneliness was not associated with brain health changes.ConclusionIn a longitudinal sample of adults aged 40+, having a larger social network was associated with better brain health, including less decline in hippocampal volumes and white matter integrity. Experiencing romantic partner violence was associated with microstructural white matter changes. Our results highlight the need to screen for positive and negative social connections in adults in mid and late life to help maintain good brain health.
Association of basal forebrain atrophy with cognitive decline in early Alzheimer’s disease
Authors: Xia Ying , Dore Vincent , Fripp Jurgen , Bourgeat Pierrick , Laws Simon M. , Fowler Christopher J , Rainey‐Smith Stephanie R , Martins Ralph N , Rowe Christopher C. , Masters Colin L , Coulson Elizabeth J , Maruff Paul 
Published: January 2025

AbstractBackgroundIn early Alzheimer’s disease (AD), amyloid‐β (Aβ) accumulation is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aβ‐related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationships between Aβ burden, BF atrophy, and the decline in memory and attention in older individuals without dementia.MethodThe 476 older adults (72.6 ± 5.9 years old, 55.0% female) from the Australian Imaging, Biomarker and Lifestyle (AIBL) study were included, who underwent Aβ‐PET imaging at baseline and repeated MRI and cognitive assessments over a period up to 13 years. At baseline, participants were classified based on their clinical dementia stage and Aβ status, which were cognitively unimpaired (CU) Aβ−, CU Aβ+, and mild cognitive impairment (MCI) Aβ+. Linear mixed‐effects models assessed atrophy in BF subregions (Ch4p – posterior segment of the nucleus basalis of Meynert; Ch1/Ch2 ‐ medial septal nucleus and vertical limb of the diagonal band of Broca) and hippocampus as well as changes in their AIBL memory and attention composite scores. Associations between baseline Aβ burden, brain atrophy, and cognitive decline were evaluated and explored using mediation analyses.ResultCompared to the CU Aβ− group, CU Aβ+ and MCI Aβ+ adults both showed faster decline in BF and hippocampal volumes as well as in memory and attention (all p < 0.001). While rates of atrophy across all regions correlated with cognitive decline, baseline Ch4p volume was associated moderately with rates of memory and attention decline (p < 0.001, η2 = 0.046 and 0.023). Furthermore, single‐mediator models demonstrated that rates of atrophy in all regions of interest significantly influenced the effects of Aβ burden on memory and attention decline (Table 1). When considering all three mediators simultaneously, hippocampal atrophy primarily mediated the effects of Aβ burden on memory decline (Figure 1A), whereas Ch4p and hippocampal atrophy play unique mediating roles in Aβ‐related attention decline (Figure 1B).ConclusionThese findings underscore the important role of early volume loss in the BF, especially in Ch4p, in the complex pathway linking Aβ to cognitive impairment in early AD.
Sex differences in the prevalence of mild cognitive impairment and dementia, and their risk factors, in Bengaluru
Authors: Venugopal Aparna Lalana 
Published: January 2025

AbstractBackgroundThe burden of dementia is expected to increase owing to the rapidly increasing number of aged populations across the world. It is widely reported that risk of developing dementia is high in women compared to men and the contributing factors resulting these discrepancies are not well understood. In this context, the goal of the current study was to assess whether the prevalence of mild cognitive impairment (MCI) and dementia differs by sex in urban Bengaluru and whether risk factors for MCI and dementia differ by sex.MethodA community‐based, cross‐sectional study was conducted in urban Bengaluru between January 2021 and December 2021. The study team performed household enumeration to identify individuals who were ≥ 60 years old. Neurologic, neuropsychological, and functionality tests and a risk profile questionnaire were administered to all participants. The assessment tools included Addenbrooke’s Cognitive Examination (ACE‐III; Mekala et al., 2020; Mathuranath et al., 2007), Clinical Dementia Rating Scale (CDR; Morris, 1991), and Instrumental Activities of Daily Living‐Elderly (IADL‐E; Mathuranath et al., 2005). The risk profile questionnaire included screening for common cardiovascular risk factors such as hypertension, heart disease, diabetes and stroke. Participants were categorized as having no cognitive impairment (NCI), MCI, or dementia. MCI was diagnosed based on Petersen’s criteria (2004) and dementia was diagnosed based on DSM‐IV criteria (1994).ResultOf the 1,234 participants, 665 (53.9%) were female and 569 were male (46.1%). Males were slightly older (mean (SD): 72.0 (8.68) vs. 70.5 (7.79) years, p = 0.001) and had more years of education (mean (SD): 13.3 (4.65) vs. 9.9 (5.75), p<0.001). Of the 1,234 participants, 80 had MCI (6.5%) and 24 (1.9%) had dementia. More males than females had MCI (7.9% vs. 5.3%, p = 0.06). In contrast, males were less likely to be diagnosed with dementia (1.1% vs. 2.7%, p = 0.04). Males had a higher prevalence of heart disease, whereas females had a higher prevalence of hypertension.ConclusionThe prevalence of MCI and dementia differs by sex in Bengaluru, as does the prevalence of vascular risk factors.
Exploring the Cognitive Health of LGBTQIA+ Older Adults from The Stonewall Generations Study
Authors: Flatt Jason D. , Klenczar Brittany , Uddin Jalal , OHala Max , Benson Sarah , Rosenblatt Andrew , Pudumjee Shehroo 
Published: January 2025

AbstractBackgroundOver 2.5 million LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, asexual or another sexual and/or gender minority identity) adults in the U.S. are aged 50 or older. Past studies have found that LGBTQIA+ older adults report worsening memory and thinking skills more often than non‐LGBTQIA+ older adults. The purpose of this study was to explore the risk and protective factors associated with the cognitive health of LGBTQIA+ older adults.MethodsWe utilized tailored recruitment and engagement strategies to recruit a community‐based sample (n = 67) of racial/ethnically diverse LGBTQIA+ older adults aged 50+ from the U.S. To examine cognitive health, we used the Telephone Interview for Cognitive Status (TICS), with scores ranging from 0‐41. Descriptive statistics were used to summarize demographic characteristics and TICS scores, and we used bivariate analyses to explore potential risk and protective factors associated with cognitive health.ResultsMean age was 64.5 with range of 50 to 87 years. About 6% had high school degree or less and 23% reported an annual income of $30,000 or less. In terms of race/ethnicity, 85% identified as White, 10% Black, 6% American Indian/Alaska Native, and 10% Hispanic/Latino. For gender identity, 36% identified as women, 39% men, 18% transgender men/women, 12% another gender identity, and one person identified as intersex. For sexual orientation, 43% identified as gay, 36% lesbian, 12% bisexual, 10% queer, 9% heterosexual, 8% asexual, and 5% another identity. TICS scores ranged from 16 to 41 with a mean of 28.05 (SD = 4.92), with 16% falling into the mildly impaired and 9% in the moderately‐to‐severely impaired ranges. A lower TICS score was associated with lower education, functional impairment, past LGBTQIA+ related discrimination (minority stress), and PTSD‐related symptoms (p‐values <0.05).ConclusionsOur current findings highlight the need for additional research on risk and protective factors for the cognitive health of diverse LGBTQIA+ older adults. Understanding the risk of cognitive impairment among LGBTQIA+ older adults is critical to defining the burden of Alzheimer’s disease and developing targeted prevention strategies for these understudied populations.
Family history and amyloid PET in white, Black, and Hispanic/Latino, cognitively normal individuals
Authors: Glenn Phelan , Mooney Katelyn Elizabeth , Kadiri Ose , Robinson Talia L , Amariglio Rebecca E , Sperling Reisa A , Deters Kacie 
Published: January 2025

AbstractBackgroundFamily history (FH) of AD increases risk for sporadic AD, and has been associated with increased amyloid accumulation. Most of these studies were done in non‐Hispanic white groups, limiting the generalizability of these findings. The goal of this study was to determine if FH was associated with levels of amyloid in White, Black, and Hispanic/Latino participants.MethodsThis study included cognitively normal individuals screening for the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s (A4) cohort whom self‐identified as Non‐Hispanic/Latino Black (NHB; N=145), Non‐Hispanic white (NHW; N=3766), or Hispanic/Latino white (HL; N=107). The effect of FH (father, mother or both, vs none) on amyloid PET SUVr was assessed using linear regression analysis within each ethnic and racialized group. Age and sex were used as covariates. This analysis was repeated adding APOE e4 allele as a moderator.ResultsNHB participants were more likely to be female (71.7%), had the lowest FH rate (56.6%), and were less likely to be amyloid positive (20%) compared to HL participants (female=64.5%; FH=62.6%; amyloid+=27.1%) and NHW participants (female=59.7%; FH=66.2%; amyloid+=30.2%). Having a FH of AD was associated with higher levels of amyloid SUVr (β=0.028, p=2e‐05) in NHW participants only (Table). This effect became non‐significant when APOE e4 was included in the model.ConclusionsFH was associated with higher levels of amyloid SUVr in White participants only, but not in the presence of APOE e4. For Black and Hispanic participants, FH was not associated with levels of amyloid. These findings support previous findings in which risk factors for AD are not shared equally across different ethnic and racialized groups.
Longitudinal Trajectories of Blood‐based biomarkers for Alzheimer’s Disease in Subjective Cognitive Decline; the SCIENCe project
Authors: Trieu Calvin , van Harten Argonde C. , van Leeuwenstijn Mardou S. S. A. , Schlüter Lisa‐Marie , Verberk Inge M.W. , Boonkamp Lynn , Aladdin Azzam , Teunissen Charlotte , van der Flier Wiesje M. 
Published: January 2025

AbstractBackgroundBlood‐based biomarkers are increasingly able to identify Alzheimer’s Disease pathology in the preclinical stages of the disease. These biomarkers hold promise to study development and progression of the disease. Our aim is to investigate the longitudinal trajectories of Aβ42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) in individuals with subjective cognitive decline (SCD).MethodFrom the SCIENCe cohort, we selected 298 individuals with SCD (age: 61.7±8.1), of whom 80 were amyloid positive (A+; 65.2±7.2) and 218 were amyloid negative (A‐; 60.3±8.0). Amyloid status was assessed using amyloid PET scans or CSF AD biomarkers. Participants underwent annual assessments to evaluate clinical progression to MCI or AD dementia (conversion: n=33). Plasma biomarkers, including Aβ42/40 ratio, GFAP, and NfL (pTau217‐pending analysis), were assessed approximately every two years with a mean follow up of 5.3±2.7 years on the SiMoA platform (Quanterix; total sample number: n=819). We used linear mixed models to examine associations between amyloid status and biomarker changes over time, with terms for amyloid status, time, and their interactions. Next, we examined associations between progression to MCI/dementia and biomarker changes over time, with terms for conversion, time, and their interactions.ResultAβ42/40 was lower in SCD A+ compared to SCD A‐ at baseline (p<0.001), but did not change over time in either group. GFAP and NfL were higher at baseline in SCD A+ (p<0.001; p=0.001). Both increased over time, but only NfL showed a more pronounced increase in SCD A+ compared to SCD A‐ (p=0.006). Aβ42/40 was lower in converters than non‐converters at baseline (p<0.001), with no longitudinal differences. NfL and GFAP were higher at baseline in converters (p<0.001; p=0.001), and both displayed a trend toward greater increase over time in converters compared to non‐converters (p=0.059; p=0.095).ConclusionOnly NfL had a more pronounced increase over time in SCD A+ compared to SCD A‐, whereas all biomarkers differed between the groups at baseline. This suggests that Aβ42/40 may have already reached a plateau in SCD A+, while the neurodegeneration marker NfL continues to increase beyond what can be attributed solely to the aging process after the initial SCD diagnosis.