bluuebunny/crossref_metadata_2025_split huggingface dataset:
p‐tau217 in a large Peruvian cohort phenotyped for Alzheimer’s Disease
Authors: Pandey Neetesh , Honig Lawrence S. , Reyes‐Dumeyer Dolly , Cieza Basilio , Montesinos Rosa , Cespedes Jennifer , Soto‐Añari Marcio F. , Custodio Nilton , Tosto Giuseppe 
Published: January 2025

AbstractBackgroundBlood‐based Alzheimer's disease (AD) biomarkers have been increasingly employed for diagnostic and prognostic purposes, thanks to high diagnostic accuracy in distinguishing AD from healthy controls or other dementia types. p‐tau217 exhibits stronger associations with AD hallmarks in CSF and brain, compared to other p‐tau isoforms. Furthermore, the majority of these studies have been conducted in non‐Hispanic Whites, limiting our understanding of the performances and utility of these biomarkers across ethnicities.MethodWe employed a cohort of Peruvians from the GAPP study, a recently‐established cohort of Peruvian mestizos from Lima and indigenous groups from Southern Peru (Aymaras and Quechuas). We generated p‐tau ALZPATH217 in 561 samples, and tested the association between p‐tau217 and clinical diagnosis (healthy controls n=359 vs. AD n=92) using regression models adjusting for sex, age, education and study site. We also explored the biomarkers level in MCI (n=100). The receiver operating characteristics area under the curve (ROC‐AUC) was used to evaluate the biomarker’s classification performances.Resultp‐tau217 was significantly associated with AD (higher quartile vs. lower quartile: OR=6.49 95%CI 2.91‐14.90) while it did not differ between controls and MCI (p=0.33; Figure 1). p‐tau217 levels were also increasingly higher in participants carrying one or two APOE‐e4 alleles (ANOVA p‐value<0.001). When classification accuracy was considered, the resulting ROC area for p‐tau217 was 74%.ConclusionTo our knowledge, this is the largest study conducted in a Hispanic cohort phenotyped for AD with available p‐tau217. We confirmed the robust performances of the blood biomarker in a non‐White population; studies on Hispanic individuals with clinical AD diagnosis reported AUC as low as 52% vs. our robust finding of 74%. Previous investigations have mostly focused on highly selected cohorts with established AD‐endophenotypes (CSF, autopsies, PET etc.), while data on population cohorts with clinical assessment are currently lacking, especially in minoritized groups.
Attenuated neural activity in processing decision‐making feedback in uncertain conditions in patients with mild cognitive impairment
Authors: Zhang Mang , Zhang Ying , wang luchun , Zheng Yaonan , Li Huizi , Xie Yuhan , Lv Xiaozhen , Yu Xin , Wang Huali 
Published: January 2025

AbstractBackgroundIndividuals with mild cognitive impairment (MCI) have decreased cognitive function, which makes them prone to making inappropriate decisions in complex and uncertain situations. However, there is currently no study being undertaken to investigate the potential neural mechanisms for processing decision‐making feedback in MCI patients. The present study aimed to explore the potential neural correlates during feedback evaluation during decision‐making under risk and ambiguity in MCI.MethodNineteen individuals with MCI and twenty age‐matched HCs were enrolled. Decision‐making performance under risk and ambiguity was examined with the modified game of dice task (GDT) and an Iowa gambling task (IGT). Using task‐related EEG data, reward positivity (RewP) and feedback P3 (fb‐P3) were used to characterize participants’ motivation and allocation of cognitive resources. Also, response time and event‐related oscillation (ERO) was used to evaluate information processing speed, and the potent of post‐feedback information integration and behavioral modulation.ResultMCI patients had lower RewP (p = 0.022) and fb‐P3 (p = 0.045) amplitudes in the GDT than HCs. Moreover, the amount and valence of feedback modulated the RewP (p = 0.008; p = 0.017) and fb‐P3 (p < 0.001; p < 0.001). In the IGT, in addition to the significantly reduced fb‐P3 observed in MCI patients (p = 0.010), the amount and valence of feedback modulated the RewP (p = 0.002; p = 0.020). Furthermore, MCI patients took longer to make decisions (t = 2.15, p = 0.041). The ERO analysis revealed that delta power was reduced in MCI (GDT: p = 0.045; p = 0.011).ConclusionThe findings suggest that, during feedback evaluation when making risky and ambiguous decisions, motivation, allocation of cognitive resources, information processing and neuronal excitability were attenuated in MCI. It implies that neural activity related to decision making was compromised in MCI.
Association between Stress and White Matter Hyperintensity Volume in Diverse Populations: A HABS‐HD Study
Authors: Trammell Antoine R , Lah James J. , Parker Monica W , Goldstein Felicia , Hales Chadwick M , Davis Crystal P , Dorbin Cornelya D , Saleh Sabria , Murphy‐Tchivzhel Elizabeth , Rose Alecia Michella , Osborne Amber , Ahmad Adiva , Al‐Amin Jahmila , O'Bryant Sid E. 
Published: January 2025

AbstractBackgroundOlder African American (AA) and Hispanic American (HA) adults have a higher risk for Alzheimer’s disease and related dementias (ADRD) than older non‐Hispanic white (NHW) adults. Adverse experiences like stress and discrimination may contribute to the higher vascular disease burden observed in AA and HA persons. Cerebrovascular disease reflected by white matter hyperintensity (WMH) lesions on magnetic resonance imaging (MRI) may affect ADRD risk in older AA and HA adults. As stress may influence vascular disease and thus ADRD risk, this study explores associations between stress and WMH burden in a diverse cohort.MethodWe analyzed stress scores and WMH volume data from self‐reported NHW, AA, and HA participants in the Health and Aging Brain Study: Health Disparities. Data obtained at the baseline study visit includes the Clinical Dementia Rating (CDR), Chronic Stress Scale (CSS), Everyday Discrimination Scale (EDS), Penn State Worry Questionnaire (PSWQ), Geriatric Depression Scale (GDS), and MRI brain scans. With this data, we used global CDR scores (normal=0, impaired≥0.5) and race to create race/cognitive groups (white/normal, white/impaired, AA/normal, AA/impaired, HA/normal, HA/impaired). We compared baseline characteristics, stress and GDS scores, and WMH burden in the groups with ANOVA and chi‐square. Next, we performed linear regression adjusted for age, education, and sex to test associations between stress scores and WMH burden.ResultData from 3,035 participants was analyzed (mean age: 65.2; female: 62.3%; impaired: 20.1%). Compared to the NHW and HA groups, AA participants had higher CSS scores (NHW: 7.44, HA: 7.1, AA: 8.42, p=.0003), EDS scores (NHW: 5.59, HA: 6.2, AA: 9.47, p<.0001), and WMH volume (NHW: 4.16, HA: 3.18, AA: 18.4, p<.0001). The HA group had higher GDS scores (NHW: 4.86, HA: 6.71, AA: 5.61, p<.0001). Regression showed that higher EDS scores were associated with higher WMH volume in the AA/impaired (β=3.48, p=.02) and HA/impaired (β=.27, p=.002) groups.ConclusionOur results suggest that higher discrimination scores may be linked to higher WMH volume in older AA and HA adults with cognitive impairment. As vascular disease may contribute to their higher ADRD risk, further study of stress, microvascular brain disease, and ADRD risk is needed.
Evaluation of Type 2 diabetes mellitus, Alzheimer's disease, and olfactory dysfunction relationships
Authors: Gutierrez‐Malacara Andres‐Ivan , Gomez‐Virgilio Laura , Silva‐Lucero Maria‐del‐Carmen , Lora‐Marin Obed‐Ricardo , Cardenas‐Aguayo Maria‐del‐Carmen 
Published: January 2025

AbstractBackgroundType 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and insulin resistance. Historically, it is linked to greater cognitive decline and risk of Alzheimer's dementia. Although deregulations in the insulin signaling pathway have been identified, further investigation is needed. Diabetic patients over 60 years of age, in addition to facing cognitive risks, show olfactory deficits like AD. Neuronal precursors in the olfactory epithelium (hONE NPCs) offer a valuable model for studying the connection between T2DM and AD. Nasal exfoliates and plasma samples were collected from diabetic patients with or without cognitive decline and healthy controls. Assessment of biomarkers, the insulin signaling pathway and the posttranslational modification OGlacNac were done.MethodWe divided our study groups into apparently healthy subjects (AHS), subjects with cognitive impairment (SMCI), subjects with T2DM without cognitive impairment (ST2DM), and subjects with type 2 diabetes with cognitive impairment (ST2DM‐SMCI). We obtained hONE NPCs cell cultures from the volunteers through a non‐invasive nose exfoliate, those cells were characterized by WB and ICC. We obtained blood samples for the detection of HbA1c and AD biomarkers. We performed MoCA Test, medical interview and an olfactory test for each volunteer.ResultWe isolated and cultured human hONE NPCs from a Mexican cohort of 60 individuals over 50 years old diabetic and nondiabetic with or without MCI. We collected clinical data, performed MoCA test, and an olfactory test, collected blood samples, and evaluated glucose levels to search for possible correlations among these variables.Our results showed increased expression of IRS‐1 between control subjects (AHI) vs subjects with SMCI+ST2DM and a significant increase in OGlacNac of the IRS‐1 receptor between the control (AHI) group versus the SMCI and SMCI+ST2DM.ConclusionWe obtained a positive correlation between the olfactory and MoCA test and a non‐significant trend of negative correlation between the MoCA score and the HbA1c. A significant increase in IRS‐1 expression between AHI vs. subjects with SMCI+ST2DM was detected, and a significant increase in OGlacNac of the IRS‐1 receptor between the AHI versus the SMCI and SMCI+ST2DM. Thus, the hONE NPC cells constitute an accessible model to study the relationship between T2DM, AD, and olfactory dysfunction.
The association between measures of subjective cognitive decline and Alzheimer’s disease plasma biomarkers in cognitively normal individuals
Authors: Bernard Mark A , Boutajangout Allal , Debure Ludovic , Briggs Anthony Q , Vedvyas Alok , Marsh Karyn , Osorio Ricardo , Shao Yongzhao , Betensky Rebecca A , Wisniewski Thomas , Masurkar Arjun V. 
Published: January 2025

AbstractBackgroundSubjective cognitive decline (SCD) is thought to be a preclinical stage of Alzheimer’s disease (AD), associated with faster disease progression and with imaging and cerebrospinal fluid biomarkers. However, it is unclear whether and how the degree of SCD correlates with plasma biomarkers. To address this, we investigated the association of plasma biomarkers of AD with established validated measures of SCD.MethodThe study included 122 cognitively normal older adults (age ≥60 years, 72 non‐Hispanic White, 50 Black/African American) evaluated at the NYU Alzheimer’s Disease Research Center. Participants underwent a comprehensive battery of psychometric tests according to NACC UDS 3 standards. Degree of SCD was quantified using the Brief Cognitive Rating Scale (BCRS) and Cognitive Change Index (CCI). Plasma levels of Aβ40, Aβ42, total tau, ptau‐181, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were measured using ultra‐sensitive, single‐molecule array (SIMOA) technology. Secondarily‐calculated measures included Aβ42/Aβ40, tau/Aβ42, and ptau‐181/Aβ42 ratios. Linear regression (models unadjusted and adjusted for age) was used to evaluate the strength of association between psychometric measures and plasma biomarkers.ResultIn unadjusted linear regression, both higher BCRS (β = .0420, r2 = .1135, F = 7.682, p = .0074) and CCI (β = .0059, r2 = .1636, F = 11.732, p = .0011), each indicative of a higher degree of SCD in this cognitively normal population, were found to be predictive of higher plasma tau/Aβ42 ratio. In age‐adjusted models, higher BCRS (β = .0368 p = .0087) and CCI (β = .0066, p = .0019) remained significantly predictive of higher plasma tau/Aβ42, with higher CCI additionally found to be predictive of lower plasma Aβ40 (β = ‐1.659, p = .0210). Statistically significant associations of SCD measures were not observed with Aβ42/Aβ40, ptau‐181/Aβ42, NfL, or GFAP.ConclusionValidated measures of SCD significantly associated with tau/Aβ42 ratio and Aβ40 levels in plasma, but do not show significant association with other biomarkers. This suggests that the degree of SCD in cognitively normal individuals could potentially signify early aspects of neurodegeneration that are distinct from other pathways. This relationship warrants further study in longitudinal studies of SCD cohorts.
Gradient Analysis for the Study of Alzheimer’s Disease
Authors: Camargo Aldo , Wang Ze 
Published: January 2025

AbstractBackgroundDys‐connectivity has been repeatedly shown in Alzheimer’s Disease (AD) but the change of connectivity gradient across the brain is under‐studied. In this study, we used resting state fMRI (rsfMRI) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to build a whole brain functional connectivity matrix. We then compared the major connectivity gradients decomposed from the connectivity matrix from normal controls (NC), mild cognitive impairment (MCI), and AD patients.Method30 NC, 11 MCI, and 40 AD were included in the analysis. Data preprocessing including motion correction, slice time correction, normalization, and artifact component removal, was performed using SPM12 and FSL. Mean rsfMRI time series was extracted from each of the 400 segments in the Schaefer atlas. A 400×400 functional connectivity matrix was calculated for each subject. Connectivity gradients were subsequently calculated using the BrainSpace toolbox. A mean connectivity matrix and its gradients were calculated for NC, MCI, and AD separately. Individual subject’s gradients were then aligned to those population level ones and compared across groups through two‐sample t‐test. Our analysis limits to the first three gradients as the corresponding eigenvalues explained >39% of the original matrix variance. Multiple comparison correction was performed using Bonferroni correction.ResultFig. 1 shows the first gradient map for each sub‐group. The gradients were lowest in occipital cortex, and increased in the motor network and temporal cortex, and then gradually went down toward prefrontal cortex. Fig. 2‐4 are the statistical comparison results. The first gradient map showed the largest cross‐sectional changes. Compared to NC, MCI had reduced gradients in occipital cortex, motor cortex, and temporal cortex. Gradients in occipital cortex and posterior part of temporal cortex further reduced in AD compared to MCI, and AD patient showed gradient reduction in prefrontal cortex.ConclusionWe found consistent functional connectivity gradient reduction in the AD continuum in occipital cortex and temporal cortex, suggesting a common pathway of AD‐related impairment to functional connectivity. Gradient reduction was identified in motor cortex in MCI compared to NC and was found in prefrontal cortex in AD compared to MCI, likely related to the escalated cognitive control and working memory decline in AD.
The relationship between right and left hemisphere regional tau and proper name recall from Logical Memory story recall
Authors: Olson Hayley A , Langhough Rebecca E. , Bruno Davide , Hermann Bruce P , Basche Kristin E , Miess Beryl , Kaminski Noelle , Mandel Olivia , Christian Bradley T. , Johnson Sterling C. , Betthauser Tobey J. , Mueller Kimberly D 
Published: January 2025

AbstractBackgroundSensitive screening for early Alzheimer’s disease (AD)‐related cognitive decline are needed. Prior research links high beta‐amyloid (Aß) levels to reduced proper name (PN) retrieval in individuals without cognitive impairment. We examined whether language‐related regional tau from PET associated with Logical Memory (LM) proper name recall, accounting for LM covariates.MethodParticipants included n=396 from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) with Logical Memory (LM) story recall, amyloid PET ([11C]Pittsburgh Compound‐B, PiB), and [18F]‐MK‐6240 tau PET; all were unimpaired at LM baseline. Outcomes included z‐scores for LM delayed total score (“total‐LM”) and PN delayed LM subscore (“PN‐score”) from the visit most adjacent to PET‐tau imaging. Amyloid PET burden (visit adjacent to tau PET) was summarized as a global PIB DVR (PiB index, cerebellum GM reference region, graphical analysis). Left and right volume‐weighted MK‐6240 SUVR (inferior cerebellar GM reference regions) averages were calculated for regions previously associated with PN retrieval, including temporal pole, anterior temporal gyrus, anterior middle gyrus, and anterior inferior gyrus (“PN‐regional‐tau‐network”). We compared results from two ANCOVA models (L vs. R regional network as predictors) for each outcome (PN‐score, total‐LM). Covariates in each model included age at LM, sex, WRAT‐3 reading, and PiB index (to replicate prior analyses). To account for unexplained variance from global tau in entorhinal cortex, residuals from a regression of global tau on PN‐regional‐tau‐network were also included.ResultTable 1 displays demographics overall and by tau status (T+/T‐). Overall mean age was 67 (SD=7); n(%)=80(20.2%) were T+. Left and right PN‐regional‐tau‐networks were significant predictors of PN‐score (ß=‐.06, R2=.190, ß=‐.08, R2=.192, respectively) and total‐LM (ß=‐.08, R2=.201, ß=‐.09, R2=.202, respectively; Table 2, Figure 1). In sensitivity analyses removing n=23 participants with MCI or dementia, Right‐hemisphere PN‐regional‐tau (but not left) was still a significant predictor of PN‐score (ß=‐.06, R2=.190), and L and R PN‐regional‐tau significantly predicted total‐LM (ß=‐.06, R2=.134, ß=‐.07, R2=.136, respectively).ConclusionLogical Memory story recall measures may be sensitive to tau burden in specific language regions; right hemisphere tau in the PN‐regional‐network may be particularly sensitive to early tau burden. Future directions include characterizing regional PET patterns and plasma‐biomarker‐related preclinical rates of change in these outcomes.
Genetic predisposition to clinical AD and AD pathology is differentially associated with baseline and 3‐year period change for specific AD‐related markers
Authors: Genius Patricia , Rodríguez‐Fernández Blanca , Shekari Mahnaz , Sánchez‐Benavides Gonzalo , López‐Martos David , Minguillon Carolina , Esteller Manel , Navarro Arcadi , Gispert Juan Domingo , Vilor‐Tejedor Natalia 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by early changes in brain structure and cognitive function before the age of onset. This study investigated whether the genetic load for clinical AD and AD pathology predicts AD‐related brain and cognitive changes over a 3‐year period, targeting the preclinical phase in cognitively unimpaired (CU) middle‐aged individuals.MethodThe sample of the study was defined by 429 CU middle‐aged participants at risk of AD from the ALFA+ nested cohort with available information on genetics, brain imaging markers and cognitive data [Table 1]. A subset of them had information at two‐time points (N = 367) [Figure 1]. Genetic predisposition for clinical AD (PRSAD and PRSADnoAPOE) and AD pathology (PRSAβ42‐CSF and PRSpTau‐CSF) were calculated. We used linear regression models to assess the association between each PRS and global amyloid PET deposition expressed in Centiloids, AD Dickerson MRI‐signature, hippocampal volume and cognitive outcomes, at baseline and rate of change over visits after controlling for confounders. PET and MRI outcomes were defined as the annual rate of change. Cognitive outcomes were z‐scores of the two‐time points difference. Models were adjusted for time between visits.ResultAt baseline, higher genetic predisposition to clinical AD was associated with increased amyloid‐PET levels and higher average thickness of AD‐affected regions. Additionally, higher PRSAD was associated with reduced AD‐related cognitive performance and worse language [Figure 2]. Over the three‐year period, AD‐genetic load predicted higher annual amyloid accumulation in the brain, independently of APOE. Conversely, genetic predisposition to higher CSF Aβ42 levels predicted lower annual rate of change for Centiloids. PRSAD was also associated with annual reduction of hippocampal volume. Finally, genetic predisposition to AD beyond the APOE region was associated with executive functioning rate of change[Figure 2].ConclusionThe results of this study showed the role of genetic predisposition to AD, affecting amyloid PET deposition, brain structure changes, and cognitive decline. These findings emphasized the importance of considering a comprehensive range of genetic markers in risk assessments for AD, particularly in its early stages, and highlight the potential of personalized genetic approaches to enhance predictions and interventions in the management of AD.
Influence of tau pathology and anxiety and depressive symptoms on metamemory in cognitively normal older adults
Authors: Crawford Jennifer L. , Adornato Alex , Matulonis Johanna , Hooker Jacob M. , Berry Anne S. 
Published: January 2025

AbstractBackgroundThe ability to accurately discern memory function (i.e., metamemory) decreases with age and is further diminished in Alzheimer’s disease (AD). As such, changes in metamemory may be a sensitive behavioral indicator of pre‐symptomatic AD.MethodCognitively normal older adult participants (N = 48) completed a neuropsychological battery consisting of episodic memory tasks (California Verbal Learning Task, Face‐Name Associative Memory Exam) and self‐reported measures of metamemory (Multifactorial Memory Questionnaire) and anxiety and depressive symptoms (Geriatric Depression Scale, Penn State Worry Questionnaire, Mood and Anxiety Symptom Questionnaire). Z‐scores from each measure were combined into three separate composite scores: memory ability, metamemory, and anxiety and depressive symptoms. All participants also had a tau PET scan ([18F]MK‐6240) completed within 12.7 (SD = 11.6) months of neuropsychological testing in which standardized uptake value ratios (SUVR) referenced to the inferior cerebellar gray matter were calculated using Freesurfer‐defined ROIs for Braak I, Braak II, metatemporal, and amygdala regions of interest (ROIs). Linear regression models were used to test for the contribution of anxiety and depression symptoms, tau pathology, and memory ability on metamemory; education, age, and sex were entered as covariates in all models.ResultBehavioral analyses suggest that anxiety and depression symptoms (t = ‐2.1, p = 0.046), but not memory ability (t = 0.4, p = 0.698), were related to metamemory. Interestingly, tau pathology helped to explain additional variance in the relationship between metamemory and anxiety and depressive symptoms. Specifically, amygdala tau interacted with anxiety and depression symptoms to predict metamemory (t = ‐2.61, p = 0.013), when controlling for age, sex, education, and memory ability, such that participants with both high levels of anxiety and depressive symptoms and high levels of amygdala tau pathology had lower self‐reported metamemory (Figure 1). This relationship was not observed in Braak I, Braak II, or metatemporal ROIs (ps > 0.07).ConclusionTogether, these results suggest that depressive and anxiety symptoms are an important metric to consider when examining the relationships between tau pathology and metamemory. Further, the results underscore that mechanisms supporting metamemory are likely distinct from those underlying memory ability and each merit unique consideration towards understanding their relationship to AD pathology.