bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSF synapse marker changes in predementia Alzheimer´s Disease: AMPA receptor modulators NPTX2 and NPTXR mediate cognition within A/T/N stages
Authors: Kirsebom Bjørn‐Eivind , Nilsson Johanna , Vromen Eleonora M. , Jarholm Jonas Alexander , Tecelao Sandra , Selnes Per , Aarsland Dag , Grøntvedt Gøril Rolfseng , Rongve Arvid , Skogseth Ragnhild E , Visser Pieter Jelle , Brinkmalm Ann , Blennow Kaj , Fladby Tormod 
Published: December 2023

AbstractBackgroundSynapse pathology has been linked to excitotoxicity and glutamate receptor dysregulation (such as AMPAR) in Alzheimer´s Disease (AD) progression. Of the core cerebrospinal fluid (CSF) AD biomarkers for amyloid, tau pathology and neurodegeneration (A/T/N), T/N status is proposed to reflect levels of neuronal plasticity, but fluid biomarkers for precision interventions in subgroups with increased excitotoxicity are lacking. Herein, we assess group differences of 19 CSF synapse markers including the AMPAR‐modulating NPTX, in both cognitively normal (CN) and Mild Cognitive Impairment (MCI) with either A+/T‐/N‐ and A+/T or N+ (A+/T/N+) as compared to CN A‐/T‐/N‐ and assess relationships with verbal memory recall and hippocampal volume.MethodsA/T/N was determined using the CSF Aβ42/40 ratio, p‐tau181 and total‐tau in predementia AD cases (n = 194) and CN participants with normal AD biomarkers (n = 145) in the Dementia Disease Initiation cohort. CSF synapse marker concentrations were determined using mass‐spectrometry (table 1) and ELISA for GAP‐43. Adjusted for age and sex, we compared marker concentrations between CN cases (A+/T‐/N‐ n = 20; A+/T/N+ n = 40) and MCI cases (A+/T‐/N‐ n = 25;A+/T/N+ n = 109) with CN A‐/T‐/N‐ (n = 145) as the reference group. Associations to verbal memory recall and brain imaging were performed in the total sample and respective A/T/N groups adjusted for covariates. Results p<.01 were considered significant.ResultsTop markers based on between‐group results are reported (Table 1 & figure 1‐2 for all markers). Compared to CN A‐/T‐/N‐, 14‐3‐3 ζ/δ concentrations were higher in all A+/T/N+ groups (p<.001), but unaltered in A+/T‐/N‐ groups. In A+/T‐/N‐, NPTX2 concentrations were lower in MCI (p<.001) but not in CN. In A+/T/N+, NPTX2 was higher in CN (p<.001) but not in MCI. 14‐3‐3 ζ/δ was associated with worse memory in the total sample (p<.001) but not in the A+ groups. Lower NPTX2 was associated with worse memory in the total sample (p<.001) and in both A+ groups (p<.01; p<001). Neither 14‐3‐3 ζ/δ nor NPTX2 were significantly associated with hippocampal volume (figure 2).ConclusionOverall, increased 14‐3‐3 ζ/δ was most closely associated with worse memory recall. Lower NPTX2 was linked to poorer cognitive status within A+ groups, suggesting links to AMPAR dysregulation and excitotoxicity.
Angiotensin receptor blockers reduced the risk of post stroke cognitive impairment among first‐ever ischemic stroke patients
Authors: Vidyanti Amelia Nur , Prodjohardjono Astuti , Hardhantyo Muhammad 
Published: December 2023

AbstractBackgroundThe effect of antihypertensive drug classes in reducing the risk of post‐stroke cognitive impairment (PSCI) remains elusive. We aimed to investigate the association between antihypertensive drug classes and the risk of PSCI among ischemic stroke patients using data collected from a tertiary hospital in Indonesia.MethodsWe carried out a retrospective analysis of data from a medical database in Sardjito General Hospital Yogyakarta, Indonesia. We identified the first‐ever ischemic stroke patients hospitalized between June 2018 to May 2019 and whose serial measurements of cognitive function were available up to 90 days after stroke. The effect of antihypertensive drug classes on PSCI was measured by using multivariate logistic regression analysis.ResultsWe found 71.11% patients developed PSCI at 90 days after stroke. Forty‐one patients (44.09%) received no antihypertensive drugs, 14 (15.05%) with angiotensin receptor blockers (ARB), 20 (21.50%) with calcium channel blockers (CCB), and 18 (19.35%) with combination of ARB and CCB. After controlling covariates, we found that ARB reduced the risk of PSCI by 64% (aOR 0.364, 95% CI = 0.14‐0.91, p<0.05), with improvement of total MoCA‐INA score by 3.113 points (p<0.05).ConclusionsAmong first‐ever ischemic stroke patients, ARB showed more favorable outcome on reducing the risk of PSCI and improving cognitive performance at 90 days after stroke. These findings may contribute to assist clinicians for selecting antihypertensive drug classes in PSCI prevention.
Blood‐based biomarkers for Alzheimer’s Disease in Down Syndrome
Authors: Jacob Charlotte , Heylen Annelies , Tollenaere Marleen , De Deyn Peter Paul , Van Dam Debby 
Published: December 2023

AbstractBackgroundPeople with DS are at high risk to develop Alzheimer’s disease dementia (AD) (Lott & Head, 2001). Predicting and monitoring decline and onset of dementia is a diagnostic challenge and of essence in daily care and support for people with DS. Behavioral and Psychological Symptoms of Dementia (BPSD) are an easily accessible tool for the prediction of dementia onset in the DS population. The BPSD‐DS II scale was developed and validated by our team to identify behavioral changes linked to AD between the last six months and pre‐existing behavior in an individual with DS (Dekker et al., 2021). This project is based on a cohort of DS individuals without AD (n = 94), with AD (n = 43), or with questionable AD (qAD) (n = 54) aged >35 years. At inclusion, the BPSD‐DS II was applied to assess AD‐linked behavioral changes, and biofluid sampling was performed as well. Changes in cerebrospinal fluid (CSF) levels of monoaminergic neurotransmitters and metabolites have been associated with BPSD in AD (Dekker et al., 2015). However, CSF sampling procedures remain difficult in DS, illustrating the need for blood biomarkers. BPSD‐DS II results will be correlated with the serum levels of monoaminergic and classical AD biomarkers. Three years post‐inclusion, a follow‐up study was conducted to assess the evolution of possible AD dementia within this group and to determine the predictive values of the BPSD‐DS II scale and the different analytes.MethodWe will use reversed‐phase ultra‐high performance liquid chromatography with electrochemical detection to determine the levels of (nor)epinephrine, dopamine, serotonin and their metabolic products in serum. We will use the Simoaâ platform on the serum of clients with DS without or with (q)AD to detect the levels of Ab40, Ab42, total tau, phosphorylated tau, Glial Fibrillary Acidic Protein and Neurofilament Light chain.ResultWe expect a correlation between the results of the BPSD‐DS II and the levels of the monoamines and classical biomarkers in patients with DS without or with (q)AD.ConclusionThe diagnosis predicted by the results of the BPSD‐DS II correlates with the levels of monoamines and classical biomarkers in individuals with DS without or with (q)AD.
Plasma biomarkers of Alzheimer’s disease in a biracial, community‐based sample
Authors: Ramanan Vijay K , Graff‐Radford Jonathan , Syrjanen Jeremy A. , Shir Dror , Algeciras‐Schimnich Alicia , Lucas John A. , Martens Yuka A , Carrasquillo Minerva M. , Day Gregory S. , Ertekin‐Taner Nilufer , Lachner Christian , Willis Floyd B. , Knopman David S. , Jack Clifford R. , Petersen Ronald C. , Vemuri Prashanthi , Graff‐Radford Neill R , Mielke Michelle M. 
Published: December 2023

AbstractBackgroundFor blood‐based biomarkers to fulfill their potential to revolutionize diagnosis and management of Alzheimer’s disease (AD), additional research in diverse populations remains critical. Here, we analyzed a biracial sample to assess the profiles of blood‐based AD biomarkers and their relationships to cognition and medical comorbidities.MethodsSelf‐reported African‐American (AA; n = 267) and non‐Hispanic White (NHW; n = 268) participants evaluated through the Mayo Jacksonville Alzheimer’s Disease Research Center were matched on age, sex, and clinical diagnosis. Plasma AD biomarkers (Aβ42/40, p‐tau181, GFAP, NfL) were measured using the Quanterix SiMoA HD‐X analyzer. Cognition was assessed with the Mini Mental State Examination. Wilcoxon rank sum tests were used to assess for differences in plasma biomarker levels by sex. Linear models tested for associations of race, chronic kidney disease (CKD), and vascular risk factors with plasma AD biomarker levels, covarying for age and sex. Additional models assessed for interactions between race and plasma biomarkers in predicting cognition, further covarying for education.ResultsThe sample included adults aged 43‐100 years, with 69% women. Education was higher in NHW participants (median 16 vs. 12 years, p<0.001). APOE (apolipoprotein E) ε4 positivity was higher in AA participants (43% vs. 34%; p = 0.04). There were no differences in plasma AD biomarker levels between AA and NHW participants. These findings were unchanged after stratifying by cognitive status (unimpaired versus impaired). Although the association between p‐tau181 and cognition appeared stronger in NHW participants while the association between Aβ42/40 and cognition appeared stronger in AA participants, these findings did not survive after excluding individuals with CKD. Women displayed higher GFAP (p = 0.002) and lower p‐tau181 (p = 0.001) levels than men. Diabetes was inversely associated with GFAP levels (p<0.001).ConclusionsIn a biracial, community‐based sample, we observed that sex differences, CKD, and vascular risk factors contributed to variation in plasma AD biomarkers, while self‐reported race did not. Our results reinforce the critical need to account for sex and systemic medical comorbidities in equitably deploying blood‐based AD biomarkers in the general population.
Evaluation of Gestational Alcohol Intake on the Hippocampus of an Adult Wistar Rats
Authors: Ojo Mayokun Afolabi 
Published: December 2023

AbstractBackgroundChronic consumption of alcohol is a leading cause of death worldwide due to it effect on differs organs of the body. The need to better understand the impact of alcohol intake on Hippocampus was the motivation behind this study.MethodThe study was performed on (20) twenty pregnant wistar rats weighing between 142‐181g which were divided into two (2) groups of ten animals each; A (Control), B (Treated). Group A (control) were administered normal saline orally on a daily basis for seven (7) consecutive days while the Group B (treated) were administered 12% Acetone orally for seven (7) consecutive days. The animals went through neurobehavioral tests for fear and anxiety with the aid of an elevated plus maze. The Hippocampus tissues gotten after the study were determined for histological analysis (H&E, Silver Stains).ResultThere was observable reduction on the body weight on administration of Alcohol and a drastic reduction in the mean cell count and size of animals in group B (treated) compared to group A (control) showing a significant effect of alcohol on the hippocampal cell count of the animals. Histo‐architectural analysis of the hippocampus showed distortion of the dentate gyrus, disorientated molecular layer, scattered granule and glail cells in the treated groups (B) indicating the effect of the administered alcohol.ConclusionMeasure should be taking in reducing the consumption of alcohol if abstinence is not possible
Amyloid‐β and tau accumulation in traumatic brain injury: A study of Vietnam war veterans
Authors: de Bruin Hannah , Groot Colin , Kamps Suzie , Vijverberg Everard G.B. , Pijnenburg Yolande A.L. , Ossenkoppele Rik , Franzmeier Nicolai 
Published: December 2023

AbstractBackgroundTraumatic brain injury (TBI) is widely viewed as a risk factor for dementia. Since amyloid‐β and tau pathology have been reported in up to a third of individuals with TBI – even after a single TBI event – their accumulation could be a potential mechanism underlying this association. The aim of this study was to examine the relationship between TBI and amyloid‐β and tau pathology more closely and to assess whether the association between amyloid‐β and tau is influenced by TBI status.MethodA total of 102 Vietnam war veterans (79% normal cognition, 21% mild cognitive impairment; 23% amyloid‐β positive) were included from the Alzheimer’s Disease Neuroimaging Initiative Department Of Defense study. Among these individuals, 65 had a history of TBI (42 mild and 23 moderate/severe TBI) whereas 37 did not. Amyloid‐PET ([18F]florbetapir) and tau‐PET ([18F]flortaucipir) SUVRs were assessed within regions from the Schaefer atlas. For both amyloid‐PET and tau‐PET ROI‐wise and global TBI group differences were determined by ANCOVAs. Moderating effects of TBI status on the association between ROI‐wise amyloid‐PET and tau‐PET SUVRs were tested using linear regression. Analyses were adjusted for age, sex, education, clinical diagnosis, and, where applicable, global amyloid‐PET and time lag between amyloid‐ and tau‐PET scans.ResultTBI groups did not show significant increases in amyloid‐ or tau‐PET uptake compared to no‐TBI groups, neither globally nor on the ROI‐level (i.e. all p>0.05 after correcting for multiple comparisons, Fig. 1). However, we found that a history of (particularly moderate/severe) TBI was associated with a weaker relationship between amyloid‐PET and tau‐PET uptake in temporal and parietal brain regions compared to no history of TBI (Fig. 2). This effect seemed to be driven by the amyloid‐β positive group. TBI groups did not differ regarding age and APOE‐status.ConclusionWhile amyloid‐β is known to promote tau spreading in Alzheimer’s disease (AD), our results indicate that in TBI there might be a detachment of amyloid‐β and tau pathology in AD‐susceptible temporo‐parietal brain regions. This finding is supportive of the view that TBI could lead to distinct changes in the interplay of pathological proteins, potentially underlying the link between TBI and dementia.
High late‐life physical activities and reduced progression from MCI to Alzheimer’s dementia
Authors: Sohn Bo Kyung , Byun Min Soo , Yi Dahyun , Jeon So Yeon , Choe Young Min , Lee Dong Woo , Lee Jun‐Young , Kim Yu Kyeong , Sohn Chul‐Ho , Lee Dong Young ,   KBASE Research Group
Published: December 2023

AbstractBackgroundPhysical activity (PA) has been reported to reduce the risk of Alzheimer`s disease (AD) dementia and related cognitive decline. We aimed to investigate the influence of PA on the progression from cognitively normal (CN) status to mild cognitive impairment (MCI) or from MCI to AD dementia in non‐demented older adults.MethodThis study included 194 non‐demented (148 CN and 46 MCI) participants from the Korean Brain Aging Study for Early diagnosis and prediction of Alzheimer’s disease (KBASE), who completed both baseline and 2‐year follow‐up clinical evaluation. At baseline, the participants underwent comprehensive clinical and neuropsychological assessment, multimodal brain imaging including [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] fluorodeoxyglucose PET and MRI, and current PA measured using the Lifetime Total Physical Activity Questionnaire.ResultAfter 2 years, five CN and 22 MCI participants progressed to MCI and AD dementia, respectively. Logistic regression analyses showed that high current PA (above the median value) reduced the risk of the progression from MCI to AD dementia even after controlling age, sex, education, apolipoprotein E e4 positivity, baseline brain amyloid deposition, AD‐signature region glucose metabolism, and AD‐signature region cortical thickness (Bonferroni corrected p‐value = 0.028). In contrast, PA had no effect on the progression from CN to MCI.ConclusionThe findings suggest that a physically active lifestyle in late‐life reduces the risk of conversion to AD dementia in MCI independently of AD‐related brain pathologies.
Age differentially mediates the relationship between plasma biomarkers and cognition detected by digital screening
Authors: Toniolo Sofia , Zhao Sijia , Scholcz Anna , Amein Benazir , Gallacher Anne , Ganse‐Dumrath Akke , Bukala Bernard R , Thompson Sian , Manohar Sanjay , Zetterberg Henrik , Husain Masud 
Published: December 2023

AbstractBackgroundPlasma biomarkers are emerging as a useful tool to measure neurodegeneration, particularly in patients with Alzheimer’s Disease (AD). Digital cognitive testing is also increasingly used to detect cognitive changes in AD. Age is a major determinant of performance at cognitive testing and can affect the levels of different plasma biomarkers. However, little is known about how age mediates the relationship between plasma biomarkers and cognition.Methods38 AD and 48 age‐matched controls were recruited from the Oxford Centre for Cognitive Disorders. We used a fully remote digital visual short‐term memory (STM) task (Figure 1) and extracted eight cognitive metrics (Figure 1): Identification Accuracy (percentage of correctly identified items), Absolute Error (distance from the response location to the original item), Target detection (probability of correctly identifying the target), Misbinding (erroneously localizing an item to the remembered location of another item in memory), Guessing (random guessing), Identification and Localization Time (time to identify and drag the correct object to its remembered location), and memory Imprecision (width of the distribution around the target). Plasma p‐tau 181, GFAP, NFL, Aβ40 and Aβ42 were measured, and the Aβ42/40 ratio was calculated. In Model 1 (Figure 2) the correlation between digital cognitive metrics and plasma biomarkers is shown, while in Model 2 age was regressed out. A mediation analysis was then performed to look at the effect of age as a mediator.ResultsIn Model 1, most cognitive metrics on the STM task were strongly associated with p‐tau 181, GFAP and NFL. Identification Accuracy was also negatively correlated with the Aβ42/40 ratio. No association with Aβ42 or Aβ40 was found. However, regressing out age had a profound impact on these correlations, particularly for GFAP and NFL, while p‐tau 181 was not significantly affected (Figure 2 and 3). The mediation analysis (Figure 3), shown for Identification Accuracy, confirmed that age had a more profound impact on GFAP and NFL compared to p‐tau 181.ConclusionsThese new digital metrics show a strong correlation with plasma biomarkers. Finally, age is an important mediator between plasma biomarkers and cognition, but that varies across different biomarkers.
Effect of Concomitant Aducanumab on AD Clinical Trial Outcomes
Authors: Kennedy Richard E 
Published: December 2023

AbstractBackgroundAducanumab was approved by the US FDA for treatment of mild cognitive impairment (MCI) and mild Alzheimer’s disease (AD). Participants taking aducanumab or other anti‐amyloid antibodies are likely to become more common in clinical trials of novel therapies, but the effect of concomitant administration on trial outcomes is not known.MethodWe used a metadatabase of 18 ADCS studies and ADNI, containing 3480 participants with mild AD, to simulate current clinical trials methods. We randomly resampled the database for sample sizes of 400 to 1000 per group for hypothetical novel “drug” and “placebo” groups in 12‐, 18‐, and 24‐month duration trials. We simulated effects on the ADAS‐cog for both the experimental treatment and aducanumab with effect sizes from 0 (no effect) to 0.25 (moderate effect), with differential dropout in the aducanumab group ranging from 0% to 20%. Mixed effects models were used to determine power to detect treatment response.ResultParticipants eligible for aducanumab were younger, more likely to be male, more highly educated, and had higher MMSE scores at baseline and lower ADAS‐cog scores over time. The approximate decrease in power was up to 20% with a moderate effect of aducanumab and a dropout rate of 20% in the aducanumab group, increasing up to 30% if differential dropout also occurred in the experimental treatment group. (Figure: Simulated power for rates of progression on an experimental AD therapy by aducanumab status, with N = 800 per group, dropout rates of 0% to 20% among participants eligible and ineligible for aducanumab) Effects on power were greater when the effect size of aducanumab was greater than the effect size of the experimental treatment.ConclusionWhile randomization can ensure approximately equal effects of an anti‐amyloid antibody in both treatment and placebo groups in clinical trials of new experimental therapies, differential dropout among aducanumab users during the trial (as seen initial studies for aducanumab) can disturb this balance, with corresponding decreases in power to detect a treatment effect. Clinical trials should assess use of anti‐amyloid antibodies at baseline to ensure balance, and incorporate ongoing monitoring of potential dropouts could negatively impact trial outcomes.
The association between menopause and dementia risk
Authors: Peterson Amalia Jo , Miller Eliza C. , De Jager Philip L , Barnes Lisa L. , Arvanitakis Zoe , Bennett David A. A , Tom Sarah E. 
Published: December 2023

AbstractBackgroundWomen have a higher prevalence of Alzheimer’s disease compared to men. Studies are conflicting as to whether an earlier age of menopause or hysterectomy prior to natural menopause, are associated with an increased risk of cognitive impairment. The goal of this study was to determine whether age of menopause and hysterectomy are associated with incident dementia in a group of older, community‐dwelling women.MethodFemale participants from three ongoing Rush cohorts, the Rush Memory and Aging Project, the Religious Orders Study, and the Minority Aging Research Study were included (total n = 3122, mean age = 77 years at baseline, SD = 7.8). Annual clinical assessments allowed for dementia status categorization, based on detailed neuropsychological testing and clinical judgment, using the NINDS‐ADRDA criteria. Age at menopause and hysterectomy status was based on self‐report at baseline. Data on ovarian preservation or removal at time of surgery was not available. Age of menopause was categorized into tertiles (<45, 45‐50, >50). Risk of dementia, with age at dementia diagnosis as the outcome, was evaluated using Cox proportional regression models adjusting for race, early‐life socioeconomic status, education, diabetes, and smoking status.ResultAt the time of these analyses, women were followed for an average of 8.3 years (SD = 5.6). Women in the earliest tertile of menopause age were less likely to be white, more likely to report having diabetes, and have longer hormone therapy use (p<0.01). In fully adjusted models, women with menopause at age 45‐50 (HR 0.80, 95% CI 0.67‐0.96) and age >50 (HR 0.74, 95% CI 0.62‐0.90) had a lower risk of dementia compared to women with menopause at age <45. Hysterectomy prior to natural menopause was not associated with an elevated risk of dementia (HR = 1.01, 95% CI 0.87‐1.19).ConclusionIn a group of older women, earlier age at menopause but not hysterectomy was associated with an elevated risk of dementia. Future research will determine whether these associations differ by race or ethnicity and the factors that may contribute to such differences.Funding: P30‐AG072975, R01‐AG17917, R01‐AG22081