bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral blood leukotriene B4 and E4 as biomarkers in Alzheimer’s disease
Authors: Xiong Lisa Y. , Yu Di , Liang Nuanyi , Shen Qing , Hegele Robert , Ramirez Joel , Goubran Maged , Rabin Jennifer S. , Lanctôt Krista L. , Black Sandra E. , Tartaglia Carmela , Lang Anthony E , Tan Brian , Symons Sean , Taha Ameer Y. , Swardfager Walter 
Published: December 2022

AbstractBackgroundWe showed recently that use of leukotriene receptor antagonists, typically used in asthma therapy, was associated with preserved executive function among people with Alzheimer’s disease (AD) dementia. The aim of this study was to determine if leukotriene B4 (LTB4) and E4 (LTE4) would be associated with longitudinal changes in cognitive performance and cerebrovascular disease markers in people with AD.MethodParticipants with clinical AD or mild cognitive impairment were identified from the Ontario Neurodegenerative Disease Research Initiative. LTB4 and LTE4 were extracted from fasting serum and quantified using ultra‐high performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS). Concentrations below the limit of detection were imputed using quantile regression imputation of left‐censored data. Cognition was assessed using composite scores for executive function (Trails Making Test B, Symbol Digit Modalities Test, Stroop switching task, and verbal fluency) and memory (Rey Auditory Verbal Learning Test and Brief Visuospatial Memory Test). White matter hyperintensities (WMH), lacunes, and perivascular spaces (PVS) were quantified using T2‐weighted structural magnetic resonance imaging (MRI). Longitudinal associations between baseline LTB4 or LTE4 and cognition and imaging markers at baseline and 1‐year‐follow‐up were assessed using mixed‐effects linear regression models, controlling for baseline demographic factors, medication use, and vascular comorbidities. Findings were corrected for multiple comparisons using a 5% false discovery rate.ResultAmong 158 participants (mean age = 69.22 years, 51% female, mean education = 14.61 years), higher baseline concentrations of LTB4 were not associated with performance in executive function or memory over time nor with changes in WMH, lacunes, or PVS over time. Higher baseline concentrations of LTE4 were associated with better performance in memory over time (β = 0.153 [95% CI = 0.026, 0.287]; however, this finding did not survive correction for multiple comparisons (adjusted p = 0.260; Table 1).ConclusionIn a group of patients with AD, higher LTB4 and LTE4 in serum were not associated with changes in cognitive performance nor markers of cerebrovascular disease. These findings suggest very little potential for serum leukotrienes as biomarkers for cognitive decline of cerebrovascular disease progression in AD.
Music and Dance Therapy; The Effectiveness of Occupational Therapy Intervention in Preventing Depression amongst Persons living with Alzheimer in Lagos Nigeria
Authors: AKINYELURE FEYIKEMI MARY 
Published: December 2022

AbstractBackgroundGlobally an estimate of 50 million people were living with Alzheimer in 2017. This number is predicted to reach 82 million in 2030 and 152 million in 2050.In older adults,Alzheimer and depression are associated with individual distress and with high societal cost of living especially in developing world.In the same vein depression is the leading cause of disability worldwide among the older adults;it co‐occurs and interacts with Alzheimer in many complex ways.In fact, depression has caused cognitive impairment, psychological and social dysfunctions which result to the increased in the risk of developing Alzheimer. Depression is very common in the early stages of Alzheimer and often lead to hospitalization.In Nigeria,Alzheimer is associated with terrible stigma on the client and affiliate stigma among the care givers leading to rejection based on the psychosis features and perceived myths of witchcraft which make people believe out of the ordinary as either mad or possessed by evil spirits. Hence there is dire need to psycho educate people of the evidence based practices on best ways in taking care of people with Alzheimer challenges.MethodDora‐care Behavioral foundation an NGO i founded is passionate about elderly care and their well being. 17 people were identified during Alzheimer awareness program. Intervention involved 16 sessions of music and dance (listening to and singing along) at one week interval, cognitive functions (memory, attention, judgment, perception, and decision making ability) were evaluated using cognitive function instruments before and after the intervention.ResultThe result indicated that 12 out of 17 clients showed significant improvement in attention, judgment, decision making ability and perception. However, there was no significant improvement in memory.ConclusionFindings show that music and dance therapies has significant improvement in treating Alzheimer and enhance self care.
Associations between FDG metabolism and fMRI connectivity in the default mode network depend on Aβ status in MCI patients
Authors: Malotaux Vincent , Dricot Laurence , Quenon Lisa , Gérard Thomas , Ivanoiu Adrian , Lhommel Renaud , Hanseeuw Bernard J 
Published: December 2022

AbstractBackgroundBrain function can be assessed using both resting‐state functional magnetic resonance imaging (rs‐fMRI) and Fluorodeoxyglucose (FDG) PET imaging. The associations between these biomarkers and their evolution with Alzheimer’s disease (AD) are unclear. We aimed to evaluate the associations between the default mode network (DMN) connectivity and glucose metabolism in mild cognitive impairment (MCI) patients with (Aβ+) and without (Aβ‐) AD pathology.MethodForty MCI patients (19 Aβ‐/21 Aβ+) performed between 2 to 4 rs‐fMRI acquisitions with an average follow‐up duration of 15 months. At baseline, DMN metabolism was estimated using [18F]‐FDG‐PET SUVr of the isthmus cingulate region‐of‐interest extracted from the Desikan‐Killiany atlas; and Aβ was measured using [18F]‐Flutemetamol‐PET. We used a Centiloid‐threshold>26 to define Aβ+. Multiple regressions were used to assess the FDG‐fMRI associations in the DMN, comparing the two subgroups using FDG‐Aβ interaction models. Table 1 provides demographics and follow‐up durations. All analyses were adjusted for age and sex.ResultsIn the entire sample, DMN connectivity and metabolism were not significantly associated to each other. However, we observed an interaction between Aβ status and FDG metabolism (0.23, p=0.03) such that, in the high‐Aβ subgroup, lower FDG metabolism was signiticantly associated with lower DMN connectivity (Fig. 1). In the low‐Aβ subgroup, no associations were observed. We also observed an FDG‐Aβ interaction when predicting longitudinal changes in DMN (‐0.27, p=0.04) such that, in the high‐Aβ subgroup, lower FDG metabolism was associated with a subsequent increase in DMN connectivity over time (Fig. 2).ConclusionIn high‐Aβ MCI patients, DMN connectivity is positively associated with FDG metabolism measured at baseline. However, the longitudinal association is negative with lower metabolism predicting increasing connectivity over time. Future research is needed to understand the mechanisms behind this inverse relationship. Hypothetically, a synchronous decrease in metabolism in several regions of the DMN could lead to an increase in the correlation between resting‐state activity measured in these regions.
Proteomic indicators of health relate to Alzheimer’s and neurodegenerative disease biomarkers
Authors: Dark Heather E , Peng Zhongsheng , Duggan Michael R , Daya Gulzar , Bilgel Murat , An Yang , Moghekar Abhay , Resnick Susan M. , Walker Keenan A 
Published: December 2022

AbstractBackgroundPrior studies suggest that peripheral health and comorbid disease can influence Alzheimer’s disease (AD) pathology and neurodegenerative processes. However, no studies to date have comprehensively examined how measures of peripheral health and risk for non‐neurological disease relate to biomarkers commonly used in AD research. The present study examined the association between 16 protein‐based health indicators and plasma biomarkers of brain amyloid‐β (Aβ) accumulation, phosphorylated tau, neurodegeneration, and reactive astrogliosis.MethodPlasma‐based biomarkers of AD pathology (Aβ42/40 ratio, pTau‐181), neurodegeneration (neurofilament light chain [NfL]), and reactive astrogliosis (glial fibrillary acidic protein [GFAP]) were measured in Baltimore Longitudinal Study of Aging participants using Quanterix SIMOA assays. Concurrently, the SomaScan proteomic platform was used to measure 7000 proteins, from which 16 proteomic signatures of health and disease risk were derived (i.e., SomaSignal Tests). A subset of participants also received PiB PET scans to assess cortical amyloid. We examined the relationship between health indicators and AD/neurodegeneration biomarkers using Pearson and Spearman correlations and linear regression analyses adjusted for age, sex, race, education, and APOEe4.ResultThe primary analysis included 720 participants (Table 1). Correlation analyses revealed several strong associations between measures of health/disease risk and plasma Aβ42/40 ratio, pTau‐181, NfL, and GFAP levels (Figure 1a). Notably, higher risk scores for heart failure, primary and secondary cardiovascular disease, and kidney disease were consistently positively associated with greater pTau‐181, NfL, and GFAP, and lower with Aβ42/40 ratio. Measures of body fat percentage, lean body mass, and visceral fat were associated with pTau‐181, NfL, and GFAP, whereas resting energy rate was only associated with NfL and GFAP. These relationships were maintained after adjusting for demographic factors and APOEe4 status (Figure 1b). Only heart failure and secondary cardiovascular disease risk scores were associated with elevated cortical amyloid (PiB+; Figure 2); these measures varied positively with cortical amyloid among participants who were PiB+, but not PiB‐ (Figure 3).ConclusionIndicators of peripheral health and disease risk demonstrate robust relationships with plasma AD, neurodegeneration, and reactive astrogliosis biomarkers. Peripheral health factors, particularly cardiovascular health, may play an important role in the pathophysiology of AD.
Effect of APOE4 on Plasma Phospho‐tau 217 and Neurofilament Light in the PSEN1 E280A Autosomal Dominant Alzheimer’s Disease Colombian Kindred
Authors: Pruzin Jeremy J. , Su Yi , Chen Yinghua , Chen Kewei , Lopez Hugo , Acosta‐Uribe Juliana , Alzate Diana , Aguillon David , Garcia Gloria , Craig‐Mueller Jennifer , Serrano Geidy E , Langbaum Jessica B. , Ríos‐Romenets Silvia , Quiroz Yakeel T. , Dage Jeffrey L. , Hansson Oskar , Blennow Kaj , Zetterberg Henrik , Kosik Kenneth S. , Lopera Francisco , Tariot Pierre N. , Reiman Eric M. 
Published: December 2022

AbstractBackgroundThe Colombian kindred affected by the autosomal dominant AD causative mutation PSEN1 E280A are an invaluable population in determining the utility of blood biomarkers (BB) and how additional risk factors may affect BB years to decades prior to symptom onset. Neurofilament light (NfL) (Quiroz et al., 2020) and phospho‐tau 217 (p‐tau217) (Palmqvist et al., 2020) diverge about 20 years prior to onset of clinical symptoms in carriers compared to non‐carriers. How APOE4 carriage may influence NfL and p‐tau217 in the kindred is unknown. We assessed cross‐sectional effects of APOE4 carriage on plasma NfL and p‐tau217 in the PSEN1 E280A kindred.MethodWe used a single molecule array immunoassay to quantify plasma NfL and a Meso Scale Discovery based plasma immunoassay to quantify p‐tau217. 1428 persons (age 18 to 75, mean 35.8, 23% APOE4 carriers, 54% PSEN1 E280A carriers) had available data for NfL analyses. A total of 612 persons (age 18 to 60, mean 35.9, 25% APOE4 carriers, 62% PSEN1 E280A carriers) had available data for p‐tau217 analyses. Age related trajectories were derived from cross‐sectional log‐transformed p‐tau217 and NfL concentrations modelled using a restricted cubic spline model. Model parameters were estimated using a Hamiltonian Markov chain Monte Carlo method in E280A mutation and APOE4 carriage defined groups. The primary comparison was made between APOE4 carrier and noncarriers within E280A carriers and noncarriers separately.ResultIn PSEN1 E280A mutation carriers, plasma NfL concentrations begin to differentiate those who were APOE4 carriers from non‐carriers at age 47.4 (figure 1). Plasma NfL concentrations did not differentiate APOE4 carriers versus non‐carriers in those without the PSEN1 E280A mutation though concentration of NfL trended higher in APOE4 carriers in the higher age range of the sample. Plasma p‐tau217 concentrations did not differentiate APOE4 carriers from non‐carriers in PSEN1 E280A mutation carriers or non‐carriers.ConclusionAPOE4 carriage results in accelerated NfL plasma increases in PSEN1 E280A mutation carriers starting at about the age of symptom onset. The inability to detect APOE4‐related ptau217 and NfL differences in the other groups may be related to the younger age of participants and limitations in statistical power.
Predicting CSF neurogranin and neurofilament light chain protein levels with a neuropathology‐based APOE genetic risk score
Authors: Whitenack Vanessa M , Deming Yuetiva , Vasiljevic Eva , Van Hulle Carol A. , Jonaitis Erin M. , Kollmorgen Gwendlyn , Suridjan Ivonne , Asthana Sanjay , Carlsson Cynthia M. , Johnson Sterling C. , Zetterberg Henrik , Blennow Kaj , Engelman Corinne D. , Bendlin Barbara B. ,   Alzheimer's Disease Research Center, Madison WI
Published: December 2022

AbstractBackgroundCerebrospinal fluid (CSF) levels of neurogranin, an index of synaptic degeneration, and neurofilament light chain (NfL), an index of neuroaxonal degradation, are both biomarkers of neurodegeneration in Alzheimer’s disease (AD). The presence of APOE is the strongest genetic risk factor for late onset AD and has also been associated with increased CSF neurogranin, a marker of neurodegeneration. To test the association between APOE and CSF biomarkers for neurodegeneration, we used a neuropathology‐based weighted risk score for APOE genotype (APOE‐npscore) and hypothesized that greater AD risk as indexed by the APOE‐npscore would be associated with higher CSF concentrations of neurogranin and NfL.MethodWe examined data collected from participants in the Wisconsin Registry for Alzheimer’s Prevention (n = 243) (avg age = 65) and Wisconsin Alzheimer’s Disease Research Center (n = 411) (avg age = 64) including participants with Dementia (n = 50) Impaired‐Other (n = 8), Mild Cognitive Impairment (MCI) (n = 55), and cognitively unimpaired (n = 545) participants. The CSF biomarkers were measured using the NeuroToolKit panel of robust prototype assays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland). Using linear regression, we tested associations between the APOE‐npscore and CSF neurogranin and NfL concentrations, adjusting for age at lumbar puncture (LP) and sex. We also tested for interactions between age at LP or sex and the APOE‐npscore.ResultsThe APOE‐npscore was significantly associated with CSF neurogranin concentration (β = 3.126, p < 0.01) but not significantly associated with CSF NfL concentration (β = 39.570, p > 0.05). Age at LP was significantly associated (p < 0.001) with CSF neurogranin and NfL concentrations. No significant interactions were found between the APOE‐np score and age at LP or sex in either test. APOE‐npscore, age at LP, and sex accounted for 7% of the variability of CSF neurogranin, and 27% of CSF NfL.ConclusionsThe current study lends additional support to the impact of APOE on neurodegeneration, and supports the utility of using the APOE‐npscore to index risk of AD. The effects of APOE were observed on markers of synaptic degeneration, which underscores the importance of synaptic dysfunction in AD.
Prevalence and Associations of Frailty in Preclinical Alzheimer’s Disease
Authors: Lee Kathryn , Huynh Andrew , Moe Thinza , Amadoru Sanka , Zisis Georgios , Raman Rema , Aisen Paul , Ernstrom Karin , Sperling Reisa A. , Masters Colin L. , Yates Paul A 
Published: December 2022

AbstractBackgroundThe prevalence of frailty in asymptomatic Alzheimer’s disease is not clear. In this cohort screened for a preclinical Alzheimer’s disease clinical trial, we aimed to compare the prevalence of frailty between participants with and without elevated amyloid as determined by PET and determine if frailty influences the relationship between amyloid and cognition.MethodAnalysis of pre‐randomization data from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study, a clinical prevention trial of an anti‐amyloid monoclonal antibody in individuals who were cognitively normal with elevated amyloid burden, to determine a cumulative‐deficits Frailty Index (FI). Logistic regression was used to investigate the difference in the prevalence of frailty, defined as a FI greater than 0.25, according to amyloid status (Aβ+/‐), adjusted for age, gender and education. ANCOVA was used to examine the influence of frailty on the relationship between amyloid status and cognition (Preclinical Alzheimer Cognitive Composite [PACC] score), including an interaction term of frailty and amyloid, adjusted for age, gender and education.Result4,486 participants were included (mean age 71.3±4.7 years, 1323 participants Aβ+(29.5%), 59.4% female). Adjusting for age, sex and education, Aβ+ participants were 1.48 times more likely to be frail compared to Aβ− (p<0.001). Frail participants had a lower PACC score compared to non‐frail participants (p<0.001). Both frailty and amyloid status were associated with poorer cognition after adjusting for age, sex and education (p<0.001), but frailty did not influence the relationship between cognition and amyloid status.ConclusionThere is strong evidence that elevated amyloid burden was associated with an increased risk of frailty and that frailty reduced cognitive performance compared to non‐frail participants in this cohort screened for a preclinical AD trial. These relationships, the potential underlying mechanisms, and whether this may be applicable to longitudinal outcomes, warrant further study.
Investigating the feasibility of creating a disease registry in Egypt: a case study of dementia
Authors: Heikal Shimaa Adel , Salama Mohamed , Barsoum Ghada 
Published: December 2022

AbstractBackgroundDisease registries have emerged worldwide to help tackle the impact of chronic diseases by providing accurate data on several aspects of the disease care process. Age‐associated diseases, particularly dementia, are growing worldwide with several implications and increased economic burden, especially in lower‐income countries. In Egypt, there is a lack of accurate dementia prevalence and statistics data which hinders the establishment of appropriate disease management and care strategies. A national dementia registry would provide a massive valuable source of patient data that will significantly advance the disease management strategies and quality of patient care and impact health policy and decision‐making.MethodThis study investigates the feasibility of creating a disease registry for dementia in Egypt through interviewing relevant national and international experts to evaluate their perceptions, knowledge, and opinions, then provide recommendations for the most appropriate registry model to be developed in Egypt.ResultSeveral core themes emerged from the analysis of experts’ interviews discussing many points that should direct the creation of any registry in Egypt. Learning from other successful registries, comparing their experiences, and applying them to the Egyptian culture imposes an excellent opportunity for the registry establishment. The findings clearly provided the proposed best practices to be followed while initiating a national registry in Egypt in terms of functionality, planning, comprehension, governance, ethics, and challenges to avoid. The initiating process should start with a leading institution that brings together the potential stakeholders and defines clear purpose and objectives of the registry to direct the planning and design. A primary phase should be the first step to test the functionality and effectiveness of the process then expansion of data and coverage can be a second step.Conclusion: Taken together, developing such a dataset is beneficial to the Egyptian healthcare system, which makes the investment worthwhile. Support and collaborative work from all stakeholders, along with suitable funding, are essential elements of the proper implementation of the project. Yet, it might seem to be an opportune time for initiating this kind of registry to address the needs and at the same time benefit from the strategic opportunities.
Prosocial Behavior in Caregivers to Older Adults with Chronic Conditions
Authors: Beadle Janelle 
Published: December 2022

AbstractBackgroundIn the United States, 1 in 9 adults 65 years of age and older have Alzheimer’s disease. Thus, there is an urgent need for caregivers to support individuals with Alzheimer’s disease, and other chronic diseases of aging. However, due to the challenging physical and emotional nature of caregiving, caregivers are at risk for experiencing chronic stress and burnout which can negatively impact the well‐being of both the care recipient and the caregiver. The purpose of the present study is to examine the degree to which currently serving in a caregiving role affects individuals’ capacity to empathize and exhibit prosocial behavior towards others.MethodThe study included 60 caregivers (Mage = 60.6) to older adults with chronic conditions, and 104 healthy comparison participants (Mage = 62.9). The groups were not significantly different in terms of age (p = .50) or gender (p = .6). Participants played an economic game in which they decided how much money they would like to allocate out of $10 to two different players. During the study, they read a series of notes from the other players which were designed to evoke either an empathetic or neutral state. (Notes were developed by the researcher prior to the study.) Monetary offers were compared between the empathy and neutral experimental conditions. Participants also completed a measure of trait empathy (the Interpersonal Reactivity Index).ResultWe found that the caregivers gave more money in the empathy condition than the non‐caregivers (p<.05), with no statistically significant group differences found in the neutral condition. Within the caregiver group, there was a positive correlation between offer amount in the empathy condition and trait emotional empathy (p<.05).ConclusionDespite the stressors involved in caregiving, we show that caregivers exhibited greater prosocial behavior than non‐caregivers towards strangers in an empathy‐eliciting context. This suggests that in specific contexts the stressors involved in caregiving may not reduce caregivers’ capacity to show prosocial behaviors towards others. Future research may investigate whether this finding extends to empathy and prosocial behavior towards care recipients.