bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levels of ADAM10 and BDNF in low‐educated healthy older adults and individuals with Alzheimer’s dementia
Authors: Pelegrini Lucas Nogueira de Carvalho , Pedroso Renata Valle , Grigoli Marina Mantellatto , Manzine Patricia Regina , Cominetti Marcia Regina 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) is the most common type of dementia among older adults (Prince et al., 2015). Research has focused on specific biomarkers for AD that could contribute to early diagnosis. Levels of ADAM10, for example, are altered in people with AD, and this protein has been studied as a potential blood‐based biomarker for this disease (Elsworthy et al., 2022). Brain‐derived neurotrophic factor (BDNF), in turn, is a protective factor involved, for example, in neurotransmitter modulation, as well as in neuronal plasticity and survival (Tarassova et al., 2020). Therefore, analyzing the possible relationship between these variables is relevant to expand the knowledge of AD biomarkers.Aimto verify whether there is a relationship between the levels of ADAM10 and BDNF among healthy older adults and individuals with AD with low educational attainment.MethodsThis is a cross‐sectional study in which community‐dwelling older adults with low educational levels (n = 85) were assigned to two groups: healthy older adults (n = 37) and participants with AD (n = 48). The interview was based on a sociodemographic questionnaire and cognitive assessment (Mini‐Mental State Examination‐MMSE and the Clock Drawing Test‐CDT). Participants had their blood collected, and SDS‐PAGE and Western Blotting techniques were used to measure plasma ADAM10 levels.ResultsParticipants with AD were older (p<.001); had less educational attainment (p<.001); worse performance on MMSE (p<.001), and on its domains [Orientation (p<.001), attention, memory (p = .028), language(p<.001), and evocation(p<.001)]; as well as worse performance on CDT (p<.001). Also, compared to the healthy group, persons with AD had significantly higher levels of plasma ADAM10 (p = .04). No difference in BDNF levels was observed between the groups (p = .07). Correlation analyses revealed a significant correlation between ADAM10 and years of education (r = ‐.234; p = .04); MMSE total score (r = ‐.328; p = .003), and its orientation (r = ‐.224; p = .04), attention (r = ‐.278; p = .01), and evocation (r = ‐.332; p = .003) domains. BNDF was not correlated with any of the variables in this study.ConclusionThis study showed that plasma ADAM10 levels in low‐educated older adults, but not BDNF, differ between healthy and AD participants. Our results reinforce the potential role of ADAM10 as a biomarker for AD.
Association of plasma Alzheimer’s and neurodegenerative disease biomarkers with brain volume loss and cognitive decline
Authors: Dark Heather E , Duggan Michael R , An Yang , Bilgel Murat , Joynes Cassie , Lewis Alexandria , Moghekar Abhay , Resnick Susan M. , Walker Keenan A. 
Published: December 2023

AbstractBackgroundAlthough plasma Alzheimer’s disease (AD) and neurodegenerative disease biomarkers have been associated with reduced cognition and lower brain volume, few studies have examined whether plasma biomarkers measured in predominately cognitively unimpaired adults are associated with longitudinal brain volume loss and cognitive decline. Using data from the Baltimore Longitudinal Study of Aging (BLSA), we examined whether plasma biomarkers of AD pathology (Aβ42/40, phosphorylated tau [pTau‐181]), reactive astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal brain volume loss and cognitive decline.MethodPlasma biomarkers (Aβ42/40, pTau‐181, GFAP, NfL) were measured using Quanterix SIMOA assays. Baseline visits were considered the earliest visits that had concurrent 3T MRI scans and plasma biomarker measurements, and the earliest visits that had concurrent cognitive assessments and plasma biomarker measurements. Composite Z scores were computed to reflect 5 cognitive domains (Figure 1). Linear mixed effects models adjusted for baseline age, sex, race, education, estimated glomerular filtration rate, and total intracranial volume (brain volume analyses), were used to examine the association of plasma biomarkers with baseline and longitudinal brain volume and cognition. False Discovery Rate correction was used to adjust for multiple comparisons.ResultBrain volume analyses included 628 participants (mean age±SD: 71.0±10.2; Table 1) with an average of 3.3 MRI scans over 4.7 years. Cognition analyses included 686 participants (mean age±SD: 71.4±10.1) with an average of 3.9 cognitive assessments over 5.7 years. Although Aβ42/40 was unrelated to brain volume changes, higher pTau‐181 was associated with longitudinal declines in total gray matter volume and regional declines in medial temporal regions. Higher GFAP was associated with longitudinal increases in ventricular volume, whereas NfL was not associated with brain volume change (Table 2). Both lower Aβ42/40 and higher pTau‐181 were associated with a decline in verbal memory. Additionally, lower Aβ42/40 was associated with a decline in visuospatial performance. Further, higher GFAP was associated with a decline in verbal fluency (Figure 1).ConclusionPlasma biomarkers of AD pathology and astrogliosis may serve as markers of future brain atrophy and cognitive decline.
Risk factor of suicidal thoughts in caregivers of dementia patients: a systematic review and meta‐analysis
Authors: Chambergo‐Michilot Diego , Custodio Nilton , Montesinos Rosa , Lanata Serggio 
Published: December 2023

AbstractBackgroundDementia is a neurologic syndrome that affects several domains of daily life. However it does not exclusively affect the patient, but relatives, friends and caregivers, who are people constantly in contact with the patient. Deterioration of cognition and daily life activities may affect mental health of the caregiver. In this systematic review, we collected evidence regarding risk factors of suicidal thoughts among caregivers of patients with dementia.MethodA search was carried out in PubMed, Scopus, and Web of Science up to January 2023. Observational studies that analyzed factors associated with suicidal thoughts in caregivers were selected and revised. Meta‐analyses were performed with R Studio.ResultFour studies were selected for this systematic review. Only one study assessed caregivers of dementia and non‐dementia patients. Total sample size was 2224. Mean age was approximately 60 years. We did not find significant differences between caregivers with and without suicidal thoughts in age, educational level, religious status, being a woman, being spouse or caring one year or more. However, we found that CES tool score for depression was higher in those caregivers who reported suicidal thoughts (MD: 8.03, 95% CI: 6.26‐9.80).ConclusionDepression is a risk factor of suicidal thoughts, however more efforts should be done to assess non‐typical risk factors of suicidal thoughts among caregivers. We highly recommend increasing the sample size for future studies.
Functional neuroanatomic validity of a novel, smartphone‐based remote assessment of processing speed in early Alzheimer’s Disease
Authors: Taylor Kirsten I , Kurniawan Irma T , Wolfer Arnaud M , Lipsmeier Florian , Perumal Thanneer M 
Published: December 2023

AbstractBackgroundThe quantification of information processing speed (IPS) and its changes over time is a cornerstone of neuropsychological assessment for early Alzheimer’s disease (eAD). Additionally, clinical practice and drug development increasingly require tools enabling the remote assessment of cognition. We previously reported the feasibility, reliability and clinical validity of a novel, smartphone‐based IPS test remotely self‐administered to healthy controls (HC) and individuals with subjective cognitive decline (SCD) and eAD. The present study performed whole‐brain voxel‐based morphometry (VBM) analyses to determine whether smartphone‐based IPS performance indeed correlated with atrophy of brain regions known to support processing speed.Method31 HC, 31 SCDn (amyloid‐PET negative), 31 SCDp (amyloid‐PET positive) and 30 eAD individuals participated in a Alzheimer’s Digital Assessment Suite (AD‐DAS) Proof‐of‐Concept study (https://www.isrctn.com/ISRCTN17035495). Participants performed 9 IPS assessments (90s digit‐symbol matching) over 28 days on provisioned smartphones. Each response sequence and digit‐symbol pairing was novel and matched for difficulty within/across sessions.High‐resolution anatomic, T1‐weighted MRI were submitted to whole‐brain VBM analyses (Computational Anatomy Toolbox, SPM12/Matlab 2021) testing whether performance (number correct) correlated with gray matter signal intensities (covariates: age, gender, years of education, study site, total intracranial volume). The statistical parametric map was thresholded at p<0.001 uncorrected (voxel‐level) and family‐wise error corrected p<0.05 (cluster‐level). Peak voxel MNI coordinates and t‐values, cluster‐level p‐values are reported.ResultPoor smartphone‐based IPS performance correlated with atrophy in five regions centered in: (1) right insula (57, ‐14, 15; t = 5.83; p<0.0001), (2) right lingual gyrus (14, ‐64, ‐8; t = 5.21; p = 0.006), (3) left hippocampus (‐36, ‐24, ‐16; t = 4.83; p = 0.021), (4) left precuneus (‐10, ‐57, 26; t = 4.73; p = 0.017), (5) right fusiform gyrus (27, ‐38, ‐15; t = 4.69; p = 0.043), replicating previous functional MRI findings with IPS (lingual gyrus, precuneus) and known neuroanatomical correlates of working memory (insula, hippocampus).ConclusionThese findings support the functional neuroanatomic validity of a novel smartphone‐based IPS task and thus remote, clinically meaningful characterization of preclinical/early AD individuals’ IPS impairments in clinical monitoring and drug trials.
Circular RNAs Associated with Idiopathic Parkinson’s Disease: Case/Control Study Results on PPMI Dataset
Authors: Sun Yichen , Beric Aleksandra , Chen Hsiang‐Han , Eteleeb Abdallah M , Cruchaga Carlos , Ibanez Laura 
Published: December 2023

AbstractBackgroundPD is the second most common neurodegenerative disease after AD, for which biomarkers do not exist. We aimed identify circular RNAs associated with Parkinson’s Disease (PD) in a longitudinal dataset and test their potential as Bioamrkers.MethodWe included 2507 European ancestry blood samples from PPMI participants, with transcriptomic data available and distributed across five time‐points. We aligned reads to the reference genome (GRCh38) using STAR in chimeric alignment mode. Annotation and quantification of circRNAs were performed using DCC, followed by a cross‐sectional differential expression analyses for each visit using DESeq2. Significance was assessed and corrected by FDR at the last visit, with nominal p‐value for the remaining visits. We used Circular RNA Interactome web tool to predict microRNA (miRNA) target sites within significantly dysregulated circRNAs. Subsequently, we performed pathway analyses using DIANA tools.ResultTwo circRNAs were significantly dysregulated in PD across all visits: circRHBDD1 (p = 3.34´10−4, Log2FC = ‐0.13) and circDHRSX (p = 1.03´10−3, Log2FC = 0.4). We identified twenty miRNAs that putatively interact with circRHBDD1. Pathway analyses showed that fourteen of them are involved in the Hippo signaling pathway, fifteen in oxytocin signaling pathway, and sixteen in the ErbB1 signaling pathway. We also identified one hundred and twenty‐eight miRNAs interacting with circDHRSX that are also part of the Hippo signaling pathway.ConclusionWe identified circRHBDD1 and circDHRSX to be dysregulated in PD across time. Both of them are enriched in binding sites for miRNAs that target the Hippo and ErbB1 signaling pathways. ErbB1 has already been associated with PD in brain studies, whereas the Hippo pathway is associated to neuronal cell death. We are conducting additional analyses in independent datasets and using mixed models to replicate the results and obtain the best predictive models.
RNA‐targeted therapy for Tau‐driven neuronal malfunction: preclinical screening
Authors: Silva Joana , Campos‐Marques Carlos , Godinho Bruno , Watts Jonathan , Sousa Nuno , Sotiropoulos Ioannis 
Published: December 2023

AbstractBackgroundTau protein is the most well‐known and studied microtubule‐associated protein, mainly due to its aberrant hyperphosphorylation and accumulation that is observed in Alzheimer’s disease (AD) and other Tauopathies. Accumulating evidence from different research teams, including ours, supports the involvement of Tau and its malfunction in brain pathologies with diverse etiologies such as epilepsy, stress‐driven depression, and more recently persistent pain, pointing towards a broader role of aberrant Tau accumulation in neuronal malfunction and brain pathology. Antisense oligonucleotides (ASOs) are small synthetic strings of nucleotides that regulate the RNA levels of the protein of interest while they have been proven to be safe for both animal and human use. As Tau reduction appears a promising therapeutic intervention against Tau‐driven neuronal malfunction, the current studies aim to design and monitor the efficiency of novel Tau‐ASOs.MethodsWe have designed 50 novel ASOs against total Tau or selectively 4R‐Tau while their efficiency was tested in differential N2a and SHSY‐5Y cell lines expressing WT and mutated human P301L‐Tau followed by hippocampal primary neuronal cultures of WT and P301L‐Tg mice.ResultsBased on the above in vitro assays, we have identified a set of novel and highly efficient ASOs for reducing Tau or modulating 4R/3R isoform ratio as assessed by different types of molecular and cellular, neurostructural, and synaptic analysis.ConclusionAltogether, these data provide solid evidence of the in vitro evidence of novel ASOs targeting total Tau or modulation of 4R/3R isoform ration to be beneficial against Tau‐related neuronal malfunction in neuronal pathologies, supporting this as an innovative RNA‐based therapeutic approach.
Longitudinal Coupling Between Depressive and Cognitive Symptoms in Ageing and Dementia: A Multi‐Cohort Analysis
Authors: Hamilton Calum Alexander 
Published: December 2023

AbstractBackgroundDepression and cognition have a complex bidirectional relationship in adulthood and later life. This association is likely heterogeneous, differing between individuals. Further complicating this association is the possible influence of unseen neuropathological changes: any associations between depression and cognitive symptoms may differ in normal and pathological ageing.We therefore aimed to examine the longitudinal coupling between depressive and cognitive symptoms in later life across multiple ageing cohorts drawing from population settings, memory services, and from a national dementia brain bank.MethodRepeated data on cognitive performance and self‐ or informant‐reported depressive symptoms were drawn from multiple cohorts: three population ageing studies, CFAS (n = 17,807), Whitehall II (n = 8249) and ELSA (n = 17,980); MEMENTO (n = 2306), a clinical cohort of people with subjective/mild cognitive impairment (S/MCI); BDR (n = 584), a clinico‐pathological cohort with autopsy‐confirmed dementia‐related neurological disease.Intercept and growth parameters for depressive and cognitive symptoms, and correlations between these, were estimated with bivariate latent growth models.ResultThe relationships between depressive and cognitive symptoms differed substantially between cohorts across the ageing continuum. In early ageing and S/MCI, worse cognitive performance was associated with worsening depression over time (r = 0.12, p = 0.022), whereas in clinical dementia groups and those with autopsy‐confirmed neurological disease, worse cognitive performance was associated with improving depression over time (r = ‐0.30, p = 0.008 and r = ‐0.49, p = 0.023, respectively).ConclusionAge‐related associations between cognitive and depressive symptoms may differ between specific ageing populations. When attempting to understand the relationship between depressive and cognitive trajectories, researchers should consider the position of the given sample along this healthy‐pathological ageing continuum.
Exploring the relationship between MRI changes and cognitive/neuropsychiatric complaints in a cohort of long COVID‐19 patients: A cross‐sectional and longitudinal study
Authors: Pérez‐Millan Agnès , Guillén Núria , Falgàs Neus , Botí María Ángeles , Tort‐Merino Adrià , Lledó‐Ibáñez Gema María , Ruiz‐García Raquel , Naranjo Laura , Rami Lorena , Balasa Mircea , Lladó Albert , Sala‐Llonch Roser , Sanchez‐Valle Raquel 
Published: December 2023

AbstractBackgroundPost‐acute Covid‐19 syndrome (PACS) frequently refers to cognitive complaints. It is not yet clear whether there is an association between cognitive symptoms with brain changes or neuropsychiatric symptoms. Our aims are 1) to study cross‐sectional and longitudinal MRI brain measures in a cohort of PACS and 2) their association with cognitive performance and mood disturbances.MethodWe performed a prospective single‐center study with 3T‐T1w MRI of 49 PACS patients at a cross‐sectional level. These participants had confirmed SARS‐CoV2 infection, ≥ 8 weeks after symptoms onset and cognitive complaints. All participants completed a comprehensive neuropsychological battery (NPS) and questionnaires assessing depression, anxiety, and subjective cognitive complaints (SCD). We obtained global MRI measures (e.g; gray and white matter volumes and mean cortical thickness) with FreeSurfer. We measured correlations of global MRI measures with SCD, memory and executive function outcomes, anxiety, and depression. All analyses were corrected for multiple comparisons. 44 PACS subjects had a 6‐month follow‐up MRI: in these, we performed longitudinal analyses with Generalized Linear Mixed‐Effects Models to study changes between visits in global MRI measures.ResultDemographics are shown in Table 1. We did not find any correlation between clinical outcomes (SCD, anxiety, depression) and MRI findings. Visual memory (Rey figure’s recall) and cognitive interference inhibition and processing speed ((Stroop’s color‐word condition) were positively correlated with global gray and white matter volume measures (Figure 1). We did not identify changes in global MRI measures at 6 months in PACS participants.ConclusionIn PACS, worse visual memory and executive function, but not other clinical outcomes, were associated with lower global structural MRI indexes. We did not observe global longitudinal changes in MRI.
The impact of self‐reported retrospective early adversity on later life biopsychosocial outcomes
Authors: Kuenzi Morgane 
Published: December 2023

AbstractBackgroundEarly adversity has been associated with several biopsychosocial outcomes later in life. Early adversity and its long‐lasting consequences may affect directly or indirectly cognitive aging and increase the risk of developing dementia in older age. Therefore, investigating the biopsychosocial outcomes associated with early adverse experiences is essential to be able to promote good development across the life course (i.e., resilience) and healthy (cognitive) aging.MethodThe goal of this study is to investigate the effect of early adversity (i.e., trauma and deprivation) on various biopsychosocial outcomes (i.e., physical and mental health, lifestyle, and cognition) in two UK cohorts (UK Biobank, N = 500,000; the English Longitudinal Study of Ageing (ELSA), N = 20,000). In both cohorts, adversities are self‐reported retrospectively, and only those adversities assessed in both cohorts were selected.ResultThe preliminary results showed that in both cohorts early adverse experiences have a significant detrimental effect on all the biopsychosocial outcomes investigated (i.e., physical and mental health, lifestyle, and cognition), Ps <.01.ConclusionIn line with the literature, early adverse experiences have long‐lasting detrimental effects on a variety of biopsychosocial outcomes. The results found will be replicated on longitudinal data, to gain more information about the associations found and their underlying mechanisms. The aim of this study is to identify target factors on which to base interventions to promote resilience and healthy (cognitive) aging.
Interrelationships between depression, diabetes, and dementia in the prospective PREVENT cohort
Authors: Reid Graham 
Published: December 2023

AbstractBackgroundMood disorders, metabolic diseases, and cognitive impairment are significant challenges facing public health. These three conditions are increasing in epidemiological prevalence and comorbidities amongst the three are common. For example, research has shown that diabetes is associated with a twofold risk for both depression and all‐cause dementia. Depression has also been associated with greater cognitive impairment and the additive effect of comorbid diabetes accelerates cognitive decline. Depression and diabetes seem to be most highly associated with cognitive impairment in middle‐aged adults, but the interrelationships between these three non‐communicable disorders have not been well characterised in this period of life.MethodAs such, the aim of the current study was to investigate the relationships between depression, cognitive abilities, and insulin resistance in 665 middle‐aged adults from the prospective cohort, PREVENT. We assessed the interrelationships in older middle‐aged adults (50‐60 years old) and younger middle‐aged adults (40‐49 years old) using structural equation modelling.ResultOur analyses showed that executive dysfunction could be predicted from insulin resistance in older but not younger middle‐aged adults. We also showed that depression could be predicted from insulin resistance in both younger and older adults in their midlife. And finally, we showed that deficits in visuospatial memory could be predicted from depression in older but not younger middle‐aged adults.ConclusionGoing beyond the existing bivariate associations in the literature and focusing on middle‐aged adults where comorbidities are most likely to occur, we have captured the complexity of the relationships between these three non‐communicable diseases. Together, we demonstrate the interrelations between mood disorder, metabolic disease, and cognitive impairment, emphasising the need for combined interventions for adults in the middle period of their life.