bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPATIAL WORKING MEMORY IN PRODROMAL STAGE: AN EYE TRACKING STUDY
Authors: Ekin Merve , Koçoğlu Koray , Boz Hatice Eraslan , Akkoyun Müge , Tüfekci Işıl Yağmur , Yalınçetin Berna , Bora Emre , Akdal Gülden 
Published: December 2023

AbstractBackgroundIndividuals at ultra‐high risk for psychosis and bipolar disorder (UHR‐P and UHR‐BD) have shown cognitive abnormalities and sub‐threshold clinical features (de Paula et al., 2015; Metzler et al., 2014). Assessing saccadic eye movements is one of the useful methods for investigating high cognitive functions like spatial working memory and inhibition (Pierrot‐Deseilligny et al., 2005; Winograd‐Gurvich et al., 2008). Memory‐guided saccade (MGS) may be described as short‐term maintenance of attention both when a peripheral target is presented, and a delay screen. The purpose of this study was to examine the differences between clinical risk groups and healthy controls (HCs) based on the memory‐guided saccade.MethodThe study was included 33 UHR‐P (age: 21.61 ± 3.24), 28 UHR‐BD (age: 21.64 ± 4.02), and 28 HCs (age: 22.11 ± 4.03). Participants were selected from cases of clinical‐high‐risk criteria in interviews made with The Structured Interview of Psychosis Risk Syndromes and Bipolar Prodrome Symptom Interview and Scale. The memory‐guided saccade was measured with the number of the correct, incorrect, anticipatory and express saccades, also latency, peak velocity and amplitude for the correct saccades. Eye movement data were recorded from the right eye using an EyeLink 1000 Plus eye‐tracker. All results were analyzed with SPSS software.ResultThe anticipatory and express saccades in the cue screen, the anticipatory saccade in the delay screen and the total error response were significant between groups (p<0.05). There was a significant increase in UHR‐BD compared to controls in the error responses (p = 0.018). The anticipatory saccades in UHR‐BD were higher than in both UHR‐P and HC on the cue screen (p = 0.005 and p = 0.014), and controls on the delay screen (p = 0.027). In addition, the express saccades in the cue screen showed statistical differences between the risk groups (p = 0.032).
ConclusionMemory‐guided saccades are used to assess the top‐down mechanism, including perceptual organization and goal‐directed behaviors, and are related to frontal lobe functions like spatial working memory and inhibitory control (Ostendorf et al., 2004). The elevation of incorrect saccades and predictive parameters like anticipatory saccades have indicated that individuals at the prodromal stage may appear spatial problems in inhibitory and exhibitory functions.
Engagement in Meaningful Activities Among Residents with Dementia in Assisted Living
Authors: Holmes Sarah D , Scherr Susan , Vigne Erin , Levy Sorah , Koenig Marcie , Galik Elizabeth , Resnick Barbara 
Published: December 2023

AbstractBackgroundEngagement in meaningful activities is beneficial for the physical and psychological well‐being of persons with Alzheimer’s disease or related dementia (ADRD). Meaningful activities are a critical dimension of person‐centered care, although challenges exist in providing them for persons with ADRD in long‐term care settings. The purpose of this study was to describe engagement in meaningful activities among residents with ADRD in assisted living.MethodThis study included baseline data collected from the first cohort of the randomized controlled trial, Meaningful Activities for Managing Behavioral Symptoms of Distress (MAC‐4‐BSD). Assisted living residents were eligible if they were ≥55 years old, live in a participating setting, and screen positive for dementia based on the Saint Louis University Mental Status exam (SLUMS) and AD8 Dementia Screening Interview. Residents were excluded if they were enrolled in hospice, admitted for short term respite, or had a significant neurological condition not related to ADRD. Residents’ engagement in meaningful activities was evaluated based on the Engagement in Meaningful Activities Survey (EMAS). Descriptive statistics were used to summarize sample characteristics and describe engagement in meaningful activities.ResultA total of 38 residents from 3 assisted living communities were included in the sample. Most participants were female (71%), White (82%), and mean age was 81 years old (SD = 7.9). Average score on the SLUMS was 4.5 (SD = 4.9). The EMAS mean score was 43.57 (SD = 10.9) with a range of 25 to 60. Participation was endorsed most frequently for activities that give them pleasure (60.7%) and a sense of satisfaction (64.3%). Participation was endorsed least frequently for activities that help other people (35.7%), contribute to feeling competent (42.9%), and have the right amount of challenge (42.8%).ConclusionFindings from this study offer preliminary insights into residents’ engagement in meaningful activities in assisted living and suggest there is limited participation in activities that help others, help with feeling competent, and have the right challenge level for those with ADRD. Although limited by small sample size, this study highlights the need for increasing engagement in meaningful volunteer activities to help others which recent research demonstrates could positively impact physical and cognitive health outcomes.
Metabolic pathways associated with multi‐morbidity among Black caregivers of persons living with dementia
Authors: Brewster Glenna S , Houser Madelyn , Yang Irene , Wells Jessica , Carlson Nicole 
Published: December 2023

AbstractBackgroundBlack adults have the highest prevalence of obesity and hypertension, and these multiple chronic conditions increase their risk of morbidity and mortality. Black adults also represent the second largest group of caregivers of persons living with dementia. Gaps exist in our understanding of the physiologic changes associated with multiple chronic conditions in Black caregivers. This study used metabolomics to compare the metabolic profiles of Black caregivers with obesity, with or without hypertension. Our goal was to identify physiologic pathways for targeted interventions to improve morbidity/mortality in this group.MethodHigh‐resolution, untargeted metabolomics assays were run on stored serum samples from Black caregivers (n = 26) with obesity (BMI > = 30kg/m2), among whom 18 also had a diagnosis of hypertension. Linear regression using the xmsPANDA package was employed to identify metabolites differentiating multi‐morbidity. Two‐way hierarchical clustering analysis was used to visualize metabolome‐wide associations with multi‐morbidity. Additionally, metabolic pathways differentially impacted in multi‐morbidity were identified using mummichog.ResultOn average, caregivers were 62.9 (±6.5) years. 88.5% were female and 43% were married. Caregivers had been providing care for about 4.33 (±4) years. A total of 129 metabolites differentiated multi‐morbidity status at a p value < .05. Among these, key metabolic pathways associated with obesity and hypertension were butanoate metabolism and fatty acid activation. Among caregivers with only obesity, metabolites in the butanoate pathway were downregulated, compared to caregivers with both obesity and hypertension. Two exceptions were butyric acid and 2‐hydroxybutyric acid, which were both upregulated in caregivers without multi‐morbidity. In the fatty acid activation pathway, caregivers with only obesity had upregulated metabolites with the exception of icosatrienoic acid and dihomo‐gamma‐linolenic acid, which were down‐regulated.ConclusionIn caregivers with obesity, pathways associated with butanoate metabolism and fatty acid activation significantly differentiated hypertensive status. Healthcare interventions targeting caregiver education on diet/exercise may help optimize fatty acid activation in Black caregivers, thereby helping to reduce their risk of developing multi‐morbidities with hypertension. In addition, expanded health assessment of Black caregivers should be considered, as they may be at high risk for metabolic syndrome due to perturbed fatty acid and butanoate pathway functioning.
Depletion of microglia with CSF1R inhibitor prevents tau aggregation in the mouse model Thy1P301S
Authors: Lombardo Sylvia , Stanek Agathe , Wuest Carolin , Reich Thomas , Secker Philipp , Sefrin Julian , Biber Knut , Mezler Mario , Klein Corinna 
Published: December 2023

AbstractBackgroundNeuroinflammation and microglia proliferation are central in Alzheimer’s disease pathology. However, the role of microglia in the accumulation and spreading of plaques and tau tangles is not yet well understood.MethodIn this study, we depleted the microglia population in the brain of Alzheimer’s disease (APP PS1) tauopathy (Thy1P301S) and dual pathology (APPPS1 Thy1P301S) mice models using a colony stimulating factor 1 receptor (CSF1R) inhibitor to achieve microglia ablation. Consequences of compound treatment on brain pathology were analyzed.ResultReduced number of microglia cells in the brain was successfully achieved in the mouse model Thy1P301S. In a chronic treatment study of 3 months, mice treated with the CSF1R inhibitor showed a significant decrease in tau aggregation and deposition compared to the control group.ConclusionHere we show that inhibition of microglia proliferation induces attenuation of tau pathology. This work demonstrates that intervention on microglia is a potential therapeutic approach in Alzheimer’s disease.
The bidirectional associations between cognition and depression in mid‐life and older adults in the CLSA
Authors: Stinchcombe Arne , Hopper Shawna 
Published: December 2023

AbstractBackgroundExisting evidence suggests that depression may be a risk factor for subsequent cognitive impairment and dementia. Concurrently, other evidence suggests that cognitive impairment may precede depression symptoms. We investigated the relationship between depression symptoms and memory performance over a three‐year time period in a sample of mid‐life (45 ‐ 64 years) and older adults (65 ‐ 85 years).MethodData were drawn from the Canadian Longitudinal Study on Aging (CLSA), a large longitudinal study of health and aging. Depression symptoms were assessed with the Centre for Epidemiological Studies Depression Scale (CESD‐10) and memory was captured using the Rey Auditory Verbal Learning Test (RAVLT). Two time points were analyzed: baseline (completed in 2015) and first follow‐up (completed in 2018). We used multigroup cross‐lagged structural equation modelling (SEM) to estimate the bidirectional relationships between depression and cognition over time, based on age group: participants aged 45‐64 years (n = 26,605) and 65 years and above (n = 17,986). Sex, education, ethnicity, sexual orientation, and general health were controlled for at baseline.ResultThe results confirmed a bidirectional association between depression symptoms and memory over time, a relationship that was moderated by age group (difference test: p = .02). Results showed that the association between depression at baseline and memory at follow‐up was stronger for the younger cohort (r = ‐.039, p<.001) compared to the older cohort (r = ‐.015, p = .026).ConclusionThe results confirm the bidirectional relationship between depression symptoms and memory. This work also highlights the role of age group as a moderator of this relationship, insofar as depression is a stronger correlate of memory for mid‐aged adults in comparison to older adults.
Microglia and neuron derived extracellular vesicles show distinct small RNA patterns in Alzheimer’s disease
Authors: Arbaciauskaite Skaiste , Allelein Susann , Scholz Alexander , Loeffler Dennis , Reiche Kristin , Blumert Conny , Kuhlmeier Dirk 
Published: December 2023

AbstractBackgroundExtracellular vesicles (EVs) are nano‐sized membranous particles that are released by almost all cells in the human body. EVs carry different cargo (e.g. protein, lipid, nucleic acids) that differs based on the EVs biogenesis and state of the cell during the release. Therefore, EVs are excellent for identifying disease patterns and biomarkers. The need to understand the pathogenetic patterns and biomarkers in neurodegenerative diseases is crucial for early diagnosis as well as potential therapeutic intervention.Studies show that small RNA, especially miRNA participate in pathologic processes connected to neurodegeneration, therefore we have specifically looked into microglia and neuron derived EVs small RNA content of patients with Alzheimer’s disease (AD) and control patients. The aim of the study was to find AD patterns coded in small RNA.MethodEVs were isolated specifically from microglia and neurons by immunomagnetic precipitation from blood plasma and cerebrospinal fluid (CSF) collected from patients with AD and healthy aged‐matched controls. Western blots were used to characterize EVs composition and assess purity. Small RNA isolation was performed on the isolate EVs and then sequenced using commercial kits. Quantitative PCR (qPCR) was performed for validation.ResultWe found that neuron‐ and microglia‐derived EVs are present in blood plasma as well as CSF and they carry a big variety of small RNA biotypes. Looking specifically into miRNA, distinct groups of miRNA were expressed only in AD patients and only in healthy controls. Also, differences between genders was observed.ConclusionWe showed distinct miRNA patterns in neurodegeneration, specifically in AD. The results of our study suggest that miRNA could be used to elucidate the pathological processes involved in AD development and help to diagnose neurodegenerative changes earlier.
Brief, Interoceptive Exposure Focused Treatment for Anxiety in Older Adults
Authors: Schubert Frederick T , Schmidt Norman B 
Published: December 2023

AbstractBackgroundOlder adults with Mild Cognitive Impairment (MCI), Alzheimer’s disease (AD) and related dementias, and their care partners often experience high levels of anxiety. This not only diminishes their quality of life but also serves as a marker for earlier onset of ADRD symptoms for individuals experiencing MCI. Moreover, there is no well‐established treatment for those with MCI/mild AD. Anxiety sensitivity (AS) is a mechanism central to the genesis and maintenance of anxiety psychopathology that exacerbates the experience of somatic and emotional sensations, leading to increased distress. Brief, computerized, mechanism‐focused interventions have been shown to effectively reduce AS. This study sought to evaluate the acceptability and efficacy of a brief AS focused intervention in older adults with probable MCI including a repeated interoceptive exposure component and the participation of a care partner.MethodParticipants (N = 16) were recruited from the community varied in age from 65 to 81 (M = 72.44; SD = 4.83). Eligible participants enrolled in an open trial consisting of a 2‐hour intervention focused on interoceptive exposure (systematic exposure to anxiety and stress symptoms to achieve habituation). All participants completed a brief cognitive assessment, AS measures pre‐ and post‐intervention, and acceptability measures post‐intervention.ResultAverage baseline Montreal Cognitive Assessment scores were 24.25 (SD = 3.24; Range = 19‐29), which is generally indicative of MCI. Paired samples t‐tests were conducted to examine changes in total ASI‐3 scores pre‐ to post‐intervention. Despite the relatively small sample, we observed statistically significant reductions in ASI‐3 total scores with a large effect size (Δ = 4.38, Hedge’s g = .80, p<.01). Additionally, the intervention was highly acceptable with 100% of participants completing the intervention and rating the quality of the intervention as good or excellent.ConclusionThis study provides encouraging evidence that brief interventions can successfully target risk mechanisms of anxiety in older adults with probable MCI. The favorable acceptability of the intervention suggests that it would be well‐received by both those with MCI and mild AD. Future research should examine this intervention in randomized‐clinical trials and study its effects longitudinally to understand how decreases in AS persist over time and relate to cognitive outcomes.
Culturally‐informed Community‐engaged Efforts to Improve Inclusion and Engagement of Underrepresented Ethnocultural Populations in the Alzheimer’s Disease Neuroimaging Initiative 3 Study: The ADNI Diversity Task Force
Authors: Okonkwo Ozioma , Mindt Monica Rivera , Ashford Miriam T. , Conti Catherine , Strong Jospeh , Raman Rema , Miller Garrett , Donohue Michael C. , Nosheny Rachel L , Coker Godfrey , Miller Melanie Jayne , Petersen Ronald C. , Aisen Paul S. S , Weiner Michael S. W. 
Published: December 2023

AbstractBackgroundEthnoculturally diverse individuals from underrepresented populations (URPs), including but not limited to Black/African American and Hispanic/Latinx adults, are disproportionally affected by Alzheimer’s disease (AD) compared to non‐Hispanic/Latinx white (NLW) adults. However, URPs have historically been under‐included in AD studies. The objective of this study is to describe efforts, and the results of those efforts, to increase enrollment and engagement of ethnoculturally diverse individuals from URPs in the Alzheimer’s Disease Neuroimaging Initiative 3 (ADNI3).MethodsEfforts undertaken by ADNI to increase enrollment and engagement of URPs included (1) launching of a Diversity Taskforce (DVTF) lead by two health disparities experts in July 2020, charged with overseeing ADNI’s mission in this space. Specific DVTF activities included: (2) the establishment, funding, and instrumental support (e.g., training, consultation, resources) of diversity at 13 ADNI3 sites; (3) changing ADNI protocol to facilitate research participation of URPs (e.g., optional lumbar puncture and sharing of amyloid PET results); (4) hiring a marketing agency to launch culturally‐informed digital/social media campaigns for the 13 DVTF Sites, with local websites; (5) development of a database to capture performance metrics of inclusion efforts at the 13 DVTF Sites; and (6) formation of a six‐member External Advisory Board, comprised of leaders in health disparities research, to guide DVTF efforts.ResultURP enrollment at these 13 DVTF sites improved from 1.1 URPs per month previously to >4 URPs per month, a 264% increase. Across all 59 ADNI sites, overall enrollment of ethnoculturally diverse individuals from URPs went from 89 (16.8%) to 126 (21.1%), representing a 25% increase in enrollment between May 2020 and September 2021. Moreover, since February 1st, 2021, ADNI enrolled 43 new participants of which 33 (77%) were from URPs.ConclusionIt is possible to improve the enrollment and retention of URPs in AD research using a multi‐pronged community engaged approach that also provides human capital, infrastructure, and financial resources. The success of the DVTF has led to the formation of a new Engagement Core in ADNI4, tasked with implementing a scaled‐up culturally‐informed, community‐engaged research approach to URP inclusion and retention across all 59 ADNI sites.
A systematic review on the perioperative use of EEG as a predictor/diagnostic tool for postoperative delirium
Authors: Bruzzone Maria , Chapin Benjamin , Arias Franchesca , Walker Jessie , Price Catherine C. 
Published: December 2023

AbstractBackgroundThe electroencephalogram (EEG) in the perioperative setting has been increasingly used as a tool for delirium prognostication and diagnosis. Delirium in the post‐operative setting occurs in 20‐25% of the patients aged 65 and older. The has been used for a long time in the intraoperative setting, with some measures being associated with the development of POD. Recently studies have been focusing on the use of the EEG preoperatively as a prediction tool, and postoperatively as a diagnostic tool for POD.MethodWe performed a systematic review to address the role of EEG in the perioperative setting as a tool for delirium prognosis and diagnosis. Twelve randomized control trials and twenty‐eight observational studies were identified.ResultCommon preoperative findings associated with the development of POD include: higher alpha power, increased alpha band connectivity but impaired structural connectivity, increased slow wave activity involving frontal and occipitoparietal cortex with accompanying break down in functional connectivity, lower EEG‐ asymmetry, lower values of pre‐operative spectral edge frequencies, and polysomnography findings of longer non‐REM stage 2 sleep. Common intraoperative findings associated with POD include: increased magnitude and duration of EEG suppression, reduced higher frequencies, increased prevalence and duration of BSR, and low BIS values. Finally, post‐operative findings associated with POD include: greater delta power while awake, alterations in delta in wake versus sleep state, and disruptions in connectivity.ConclusionThe use of EEG as a diagnostic and prognostic tool has promising utility in the perioperative setting. In the pre‐and intraoperative setting, certain EEG markers may be utilized to predict delirium or triage which patients are at a higher risk of developing POD. Postoperatively, EEG use can predict and help diagnose POD. More studies are needed to further systematize and validate this data.
GABAB receptor activation promotes synaptic resilience in Alzheimer’s disease
Authors: McArdle Colin J , Uneri Ayse , Niere Farr , Raab‐Graham Kimberly F 
Published: December 2023

AbstractBackgroundHyperexcitability and glutamate excitotoxicity are the primary contributors towards synapse loss in Alzheimer’s disease (AD). The goal of this project is to examine how other neurotransmitter systems, such as the inhibitory GABAergic system, are responding to hyperexcitability in AD. Therefore, we examined the role of metabotropic GABAB receptors (GABABRs) towards synapse loss.MethodsPrimary hippocampal neurons were cultured from both wildtype (WT) and transgenic APP/PS1 mice. In addition, treatment of non‐transgenic hippocampal neurons with Aβ oligomers (500nM) were used as another model of AD‐related pathology. Immunocytochemistry was used to determine the dendric expression of GABAB1R and GABAB2R, the two principal subunits of GABABRs. To examine changes in GABABR function, a calcium imaging protocol was utilized to quantify changes in calcium florescence following GABABR activation with baclofen (50μM). To understand whether GABABR activation is protective against synaptic loss in AD, APP/PS1 hippocampal neurons were treated with 50μM baclofen (GABABR agonist), 100μM CGP35348 (GABABR antagonist), or vehicle. This study used both colocalization of presynaptic (Synapsin‐1) and postsynaptic (PSD95) markers as well as a novel method, DetectSyn, to quantify changes in synaptic density.ResultsDendritic GABAB1R and GABAB2R expression is upregulated in APP/PS1 hippocampal neurons as compared to WT. Non‐transgenic neurons treated with Aβ‐oligomers also show upregulations in GABAB2R, with no changes in GABAB1R. Treating WT neurons with baclofen resulted in an approximate 10% decrease in calcium florescence. The same treatment applied to APP/PS1 neurons resulted in a significantly greater decrease (∼40%) in calcium florescence. Activating GABABRs in APP/PS1 neurons increased synaptic density as compared to vehicle treated neurons. This was indicated by a greater Pearson’s coefficient between Synapsin‐1 and PSD95, as well as a greater number of DetectSyn‐PLA puncta. Antagonizing GABABRs in APP/PS1 neurons failed to rescue synaptic density (no changes in Pearson’s coefficient/DetectSyn‐PLA puncta) when compared to vehicle treated neurons.ConclusionsUnder pathological conditions, upregulation and activation of GABABRs serves as a potential mechanism to combat against hyperexcitability, therefore preventing hippocampal synaptic loss in AD.