bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human and mouse seeds differentially affect Aβ aggregation by modulating the inflammatory response
Authors: Andreo‐Lopez Juana , Cantero‐Molina Francisco , Bettinetti‐Luque Miriam , Huynh Kelly Do , Nguyen Marie Minh Thu , Cheung Alwin , Tran Janine Pham , Da Cunha Celia , Trujillo‐Estrada Laura , Nuñez‐Diaz Cristina , Martini Alessandra Cadete , Forner Stefania , Gutierrez Antonia , LaFerla Frank , Baglietto‐Vargas David 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) is a neurodegenerative proteinopathy in which Aβ can misfold and aggregate into seeds that structurally corrupt native proteins, mimicking a prion‐like process. These amyloid aggregation and propagation processes are influenced by three factors: the origin of the Aβ seed, time of incubation and host. However, the mechanism underlying the differential effect of each factor is poorly known. Previous studies have shown that the Aβ source is relevant for the amyloid process, since its pathogenicity is different according to its origin. Furthermore, recent evidence suggests that microglia plays a key role in the amyloidogenic event, and can modulate the propagation and aggregation process. Here, we seek to perform a comparative study to determine whether Aβ seeds from humans vs a familial AD line (the 3xTg‐AD model) are more efficient to generate amyloid aggregates, as well as the role of the microglia in the propagation process.MethodAmyloid seeds from AD patient (stage C for amyloid; from the Alzheimer’s Disease Research Center at UCI) and 25 mo‐3xTg‐AD mice were injected into the hippocampus of 7‐8‐month‐old 3xTg‐AD mice. They were analyzed 10 months post‐surgery for amyloid and microglia markers.ResultOur findings demonstrated that amyloid seeds from the human patient seem to induce a more aggressive amyloid pathology compared to seeds from aged 3xTg‐AD mice. Moreover, human and mice seeds differentially affect the presence of plaque‐associated microglia in 3xTg‐AD mice.ConclusionThese results suggest that seeds from human patients seem to be more amyloidogenic than from aged 3xTg‐AD mice, and also microglia cells may play a key role in this differential effect. Therefore, more profound understanding these factors will provide key insight on how amyloid pathology progresses in AD.
Grant support: This study was supported by Minister of Science and Innovation grant PID2019‐108911RA‐100 (D.B.V.), Alzheimer’s Association grant AARG‐22‐928219 (D.B.V), Beatriz Galindo program BAGAL18/00052 (D.B.V.) and Institute of Health Carlos III (ISCiii) grant PI18/01557 (A.G.) co‐financed by FEDER funds from European Union.
Wisconsin Longitudinal Study (WLS), the Initial Lifetime’s Impact on Alzheimer’s Disease (WLS‐ILIAD): A Novel Opportunity to Study the Influence of Education on ADRD
Authors: Lange Kate , Williams Victoria J. , Strait Brittani J , Fischer Anne M , Herd Pamela , Asthana Sanjay 
Published: December 2023

AbstractBackgroundThe importance of education in shaping brain health and dementia risk are increasingly supported, although the mechanisms by which these life course factors impact late life cognition remain elusive due to a scarcity of full life‐course longitudinal studies. A new data collection wave of the Wisconsin Longitudinal Study (WLS), the Initial Lifetime’s Impact on Alzheimer’s Disease (WLS‐ILIAD), stands to address this gap. The WLS cohort is a randomly selected community sample that’s been followed since 1957, offering a wealth of prospectively collected lifespan data to pull from. Now that this cohort has reached their 80’s, the ILIAD study aims to detect dementia prevalence in this sample, and when combined with prior data waves, offers an unparalleled opportunity to explore how full life‐course and sociodemographic factors shape the relationship between education and dementia risk and resilience.MethodWLS‐ILIAD employs a multi‐phasic study design. In Phase 1, the modified Telephone Interview for Cognitive Status (TICS‐m) was administered to all eligible participants to screen for dementia risk. Those performing below cutoff (TICS‐m≤28) were selected for Phase 2 to complete more robust cognitive assessment and to obtain comprehensive health history. Cognitive diagnoses were determined by multidisciplinary consensus panel. Proxy assessments were employed for participants who were deceased or unable to complete the assessment.ResultPreliminary results indicate a response rate of ∼78%. Approximately 4,800 participants completed Phase 1, with 1,227 (26%) falling below cutoff for dementia risk (TICS‐m≤28). Of those completing Phase 2, 460 participants were classified as normal cognition, 443 mild cognitive impairment (MCI), and 197 dementia. Another 300 dementia cases were identified via proxy. Participants diagnosed with MCI or dementia tended to be older, ApoeE‐4 allele carriers, and had a lower high school IQ. Of those diagnosed with dementia, 88% reported no prior clinical workup or existing cognitive diagnosis.ConclusionResults of the WLS‐ILIAD study yields detailed cognitive diagnostic classifications for this sample. When combined with prospectively collected life course data, the WLS cohort offers a unique opportunity to explore the impact of education on risk and resilience factors for dementia outcomes, leading to important public policy and public health implications.
The decline of quantitative EEG goes along with neuropathology in Alzheimer’s Disease
Authors: Poloni Tino Emanuele , Negro Giulia , Cassini Paola , Profka Xhulja , Rossi Michele , Davin Annalisa , Ferrari Riccardo Rocco , Terzoli Valeria , Guaita Antonio , Ceroni Mauro , Medici Valentina 
Published: December 2023

AbstractBackgroundFew studies investigate the correlation between the quantitative EEG (QEEG) and the neuropathological picture. The purpose of this study is to explore how QEEG can recognize the type and extent of neuropathological changes.MethodThe EEG traces and brains belonging to 14 donors of the Abbiategrasso Brain Bank were analyzed. The subjects suffered from neurocognitive disorders due to AD, LBD or AD/vascular lesions (mixed dementia‐MD), with different stages of clinical and neuropathological severity. Clinical and neuropathological characterization was performed according to our protocol; biochemical measurements to determine the amount of proteinopathies are in runtime on frozen samples. QEEG analysis considered the relative power distribution (RPD) of the frequency bands (β, α, θ, δ) and the peak frequency (PF), i.e. the most represented frequency considering all the leads. The PF was measured every 2 seconds for 200‐400 samples, and then averaged. The Kruskall‐Wallis test was used for the comparison between groups.ResultThe clinical diagnosis included: 2 MCI, 4 AD, 6 MD, and 2 LBD. The neuropathological definite diagnosis demonstrated frequent co‐pathologies, and some discrepancies compared to the clinical diagnosis. The neuropathological characterization identified 2 cases with low AD pathology (corresponding to the 2 MCI), 8 cases with intermediate or high AD pathology (4 MD with concomitant cerebrovascular disease), and 4 cases with prevalent LBD pathology. Considering both clinical and neuropathological diagnoses, the comparison between groups revealed no significant differences in QEEG parameters. Nonetheless, a trend emerges towards a lower β‐RPD and a higher θ‐RPD in cases with prevalent LBD pathology. Grouping based on the severity of AD pathology (2 low, 4 intermediate, 4 high) demonstrated significant differences depending upon the neuropathological scoring with a progressive decrease of α‐RPD (p = 0.029) and PF (p = 0.019), and an increase of δ‐RPD (p = 0.020).ConclusionRPD and PF show low discriminatory capacity on etiology. Nonetheless, the presence of LBD seems to boost the EEG slowing. The PF slowing down parallels the increase of AD pathology, representing an indicator for the degenerative load. PF is a simple QEEG parameter, easily obtainable through standard digital EEG; it can be useful for monitoring neurodegenerative burden and disease evolution.
Predicting Poor Sleep in People Living with Dementia: An Analysis of In‐Home Activities and Physiology Measurements During the Daytime
Authors: Chen Yu , Nilforooshan Ramin , Barnaghi Payam 
Published: December 2023

AbstractBackgroundThe use of Internet of Things (IoT) technologies can help with remote monitoring of People Living With Dementia (PLWD) at their homes, ensuring effective and prompt provision of healthcare services. This study provides an analysis of data collected as part of a long‐term research project initiated by the UK Dementia Research Institute’s Care Research and Technology Centre, which aims to understand and slow down the progression of dementia. The goal of this work is to examine the relationship between daytime living status (i.e. activities and psychiatric measurements) and nighttime sleep quality, as poor sleep has been linked to the development of dementia. Early prediction of poor nighttime sleep through monitoring daytime activities may offer an opportunity for intervention, leading to an improvement in sleep quality. In order to achieve this goal, we have developed a classification model to predict poor sleep based on daytime living status.MethodThe activity data is from sensors placed throughout each participant’s home, tracking their movements between 6:00 AM and 7:00 PM each day. The physiological measurements are also taken daily, primarily in the daytime. Sleep is considered poor if more than 50∖% of the time is spent in the “Awake” state out of the total sleep duration (the sum of four sleep states: “Awake”, “Deep”, “Light”, “REM”). Machine learning classification models are applied to predict whether nighttime sleep is poor or not. Also, feature importance analysis can be conducted to identify activity patterns that contribute to poor sleep.ResultThe dataset includes 91 participants with dementia and the collection period spans from June 29th, 2021 to December 31st, 2022. A Gradient Boosting tree classifier was trained and evaluated using 10‐fold cross‐validation. 7% of the data are positive samples. The average sensitivity was 81.1% with a standard deviation of 6.6%, and the average specificity was 78.3% with a standard deviation of 2.3%.ConclusionThe study suggests that further improvement can be made by analysing time‐dependency within the data and utilising more advanced models. The combination of IoT and machine learning shows the potential to greatly benefit healthcare services for PLWD on a daily basis.
Clinical effectiveness of treatments for the management of anxiety in community dwelling people living with dementia: a systematic review and meta‐analysis
Authors: Nimmons Danielle , Aker Narin , Jordan Kelvin P , Cooper Claudia , Davies Nathan , Manthorpe Jill , Chew‐Graham Carolyn A , Kingstone Tom , Petersen Irene , Walters Kate 
Published: December 2023

AbstractBackgroundPeople living with dementia commonly experience distress or behavioural and psychological symptoms, such as anxiety, which are associated with worse outcomes in this population. Symptoms of anxiety can be challenging to manage, as there is limited evidence supporting the prescription of psychotropic medications and it is unclear if conventional psychological treatments, such as cognitive behavioural therapy, are effective. The aim of this systematic review and meta‐analysis was therefore to investigate the effectiveness of pharmacological and non‐pharmacological treatments for the management of anxiety in community dwelling people living with dementia.MethodA systematic review and meta‐analysis was conducted of randomised controlled trials until January 2022, searching EMBASE, CINAHL, MEDLINE and PsycInfo. This is currently being updated to Jan 2023. Standardised mean differences were estimated at follow‐up between treatments and pooled across studies using random‐effects models. The Cochrane risk‐of‐bias tool for randomized trials assessed risk of bias and meta‐analysis was performed if three or more studies of a treatment group were available.ResultTwenty‐seven studies (comprising 2517 participants) were included. We categorised these as pharmacological interventions (n = 8), non‐pharmacological group interventions (n = 8) and non‐pharmacological individual interventions (n = 11). Pharmacological interventions with evidence of potential effectiveness included olanzapine, loxapine, citalopram, buspirone and risperidone; and those with no evidence of effectiveness were thioridazine and haloperidol. Meta‐analyses was not performed due to study heterogeneity.Some non‐pharmacological treatments were found to be effective in reducing anxiety in people living with dementia, compared to usual care or active controls. For interventions aimed at individuals the pooled standardised mean difference was ‐0.41 (CI: ‐0.71, ‐0.11) and for those aimed at groups it was ‐0.44 (CI: ‐0.79, ‐0.09). When examining different type of intervention, results suggest music therapy and muscular approaches (e,g, relaxing massage) were effective in reducing anxiety symptoms, while cognitive approaches and sensory stimulation were not. We will present additional findings from updated searches.ConclusionResults suggest non‐pharmacological interventions can be effective in reducing anxiety in community‐dwelling people living with dementia. This supports the development and use of more group‐based non‐pharmacological interventions to help reduce anxiety among people living with dementia in the community and their carers.
Recruitment and Retention for Alzheimer’s Disease Diversity Genetic Cohorts in the ADSP (READD‐ADSP)
Authors: Byrd Goldie S. , McInerney Katalina 
Published: December 2023

AbstractBackgroundGenomic studies constitute a proven approach for identifying new therapeutic targets. However, there is a strong European bias that exists in AD genetic studies. This study will increase the global resource of the (ADSP) by including underrepresented African ancestry (African Americans (AA), African (Af)) and Hispanic/Latinx (HL) individuals. Reasons underlying these disparities are complex, but notable barriers to research participation for AA and HL communities must be addressed to improve participation.MethodREADD‐ADSP will recruit, retain, and evaluate 13,000 participants of diverse ethnicity, including 5,000 Af, 4,000 AA, and 4,000 US HL. The study in Africa involves multiple sites in 9 African countries operating under the African Dementia Consortium (AfDC). Socio‐demographic, clinical, and neurocognitive data will be obtained using protocol‐guided evaluation procedures that were developed to accommodate different cultures, to support phenotype harmonization, and for joint studies of biological and social risks of AD. A US and AfDC clinical adjudication committee will apply culturally algorithms for AD to adjudicate data from the cohorts.Communities are engaged through culturally informed efforts to improve trustworthiness and to understand how to both recruit and retain diverse populations,ResultSuccessful recruitment and retention of a globally diverse, well‐phenotyped cohort for genetic studies requires a multi‐level recruitment strategy, which includes building trust in diverse communities, and using evidence‐based community engaged research principles. In order to reach our enrollment goal, we engage diverse communities through a culturally relevant marketing campaign, using market research to inform best practices. We use clinic‐based strategies, as well as family and stakeholder involvement for snowball recruitment. Finally, we provide culturally appropriate training and resources to assure highly skilled multi‐site recruitment teams. We have recruited over 2,500 underrepresented participants, including 200 multi‐plex families using these strategies.ConclusionOutcomes from READD‐ADSP will enhance focused, precision medicine approaches for AD and reduce global health disparities across ancestries. In addition to clinic‐based strategies, community‐based strategies that recruit and retain diverse populations require intentional investments that remove trust barriers and support community priorities.
PREVENT‐AD cohort: from normal to impaired cognition, who are declining and why? Preliminary results
Authors: Tremblay‐Mercier Jennifer , Picard Cynthia , Breitner John C.S. , Villeneuve Sylvia , Poirier Judes ,   PREVENT‐AD Research Group
Published: December 2023

AbstractBackgroundThe StoP‐Alzheimer Center follows a cohort of cognitively normal participants at risk of developing Alzheimer’s disease (AD) due to their parental history (PREVENT‐AD cohort). Cognitive impairments were detected in 17% of the cohort (66 out of 386) mostly after between 4 to 6 years of follow‐up, at an average age of 70 ± 7 years of age.MethodWe looked at various variables at baseline (demographics, blood results, medical history, cognition, genetic variants, AD pathology, mood) to describe the differences between the participants who maintained a normal cognition versus those who declined.ResultDifference in ApoE4 status was not as important as expected with 39.4% ApoE4 carriers in the decliner group compared to 38.2% in the normal group (Table 1). Despite a normal cognition at baseline, we found subtle but significant lower cognitive performance in the decliner group on the MoCA (‐1 pt) and the Repeatable Battery for the Assessment of Neuropsychological Status (‐5 pts). Systolic blood pressure and glycosylated hemoglobin were slightly more elevated in the decliner group (132 mmHg versus 128 mmHg and 5.6% versus 5.4% respectively). When asked about their past medical history, more participants were treated for hypertension, hyperlipidemia and diabetes in the decliner group. At the level of brain AD pathology measured by PET, the decliner group presented higher levels (standard uptake values) of amyloid and tau. Overall, 27% of the decliner group were amyloid AND tau positive compared to 7% in the normal group. The decliner group also showed lower smell identification performances at baseline when compared to the group who didn’t decline.ConclusionMain differences between the groups at baseline are related to AD pathology, vascular risk factors and cognitive and smell identification capacities. Other available variables such as brain structure, cerebrospinal fluid proteins, additional cognitive tests, lifestyle questionnaires, and genetics variants need to be analyzed along with trajectories and change over time. As a growing number of participants are declining cognitively and are still followed annually with multimodal evaluations, we trust that further investigations will help better understand the development of cognitive impairment.
Preliminary Acceptability and Efficacy of a Brief Computerized Intervention Targeting Loneliness in Older Adults
Authors: Schubert Frederick T , Schmidt Norman B 
Published: December 2023

AbstractBackgroundLoneliness in older adults has been linked to an increased risk for dementia as well as physical and mental health issues. In recent years, computerized interventions have emerged as a promising strategy for addressing mental health issues such as loneliness given their ease‐of‐use, efficiency, and high level of scalability. “Combatting Social Isolation” (CSI) is one such intervention that is brief, web based, and has demonstrated efficacy in targeting two risk factors central to social disconnection (perceived burdensomeness and thwarted belongingness). This study sought to adapt the existing CSI protocol for older adults reporting loneliness and obtain preliminary acceptability and efficacy data in a randomized clinical trial.MethodParticipants were community‐dwelling adults 60 years of age or older who reported experiencing loneliness. This is an ongoing clinical trial with an expect final sample size of 60. Currently, 13 participants have been randomized to complete either CSI or a similar web‐based control which provides information regarding a healthy lifestyle. Participants completed measures assessing acceptability and loneliness pre‐intervention, post‐intervention and at 1‐month follow up. The sample was 53.8% female and varied in age from 63 to 80 years old (M = 70.54; SD = 5.40).ResultFollowing completion of the CSI intervention, 100% of participants (N = 7) reported that the intervention was at least somewhat logical, 85.7% reported that they expected it to be at least somewhat successful in reducing their symptoms, and 85.7% of participants rated the quality of the intervention as good or excellent. Descriptive statistics revealed that total UCLA loneliness scale scores for both groups were lower at post (M/SDCSI = 50.33/7.63; Control = 40.83/8.08) and 1‐month follow up (M/SD CSI = 51.33/8.00; Control = 40.17/9.24) compared to pre‐intervention (M/SD CSI = 54.43/9.25; Control = 44.50/9.96). Mean scores were not compared between groups due to small sample size, however, data continues to be collected and inferential statistics will be available for presentation.ConclusionThese preliminary results suggest that most participants considered the CSI intervention to be acceptable. Though the current sample is underpowered to detect between‐groups differences in loneliness, initial trends support a decrease in loneliness over time. However, more data needs to be collected to determine whether these reductions are unique to the intervention.
Consequences of mitochondrial DNA depletion in microglial cells
Authors: Molina Carmen Romero , See Wen Yi , Liu Yiyuan , Pa Judy , Wilkins Heather M , Swerdlow Russell H , Goate Alison , Andrews Shea J 
Published: December 2023

AbstractBackgroundMitochondrial dysfunction is an early and prominent feature of Alzheimer’s disease (AD). We have recently published that lower brain mitochondrial DNA copy number (mtDNAcn) is associated with a greater odds of AD neuropathological change and worse cognitive performance. As it is known that microglial cells play an important role in AD, we want to address how a reduction in mtDNAcn may affect microglial function.Methodsmicroglial BV2 cells were treated with ethidium bromide (etbr) (1ug/ml) for 5 days to achieve a 95% reduction of mitochondrial‐encoded genes expression. Cells were characterized by RNAseq and Seahorse experiments. BV2 cells were challenged with latex beads and 10uM zymosan‐pHrodo for 24 hours and phagocytosis was analyzed by flow cytometry. BV2 cells were stimulated with LPS (100ng/ml) for 3 hours to measure cytokine release by qPCR and ELISA. After BV2 stimulation, fresh media (without LPS or etbr) was conditioned for 6 hours and collected to treat neurons (SH‐SY5Y cells) and human primary astrocytes for 24 hours. RNA and protein samples were collected.ResultsmtDNAcn reduction led to a dramatic reduction in oxidative phosphorylation and a mild reduction in proliferation. RNAseq data showed an increase in the hypoxia signature and cellular senescence, coupled with a reduction in biosynthetic process and response to interferon. No changes were observed in phagocytic capacity. However, after LPS stimulation, etbr‐treated cells showed a reduction in the production of IL1B and IL6 cytokines, suggesting an impairment in the response to challenge. Neurons exposed to media from etbr‐treated BV2 cells showed an increase in MAPT and APOE expression. Samples from astrocytes are currently being analyzed.ConclusionsmtDNAcn reduction impairs mitochondrial respiration, which affects the production of cytokines in response to stimulus and leads to cell senescence in microglial cells. Cytokines released by microglia affected neuronal expression of AD‐related genes.