bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Independent Review on Potential MMSE Score Inflation at Screening in AD trials
Authors: Echevarria Barbara , Welch Matthew , Negash Selam , Cunha Catarina , Veronika Cimermanova , Randolph Christopher 
Published: December 2023

AbstractBackgroundThe Mini‐Mental State Examination (MMSE) is widely used as a screening tool in Alzheimer’s Disease (AD) clinical trials. Screening score inflation is documented in clinical trials of depression and anxiety. We investigated whether score distributions on several multi‐site multinational AD trials showed truncated scores around MMSE inclusion criteria cut‐off, and whether Independent Review (IRev), where site assessments are reviewed by independent clinicians, is an effective methodology to mitigate inclusion bias.MethodMMSE screening score distributions from several clinical trials of Early Symptomatic and Mild to Moderate AD were examined. To assess the impact of IRev on screening score distribution, we compared two studies with similar inclusion criteria (Early AD, MMSE ≥ 22; CDR GS = 0.5 or 1) one with no IRev and one with IRev via audio recording.ResultMMSE screening frequency distributions showed a statistically significant difference between IRev and No‐IREV groups (p < 0.001). The distributions for the two groups were also compared using several score ranges around the threshold. Significant group differences were observed across the score ranges; 20‐24 (D = 0.099, p = 0.01), 19‐25 (D = 0.094, p = 0.002), and 18‐26 (D = 0.0987, p < 0001), suggesting a smaller inclusion bias around the threshold in the IRev group.ConclusionWe observed that screening score inflation occurs in AD trials and Independent Review may be an effective strategy to reduce the number of subjects inappropriately enrolled in the study. IRev should be applied to assessments that fall around the required scored for study participation.
Associations among Drinking Water Quality, Dyslipidemia, and Cognitive Function for OlderAdults in China
Authors: Pan Xi 
Published: December 2023

AbstractBackgroundEpidemiological evidence has shown that poor drinking water quality can lead to dyslipidemia, which might be associated with cognitive decline or lower domain‐specific cognitive function in older adults. Given the prevalence of water pollution, dyslipidemia, and dementia in China, it is important to examine the association between drinking water quality and cognitive function in older Chinese and to identify the direct and indirect effects of drinking water quality and dyslipidemia on their cognitive function.MethodPrimary data for the study were selected from China Health and Retirement Longitudinal Study (CHARLS, 2015) and 4,951 respondents aged 60 and above were included. Data on drinking water quality were selected from the 2015 prefectural water quality data from the Institute of Public and Environment Affairs in China. Mixed effects models were conducted to assess the associations of cognitive function with drinking water quality and dyslipidemia. The mediation effects of dyslipidemia were examined by path analyses.ResultExposure to high quality drinking water was significantly associated with higher scores in mental status, episodic memory, and global cognition (β = 0.34, p < 0.001 for mental status; β = 0.24, p < 0.05 for episodic memory; β = 0.58, p < 0.01 for global cognition). Respondents who reported dyslipidemia diagnosis had higher scores in the three composite measures of cognitive function (β = 0.39, p < 0.001 for mental status; β = 0.27 p < 0.05 for episodic memory; β = 0.66, p < 0.001 for global cognition). An elevated blood triglycerides was only associated with higher scores in mental status (β = 0.21, p < 0.05). Self‐reported dyslipidemia diagnosis was a suppressor, which increased the magnitude of the direct effect of drinking water quality on mental status, episodic memory, and global cognition.ConclusionDrinking water quality was associated with cognitive function in older Chinese and the relationship was independent of natural or socioeconomic variations in neighborhood environments. Improving drinking water quality could be a potential public health effort to delay the onset of cognitive impairment and prevent the dementia pandemic in older people.
NETS‐seq advances the understanding of neuronal vulnerability in AD progression facilitating the identification of novel therapeutic targets at the single cell type level
Authors: Bayraktar Gonca , Christie Louisa , Brice Nicola , Xu Xiao , Stirparo Giuliano , Lizio Marina , Powell Justin , Cadwalladr David , Cheung Toni , Sheardown Steven , Page Keith , Dawson Lee A , Carlton Mark 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) is a complex, heterogeneous, and multi‐factorial disease of predominantly the aging population. Throughout disease progression, different brain regions and cell types within each region show varying levels of resilience to ongoing disease pathology. A better understanding of the biological properties of different cell types and an integrated analysis approach that incorporates information about the interplay between cell type vulnerability, pathological deposits, and inflammatory signatures are required for the development of novel therapeutics that delay the onset or slow the progression of AD.MethodCerevance has developed a proprietary Nuclear Enriched Transcript Sort sequencing (NETS‐seq) method that provides deep molecular insight into the dynamics of the brains of early‐stage AD, late‐stage AD, and non‐neurodegenerative age‐matched control donors at the individual cell type level. Machine learning methodologies based on gene expression were employed to stratify donors across the disease continuum and to identify gene changes associated with disease progression.ResultNETS‐seq enabled us to profile more than a dozen distinct cortical cell types. These data show that many known AD risk genes, as well as many lesser described genes, change in expression in disease. We have also used pseudotime trajectory analysis to rank donors across disease progression from control to early‐ and late‐stage AD. Comparisons made across different cell types within the same brain region and the same cell types from different brain regions, have identified genes that may be contributing to AD progression at different stages of disease. These genes may contribute to ongoing neuronal vulnerability.ConclusionWe have produced highly reproducible molecular profiles from neuronal (and glial) cell types from the human brain and demonstrated that many genes are specifically expressed in cortical neuronal subtypes and change across the AD disease continuum. Identifying changes in the transcriptomic signatures of vulnerable neuronal populations at different stages of disease has enabled the identification and selection of novel targets for AD drug discovery.
Modulation of the Immunoproteasome Affects Pathological Tau Aggregation in Alzheimer’s Disease
Authors: Nashman Zarrar , Runyan Avery , Sydney Eric , Myeku Natura 
Published: December 2023

AbstractBackgroundThe Immunoproteasome is a dynamic system found in microglia that is induced under inflammatory conditions and previously hypothesized to be causative of neurodegenerative disorders like Alzheimer’s Disease.MethodMice with immunoproteasome deficiency (LMPPS) and mice with intact immunoproteasome (PS19) were analyzed for AD progression through total tau aggregation and microglia activity. Primary microglia were extracted from normal and LMPKO mouse strains and their total engulfment of tau‐aggregate containing cells were compared.ResultLMPPS mice had significantly higher mean aggregation of tau compared to PS19 mice. LMPPS mice also showed a significantly increased activation of microglia and a slightly increased number of total microglia compared to PS19 mice. In‐vitro results showed increased total engulfment of tau‐aggregate containing cells for LMPKO microglia but statistically insignificant difference when comparing proportion of engulfing microglia.ConclusionTo our knowledge, our results are the first to show that the immunoproteasome is neuroprotective against tauopathies like Alzheimer’s Disease in mice.
Pathways explaining racial/ethnic and socio‐economic disparities in dementia incidence: The UK Biobank Study
Authors: Beydoun May A , Beydoun Hind A. , Fanelli‐Kuczmarski Marie T. , Weiss Jordan , Georgescu Michael , Meirelles Osorio , Lyall Donald M , Evans Michele K , Zonderman Alan B 
Published: December 2023

AbstractBackgroundPathways explaining racial/ethnic disparities in dementia risk are under‐evaluated.MethodWe examine those disparities and their related pathways among UK biobank study respondents (50‐74y, N = 323,483; 3.6% non‐White minorities) using a series of Cox proportional hazards and generalized structural equations models (GSEM).ResultAfter ≤15 years, 5,491 all‐cause dementia cases were diagnosed. Minority status increased dementia risk by 24% (HR = 1.24, 95% CI: 1.07‐1.45, P = 0.005), an association attenuated by socio‐economic status (SES), (HR = 1.12, 95% CI: 0.96‐1.31). Total race‐dementia effect was mediated through both SES and Life’s essential 8 lifestyle sub‐score (LE8LIFESTYLE), combining diet, smoking, physical activity, and sleep factors. SES was inversely related to dementia risk (HR = 0.69, 95% CI: 0.67, 0.72, P<0.001). Pathways explaining excess dementia risk among minorities included ‘RACE_ETHN(‐)→SES(‐)→◊ DEMENTIA’, ‘RACE_ETHN(‐)→ SES(‐)→ COGN(+)→ DEMENTIA’ and ‘RACE_ETHN(‐)→SES(+)→ LE8LIFESTYLE(‐)→`DEMENTIA’, with SES reflecting higher socio‐economic status, COGN reflecting poorer cognitive performance and LE8LIFESTYLE reflecting better cardiovascular health, specifically lifestyle factors, with higher scores. RACE_ETHN is the Non‐White minority vs. White contrast.ConclusionPending future interventions, lifestyle factors including diet, smoking, physical activity and sleep are crucial for reducing racial and socio‐economic disparities in dementia.
Finance management and inequalities in care spending in dementia since the COVID‐19 pandemic
Authors: Giebel Clarissa , Halpin Kath , O'Connell Lena , Carton Joan 
Published: December 2023

AbstractBackgroundThe ability to manage finances is one of the first daily activities to deteriorate in dementia. With finance tasks having gone even more remotely and digitalised since the pandemic, the aim of this qualitative interview study was to explore how finance management and spending habits of people with dementia living in the community may have been affected by the pandemic.MethodWe remotely interviewed 30 unpaid carers and people with dementia across the UK from February to May 2022 about their experiences of managing finances and spending habit changes during the pandemic. The topic guide was co‐developed with two unpaid carers. Data were analysed using inductive thematic analysis.ResultThe pandemic fast‐tracked the digitalisation of finance management tasks for people with dementia, which caused inequalities for many who were unfamiliar with digital formats. This necessitated further involvement of unpaid family carers in all aspects of finance management on behalf of the person living with dementia, leading to increased caring duties on top of existing tasks. Navigating the legalities surrounding financing care for dementia was similarly found to be characterised by barriers for most, with those from more socio‐economically disadvantaged backgrounds receiving less help to source financial support.ConclusionSupport needs to be in place for people with dementia to manage their finances digitally, whilst carers need to be provided with clear guidance and support in how to navigate this daily activity. Legal arrangements with banks and other organisations should be in place as soon as possible to enable equitable support with this key daily activity.
Exploring Social Engagement in a Virtual Participatory Culinary Nutrition Education Intervention for Dementia Prevention
Authors: Beitel JulieAnne E , O'Connell Megan E , Lieffers Jessica , Lawson Karen , Cammer Allison 
Published: December 2023

AbstractBackgroundProviding nutrition education through participatory cooking programs is a strategy to support adoption of healthy eating practices for dementia risk reduction. Social engagement, a modifiable risk factor for dementia, is an important feature of in‐person culinary interventions; few recommendations exist for virtual delivery. We aimed to examine participant social engagement within ‘The Cognitive Kitchen: Virtual Culinary Intervention for Dementia Prevention’.MethodA six‐week virtual nutrition education and applied cooking class was delivered to two groups of 10 older adult participants. Two Registered Dietitians led discussions and cooking demonstrations focused on dementia risk reduction. Participants were invited to cook during sessions or prepare the recipes at their convenience. The study was guided by Interpretive Description methodology. Data included facilitator session notes, participant weekly virtual journal entries, two virtual focus group discussions, and individual interviews with 15 participants. The Positive emotion, Engagement, Relationships, Meaning, and Accomplishments (PERMA) model of well‐being helped structure thematic analysis examining participants’ experiences in the program and the function of social interaction.ResultParticipants appreciated the flexibility of the virtual setting and very few technical issues were observed. Thematic analysis revealed commonalities among participants’ experiences, including enjoyment of learning about creative ingredient transformation, enhanced accountability for meal preparation, and an appreciation for cooking as a social activity. Many participants recorded notes about meal preparation practices shared by other group members, and some participated in virtual recipe‐sharing, suggesting peer learning was a valuable component. Though the virtual program could not include casual social contact that would normally occur in an in‐person program, participants appreciated discussion questions to encourage social interaction. However, some found that cooking along with the demonstration limited their ability to learn and socialize.ConclusionBenefits to virtual delivery of a participatory cooking program include ability to expand program reach and reduced barriers to participation (e.g., travel, inclement weather, time). These considerations may be even more relevant for older adult care partners of persons with dementia. However, some elements of in‐person participation that foster social engagement are challenging to replicate virtually; additional effort by facilitators is required to ensure this important program component is maintained.
Incorporating clinical trial outcomes in health economic evaluations of disease‐modifying therapies for AD
Authors: Jönsson Linus , Gustavsson Anders , Handels Ron 
Published: December 2023

AbstractBackgroundEvidence on cost‐effectiveness of novel therapies for Alzheimer’s disease (AD) is of increasing importance for patient access. Challenges involved in implementing treatment effects in health economic (HE) models is an important source of uncertainty around the value of new AD therapies. HE models are developed from observational studies that often include different patient populations and different endpoints and scales from clinical trials.MethodsThe International Pharmacoeconomic Collaboration on Alzheimer’s Disease (IPECAD) conducted a series of workshops with research groups developing HE models in AD, to systematically characterize methodological approaches to modelling and benchmark results from these models in standardized scenarios. We reviewed published models and contrasted the characteristics of these models with study design specifications of recent late‐stage clinical trials of AD DMT to highlight potential issues with incorporating efficacy data from clinical trials in existing HE models. Identified issues included: need for mapping between different scales used to assess cognition, function and other efficacy domains, incorporating effects on multiple domains, differences in trial populations and expected patient populations treated in routine care, and statistical methods for generating efficacy estimates for use in HE models.ResultsThree options were identified for translating trial efficacy estimates into HE models: 1) use actual trial data and model disease course post trial, 2) assume treatment reduces transition probabilities to more severe states, and 3) implement treatment effect as a proportional reduction of progression on the time scale.ConclusionsThe design of future clinical trials of DMT need to take into account the need to generate data to populate HE models. Pre‐specifying analyses of trial data for HE modeling purposes can reduce uncertainty and improve confidence in results.
Discriminant Validity and Time‐effectiveness of A Stepwise Dementia Case‐finding Approach in an Asian Elderly Community
Authors: Xu Xin , Chen Christopher , Yu Cheng Ching‐ , Venketasubramanian Narayanaswamy , Yuan Changzheng 
Published: December 2023

AbstractBackgroundTo investigate the discriminant validity and time‐effectiveness of a stepwise dementia case‐finding approach in a community‐based Singaporean older adult population.MethodParticipants who completed the Progressive Forgetfulness Question (PFQ) and the Abbreviated Mental Test (AMT) were invited to phase II and administered the Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a formal neuropsychological battery. Participants were diagnosed by cognitive performance and DSM‐IV criteria into No Cognitive Impairment (NCI), Cognitive Impairment‐No Dementia (CIND) mild (≤2 cognitive domains impaired), CIND moderate (>2 domains impaired) and dementia. Receiver Operating Characteristic were conducted for different cognitive instruments (AMT, MoCA, MMSE) between PFQ = Yes and PFQ = No groups. All discriminant indices including sensitivity, specificity, positive (PPV), negative predictive values (NPV) and accuracy were calculated. Bayesian correction methods were used to adjust the verification bias. Screening time saving and number of subjects further evaluated was estimated in two scenarios with or without the PFQ.ResultThe PFQ showed an NPV of 94.2% for excluding dementia‐free cases after adjustment. After excluding PFQ = No participants, all cognitive tools achieved optimal NPV (>99%). Furthermore, the number of people requiring further evaluation decreased by 129 (42.7%), 58 (36.5%), 25 (14.3%) subjects, corresponding to 48.2%, 48.2%, and 47.8% of screening time being saved, when the PFQ was conducted prior to the MoCA, MMSE, and AMT, respectively.ConclusionUsing a single‐question assessment as the first step of a case‐finding approach, followed up a cognitive test such as the MoCA, could minimize time and resources for further investigation in the community.
REMIND – a novel “Music‐Movement‐Mind” intervention for the prevention of dementia
Authors: Podolski Odile Sophie , Nicotra Angela , Köbe Theresa , Cardona Maria Isabel , Cornaro Clara , Koch Sabine , Wirth Miranka 
Published: December 2023

AbstractBackgroundLifestyle‐based motor, sensory and cognitive enrichment can target several health risk factors in the older populations by improving psychosocial, cognitive and physical (dys)function1,2. Based on these findings, we developed a novel intervention called REMIND (An Envi
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onmental
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nrich
m
ent
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ntervention to Preve
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t
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ementia) for the promotion of healthy aging. REMIND uses dance movement therapy (DMT) and Tango Sistema Dinzel© to integrate enriching activities based on music, movement and mind into a multimodal program.ObjectiveTo present the REMIND program and feasibility check of the telehealth adaptation.MethodsThe intervention was developed and manualized in collaboration with neuropsychologists, neuroscientists and DMT specialists. Several modes of training are employed throughout the program, consisting of the three core components “Music, Movement, and Mind”. These core components are practiced simultaneously using facilitator‐guided exercises, each consisting of motor, sensory, cognitive, emotional, and social stimulations with increasing complexity. As such REMIND enables multimodal enrichment with the goal to improve cognitive and mental health of older adults by activating beneficial brain plasticity. The adaptation of the program into the telehealth setting was assessed qualitatively in four online expert sessions for feasibility.ResultsThe REMIND program is published as an open access manual (doi.org/10.30819/5504) targeting the older population3. Through the simultaneous combination of motor (Movement), sensory (Music), and mental (Mind) stimulations, REMIND promotes enrichment of the body and mind. In the telehealth setting, the multimodal exercises are best practiced via an interactive video‐conference platform, adapted to the needs of older people, using small groups (n = 4‐8) and guidance of a trained facilitator. Break‐out groups, feedback rounds, and joined participation of family members are used to enhance and sustain inter‐personal contact and positive learning experiences in the digital environment. Supplementary on‐site sessions can facilitate social integration and participation.ConclusionThe REMIND program provides a low‐threshold prevention and early intervention tool that is accessible to the target group and health care system. Adaptation to the telehealth setting is cost‐effective, adaptable to individual needs and can be integrated into everyday life. A proof‐of‐concept study will evaluate feasibility and effectiveness of the REMIND program to promote psychosocial, cognitive and physical wellbeing in older adults.
Association of baseline dementia stage with cognitive markers during follow‐up in patients with dementia of Alzheimer type with and without post‐mortem Alzheimer pathology
Authors: Rosen Jurij , Jessen Frank 
Published: December 2023

AbstractBackgroundPrediction of the course of cognitive function is of central importance in the care of patients with dementia of Alzheimer type (DAT) for individual management, counseling and treatment. Baseline clinical examination and cognitive function testing are decisive in the classification of the dementia type and stage, but their predictive value to foresee the future course of the disease is critical. This project aims to examine the relationship of baseline dementia stage and Alzheimer’s disease neuropathological changes (ADNC) at autopsy with cognitive function during the course of the disease.MethodThis study is based on longitudinal data from The National Alzheimer‘s Coordinating Center (NACC)‐Uniform and Neuropathology Data Set. Participants were retrospectively included based on the following criteria: Clinical diagnosis of DAT, cognitive function testing by Mini‐Mental State Examination (MMSE), and report of ADNC at autopsy (ABC score). Baseline dementia stages were defined by the MMSE score (≥27/20‐26/10‐19/≤9). Neuropathological diagnosis of Alzheimer’s disease was defined by ABC score levels “High” or “Intermediate” (confirmed‐ADNC) as opposed to ABC score levels “Low” or “Not” (no‐ADNC).ResultOf 44,359 participants, 1,469 met inclusion criteria with 5,649 cognitive data points (i. e., on average 4.6±1.9 MMSE scores/participant). At baseline, 33%/49%/16%/2% of participants were assigned MMSE ranges of ≥27/20‐26/10‐19/≤9 respectively. The proportion of confirmed‐ADNC within the respective groups increased as a function of the baseline MMSE range (76%/90%/95%/96% respectively). Cognitive function changes from baseline to last visit depended on the neuropathological diagnosis (‐7 vs. ‐4 MMSE score points for confirmed‐ADNC vs. no‐ADNC respectively), but not on MMSE score at baseline (all ‐7 score points). Participants with a baseline MMSE score ≤9 decreased even less (‐3 score points).ConclusionThe present descriptive analysis does not provide evidence for a clear association of cognitive function decline during follow‐up and baseline MMSE scores, in contrast to ADNC which predicted faster decline, in patients with DAT. Modelling analyses including covariates will be presented.