bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of combination mixture of Cannabis sativa with psychoactive drugs on adenosine deaminase, ectonucleosides enzymes, redox status, cognition and hemodynamic function in male rats
Authors: Ajeigbe Olufunke Florence , Ademosun Ayokunle Olubode , Oboh Ganiyu , Lawrence Bodun Oluwaseun 
Published: January 2025

AbstractBackgroundThe effect of high consumption of psychoactive substances of codeine (CDE), tramadol (TMD), and Cannabis sativa (CNB) as concoction has been associated with altered brain cognitive and neurochemical functions. However, the understanding of the complex mechanism behind the intake of Cannabis sativa co‐administration with tramadol and codeine on both cardiac and brain function, neurotransmitters, purinergic, and antioxidant enzymes activities in the brain and heart of rats remains unreported.MethodThe measure of cognition using morris water maze (MWM) and Y‐maze tests, hemodynamic parameters namely systolic blood pressure (SBP) and heart rate (HR), acetylcholinesterase (AChE), butyl‐cholinesterase (BCHE), adenosine deaminase (ADA), arginase, catalase (CAT), superoxide dismutase (SOD) enzymes’ activities, reduced glutathione (GSH) and malondialdehyde (MDA), nitric oxide (NO) levels, in the brain and heart of CNB, TMD, and CDE exposed rats was done. Forty‐eight male Wistar rats were divided into 8 groups, n = 10. Group 1 was the control group, groups 2, 3, and 4 received oral doses of CDE (2 mg/kg bw), TMD (10 mg/kg bw), and CNB (200 mg/kg bw), while groups 5, 6, 7, and 8 received oral doses of CDE+TMD, CNB+ TMD, CNB+CDE, and CNB+TMD+CDE for a 28‐day period.ResultCoadministration of CNB, TMD, and CDE was seen to led to the significant decrease in cognitive function, acetyl‐cholinesterase (AChE), butyl‐cholinesterase (BChE), monoamine oxidase (MAO) enzyme activities, and antioxidant enzyme activities in rats' brains when compared against control rats (P< 0.05). Interestingly, CNB, TMD, and CDE co‐administration led to significant decrease in SBP and HR whereas, the activities of ectonucleosides (NTPdase), adenosine deaminase (ADA), and malondialdehyde levels produced in the brain and heart were significantly elevated (P< 0.05) in rats.ConclusionTherefore, coadministration of CNB, TMD, and CDE led to neurotransmitter poisoning and hypotensive potential in rats which are a notable mechanism of actions in the understanding of the drug development and synergistic neurotoxicity effects of CNB, TMD, and CDE on rats' hemodynamic and cognitive functions, as well as cholinergic, purinergic, and antioxidant systems.
The Alzheimer’s Tau Platform (ATP): a Phase 2, combination amyloid and tau therapy clinical trial for early AD
Authors: Boxer Adam L. , Sperling Reisa A , Aisen Paul S. S , Petersen Ronald C. , Donohue Michael C. , Raman Rema , Bateman Randall J. , Barragan Eden V. , Rentz Dorene M. , Grill Joshua D , Karlawish Jason , Rissman Robert A , Johnson Keith A ,   Alzheimer’s Clinical Trial Consortium (ACTC)
Published: January 2025

AbstractBackgroundAnti‐amyloid immunotherapies modestly slow disease progression in early symptomatic AD; addition of other therapeutic modalities may be necessary to achieve larger treatment effects. Therapies that directly target tau can potentially produce substantial clinical benefit because the accumulation of insoluble tau protein is strongly correlated with the progression of AD. Which tau therapies are likely to be efficacious, whether or not to combine them with anti‐amyloid therapies, and which individuals are most likely to benefit are important unresolved questions that would require multiple parallel design trials to answer. Platform (umbrella) trials test multiple therapies in the same trial, allowing for substantial savings in time, cost and participant burden.MethodATP is a new NIH‐funded Phase 2 clinical trial platform that will be conducted as part of the AD Clinical Trials Consortium (ACTC) in partnership with industry and philanthropic groups. The goal is to investigate the effects of tau therapies on the biological hallmarks of AD including insoluble and soluble tau species, amyloid and other biomarkers of neurodegeneration. ATP will initially evaluate two tau therapies alone or in combination with an anti‐amyloid therapy. 900 participants with late preclinical or early prodromal AD (CDR 0 or 0.5) will be randomized to six arms for two years of blinded treatment, followed by an optional open label extension (Figure 1). At least 20 percent of participants will be from underrepresented groups. The primary endpoint is 18F MK6240 tau PET, with key secondary endpoints including plasma P‐tau and MTBR243‐tau, amyloid PET and clinical assessments (CDR‐SB, PACC5). Inclusion criteria are based on plasma P‐tau217, clinical status and regional 18F MK6240 uptake.ResultTwo tau therapies and an anti‐amyloid therapy have been chosen for inclusion in ATP and startup is underway. The final design, choice of therapies and design as well as plans for inclusion of additional tau therapies after the trial begins and other details will be presented.ConclusionThe ATP is a six arm factorial design platform trial that is planned to begin in late 2024 or early 2025 that will support efficient development of tau and combination therapies for early, sporadic AD.
Improving young adult knowledge and attitudes towards reducing dementia risk
Authors: Savage Sharon A , Trotter Eloise 
Published: January 2025

AbstractBackgroundDementia may not be imminent for most young adults, however, lifestyle choices in early and midlife can play a significant role in dementia risk. Improving knowledge around modifiable factors and encouraging protective behaviours across the lifespan provides one important approach to lowering dementia incidence. This study aimed to test whether a short educational video, developed specifically for young adults, could improve knowledge of dementia risk factors and shift perceptions around when behaviour change may be relevant.MethodAn online, randomised controlled study was conducted with 88 Australian, aged 18‐24 years. Participants were allocated to view one of two 5‐minute, age‐targeted health videos: “Let’s Talk Dementia” (n = 41) or “Let’s Talk Health” (n = 47). Videos discussed health facts and provided easy‐to‐implement actions young adults could take to protect their future health. Participants were assessed prior to and immediately after watching the video. Assessment involved answering true/false statements regarding modifiable dementia risk factors and indicating the age at which participants believed it was important to make lifestyle changes to reduce dementia risk.ResultAt baseline, no differences were present between the two groups. Knowledge of dementia risk factors was limited (overall mean accuracy of 42%). Only 27% of participants showed awareness regarding the risk of hearing loss in midlife. Approximately 40% were unaware of the risks of hypertension and hyperlipidaemia. Following the video presentations, both groups improved their knowledge, although the greatest change was observed in the dementia video group (up to 76% accuracy vs 58% accuracy for general health video, t(87) = 4.24, p <.001). Here, more than 90% of participants now showed awareness of the risks of smoking, hypertension, and hyperlipidaemia, with 63% responding correctly regarding hearing loss. Majority of participants (69%) already indicated positive attitudes towards implementation of risk‐reducing behaviours by age 30, but increased to 93% of participants at immediate post‐intervention.ConclusionAge‐targeted educational videos appear a promising method to increase knowledge of dementia risk factors and encourage positive attitudes towards healthy lifestyle choices in young adults. Further investigation is now needed to understand motivational and behaviour change mechanisms to ensure knowledge is put into action.
Distinctive pattern mapping between cardiometabolic multimorbidity and neuropsychiatric disturbance in multi‐regional‐ethnical older adults
Authors: Zhang Haoran , Wen Haoxuan , Zhao Xuhao , Chen Christopher , Xiao Shifu , Liu Zuyun , Xu Xin 
Published: January 2025

AbstractBackgroundPresence of cardiometabolic multimorbidity (CMM) has been linked to depressive symptoms in adults. The present study aimed to investigate the distinctive mapping between CMM and differential neuropsychiatric subsyndromes among multi‐regional and ethnical older adults.MethodThe present study included discovery and validation datasets. The discovery dataset consisted of two longitudinal and two cross‐sectional studies from Asian older adults from both clinical and community settings. The longitudinal validation dataset was from the UK Biobank (UKB). CMM was defined as the coexistence of ≥2 conditions including hypertension, hyperlipidaemia, diabetes mellitus, stroke, and other cardiovascular diseases (CVD). Subsequently, two CMM patterns, including metabolic (≥2 of hypertension, hyperlipidaemia and diabetes mellitus) and cardio‐cerebrovascular multimorbidity (≥2 of hypertension, stroke and CVD) were identified respectively. The neuropsychiatric inventory (NPI) was applied to define four neuropsychiatric subsyndromes in the discovery dataset: psychosis, hyperactivity, affective and apathy. In the validation dataset, the four subsyndromes were defined using previously established methods. Short‐term incidence of subsyndromes was defined as the development of neuropsychiatric symptoms (NPS) in recent 1‐2 years. Two‐step individual participant data was used to establish the cross‐sectional association between CMM and NPS. Cox regression models explored baseline CMM patterns and NPS incidence in both discovery and validation datasets.ResultThe discovery dataset included 2950 Asian participants for cross‐sectional analysis and 967 participants (675 NPS‐free at baseline) for longitudinal analysis. The validation dataset included 885 participants (765 NPS‐free at baseline) for longitudinal analysis. People with CMM had a higher presence of NPS and a higher risk of 1‐year incidence of affective syndrome (hazard ratio [HR] = 3.95, 95%CI = 1.44‐10.82). Regarding CMM patterns, metabolic multimorbidity was associated with affective syndrome at baseline (odds ratio [OR] = 1.35, 95%CI = 1.01‐1.81), as well as its short‐term incidence (HR = 3.88, 95%CI = 1.53‐9.85). In the validation dataset, CMM, especially metabolic multimorbidity, was also associated with an increased risk of short‐term incidence of affective subsyndrome (HR = 8.04, 95%CI = 2.65‐24.40, and HR = 6.44, 95%CI = 2.11‐19.62, respectively). Cardio‐cerebrovascular multimorbidity was not associated with incidence of any NPS in both datasets.ConclusionCMM, especially metabolic multimorbidity was associated with affective disturbances in multi‐regional‐ethnical older adults. Our findings emphasized the importance of targeted management of metabolic multimorbidity.
Effects of a multi‐domain intervention against cognitive decline on dementia risk profiles – Results from the AgeWell.de‐trial
Authors: Zülke Andrea , Pabst Alexander , Luppa Melanie , Czock David , Wiese Birgitt , Hoffmann Wolfgang , Frese Thomas , Gensichen Jochen , König Hans‐Helmut , Kaduszkiewicz Hanna , Thyrian Jochen René , Riedel‐Heller Steffi G. 
Published: January 2025

AbstractBackgroundDementia risk scores have been suggested a promising surrogate outcome for lifestyle interventions targeting cognitive function and dementia risk. First evidence suggests beneficial effects of multidomain lifestyle interventions on dementia risk scores. We investigated effects of the multidomain AgeWell.de‐intervention on dementia risk, assessed using the LIfestyle for BRAin health (LIBRA)‐index.MethodSecondary analyses of AgeWell.de, a multicomponent intervention (including optimization of nutrition, medication, physical, social and cognitive activity) in older adults at increased risk for dementia (trial registration: German Clinical Trials Register, DRKS; ID: DRKS00013555). We analyzed data from n = 461 participants (age: 60‐77 years) with available information on all n = 12 risk/protective factors comprised by the LIBRA (coronary heart disease, diabetes, hypercholesterolemia, hypertension, depression, obesity, smoking, physical inactivity, renal disease, low‐to‐moderate alcohol use, high cognitive activity, healthy diet) at baseline and 24 months‐follow‐up. Intervention effects on LIBRA‐scores and individual LIBRA‐components were assessed using generalized linear models.ResultThe intervention reduced total LIBRA‐scores, indicating a decreased risk for dementia at 24 months follow‐up (b = ‐0.63, 95% CI: ‐1.14, ‐0.12). Intervention effects on LIBRA‐scores were particularly due to favorable changes in diet (OR = 1.60, 95% CI: 1.16, 2.22) and hypertension (OR = 1.61, 95% CI: 1.19, 2.18). In younger participants (60‐69 years), the intervention increased the odds of high cognitive activity at follow‐up (OR = 2.00; 95% CI: 1.20, 3.34).ConclusionThe AgeWell.de‐intervention successfully reduced dementia risk, assessed using the LIBRA‐score, underscoring the usefulness of the LIBRA as a surrogate outcome when interpreting success of multidomain lifestyle interventions. However, several risk factors for dementia captured in the LIBRA, e.g., physical inactivity, did not change due to the intervention, possibly requiring more intensive interventions and support of participants in conducting the intervention.
The co‐design of a Brain Health Game for children to reduce risk of dementia
Authors: Wilson Christine Brown , Townsend Rebecca , Mitchell Gary , Craig Stephanie , Carter Gillian , Stark Patrick , Clarke Sonya , Wilkie Susie , McEvoy Claire T 
Published: January 2025

AbstractBackgroundDementia prevalence is projected to treble worldwide by 2040 highlighting the critical need for effective primary dementia prevention strategies. Initiatives to shape health behaviours/beliefs in childhood increase likelihood of engagement in healthy lifestyle behaviours during adulthood however some subgroups of children are more vulnerable to poor brain health during ageing. Therefore, children must have opportunities to learn about how they can engage in behaviours to improve cardiovascular and psychological health that will protect their brain as they age, contributing to dementia risk reduction (DRR) in later life. Serious digital games (SDG) are fun, interactive and engaging, having been used successfully for education and behaviour change. No SDGs to promote brain health/DRR for children currently exist.MethodA SDG, ‘my Superbrain’ was codesigned with primary school children in Northern Ireland. The aims of this study were: to examine changes in understanding brain health/DRR via pre/post‐test evaluation of the SDG among children aged 8‐11 years old and determine the acceptability and feasibility of a novel SDG for DRR in children. Children completed the Kids Brain Health Questionnaire pre/post playing the Game with a modified System Usability Scale (SUS). All data analyses were conducted in SPSS version 29 following matching of pre/post data. Due to non‐normally distributed data, the non‐parametric Wilcoxon signed‐rank test was used to examine the change from pre‐test to post‐test scores on the Kids Brain Health Questionnaire.ResultThe SDG was evaluated with 46 participants. Most participants reported not having a family member/close friend living with dementia (71.7%). A Wilcoxon signed‐rank test showed a statistically significant median increase (Mdn = 1.00) in Kids Brain Health Questionnaire scores from pre‐test levels (Mdn = 52.00) to post‐test levels (Mdn = 53.0), z = 2.90, p = .004. A mean score of 36.15 out of a possible 50 was found for the SUS.ConclusionThe findings demonstrate ‘evidence of promise’ for early intervention stage testing with a small but statistically significant increase in knowledge for children after using the SDG, ‘my Superbrain’. Participants also found the game acceptable, suggesting further work is warranted to test the SDG on a larger sample of children.
Comparing the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer’s disease: A novel meta‐analysis model
Authors: Sheppard Athena L , Quinn Terry J , Bujkiewicz Sylwia , Owen Rhiannon K 
Published: January 2025

AbstractBackgroundThe emergence of new biomarkers for Alzheimer’s disease is accompanied by the urgent need to evaluate their diagnostic performance in comparison to existing technologies. Meta‐analysis methods make best use of the available evidence by synthesizing all relevant published studies. Meta‐analytic models that estimate comparative diagnostic accuracy are key to informing healthcare decision‐making around which tests should be used in clinical practice. To produce robust and precise estimates of sensitivity and specificity, models must take into account associations between multiple tests evaluated in the same patient group.MethodA novel Bayesian meta‐analysis model for jointly synthesizing accuracy data on two diagnostic tests was developed using a motivating example in Alzheimer’s disease dementia. A statistical technique known as a copula was used to flexibly capture the associations between the two tests. Comparative diagnostic accuracy data was sourced through electronic searching of The Cochrane Library. The model was fit to studies comparing the diagnostic accuracy of cerebrospinal fluid (CSF) amyloid‐β 42 (Aβ42) and total tau (t‐tau) to detect patients with mild cognitive impairment who would convert to Alzheimer’s disease dementia.ResultCSF Aβ42 (80.6%; 95% credible interval [CrI] 70.8%, 88.3%) was more sensitive to detect Alzheimer’s disease dementia than CSF t‐tau (74.6%; 95% CrI 65.4%, 82.2%). However, CSF t‐tau demonstrated slightly higher specificity (75.5%; 95% CrI 64.9%, 84.4%) than CSF Aβ42 72.6% (95% CrI: 62.9%, 81.2%). In comparison to the meta‐regression approach currently recommended by evidence synthesis guidelines, which ignores associations between tests, the newly proposed model led to increased precision around summary sensitivity and specificity estimates.ConclusionThe proposed model reduces uncertainty around summary test accuracy, aiding decision‐making around diagnostic strategies for Alzheimer’s disease dementia. This novel methodological development is applicable to a range of diagnostic tests for Alzheimer’s disease, including newly emerging blood‐based biomarkers. Continued development of early and minimally‐invasive diagnostic biomarkers will require comprehensive evaluation in the context of existing tests, using appropriate statistical models that capture associations between tests.
Co‐creating practical social media recommendations for dementia prevention researchers: A Delphi study
Authors: Hrincu Viorica , Roy Katie T. , Robillard Julie M. 
Published: January 2025

AbstractBackgroundSocial media provides dementia prevention researchers with additional opportunities to engage diverse audiences, including healthy individuals who unaware of their eligibility to take part in dementia‐related research. However, practical social media guidance that reflects the values and priorities of potential participants is needed. To address this gap, we sought to create consensus recommendations with research professionals and community experts.MethodWe conducted a three‐round, modified Delphi consisting of three online surveys and three conferences calls. Based on data from earlier project phases, a group of 16 experts with lived (n = 10) and professional (n = 6) experiences co‐created a set of recommendations to guide ethical social media use for dementia prevention research. Consensus was defined a priori as ≥70% agreement.ResultTwenty‐six items attained panelist agreement. Two privacy‐related items reached consensus in Round 1: the ethical appropriateness of closed social media groups (88%) and accessing individuals not on social media through social media contacts (79%). Nine items reached consensus in Round 2, including addressing misinformation (79%), stigma (93%), and other pertinent items for social media communication (e.g., public criticism, explaining process of science). Fifteen of the sixteen remaining items reached consensus after revision in Round 3. These items included defining appropriate comments (100%), rules of engagement on dementia social media pages (100%, e.g., positive messaging, relevant topics), and ranking appropriate prevention language use for different audiences (e.g., young, healthy adults, individuals with a family history). One item pertaining to language use for people living with dementia did not reach consensus.Recommendations were organized into seven social media use cases: setting up a social media page, handling online misinformation, actively challenging stigma, handling difficult online interactions, introducing new research to the public, help with study recruitment, and the language of prevention when writing posts.ConclusionResearch professionals and community members co‐created consensus recommendations to facilitate the ethical use of social media by dementia prevention researchers. By providing practical guidance, these recommendations will uphold ethical decision‐making on social media. Next steps are to create an evaluation tool and distribute the recommendations to relevant audiences.
Gray‐White Matter Boundary Z‐Score and Its Volume as Imaging Biomarkers of Alzheimer’s Disease
Authors: Jahng Geon‐Ho , Tian Yunan , Oh Jang‐Hoon , Rhee Hak Young , Park Soonchan , Ryu Chang‐Woo 
Published: January 2025

AbstractBackgroundAlzheimer's disease (AD) presents typically gray matter atrophy and white matter abnormalities in neuroimaging, suggesting that the gray‐white matter boundary could be altered in individuals with AD. The purpose of this study was to explore differences in gray‐white matter boundary Z‐score (gwBZ) and its tissue volume (gwBTV) between patients with AD, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) elderly participants.MethodThree‐dimensional T1‐weight images of a total of 227 participants were prospectively obtained to map gwBZ and gwBTV on images using a 3‐T MR system. Statistical analyses of gwBZ and gwBTV maps were performed using the full factorial one‐way analysis of covariance (ANCOVA) to compare among the three groups and the multiple regression analysis to assess the association between each map and MMSE score with both age and TIV as covariates.ResultThis study included 62 CN participants (71.8 ± 4.8 years, 20 males, 42 females), 72 MCI participants (72.6 ± 5.1 years, 23 males, 49 females), and 93 AD participants (73.6 ± 7.7 years, 22 males, 71 females). It was found that gwBZ and gwBTV were lower in AD than in CN or MCI and lower in MCI than in CN. The AD group had lower gwBZ and gwBTV than the CN and MCI groups. MMSE showed positive correlations with gwBZ and gwBTV whereas age showed negative correlations with gwBZ and gwBTV. The combination of gwBZ or gwBTV with MMSE had a high accuracy in classifying AD from CN in the hippocampus with an area under curve (AUC) value of 0.972 for both.ConclusiongwBZ and gwBTV were reduced in AD. They were correlated with cognitive function and age. Moreover, gwBZ or gwBTV combined with K‐MMSE had a high accuracy in differentiating AD from CN in the hippocampus. These findings suggest that evaluating gwBZ and gwBTV in the AD brain could be a useful tool for monitoring AD progression and diagnosis.