bluuebunny/crossref_metadata_2025_split huggingface dataset:
Needs Assessment Study in Colombia: Recruitment Phase‐Design of Remote Communication Strategies to Encourage participation in dementia research during COVID‐19 pandemic
Authors: Romero‐VanegasPardo Sara JulietaRodrigo , Moreno‐Angarita Marisol 
Published: December 2022

AbstractBackgroundDuring the pandemic, we face multiple challenges during the research. One of them was recruiting participants in the age of social distancing. As a result, we had to use creative approaches that would allow us to access the study population contemplating all the complexities, difficulties or problems that research during a pandemic demands. For dementia, we design a method to encourage the participation of patients, caregivers, professionals and associations in Colombia. Combining different virtual frameworks, tools and techniques. We embraced biosafety provisions from health policy authorities mitigating the exposition of our high‐risk groups, making up the majority of our target population.ObjectiveDesign a methodological communication strategy that allows the dissemination of project knowledge and participation of the target populations (patients with mild dementia, formal and informal caregivers and health care professionals).MethodWe summoned caregivers, people with dementia and health care professionals through multiple channels: Social media, e‐mail, caregiver´s databases, press, radio, physician specialists invitation, Dementia Research Groups (Antioquia University and Colombia National University), and voluntary associations (Alzheimer Colombia Family Action Foundation, Grupo Cuídame). We presented remote conferences about the project, panel discussions about the invisible needs of the population with dementia in Colombia. Also, we sought collaborative efforts with radio and television programs to increase the awareness in the population about the dementia challenges.ResultOver 100 people attended each event. We carried out collaborations with national groups increasing visibility of the project and amplifying citizen participation. Interviews with written, oral, and electronic media contributed to fostering interest in the study population. Remote communication strategies stimulated the involvement of various actors (patient‐family‐caregiver‐professional) from multiple cities and contexts.ConclusionResearching pandemic time has tested our creative ability to address the various challenges we face as researchers. Accessing the participants contemplated by the study has led to a little‐explored space, which has directed us towards non‐face‐to‐face alternatives, prompting us to design a methodological communication strategy that allows the dissemination of the project and participation of the dementia population in Colombia without requiring in‐person attendance.
Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND‐China): an Update 2018‐2021
Authors: Wang Yongxiang , Tang Shi , Hou Tingting , Cong Lin , Du Yifeng , Qiu Chengxuan 
Published: December 2022

AbstractBackgroundAround one‐third of people with dementia worldwide might be attributable to seven modifiable risk factors, implying that interventions to control these risk factors may delay the onset of dementia. Therefore, we initiated the multimodal interventions to delay dementia and disability in rural China (MIND‐China) in 2018 and updated the main progresses of the project in 2018‐2021.MethodsMIND‐China is designed as a community‐based 2‐year cluster‐randomized, controlled, multimodal intervention study, which targets people who are aged 60‐79 years and living in the rural communities of Yanlou Town, western Shandong Province, China. Following the baseline examination in 2018, 52 villages in Yanlou Town are randomly (cluster‐randomization) divided into three groups: control group (regular primary health care service), vascular intervention group, and multimodal intervention group. The vascular intervention includes healthy lifestyle guidelines and the national guidelines‐based medical treatment of major cardiometabolic risk factors. The multimodal intervention group receives, in addition to the interventions planned for vascular intervention, group physical exercise, personalized leisure activities, and cognitive training.ResultsIn March‐September 2018, 5,765 participants underwent the core module assessments via face‐to‐face interviews, clinical examinations, neuropsychological testings, and laboratory tests (74.9% of all eligible residents). The mean age was 70.9 years (SD 5.9), 57.2% were women, 40.6% were illiterate, and 88.3% were farmers. Specific modules of examination were performed for subsamples (e.g., brain MRI scans, genetic and blood biomarkers, physical function, sleep quality, audiometric testing, and OCT examination). In May‐September 2019, the pilot study was completed to test the feasibility of the intervention programs and the implementation procedure in 7 villages (2 villages in control group, 3 villages in vascular intervention group, and 2 villages in multimodal intervention group). Recruitment of participants for interventions started in October 2019. In July‐November 2021, we conducted the 1‐year follow‐up assessments of participants in the interventions.ConclusionBy the end of 2021, MIND‐China had completed baseline screening assessment, recruitment of intervention participants, and the first follow‐up assessments following the initiation of interventions. MIND‐China demonstrates the feasibility of implementing the multimodal interventions in rural communities. COVID‐19 has minimal impact so far on the project.
Genetic risk for attention‐deficit/hyperactivity disorder is associated with amyloid‐dependent cognitive decline in older adults
Authors: Leffa Douglas Teixeira , Ferrari‐Souza João Pedro , Bellaver Bruna , Ferreira Pamela C.L. , Tissot Cécile , Brum Wagner S. , Caye Arthur , Lord Jodie , Proitsi Petroula , Tudorascu Dana L , Lopez Oscar L. , Villemagne Victor L , Cohen Ann D , Klunk William E , Rosa‐Neto Pedro , Zimmer Eduardo R. , Karikari Thomas K , Rohde Luis Augusto , Pascoal Tharick A 
Published: December 2022

AbstractBackgroundRecent epidemiological studies using population‐based registers showed that patients with Attention‐Deficit/Hyperactivity Disorder (ADHD) are more likely to be diagnosed with mild cognitive impairment (MCI) and Alzheimer’s disease (AD), suggesting a higher risk for cognitive impairment in older age. Here, we aimed to assess whether genetic liability for ADHD, as measured by a validated polygenic risk score (ADHD‐PRS), is associated with cognitive decline in cognitively unimpaired (CU) subjects and whether these effects vary according to baseline amyloid‐β (Aβ) burden.MethodWe studied 212 CU participants (116 women [54.7%], mean [SD] age of 73.1 [5.9]) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Subjects had available baseline Aβ burden (measured by [18F]Florbetapir Aβ‐PET) and genetic information, as well as a minimum of 2 cognitive assessments (Preclinical Alzheimer Cognitive Composite [PACC] and MMSE) in a 6‐year period. Aβ positivity was defined using a previously published cutoff of global [18F]Florbetapir PET SUVR > 1.11. We calculated ADHD‐PRS using data from the latest genome‐wide association study on ADHD, with a p‐value threshold of 1. Statistical analyses were performed using linear mixed‐effects models adjusted for age, sex, APOE ε4 status, and the first seven principal components to adjust for population stratification.ResultADHD‐PRS was normally distributed and was not associated with age, sex, or APOE ε4 status (Figure 1). We observed a significant ADHD‐PRS by time interaction (β=‐.03, 95% CI ‐.05 to ‐.01, p‐value=.001 for PACC, β=‐.04, 95% CI ‐.07 to ‐.009, p‐value=.01 for MMSE) on cognitive performance, indicating that higher ADHD‐PRS is associated with decreased cognitive function over time (Figure 2). Additionally, we observed a significant interaction between ADHD‐PRS, time, and baseline Aβ burden (β=‐.05, 95% CI ‐.10 to ‐.008, p‐value=.02 for PACC, β=‐.08, 95% CI ‐.15 to ‐.01, p‐value=.02 for MMSE), suggesting that higher ADHD‐PRS is associated with longitudinal cognitive decline only in Aβ‐positive individuals (Figure 3).ConclusionOur findings indicate that higher genetic liability for ADHD is associated with cognitive decline in Aβ‐positive older adults without cognitive impairment. These findings support the hypothesis that higher rates of MCI and AD in patients with ADHD may result from decreased resilience to Aβ pathology.
Influence of Sex Hormones in a Mouse Model of Multi Etiology Dementia
Authors: Abi‐Ghanem Charly , Kelly Richard D , Salinero Abigail E , Kyaw Nyi‐Rein , Wang Matthew , Riccio David , Gannon Olivia J , Mansour Febronia , Kordit David , Sura Avi , Zuloaga Kristen L 
Published: December 2022

AbstractBackgroundUp to 80% of Alzheimer’s Disease (AD) patients suffer from concurrent vascular contributions to cognitive impairment and dementia (VCID) resulting in multi‐etiology dementia. VCID (the 2nd leading cause of dementia) is more common in men throughout most of the lifespan. while the majority (approximately 2/3) of Alzheimer’s Disease (AD) patients are women. Ageing is a main dementia risk factor which may act through the depletion of sex hormones. Both testosterone, in men, and estrogen, in women, have been shown to be neuroprotective. In this study we examine the effect of gonadal hormones on cognitive changes in a mouse model of multi etiology dementia using the AppNL‐F/NL‐F knock‐in Alzheimer’s disease mouse model that does not overexpress amyloid precursor protein.Methods5‐6 months old App
NL‐F/NL‐F mice were subjected to gonadectomy or sham surgery and left to recover for 3 weeks to clear any endogenous gonadal hormones. Multi‐etiology dementia was modeled using chronic cerebral hypoperfusion (unilateral carotid artery occlusion). Control animals (App
NL‐F/NL‐F without hypoperfusion; AD only model) received a sham surgery. Mice were then subjected to a battery of behavioral tests before being euthanized and then brains and serum were collected.ResultsCognitive impairment differences between groups were investigated using several behavioral tests: anxiety‐like behavior and activity levels using an open field testing, episodic‐like memory using a novel object recognition test, spatial learning and memory via Barnes maze testing and activities of daily living using a nest building test. Our next step is to evaluate the underlying pathology in the brain that could mediate cognitive deficits (i.e. amyloid pathology, white matter damage and neuroinflammation).ConclusionsWe hope that this work will highlight the importance of modeling endocrine aging in animal models of dementia and will contribute to further understanding of sex differences and sex specific risk factors for dementia.
An amyloid‐cognition composite score for estimating time‐consistent biomarker trajectories across the Alzheimer’s continuum
Authors: Raket Lars Lau , Palmqvist Sebastian , Mattsson‐Carlgren Niklas , Hansson Oskar 
Published: December 2022

AbstractBackgroundWhile the temporal dynamics of biomarkers in Alzheimer’s disease (AD) have been studied in much detail, the lack of established methods for accurately staging pre‐dementia individuals in a time‐consistent manner has resulted in uncertain trajectories and lack of accurate estimates on the temporal relations between biomarkers and clinical milestones.MethodsA novel latent‐time disease progression model was developed to estimate a multivariate time‐consistent trajectory describing the typical timeline of clinical scales (CDR‐SB, ADAS‐cog, MMSE) and amyloid PET along the AD continuum based on data from amyloid‐negative (A‐) cognitively unimpaired (CU) and the full cognitive spectrum of A+. For each subject, the model predicted amyloid‐cognition (AC) scores that represented the progression along the estimated timeline. Correlation to unseen variables was used to validate the AC score construct. AC scores were then used as a natural timescale for comparing a range of biomarker trajectories.ResultsUsing 1424 individuals (6236 visits, 4581 follow‐up years) from the Alzheimer’s Disease Neuroimaging Initiative, we estimated a timeline of Alzheimer’s disease that spanned almost 20 years from the earliest stages of CU amyloid PET positivity (AC score 0) to severe dementia (Figure 1).The predicted subject‐level AC scores had the best cross‐domain correlation among all compared staging methods (Table 1).CSF biomarkers (Aβ1‐42/p‐tau181) showed the earliest changes, followed by amyloid PET, plasma p‐tau181 and finally tau PET (Figure 2). In terms of abnormality relative to A‐ CU, CSF Aβ1‐42 reached a population‐level mean value above the A‐ CU 95%‐percentile 1.5 years before amyloid PET. Tau PET reached this level 8 years after amyloid PET (Figure 3). In early pre‐clinical stages, CSF Aβ1‐42 was the biomarker that was most sensitive to change. In the later pre‐clinical and early symptomatic stages amyloid PET was most sensitive followed by tau PET in prodromal stage, and measures of cognition and function in the dementia stage (Figure 4).ConclusionThis analysis supports the AC score as a data‐driven approach for studying biomarker trajectories across the Alzheimer’s continuum. The analysis highlighted the value in using different biomarkers to detect subject‐level changes across disease stages. Replication analyses in the BioFINDER study are ongoing.
Plasma levels of exosome‐bound Aβs accurately identify Alzheimer’s disease patients
Authors: Park Min Cheol , Kim Hye‐Ri , Kang JiYoon , Kim SangYun , Heo Youhee 
Published: December 2022

AbstractBackgroundBlood‐based diagnosis of Alzheimer's disease may be the most efficient, non‐invasive, and cost‐saving method. However, in contrast to CSF, the performance of plasma Aβ42/40 ratio is still arguable in AD diagnosis. Recently, exosome‐based biomarkers have been found that is more reliable biomarker especially in blood‐based AD diagnosis. Here, we assessed the performance of plasma levels of exosome‐bound Aβs.MethodWe quantified plasma levels of exosome‐bound Aβs with a high‐sensitive ABSOL HS system, which is based on PIFA (Photooxidation‐Induced Fluorescence Amplification) technique to detect very small amount (sub pg/mL) of biomarkers (FIG.1). The ABSOL HS system fully‐automated the entire ELISA steps and PIFA measurement using a disposable strip‐well cartridge and tip within 30 minutes. To assess the feasibility of plasma levels of exosome‐bound Aβs, 61 Alzheimer’s disease patients and 60 normal controls were enrolled in this study.ResultAD group had lower level (3.447 ± 2.114 pg/mL) of exosome‐bound Aβs than NC group (10.153 ± 6.616 pg/mL). The plasma levels of exosome‐bound Aβs identified Alzheimer’s disease with an area under the ROC curve (AUC) of 0.9124 at a cutoff of 5.564 pg/mL, which was equivalent to 81.97% of sensitivity and 81.67% of selectivity (FIG 2, FIG 3).ConclusionThe plasma levels of exosome‐bound Aβs showed similar tendency with plasma Aβ42/40 ratio, but the diagnosis accuracy is higher with AUC of 0.9124 than the plasma Aβ42/40 ratio (AUC about 0.8). In this study, the plasma levels of exosome‐bound Aβs accurately identified Alzheimer’s disease patients, which means the exosomal Aβs could serve as a more reliable biomarker to diagnosis Alzheimer’s disease.
Identifying heritable brain networks that may confer cognitive reserve to Alzheimer's disease
Authors: Murdy Thomas J , Dunn Amy R , Telpoukhovskaia Maria , Zhang Shanrong , Febo Marcelo , Kaczorowski Catherine C. 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disease that affects 50 million people worldwide (Breijyeh & Karaman, 2020). Among individuals with AD, cognitive dysfunction varies, giving rise to the hypothesis that neural function and anatomical substrates provide “cognitive reserve” against AD. This idea inspired the brain reserve hypothesis, which states that structural features of the brain may protect against AD‐related cognitive decline (Stern, 2012). One potential source of brain reserve is neural microanatomy, which varies across individuals (Wang et al., 2020) and may then explain the differential cognitive outcomes in AD associated with cognitive reserve.MethodWe utilized a population of genetically distinct AD mice produced by crossing the 5XFAD model of AD to five mouse strains (C57BL/6J, DBA/2J, FVB/NJ, CAST/EiJ, and WSB/EiJ). At 3 months of age, these mice underwent diffusion magnetic resonance imaging (dMRI), a collection of techniques that characterizes brain microstructure (Campbell & Pike, 2019), to probe variation of neural microanatomy in 430 regions of interest (ROIs). At 5 months of age, when cognitive decline is expected (Oakley et al., 2006; Devi & Ohno, 2010), these mice underwent contextual fear conditioning (CFC) and contextual fear memory (CFM) paradigms. Hierarchical clustering was performed on the correlations between dMRI measurements in each brain region influenced by strain and CFC and CFM performance.Result362 ROIs had dMRI metrics with significant effects of sex, strain, and/or 5XFAD genotype. Of these ROIs, 348 had a significant effect of strain, 68 had a significant effect of sex, and 30 or fewer had a significant effect of genotype or any variable interactions. We identified one network of ROIs in which nearly all dMRI parameters correlated positively and strongly to CFC performance and two networks whose dMRI measures correlated strongly to CFM performance, although the directionality of these correlations varied within these two networks.ConclusionOur work identifies three neural networks that are influenced by strain and correlate strongly to CFC and CFM performance. Further analyses should explore genetic factors influencing these networks and the structural and functional connectivity of brain regions in these networks.
Synaptic loss in behavioural variant of frontotemporal dementia:an in vivo [11C]UCB‐J PET study
Authors: Malpetti Maura , Jones P Simon , Cope Thomas E , Holland Negin , Naessens Michelle , Rouse Matthew A , Savulich George , Fryer Tim D , Hong Young T , Milicevic‐Sephton Selena , Aigbirhio Franklin I , O'Brien John T , Rowe James B 
Published: December 2022

AbstractBackgroundPost‐mortem clinical studies and animal models described severe synaptic loss as an early feature of neurodegenerative disease, including frontotemporal dementia. Recently, PET radiotracers that bind to synaptic vesicle glycoprotein 2A have been developed and proven to enable in vivo quantification of synaptic loss in people with neurodegenerative diseases. This study used [11C]UCB‐J PET to quantify synaptic loss in people with behavioural variant frontotemporal dementia (bvFTD).MethodWe recruited 10 people with a clinical diagnosis of bvFTD and 24 age‐ and sex‐matched healthy controls. Participants underwent dynamic [11C]UCB‐J PET‐MR, and a neuropsychological assessment, including the Addenbrooke's cognitive examination (ACE‐R) as a global measure of cognitive performance, and the INECO frontal screening. Synaptic density was estimated using [11C]UCB‐J non‐displaceable binding potential (BPND) at voxel level and in whole‐brain regions of interest. General linear models were used to compare [11C]UCB‐J binding voxel‐wise between groups, and correlate synaptic density with cognitive performance in bvFTD cohort. These analyses were also performed using regional [11C]UCB‐J binding potentials, with and without partial‐volume correction. Regional correlations were performed with both frequentist and Bayesian approaches.ResultPeople with bvFTD showed severe synaptic loss compared to controls at individual level and as a group. [11C]UCB‐J binding was significantly reduced bilaterally in medial and dorsolateral frontal regions, inferior frontal gyri, anterior and posterior cingulate gyrus, insula cortex and medial temporal lobe (5.1 ≤ t ≤ 9.3, p < 0.05 FWE at voxel level, Figure 1A). Results from ROI‐based analyses mirrored the voxel‐wise results, with and without partial‐volume correction. Synaptic loss in the left frontal and cingulate regions significantly correlated with cognitive impairments as assessed with ACE‐R and INECO (r > 0.8, p<0.001 at voxel level, p<0.05 FWE at cluster level, Figure 1B). Correlations were confirmed by regional‐based analyses, with both frequentist and Bayesian approaches (Figure 1C).ConclusionDifferent analytic approaches converged showing a significant and widespread frontotemporal loss of synapses in symptomatic bvFTD, in proportion to disease severity. [11C]UCB‐J PET could therefore be a useful supporting tool for translational studies and experimental medicines strategies for new disease‐modifying treatments in this condition.
Pharmacological preconditioning with mitochondrial dynamic modulators exerted neuroprotection against cardiac ischemia‐reperfusion injury in obese rats via suppressing microglial inflammation
Authors: Maneechote Chayadom , Arunsak Busarin , Nawara Wichwara , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: December 2022

AbstractBackgroundObesity is widely acknowledged as a major risk factor for brain and heart complications. Brain inflammation and microglial activation can be induced by either cardiac ischemia/reperfusion (I/R) injury or obese condition. While mitochondrial fission inhibitor (Mdivi‐1) and fusion promoter (M1) have already been reported as potential cardioprotective therapies, their protective effects in the brain suffered from cardiac I/R injury under obese condition have not been investigated.MethodThirty male Wistar rats were fed with a high‐fat diet (HFD) for 12 weeks to induce obese‐insulin resistance, and then were randomly divided into the sham (HFS, n=6) and the cardiac I/R (n=24) groups. Cardiac I/R rats were intravenously injected with either vehicle (HFV, n=6), Mdivi‐1 (HFMD, n=6), M1 (HFM1, n=6), or Mdivi‐1+M1 (HFMD+M1, n=6) 15 min prior to a 30‐min ischemia by left anterior descending coronary artery ligation, followed by 120‐min reperfusion. At the end of the protocol, the brain was rapidly removed to determine the protein expression of brain inflammation, microglial markers, and brain pathological conditions.ResultCardiac I/R markedly induced brain pathology via increasing inflammation, microglial activation, and brain pathologies, as shown by increased levels of tumor necrosis factor alpha (TNF‐α), ionized calcium binding adaptor molecule 1 (IBA1), and beta‐amyloid (Aβ) per amyloid‐beta precursor protein (APP) ratio in the HFV group, compared with those of HFS group (p<0.05, Figure 1). In HFD‐fed rats with cardiac I/R injury, either Mdivi‐1, M1, or combined therapies provided neuroprotection by restoring TNF‐α, IBA1, and Aβ/APP protein levels (p<0.05, Figure 1), as well as improved left ventricular ejection fraction [58±5% HFMD; 53±3% HFM1; 55±6% HFMD+M1 vs 42±2% HFV].ConclusionRebalancing brain mitochondrial dynamics rescued brain inflammation and brain pathologies induced by cardiac I/R injury of obese rats. These findings suggest that the modulators of mitochondrial dynamics may act as a novel therapeutic approach for combating brain damage caused by cardiac I/R in an obese subject.