bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wisconsin ADRC research education component: Qualitative observations
Authors: Spensley Sheryl , Kohli Akshay , Puglielli Luigi , Shah Manish N , Kind Amy J , Bendlin Barbara B 
Published: December 2020

AbstractBackgroundIncreases in the prevalence of Alzheimer’s disease (AD) and related dementias (ADRD) in the coming years will require a workforce capable of addressing this health epidemic. The National Institute on Aging has introduced Research Education Components (RECs) to “support research educational activities to complement the training of a workforce to meet the nation's research needs in AD and related dementias.” By recruiting and training promising researchers, the goal of RECs are to increase the pool of researchers dedicated to studying ADRD, advance the mission of translating research advances into improved diagnosis and care, as well treating and preventing ADRD.MethodThe Wisconsin Alzheimer’s Disease Research Center (ADRC) REC was funded in 2019, and aims to SA1: Deliver a rigorous mentored training program to ensure research proficiency in AD research and preclinical biomarkers; SA2: Infuse research concepts related to AD into University of Wisconsin predoctoral, postdoctoral fellowship, and junior faculty training programs and provide training opportunities; and SA3: Measure the effectiveness of the Wisconsin ADRC REC training program using mixed methods approaches.ResultThree REC scholars were selected. All are Assistant Professor level faculty supported by career awards. The REC provides funding to carry out a mentored, 2‐year, research project. The REC Scholars gain competency in research skills through a blend of self‐directed modules, seminars, and experiential activities. To reach a broader base of trainees, a database was created to track training needs, career goals/promotions, trainee demographics, and to communicate specific training and funding opportunities. Since the REC started its promotional activities and tracking, didactic series attendance has increased by 415%. Finally, the REC has collaborated with UW Madison PEOPLE (Precollege Enrichment Opportunity Program for Learning Excellence) to create the REC Junior Fellowship. The fellows, diverse high school students, will intern at Wisconsin ADRC research labs and learn more about career paths in AD research.ConclusionQualitatively, the first year of REC funding appears to be positively impacting training. Formal evaluation of the REC will occur via the “Learning through Evaluation, Adaptation, and Dissemination” (LEAD) Center. Outcomes will include improved research competency and retention in AD‐related research fields.
Validation of a new serum anticholinergic assay using anticholinergic burden scales and cognitive assessments in older adults with mild cognitive impairment or major depressive disorder
Authors: Chandramouleeshwaran Susmita , Rajji Tarek K , Ahsan Naba , Raymond Roger , Nobrega Jose , Fischer Corinne E , Flint Alastair , Herrmann Nathan , Kumar Sanjeev , Mah Linda , Mulsant Benoit H , Pollock Bruce G 
Published: December 2020

AbstractBackgroundA high anticholinergic burden has been associated with deleterious effects on cognition, especially in the elderly. We developed a new serum anticholinergic assay (SAA) to measure the anticholinergic burden, and report on validating this new SAA using established anticholinergic burden scales and cognitive assessments in older patients with mild cognitive impairment (MCI) or major depressive disorder (MDD).MethodBaseline serum samples were collected from 311 participants (154 with MCI, 57 with MDD, and 100 with MCI + MDD). The new SAA assay uses radio‐ligand binding to cultured cells stably expressing the muscarinic M1 receptors, with an added procedure to remove potential confounds associated with the effects of proteins in serum. We then calculated correlations between new SAA scores and each of the Anticholinergic Burden Scale (ACB) and Anticholinergic Drug Scale (ADS) total scores. Multiple regression models assessed the relationships between SAA and cognitive performance on a comprehensive cognitive battery.ResultBaseline serum samples were collected from 311 participants (154 with MCI, 57 with MDD, and 100 with MCI + MDD). The mean SAA value was 1.65 pmol/L, SD = 1.83). Mean age of the sample was 71.96 years, range 60‐90 years, SD=6.2. 38.7 % were males. In both the ACB and ADS scores, participants with the highest total scores had the highest SAA values. ADS: F (2,98) = 7.84, p = 0.001, SAA (3+) > SAA (1); ACB: F (2,121) = 5.89, p = 0.004, SAA (3+) > SAA (1) and > SAA (2). SAA was significantly associated with performance on executive function after adjusting for age, gender, education, diagnosis, controlling for multiple testing. (β = ‐0.152, SE = 0.024, p = 0.007) There was no association with overall cognitive composite score combining all domains.ConclusionThe above results support the use of the new SAA as a measure of anticholinergic burden. Of note, the effect of SAA on executive function was almost equivalent, though in the opposite direction, to the effect of education on executive function.
Mining of differentially co‐expressed gene modules reveals perturbed functional network and key regulators in Alzheimer's disease brains
Authors: Xiang Shunian , Ni Dong , Huang Kun , Zhang Jie 
Published: December 2020

AbstractBackgroundCo‐expression network module mining is an efficient approach to identify novel disease pathways, predicting new gene functions and search for disease biomarker genes. However, integrating transcriptomic data of Alzheimer’s disease (AD) patients from multiple cohorts and identified consensus (frequent) co‐expressed gene modules that are differentially expressed in AD vs. normal brains have not been explored.MethodIn this study, we analyzed eight large AD brain transcriptomic datasets from major AD cohort studies and looked for differentially co‐expressed genes that form network modules (difFGCN), through which we identified pathways and key regulators that are associated to AD pathology.ResultWe obtained six AD specific difFGCN modules which have higher co‐expression frequency in AD brains samples as compared with normal ones, and 19 such modules with higher co‐expression frequency in normal brain samples. Functional and pathway enrichment analysis revealed function categories related to AD pathology. Remarkably, we identified two transcription factors, down regulated gene EGR1 targeting the genes in AD specific module accounting for negative regulation of apoptotic pathway and up regulated gene SP1 targeting the genes in normal specific module accounting for mitochondrial pathway, which may be key regulators for AD pathological changes. Combined with differential expression analysis, we also confirmed the key regulators change in AD brains.ConclusionThrough the differential frequent coexpression module mining, we identified several AD specific coexpressed gene modules and normal ones, which revealed functional change in the network level as well as key regulators which may cause such pathological changes in AD brains. Our results provide new insights in AD mechanism study and the key regulators we identified could be potential therapeutical targets for AD drug development.
Depression in Alzheimer’s disease: Is the combination of citalopram and rivastigmine better than rivastigmine alone? A longitudinal clinical trial
Authors: Pathak Krishna Prasad P. , Tsolaki Magda , Verikouki Eleni P. 
Published: December 2020

AbstractBackgroundPharmacological treatment for AD and depression are unfortunately few and of limited efficacy to cure the disease.MethodLongitudinal clinical prospective study with 1278 AD patients on rivastigmine 9,5mg/patch and citalopram 20‐40 mg/day over 48 months was assessed on the basis of NINCDS‐ADRDA, MMSE, DSM‐IV, FRSSD, GDS, HRS‐D and follow up of the patients.ResultFour years after the baseline assessment, there were no significant differences in MMSE, Geriatric depression scale and Hamilton rating scale for depression between patients treated with rivastigmine alone or combined rivastigmine with citalopram with or without depression (p>0.05). Functional Rating Scale for symptoms of dementia, Activities of Daily Living of patients with AD and depression treated with rivastigmine was significantly worse than patients treated with rivastigmine and no depression (p=0.027).ConclusionThe combination of rivastigmine and citalopram had no better results than rivastigmine alone in patients with AD.
What do I really need? Assessment of caregiver support for people with intellectual and developmental disabilities (IDD) and dementia
Authors: Service Kathryn , Clifford Christine J 
Published: December 2020

AbstractBackgroundThe increased needs of people with an intellectual and developmental disability (IDD) and a dementia related disorder can strain caregivers and existing community support systems. The project team, comprised of IDD and Aging experts and funded, in part, through a federal grant, conducted a needs assessment on the awareness and use of typical community‐based resources such as senior centers. The assessment consisted of both telephone interviews and home visits with group home, shared living, and family caregivers.MethodNurse Practitioner (NP) conducted a total of 95 interviews with 54 site visits, and the evaluator completed 40 interviews with caregivers of people with IDD and dementia diagnosis. Analysis included both qualitative and quantitative data.Caregivers were asked about the following: functional and health status of person with IDD since dementia diagnosis, receipt of dementia specific caregiving training, care confidence levels, perceived barriers to care, and access to community‐based aging resources.ResultCaregiver’s most frequent concerns included lack of suitable day programming, planning for the person’s future, and caregiver burnout and stress. 78% reported feeling confident providing care currently and 68% were confident about providing care in the future. Most caregivers are aware of local community resources such as senior centers, Alzheimer’s Association Counseling and an on‐line training series on aging, but rarely used the resources.ConclusionCaregivers generally relied on support from provider agencies indicating a need for increased collaboration across the IDD and Aging human service support systems. Trainings, delivered to both aging advocates and caregivers of people with IDD, and designed to improve communication and collaboration focused on dementia capable care, state systems, and available community resources. In addition, a series of web‐based resources were developed with a focus on IDD and dementia. Results of the assessment will continue to guide resource and training development to improve collaboration and support the relationship between the Aging and IDD communities.
ICF‐based health and social‐needs assessment system for person‐centered dementia care
Authors: Park Myonghwa , Go Younghye , Lee Mihyun 
Published: December 2020

AbstractBackgroundThis study explained the development of health and social needs assessment system for patients with dementia based on International Classification of Functioning, Disability and Health International Classification (ICF) model to enhance person‐centered dementia community care. ICF is the WHO framework for measuring health and disability at both individual and population levels. Many countries including Korea have been participating in trials for implementation of the ICF in hospitals and community settings. The use of ICF domains as intervention targets for persons with dementia and their family members can be an innovative attempt to facilitate person‐centered community care.MethodsUsing methodological study design, the following steps were performed. First, the concepts and domains of ICF were compared with existing instruments to measure health and functional status of persons with dementia. Second, the health and social needs assessment tool sets were developed and mapped with the framework of ICF. Third, the expert validated the health and social needs assessment system tool using Delphi method and focus group interview. Fourth, the pilot test was conducted with two community social service centers and two day care centers.ResultsSix domains of health and social needs assessment were developed and embedded in the assessment tools; Health condition (diagnosis, severity of dementia), body functions and structure (health assessment, health habit, nutrition physical exercise), activity (cognitive function, daily life activities), participation (social activity, emotional function, social relationship), environmental factors (home, community, facility environment, social support) and personal factors (personal history).ConclusionThe use of the health and social needs assessment system based ICF framework can help health care and social service professionals to evaluate person centered health and social needs. It facilitates mapping the assessed needs to individualized care plans, and guide the persons with dementia to the best services. Using a larger sample, further studies to verify reliability and validity of the developed assessment system are needed.
Development and feasibility testing of a person‐centered cognitive service manual to enhance community care for people with dementia in Korea
Authors: Park Myonghwa , Go Younghye , Lee Mihyun 
Published: December 2020

AbstractBackgroundIn order to improve the quality of life for persons with dementia and their families and to ensure the efficiency of national cost for managing dementia, there is a need to support them in their communities as long as possible. Therefore, person‐centered cognitive interventions for early detecting of dementia and delaying its progression in the community is an urgent priority at the international level. This study aimed to develop a person‐centered cognitive service manual for early dementia to use for national long‐term care agencies and test its feasibility.MethodsThis study was conducted from February to July, 2019. The theoretical rationale for the manual was developed through systematic review of previous guidelines and studies. The focus group interviews identified the needs and preferences of stakeholders. The manual consisted of assessment, intervention, and outcome based on six domains. Six domains were individuality, independence, psychological health, physical health, safety, and social support. The manual provides comprehensive needs assessment tools and algorithms to plan and provide individualized service plan. The feasibility study was conducted at 47 senior welfare centers in Korea.ResultsThis study found that the manual was effective for initial consultation (63.0%), comprehensive evaluation (50.0%), service planning (72.7%), service provision (78.3%), goal achievement evaluation (50.0%), and service termination (100.0%). However, service provider’s increased workloads and the time for completing the needs assessment were identified as barriers to apply the manual. In addition, service providers experienced lack of knowledge and skills in comprehensive evaluation (55.9%) and service planning (29.4%). The continuous educational support for manual application was suggested.ConclusionThe national manual of person‐centered cognitive service can be useful to provide the best community services to improve the quality dementia community care. Development and dissemination of ICT based care pathways into the long‐term care service system to support best practices through the manual can be suggested.
Cell type‐specific enhancer‐promoter connectivity maps in the human brain and associations with Alzheimer’s disease risk
Authors: Nott Alexi , Holtman Inge , Coufal Nicole , Schlachetzki Johannes CM , Yu Miao , Rissman Robert A , Brewer James B , Ren Bing , Gage Fred H , Glass Christopher K 
Published: December 2020

AbstractBackgroundThere is no clear genetic cause for most cases of late‐onset Alzheimer’s disease (AD), however, genome‐wide association studies have identified multiple genetic variants associated with increased risk of AD. These AD‐risk variants are often located in non‐coding DNA regulatory regions called enhancers, which upon transcription factor binding, modulate the expression of nearby genes. One of the major challenges facing the field of AD research is the assignment of cell‐type specificity and functionality to these genetic variants.MethodNuclei of microglia, neurons, astrocytes and oligodendrocytes were isolated from frozen human cortical tissue. Sorted nuclei were processed using chromatin immunoprecipitation and sequencing (ChIP‐seq) to define cell type promoter and enhancer regions. The assay for transposase accessible chromatin sequencing (ATAC‐seq) was used to define open chromatin regions, which indicates likely transcription factor binding sites. Proximity Ligation‐Assisted ChIP‐seq (PLAC‐seq) is a chromatin conformation assay that was used to link distal enhancers to target genes. Enhancers were validated by CRISPR‐mediated deletion of putative regions in induce‐pluripotent stem cells (iPSCs) that were derived into neurons, microglia and astrocytes followed by gene expression analysis.ResultGenetic variants associated with increased risk of AD were largely confined to microglia enhancers, whereas genetic variants for psychiatric disorders such as autism and schizophrenia were enriched in neuronal enhancers. Enhancer‐promoter interactome maps connected disease‐risk variants located in enhancers to gene promoters. Integrative analysis of promoter‐enhancer interactome maps has not only revised and expanded the gene repertoire influenced by AD‐risk variants but has also revealed the probable cell types in which they function. Lastly, the BIN1 locus, the second highest putative AD‐risk gene after APOE, has a microglia‐specific enhancer that harbors AD‐risk variants. CRISPR‐deletion of the microglia BIN1 enhancer in iPSCs ablated BIN1 gene expression in iPSC‐derived microglia and not neurons or astrocytes.ConclusionThere has been intense interest in elucidating mechanisms that link human non‐coding genetic variation to risk of neurodegenerative and psychiatric diseases. Towards this effort, enhancer‐promoter connectivity maps in the human brain has enabled an initial cell‐type‐specific interpretation of human genetic variation associated with disease risk for AD and other brain disorders.
Impact of familiar olfactory stimulation on self‐consciousness
Authors: Castro Arbeláez María Alejandra , Arrollo‐Anlló Eva María , Acosta Daysi 
Published: December 2020

AbstractBackgroundAutobiographical memory facilitates the construction and meaning attributed to a lifetime story. The episodic autobiographical memory involves the personal experiences related to a place and a specific time, and the semantic autobiographical memory is associated to a general knowledge related to repetitive events and past experiences over a long period of time (Allen, Doyle, Commins & Roche, 2018). Autobiographical events trigger an autonomic consciousness in which it revives the past memories, while the autobiographical semantic knowledge involves a consciousness of past limited and noetic familiar sensation (Irish et al., 2018; El Haj, Nandrino & Kapogiannis, 2015; Rathbone, Ellis, Ahmed, Moulin, Ernst, & Butler, 2019). Decline of autobiographical episodic memory involves a progressive loss of self‐consciousness in Alzheimer’s disease (A.D). Some studies like Glachet, Gandolphe, Gallouj, Antonie, and El Haj (2018) demonstrate positive effects of olfactory stimulation on autobiographical memory. However, no research has evaluated the influence of familiar olfactory stimulation on A.D related to improve self‐consciousness in Dominican Republic. This study aims to evaluate the evoked autobiographical memories from familiar olfactory stimulation has an enforcement or facilitator effect on self‐consciousness.MethodFifty people with mild and moderate A.D will participate. The Control group, will have an olfactory stimulation without familiar smells and the experimental group, will have an olfactory stimulation with familiar smells. After intervention: Evaluation of autobiographical episodic memory (controlled process) and self‐consciousness. During Intervention: Olfactory familiar stimulation with experimental group and placebo olfactory stimulation with control group. Then there will be an evaluation of autobiographical episodic memory (automatic process). Before intervention: Post olfactory stimulation of self‐consciousness.ResultsWe expect that the positive valiance of familiar olfactory intervention will be evoked more in the autobiographical episodic memories than the placebo stimulation olfactory in patients with A.D; and that autobiographical episodic automatic or involuntary memories evoked will be more elevated about subjective content that the voluntary or explicit ones. We also hope that the group of patients with familiar olfactory stimulation evoke autobiographical episodic memory and improve their level of self‐consciousness.ConclusionThis study will be a framework for non‐pharmacologic interventions and future clinical trials with familiar olfactory intervention.
Hypoxia‐induced changes in microglia in the vhl‐/‐ zebrafish
Authors: Almasnouri Taghreed S , Hamilton Noémie , Heath Paul , van Eeden Van Eeden Freek , Simpson Julie E 
Published: December 2020

AbstractBackgroundAge‐associated white matter lesions are associated with chronic cerebral hypoperfusion resulting in a hypoxic environment, and are characterised by high levels of microglia with an amoeboid phenotype. These observations suggest that sustained activation of the hypoxia‐inducible factor (HIF) signalling pathway modifies the microglial phenotype. This study aimed to perform a detailed characterisation of the microglial response associated with hypoxia by exploiting vhl‐/‐ zebrafish, a model which displays highly up‐regulated hypoxic signalling.MethodIn order to exploit the in vivo imaging capabilities of zebrafish and visualise microglia, a reporter for macrophage‐expressed gene‐1 (mpeg1) was crossed into the vhl‐/‐. The number and morphology of mpeg1::mCherry microglia were characterized by light‐sheet florescence microscopy for ten mutant vhl‐/‐ zebrafish and their wild‐type siblings, at a single time point between the ages 3.2 ‐ 3.6 dpf. Furthermore, time lapse video was employed to monitor the microglial response to hypoxia across 24 hours.ResultAt the single time‐point measurement, vhl‐/‐ zebrafish contained 59±0.1 microglia (14±1.3 with a resting morphology, 46±0.2 with an amoeboid morphology), while their wild‐type siblings contained 59±2 total microglia (12.5±1.5 resting morphology and 45±1.8 amoeboid morphology. There was no significant different in the total (p=0.69), resting (p=0.26) or amoeboid microglia (p=0.91). Time‐lapse recordings over 24 hours confirmed this result.ConclusionNo significant differences in microglia numbers or morphology was detected at 3 dpf. At 5 dpf, microglia number increased and adopted a round, amoeboid morphology. This represent is similar to the microglia phenotype associated with age‐associated WML.