bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Alzheimer’s prevention initiative Generation program: A global perspective on best practices for site support and engagement to accelerate participant recruitment
Authors: Walsh Trisha L. , Riviere Marie‐Emmanuelle , Tariot Pierre N. , Alred Melody , Doak Karen , Liu Fonda , Ricart Javier , Scholten Ingo , Arbuckle Julian , Quinn Matt , Duff Laurie , Smith Molly , Graf Ana , Langbaum Jessica B. 
Published: December 2020

AbstractBackgroundThe API Generation Program consists of two trials: Generation Studies 1 and 2. Generation Study 1 enrolled cognitively unimpaired APOE4 homozygotes (HMs) ages 60‐75; Generation Study 2 enrolled cognitively unimpaired APOE4 carriers (HMs and heterozygotes (HTs), HTs had to have elevated brain amyloid). To address the unique challenges with recruitment of this population, we developed a multifaceted approach to maintaining engagement with sites and sharing best practices for recruitment among study site teams.MethodWe designed a flexible menu of novel recruitment tactics and implemented strategies, some of which were country‐specific, and collaborated with site teams on a regular basis. We conducted individualized “recruitment planning and implementation” calls with sites soon after they were activated, traveled to sites for in‐person meetings, held regional and country‐wide workshops and roundtable meetings, bi‐monthly study coordinator calls, and monthly media training calls. In addition, we developed an online recruitment and retention toolkit to provide a one‐stop shop for sites to review available, IRB approved materials that could be ordered and customized to meet their site‐specific needs. In the US, we consulted with UsA2 for cultural competency to develop a tip sheet for minority community engagement, postcards, ads, and brochures specific to the Latino and African American communities near study sites.ResultRecruitment was terminated in July 2019 after an early signal of mild worsening in some measures of cognitive function with umibecestat. At the time the program closed, 35,333 participants had come to a study site for genetic testing, 9,623 screened and 1,626 were randomized. 50% of activated sites had enrolled at least five participants between both studies. Despite the unprecedented challenges for recruitment of cognitively normal APOE4 HMs and HTs, we were on target to complete enrollment by end of 2019. Results from specific engagement and recruitment strategies, along with characteristics of high enrolling sites, will be presented.ConclusionCollaboration between study sponsor and site teams and the development of flexible recruitment plans and materials that can be adapted to meet sites’ needs played a crucial role in the successful recruitment, enrollment, and retention of participants for the API Generation Program.
The dual GLP‐1/GIP receptor agonist DA4‐JC shows superior protective properties in the APP/PS1 mouse model of Alzheimer’s disease
Authors: Maskery Mark , Gengler Simon , Goulding Elizabeth Mary , Melchiorsen Josefine Ulrikke , Rosenkilde Mette M. , Edison Paul , Holscher Christian 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder for which there is no cure. Type II diabetes is a risk factor for developing AD, and drugs that initially have been developed to treat diabetes have shown good neuroprotective effects in animal models of AD. We have tested the agonist of glucagon‐like peptide 1 (GLP‐1) liraglutide in patients with Alzheimer’s disease and present the results at this meeting. In addition, GLP‐1 analogues and Glucose‐dependent insulinotropic polypeptide (GIP) analogues have shown good effects in animal models of AD.MethodHere, we test a dual GLP‐1/GIP receptor agonist (DA4‐JC) that has a cell penetrating sequence added to enhance blood‐brain barrier penetration. We test the receptor activation properties in cell culture measuring cAMP levels and test liraglutide and DA4‐JC head‐to‐head in the APP/PS1 transgenic mouse model of AD. Memory formation in the water maze, synaptic plasticity (LTP) in the hippocampus, amyloid plaque load, and chronic inflammation was evaluated.ResultWe show in a receptor activation study that when measuring cAMP levels, DA4‐JC has balanced activity on both GLP‐1 and GIP receptors but not on GLP‐2 or Glucagon receptors. A dose‐response study in the APP/PS1 mouse model of AD showed a dose‐dependent drug effect on both the chronic inflammation response and the reduction of amyloid plaques in the brain. When comparing DA4‐JC with the GLP‐1 analogue liraglutide at equal doses of 10nmol/kg bw ip. once‐daily for 8 weeks, DA4‐JC was more effective in reversing memory loss, enhancing synaptic plasticity (LTP) in the hippocampus, reducing amyloid plaque load in the cortex, and reducing the number of activated microglia and astroglia and lowering pro‐inflammatory cytokine levels in the brain.ConclusionThe results show good neuroprotective effects of liraglutide and DA4‐JC, and suggest that the dual GLP‐1/GIP receptor agonist DA4‐JC may be more effective in treating AD than a single GLP‐1 receptor agonist. Funded in part by the Alzheimer Society UK.
Strategies to improve dementia clinical research participation at the local level
Authors: Bouranis Nicole , Gelmon Sherril B , Lindauer Allison , Waddell Elizabeth N , Richardson Dawn M , Woo Hyeyoung 
Published: December 2020

AbstractBackgroundThe National Institute on Aging’s 2018 National Strategy for Recruitment and Participation in Alzheimer’s and Related Dementias Clinical Research emphasizes local community collaboration. Current literature focuses on national factors affecting a person with dementia’s decision to participate in research. Although these factors affect local dementia research efforts, they do not speak to specific state or local factors nor the effects of local efforts. This study aimed to develop strategies to improve dementia research participation in the Portland, OR metropolitan area.MethodA community advisory board (CAB) comprised of clinicians, researchers, advocates, people with dementia, family caregivers, and older African Americans was established for this project. Thirty‐three interviewees were conducted with clinicians, researchers, advocates, people with ADRD, and family caregivers. An inductive approach was used to allow themes to emerge from the data organically and mitigate the possibility of coding themes based on current literature rather than the interviews. The investigator was the single coder and the CAB interpreted findings by identifying what was most important, surprising, or missing in the interviews.ResultThe Robert Wood Johnson Foundation’s Culture of Health Action Framework was used to conceptualize motivation strategies and reflect elements that describe research participation among people with dementia. Six strategies were identified to improve dementia clinical research participation: 1) Identify and promote local champions for ADRD clinical research participation; 2) Promote policies and processes the incentive cross‐sector collaboration; 3) Recognize caregivers as full research participants; 4) Include people with ADRD and caregivers in the research design process; 5) Offer alternative options to reduce participation burden; 6) Evaluate and improve relationships between healthcare/research staff and patients/participants.ConclusionThese six strategies can be used in conjunction with the Culture of Health Action Framework as a roadmap to form organization‐community partnerships, facilitate motivation and empowerment, give back decision‐making power to people with ADRD and promote a culture of research at the local level. Implemented strategies should be routinely evaluated to determine their feasibility and effectiveness. This study should be conducted in a larger context or as pilots in other communities to determine contextual relevance and generalizability for other areas.
Dementia in Vietnam: A situational analysis
Authors: Nguyen Tuan Anh , Dang Thu Ha , Tran Kham , Kim Giang Bao , Brodaty Henry , Pham Thang , Pham Tuan Le , Crotty Maria , Kurrle Susan , Hinton Ladson , Esterman Adrian , Nguyen Trung Anh , Roughead Elizabeth E 
Published: December 2020

AbstractBackgroundVietnam has decided to develop an integrated national action plan that integrates dementia into existing non‐communicable diseases (NCD) initiatives. Prior to formulating an effective plan, however, reliable information on current situation of dementia care, treatment and support in Vietnam is needed. This study was conducted to better understand the context, barriers and opportunities for improving dementia care, treatment and support in Vietnam and guide the plan development.MethodA desk review was conducted using the Situational Analysis Desk Review Topic guide developed by the Strengthening responses to dementia in developing countries (STRiDE) project. Key WHO Global Dementia Observatory (GDO) indicators were collected, focusing on Policy, Service Delivery and Epidemiological assessments.ResultVietnam has a high level institutional and policy framework on aging, NCD, mental health and disability including the 2009 Law on the Elderly, which provides the legal umbrella for policies on older people. However, no dementia‐specific policy exists and policies to promote healthy brain remain weak. Rapid aging significantly contributes to the explosion of NCD including dementia in Vietnam. There are 660000 Vietnamese people estimated to be living with dementia, with resultant dementia related costs of US$ 960 million. The healthcare system is not yet prepared for the shift to NCD from an acute, communicable disease burden in the past. Health service delivery is hospital‐centric, with over‐reliance on hospitals and under‐utilization of primary care system that in turn is fragmented and poorly prepared to address the rising challenge of dementia. Social care and support specific for dementia is lacking although there is an impressive grassroots organisation of older people with nearly 100,000 branches.ConclusionTo allow for a more harmonized response across the health sector and more effective use of limited resources, an integrated national action plan for dementia is sensible. However, Vietnam should take into consideration the potential for fragmentation and lack of dedicated resources being allocated to dementia. A new, integrated model of care focusing on a stronger primary healthcare system, community‐based social care and a healthy aging approach is needed to improve dementia prevention, care, treatment and support in Vietnam.
Distribution of isomerized and racemized amyloid β isoforms in sporadic Alzheimer’s disease using ion‐mobility mass spectrometry
Authors: Mukherjee Soumya , Perez Keyla , Lago Larissa Cristina , Klatt Stephan , Birchall Ian , Barnham Kevin J. , Masters Colin L. , Roberts Blaine Russell 
Published: December 2020

AbstractBackgroundExtracellular amyloid plaques and intracellular neurofibrillary tangles are the pathological hallmarks of Alzheimer’s Disease (AD). It takes on average 19 years for amyloid β (Aβ) peptides to deposit as insoluble plaques from onset to clinical dementia symptoms in AD. Such long‐lived nature of amyloidosis predisposes the polypeptide chains to undergo multiple spontaneous and non‐enzymatic post‐translational modifications (PTMs), which can render them resistant to normal cellular proteolysis mechanisms. Several biochemical approaches have estimated very high degree of isomerization and racemization of Asp and Ser residues in Aβ purified from the insoluble plaques. This goes along with a sequential loss of N‐terminal amino acids. However, comprehensive characterisation of these isomers as well as their quantitative estimation is yet to be done.MethodFreshly frozen post‐mortem frontal temporal cortex samples from non‐demented brains (n=10) and AD brains (n=11) were homogenised and fractionated into distinct soluble, vesicular, membranous and insoluble/aggregated biological pools of Aβ. The Aβ rich pools were enzymatically digested and separated on UHPLC coupled to ESI‐drift tube ion mobility (DTIM) mass spectrometer (Agilent Technologies, Santa Clara, USA). Stable isotope labeled peptides (SIS) were spiked in these brain homogenates to quantify the amount of these isomers/racemers in the different fractionated biochemical pools of the temporal cortex grey matter of human AD and control brains.ResultWe have characterised and quantified the most relevant Aβ isomers (stereoisomers of the N‐terminus) from AD brains by using their SIS peptides. Isomer separation was achieved by LC and their collisional cross section (DTCCSN2) values. Significant isomerization was observed in AD compared to controls brains. Moreover, the amount of these isomerized and racemized peptides differed from lower levels in the soluble/peripheral membranous to higher levels in the insoluble/aggregated debris in AD brain. These findings have implications in Aβ neurotoxicity, oligomerization, structures of amyloid fibrils present in the AD brain.ConclusionThe results show that isomerized/racemized Aβ peptides are intricately associated with the accumulation and deposition of amyloid in the brain, allowing distinct differentiation between old plaques and freshly generated Aβ. Specifically targeting these long‐lived isomers for enhanced clearance from the CNS would be crucial in developing any therapeutics targeting Aβ.
Development of the elderly lifestyle profile: A Delphi survey of multidisciplinary health care experts
Authors: Park Kang‐Hyun , Park Ji‐Hyuk 
Published: December 2020

AbstractBackgroundLifestyle has been considered as a crucial key factor which effect on one's health and quality of life and it has become a focus of increasing research interest worldwide. As research shown that lifestyle is reconsidered an important health determinant in preventive health care. However, lifestyle is a multifaceted construct and there was a limited evident regarding lifestyle assessment which is able to evaluate individual's multi‐domain lifestyle factors. This study attempt to develop evaluation items used to measure a multifaceted lifestyle profile for community‐dwelling elders in order to prevent chronic disease and improve their health and quality of life.MethodOpinions from 21 Delphi panels who have experience with elderly and lifestyle research were collected from December 2019 to January 2020. A Delphi survey was carried out three times, and based on previous research. The first Delphi survey gathered opinions using a mix of open‐ended questions and closed‐ended questions reconstructed regarding the evaluation items of elderly's multifaceted lifestyle profile. The second Delphi survey was conducted after the processes of deleting and modifying several items based on the first Delphi survey. In the third Delphi survey after the results of second Delphi survey were presented to expert panels, final opinions from experts were converged. Ethics approval was granted by the Yonsei University(YUWIRB‐1041849‐201901‐BM‐012‐01)Result65 items were selected as the first Delphi results, and as the second Delphi result, 62 items were analyzed after the processes of deleting and modifying the values below a content validity ratio of .42. Finally, in the third Delphi survey, 62 items were analyzed as appropriate items. The average content validity ratio of the final Delphi survey was .92 stability .18, and consensus .80, which were highConclusionThis study verified the content validity of the evaluation items for community‐dwelling older' multifaceted lifestyle profile. In the future, it is expected that through verifying validity and reliability, there will be used as a standardized assessment tool in the clinical environment.
Masupirdine (SUVN‐502) in combination with donepezil and memantine in moderate Alzheimer's disease: Effect of AD duration since diagnosis and patient’s age on efficacy endpoints
Authors: Nirogi Ramakrishna , Shinde Anil K , Benade Vijay , Subramanian Ramkumar , Bhyrapuneni Gopinadh , Ravulu Jyothsna , Jetta Satish , Rasheed Mohammed Abdul , Badange Rajesh Kumar , Jasti Venkat 
Published: December 2020

AbstractBackgroundMasupirdine (SUVN‐502), a selective 5‐hydroxytryptamine‐6 (5‐HT6) receptor antagonist is in clinical development for the treatment of moderate Alzheimer’s disease (AD). Masupirdine was studied in a phase 2 POC, multicenter, randomized, double‐blind, parallel group, 26‐week, placebo‐controlled proof‐of‐concept study in patients with moderate AD receiving stable doses of donepezil and memantine.MethodA total of 564 moderate AD patients with MMSE scores between 12 ‐ 20 were randomized (1:1:1) to receive either 50 mg or 100 mg of masupirdine or placebo once daily for 26 weeks. The study recruited patients in the age range of 50‐85 years, both inclusive and AD duration since diagnosis of 1 year or more. The primary efficacy endpoint was change from baseline in the Alzheimer's Disease Assessment Scale ‐ Cognitive Subscale (ADAS‐Cog 11). In subgroup analyses, impact of AD duration since diagnosis and patient’s age on the effects of masupirdine on the clinical functions were assessed using primary and secondary endpoints. To evaluate the effect of AD duration, subgroup analysis of different diagnosis durations at screening visit were performed. To evaluate the effect of patient’s age, subgroup analysis of 50‐70 years and 71‐85 years of age at the screening visit, both inclusive were performed. Further stratification was carried out based on memantine plasma concentrations at week 26 in both the subgroups. Safety was assessed throughout the study.ResultMasupirdine slowed down the cognitive decline in patients with AD diagnosis duration of >3 years. Beneficial effects of masupirdine increased with increasing disease duration; longer the AD duration, better the effect. Patients aged 50 ‐ 70 years had better improvement with masupirdine treatment on efficacy endpoints (ADAS‐Cog 11, CDR‐SB, MMSE) compared to placebo; difference reached to the level of minimum clinically important difference for cognitive endpoints. Subgroup analyses suggest further exploration of masupirdine as a treatment option in patients where current therapy is not responding.ConclusionTogether with the safety profile of masupirdine, the outcome from these subgroup analyses supports the potential clinical utility of masupirdine in patients with AD.
Selective upregulation of FynT tyrosine kinase in neurodegenerative dementia correlates well with tau pathology and neuroinflammation
Authors: Lim Frances Ting Wei , Low Clara Ying Bei , Lee Jasinda , Lee Chingli , Francis Paul T. , Lai Mitchell Kim Peng , Tan Michelle Guet Khim 
Published: December 2020

AbstractBackgroundFyn tyrosine kinase is involved in the disease progression of Alzheimer’s disease (AD). Our lab has previously reported an isoform‐specific role of FynT tyrosine kinase in AD brain which is associated with neurodegeneration and reactive astrogliosis [Lee et al., 2016]. In view of AD‐related neuropathology and neuroinflammation were not exclusively found in AD, the objective of the study is to investigate whether differential alternative splicing of Fyn to favour FynT expression could also be detected in other neurodegenerative dementias including dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD).MethodPost‐mortem human brain tissues (prefrontal cortex Brodmann area 9 (BA9) and temporal cortex (BA21) derived from subjects diagnosed with AD, DLB, PDD, as well as controls (CTRL) without neurological or psychiatric diseases were provided by the Brains for Dementia Research (BDR). The brain tissues were recorded for Mini‐Mental State Examination (MMSE) and Braak staging. The brain tissues were processed accordingly for ELISA, real‐time PCR, capillary electrophoresis and HTA array studies.ResultSelective and significant up‐regulation of FynT isoform expression in prefrontal and temporal cortex of AD, DLB and PDD when compared with CTRL was observed to significantly correlate with cognitive impairment and neuropathological characteristics. FynT induction in AD, DLB and PDD was associated with neuroinflammatory markers. Synaptic dysfunction could be the adverse impacts of FynT induction in neurodegenerative dementias.ConclusionUsing an independent cohort, we reported that FynT induction was not exclusive to AD, but also detected in neurodegenerative dementia including DLB and PDD. FynT induction was closely associated with tau pathology and neuroinflammation, which likely contributed to synaptic dysfunction and cognitive impairment. Potential therapeutic treatment should specifically target the disease‐associated isoform of Fyn.
Dual‐task gait as a differential marker of dementia disease subtype: Considering a declarative memory task
Authors: Ardle Ríona Mc , Galna Brook , Thomas Alan J , Rochester Lynn 
Published: December 2020

AbstractBackgroundDual‐task (DT) gait involves walking while concurrently engaging with a cognitively‐demanding task. It may be useful to identify dementia and differentiate cognitive subtypes [Montero‐Odasso etal., 2019]. Gait performance deteriorates under DT conditions due to added attentional demand. The majority of studies employ attentional DTs, limiting our understanding of the impact of alternative cognitive domains (e.g. memory or visuospatial abilities). Different dementia subtypes have unique cognitive profiles. Applying cognitive DTs related to these discrete profiles may improve the discriminatory ability of DT gait. This study aimed to assess the feasibility and efficacy of employing a concurrent declarative memory test on gait performance to differentiate Alzheimer’s disease (AD) and Lewy body disease (LBD).Method110 participants were recruited. This included 29 people with cognitive impairment due to AD (Age:77±9; sMMSE:24±4), 31 due to LBD (Age:75±6; sMMSE:25±3) and 29 similarly‐aged controls (Age:74±9; sMMSE:29±1). Gait was assessed using an instrumented walkway (GAITRite) under single‐task (ST) and DT conditions (performing a story recall task). Gait outcomes in ST and DT conditions included measures of pace, variability, rhythm, asymmetry and postural control. Kruskall Wallis tests with Mann Whiney U post‐hocs assessed group differences.Result89 participants successfully completed both conditions. The declarative task was too difficult for 21 participants (AD:7; LBD:14). There were no differences in gait performance between disease groups during the DT. During ST, the LBD group showed greater step length variability (p=.035) and stance time asymmetry (p=.037) compared to AD. Both disease groups demonstrated impaired gait compared to controls (p≤.05) in both conditions. There were no significant differences between disease groups on performance of the story recall task in either condition, but performance was significantly worse (p≤.001) compared to controls.ConclusionThis study demonstrated limited feasibility for people with cognitive impairment to complete a declarative memory DT. This particular DT was not as useful as ST gait for differentiating dementia subtypes. It is important to understand how feasible and effective different cognitive tasks are when using DT gait as a clinical tool. Future research should consider the efficacy of this task to predict dementia in “at‐risk” groups, such as those with genetic risk factors.