bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twinning program: The Netherlands‐Indonesia
Authors: Utomo Amalia Fonk 
Published: December 2020

AbstractBackgroundAlzheimer Indonesia & Alzheimer Netherlands have a strong collaboration under the Twinning Program of Alzheimer's Disease International. This is a 3 years collaboration for 2017‐2019. To exchange information, support & learn from each other and for Alzheimer Indonesia to benefit from the experience from Alzheimer Netherlands to improve quality life of people with dementia & caregivers.Method6 work areas: Knowledge transfer from science & practice; Building network of volunteers for Indonesia Netherlands (ALZI – NL); Development of support activities of the Alzheimer's Organization in Indonesia; Organizing a public event in Indonesia; Train the trainer program (Dementia Care Skills training) in Indonesia; Project coordinationResult• Knowledge transfer & support: ADI Asia Pacific Conference on 2‐5 November 2017, the 1st integrated multidisciplinary gathering on Dementia in Jakarta, Indonesia with 7 expert speakers from the Netherlands. Attended by over 700 participants from 20 countries (healthcare workers, ALZI Chapter leaders, youth community leaders, general public, government officials & volunteers). • Capacity building for Alzheimer Indonesia by extending it's network to 22 chapters/cities, conducted 173 caregivers meetings and 12 intergenerational home visits across Indonesia. • 3 Dementia Care Skills training conducted with participation from 26 caregivers. • Hosted Hope Love Care on Dementia, medical symposium and public event on 19‐21 October 2018 in Malang, East Java. Over 700 participants (healthcare workers, ALZI Chapter leaders, youth community leaders, general public, government officials and volunteers) with 6 international speakers & 8 national speakers. • Chapter Meeting on 22‐24 November in Denpasar Bali Attended by all chapter manager across Indonesia and overseas (through zoom) to have workshop & sharing session. Conducted Alzheimer’s Indonesia Annual Chapters Meeting as part of internal organization strengthening and capacity building. • Support activities for Indonesians in the Netherlands through Stichting Alzheimer Indonesia Nederland. • Knowledge transfer by book adaptation ‘Dementie? en nu?’ ‐ Alzheimer Nederland to Indonesian language and culture ‘Demensia? Lalu Bagaimana’.ConclusionExtension for the project is needed. The first 3 years build a good foundation& at least another 3 years to reach sustainable organization. Other countries with related culture and historical should consider of doing this.
Classification accuracy of the English version of the Canadian Indigenous Cognitive Assessment (CICA) in a majority culture memory clinic sample
Authors: O'Connell Megan E. , Walker Jennifer D. , Jacklin Kristen , Bourassa Carrie Ann , Kirk Andrew , Hogan David B. , Morgan Debra G. 
Published: December 2020

AbstractBackgroundMost cognitive screening tools are culturally inappropriate for Indigenous peoples. The Kimberly Indigenous Cognitive Assessment (KICA) screening tool was collaboratively developed in Australia with, and for, Indigenous peoples. Using a similar community‐based method, the KICA was adapted to Canadian Indigenous peoples’ culture and translated into other languages, beginning in Ontario on Manitoulin Island, and was re‐named the Canadian Indigenous Cognitive Assessment (CICA). The classification accuracy of the CICA‐Ontario version, English translation, was explored in the current project in a memory clinic setting where the majority of patients were of Eurocentric origin.MethodOf 79 consecutive cases presenting to an interdisciplinary diagnostic memory clinic, 58 completed the CICA. Inclusion criteria included consent for participation in research and planned administration of the typical 2 hour long neuropsychological battery. CICA data were not used for any clinical process; consequently, diagnosis was independent. Diagnosis was made by consensus of the neurologist and neuropsychologist after patient and collateral informant interviews and nursing, neurological, medical (comprehensive blood work, neuroimaging), neuropsychological, and physical therapy evaluations.ResultPatients’ ages ranged between 38 and 90 (M= 65.3, SD= 12.3) and 52 percent were male. Diagnoses included no objective cognitive impairment despite cognitive concerns termed subjective cognitive impairment (SCI; n= 23; CICA
M
= 37.09; CICA
SD
= 1.08), mild cognitive impairment (MCI; n= 14; CICA
M
= 34.93; CICA
SD
= 2.46), dementia due to Alzheimer disease (AD; n= 9; CICA
M
= 31.44; CICA
SD
= 3.00), and non‐AD dementias (n= 12; CICA
M
= 32.75; CICA
SD
= 5.07). Classification accuracy as measured by the area under the receiver operating characteristic (ROC) curve (AUC) for groups with diagnoses of dementia (n= 21) vs no dementia (SCI or MCI; n= 37) was .78 (AUC confidence interval (CI) .66‐.92). Accuracy was high for cognitive impairment (dementia and MCI; n= 35) versus SCI (n= 23) (AUC=.84 CI .74‐.94) and lower for MCI (n= 14) vs dementia (n= 14)(AUC=.67; CI .49‐.85).ConclusionAlthough additional validity data from Indigenous peoples is needed, these data support the measurement properties of the CICA‐Ontario English‐version in a majority culture sample.
Improvement of cognitive function after paper‐based cognitive training intervention in early‐stage Alzheimer's disease
Authors: Han Jeong Ho , Kang Min Ju 
Published: December 2020

AbstractBackgroundCognitive training refers to cognitive exercises with inherent challenges that target enhance performance in specific cognitive domain. There has been number of studies reported positive outcome of cognitive training in persons with Alzheimer's disease. In this study, we newly designed set of paper‐based cognitive training program, "Gipum‐seo" which consists of different levels of difficulty using predesigned exercises and evaluated its efficacy of cognitive enhancement on patients with early stage of Alzheimer's disease.MethodForty participants who are diagnosed with early stage of Alzheimer’s dementia participated in this study. To test the efficacy of paper‐based cognitive training programs to cognition, all patients were randomly allocated to either an intervention group (n=20) or a control group (n=20). The intervention group regularly received 24 sessions of paper‐based cognitive training, over a 12 week period. Neuropsychological examinations were conducted before and after this training period.ResultAfter 12 weeks, the intervention group showed a significant change in Korean version of the Mini‐Mental State Examination (25.90±3.8), compared to the control group (23.7±2.8) (p=0.04). Also, there was significant improvement in language, attention and executive function for the training group, as compared with controls.ConclusionPaper‐based cognitive training might have beneficial effects on the general cognitive functions in early stage of Alzheimer’s dementia.
The importance of care partner input in Alzheimer’s disease (AD) drug development
Authors: Majid Tabassum , Paulsen Russ , Callahan Leigh F. , Potashman Michele , Lee Daniel , Hartry Ann , Wunderlich Glen , Hoffman Deborah , Wieberg Dan , Kremer Ian N. , DiBenedetti Dana B. 
Published: December 2020

AbstractBackgroundIn AD, the role of the care partner (CP) is essential to therapeutic development due to their gradually increasing role over the course of disease progression. Many current trials require CPs to report on patient symptoms later in the disease. Studies have also suggested that the role of the care partner‐patient dyad may be linked to reliable outcomes in drug development. However, there are issues in data collection via patient proxy due to concerns around reliability of information and reporting bias.MethodsThe AD PACE WMM Study assessed needs and priorities of patients and CPs throughout AD through both qualitative and quantitative methods. In both phases of the WMM study, patients in the earlier stages of disease served as their own reporters: those with clinical pathology of AD (Group 1), with MCI (Group 2), and with mild AD (Group 3) served as their own reporters. CPs for those with moderate (Group 4) or severe AD (Group 5) reported what was important to them as CPs. Qualitative results were used to develop patient and CP surveys in which respondents rated the importance of 42 items.ResultsCPs (n=119) were mostly women in their mid‐50s with high SES statuses. The average age of the corresponding care recipients was approximately 80 years and most were women. In general, CPs rated items related to the emotional well‐being of the care recipient (e.g., having a sense of self‐worth; not feeling down, depressed, anxious, anxious, worried, stressed; not feeling like a burden to others) highly. When taken as a whole, mean CP ratings for what is important to them were equal to or lower than mean patient ratings, especially for items with lowest importance ratings (driving, not having difficulty with work, planning and organizing activities).ConclusionUnderstanding and identifying the multiple ways in which CPs can provide critical input in AD therapeutic development needs further investigation. The WMM study identified emotional well‐being as a key priority for CPs for those with moderate or severe AD. Future studies and guidance should examine opportunities for CP input on drug development as CPs provide critical perspectives on the AD patient experience.
Evaluation of what matters most in existing clinical outcomes assessments in Alzheimer's disease
Authors: Hartry Ann , Menne Heather , Wronski Samantha L. , Paulsen Russ , Callahan Leigh F. , Potashman Michele , Lee Daniel , Wunderlich Glen , Hoffman Deborah , Wieberg Dan , Kremer Ian N. , Hauber Brett , DiBenedetti Dana B. 
Published: December 2020

AbstractBackgroundThe Alzheimer's Disease Patient and Caregiver Engagement (AD PACE) Initiative works to identify and measure treatment‐related needs, preferences, and priorities of individuals with or at risk for Alzheimer’s disease (AD) and care partners across the continuum of AD. First, the What Matters Most (WMM) study assessed needs, preferences and priorities of individuals in these populations. The next work will compare the WMM results to concepts in existing clinical outcome assessments (COAs) used in AD trials. This study identifies the most commonly used measures in AD research throughout the disease continuum.MethodTargeted literature and ClinicalTrials.gov searches identified COAs used in AD populations. Studies included pharmacological intervention or registry studies with individuals with preclinical or prodromal AD, mild cognitive impairment (MCI), mild, moderate, or severe AD, or caregivers of these individuals, and at least one type of COA.ResultsOver 900 records were retrieved. Records from the literature and Clinicaltrials.gov searches were combined and coded, yielding a total of 109 records for final review. Performance measures were the most common type of COA identified. COAs were most frequently used in MCI, and mild and moderate AD populations; COAs were used less often among prodromal/preclinical and severe AD populations. The six most frequently reported COAs identified were ADAS‐Cog, Mini‐Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Alzheimer's Disease Cooperative Study ‐ Activities of Daily living Inventory (ADCS‐ADL), Clinical Dementia Rating Scale (CDR), and Alzheimer's Disease Cooperative Study ‐ Clinical Global Impression of Change (ADCS‐CGIC).ConclusionPerformance measures (e.g., MMSE & CDR) were the most common type of COA identified, followed by clinician‐reported and observational measures. Only three COAs were used in all 5 AD populations: MMSE, ADCS‐ADL, NPI. Very few patient‐reported measures were identified; the most frequently being the EQ5D ( used in 4/5 AD populations). The most commonly used clinician‐reported measures included the NPI, ADCS‐CGIC, and Columbia Suicide Severity Rating Scale (C‐SSRS). The next phase of this work will assess the extent to which these existing measures capture the concepts that are most important to individuals with or at risk for AD and their care partners as identified in the WMM study.
Adaptation of the Canadian indigenous cognitive assessment in three provinces and evidence for validity
Authors: Walker Jennifer D , O'Connell Megan E , Crowshoe Lynden , Jacklin Kristen , Boehme Gail , Hogan David B , Pitawanakwat Karen , Blind Melissa J , Warry Wayne , Akan Nicole , Patterson Christopher , Allaby Cheryl 
Published: December 2020

AbstractBackgroundThe Canadian Indigenous Cognitive Assessment (CICA) tool is an innovative culturally‐grounded dementia case finding tool. Currently, dementia is underdiagnosed and when diagnosis occurs it is at later stages in Indigenous populations in Canada when compared to the general population; a trend documented in Indigenous populations beyond Canada, including Australia and New Zealand. As communities and health systems prepare for rapidly aging Indigenous populations with high rates of multiple chronic conditions, the need for an accurate, reliable dementia case‐finding tool in Canada is critically needed to inform necessary supports and services.MethodAn interdisciplinary, international team composed of researchers and Indigenous community partners led the development of the CICA. The CICA is a community‐based adaptation of the Kimberley Indigenous Cognitive Assessment (KICA) tool, which is a validated dementia screening assessment that was originally developed with Indigenous populations in Western Australia. To adapt the KICA for Canadian contexts, we undertook iterative and community‐specific processes of translation, adaptation, and piloting before we conducted reliability and validity testing in three different sites: Manitoulin Island, Ontario, which is home to seven First Nations communities; an urban Indigenous population in Calgary, Alberta; and File Hills Qu’Appelle Tribal Council, Saskatchewan, which serves 11 First Nations communities. The adaptation process was community‐driven in each site and integrated both Indigenous community knowledge and trauma‐informed approaches to cognitive assessment. The intersections of culture, geography and colonial trauma were explored across these diverse Indigenous communities.ResultThe resulting CICA adaptations were scored out of a possible 39 points and took approximately 15 minutes to administer. The CICA assessed 11 domains of cognition including orientation, recognition and naming, registration, verbal comprehension, verbal fluency, recall, visual naming frontal/executive functioning, free recall, cued recall, and praxis using culturally safe methods in English, Anishinaabemowin, and Nakota. For successful adaptation from the KICA, the orientation, verbal comprehension, verbal fluency, praxis, and naming domains required the most adaptation. Preliminary results indicate that the CICA demonstrated strong inter‐rater reliability, test‐retest reliability, and criterion validity.ConclusionThe CICA is the first tool of its kind in Canada and offers promising applications in the detection of dementia among Indigenous populations.
Selective knocking out of FynT‐isoform‐attenuated tau pathology, synaptic degeneration and neuroinflammation in P301S mutant human tau transgenic mouse model
Authors: Low Clara Ying Bei , Lee Chingli , Lim Frances Ting Wei , Lee Adrian Kian Long , Lo Juliette Min Huey , Lin Valerie Chun Ling , Tan Michelle Guet Khim 
Published: December 2020

AbstractBackgroundAccumulating data demonstrate that Fyn tyrosine kinase is involved in oligomeric amyloid‐β toxicity and tau pathology in Alzheimer's disease (AD). We reported that selective up‐regulation of FynT isoform in post‐mortem AD brains was associated with tau pathology and neuroinflammation (Lee et al., 2016). Furthermore, our preliminary data demonstrated that FynT induction could be recapitulated in aged P301S mutant human tau transgenic mice, which also correlated significantly with tau pathology and neuroinflammation. We thus hypothesize that FynT could be the pathogenic isoform of Fyn in AD. In this study, we generate double transgenic model by knocking out FynT in P301S mice and monitor the possible protective effects on disease progression.MethodFynT‐knockout (KO) is a transgenic model with specific knockdown of FynT isoform but retains FynB expression. Double transgenic mice (DTg) have been generated by crossing KO with P301S mutant human tau transgenic mice. HTRF technology‐based Cisbio assay kits, real‐time RT‐PCR and immunoblots are used to monitor changes of tau pathology, neuroinflammation and synaptic markers in the brains, respectively.ResultSubsequent studies were conducted and analyzed in males because we noticed that P301S males significantly manifested more severe tau pathology and neuroinflammation than P301S females. Significant decrease of phosphorylated tau, aggregated tau and GFAP expression were detected in DTg when compared with P301S. Consistently, reduction of synaptic markers in P301S mice can also be rescued by depletion of FynT in DTg.ConclusionSelective knocking out of FynT isoform led to the attenuation of tau pathology, neuroinflammation and synaptic degeneration in mice with P301S background. This suggests that FynT could be the pathogenic isoform of Fyn in AD. This study further ascertains the isoform‐specific role of FynT as a therapeutic target for AD.
Stage‐dependent amyloid beta‐ and tau‐associated longitudinal white matter degeneration in early stages of Alzheimer’s disease
Authors: Vipin Ashwati , Ng Kwun Kei , Ji Fang , Shim Hee Youn , Lim Joseph K.W. , Pasternak Ofer , Zhou Juan Helen ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2020

AbstractBackgroundAlzheimer’s disease(AD) is associated with pathological deposition of amyloid‐beta(Aβ) plaques and neurofibrillary tau tangles which have been shown to be related to poorer white‐matter(WM) integrity using diffusion‐MRI(dMRI) [Vipin et al.,2019;Jacobs et al.,2018]. However, possible interactive effects between Aβ and tau on microstructural WM changes remain unclear. Additionally, partial volume artefacts impact dMRI sensitivity but can be corrected through free‐water(FW) correction to provide FW and FW‐corrected tissue measures(FAt)[Pasternak et al.,2009]. Thus, we examined additive and interactive effects of Aβ and tau burden on temporal progression of FW‐corrected WM changes in temporoparietal WM fibres at baseline and over‐time in cognitively normal elderly(CN) and mild cognitive impairment(MCI). We hypothesize that MCI subjects would show more widespread Aβ and tau‐related temporoparietal WM alterations than CN. Additionally, based on prior evidence, Aβ and tau interactive effects would be more prevalent for FW than tissue‐based measures.MethodWe used dMRI data from 72 CN and 82 MCI subjects from the Alzheimer’s Disease Neuroimaging Initiative followed over 2‐4 time‐points(55‐90 years). Aβ burden was quantified using AV‐45 PET standardized uptake value and tau burden was quantified using cerebrospinal fluid phosphorylated‐tau(Ptau) levels. We derived subject‐specific FW and FAt fibre maps using the longitudinal TRActs‐Constrained‐by‐UnderLying‐Anatomy method[Yendiki et al.,2016].ResultCN with higher Aβ burden showed faster decline in RUNC FAt (uncorrected‐p=0.0055; Fig.1). However, in MCI, widespread Ptau effects were found(Fig.2) i.e. higher baseline Ptau burden was associated with lower fibre FAt in left superior longitudinal fasciculus parietal (SLFP; uncorrected‐p=0.039) and left(uncorrected‐p=0.0062) and right(uncorrected‐p=0.026) superior longitudinal fasciculus temporal(SLFT). Synergistic Aβ*Ptau effects were instead observed in right cingulum angular bundle(CAB) FW in CN at baseline and over‐time (FDR‐corrected:p<0.05; Fig.3). This effect was more widespread in MCI‐ higher Aβ combined with higher Ptau associated with higher FW in right CAB, SLFP, SLFT and uncinate fasciculus fibres at baseline(Fig.4).ConclusionOur findings provide insights into stage‐dependent differences in additive and synergistic influences of Aβ and Ptau between tissue‐based and FW‐based WM metrics. Thus, together with Aβ and Ptau burden, FW‐corrected WM measures likely provide more detailed insight regarding the regions showing alterations related to the interaction between neuropathological hallmarks of AD to collectively inform regarding disease progression.
Optimization of early‐phase florbetapir as a surrogate of FDG‐PET in ageing and Alzheimer’s clinical syndrome
Authors: Vanhoutte Matthieu , Landeau Brigitte , Sherif Siya , la Sayette Vincent De , Dautricourt Sophie , Abbas Ahmed , Manrique Alain , Chocat Anne , Chetelat Gael ,   the Medit‐Ageing research group
Published: December 2020

AbstractBackgroundFDG‐PET is a validated and widely used sensitive biomarker for neurodegeneration (N) in ageing and Alzheimer’s clinical syndrome as highlighted in the β‐amyloid (A)/tau (T)/N scheme (Jack et al., 2016, 2018). Early‐phase Florbetapir (eAV‐45) appears as a promising proxy for FDG‐PET but needs further validation. Optimization of the time window and preprocessing methods of eAV‐45 are scarce, and no previous study assessed the sensitivity and the reproducibility of this measure in individual cases.MethodWe included 191 participants including young to elderly volunteers and Alzheimer’s clinical syndrome patients, all of whom had both FDG‐PET and dual‐phase Florbetapir acquired on the same scanner, along with structural MRI and neuropsychological examinations. The time window was first optimized at the vertex level by correlation maximization between eAV‐45 and FDG‐PET, and correlation minimization between eAV‐45 and late AV‐45 (lAV‐45). Then, the six reference regions used for PET intensity scaling were compared by computing metrics of: (i) vertex‐wise pattern overlap between eAV‐45 and FDG‐PET (derived from patients versus controls comparisons and correlation with cognitive scores), and (ii) machine learning classification performance reflecting the discriminative power of both eAV‐45 and FDG‐PET at the individual level.ResultThe time interval from 0 to 4 minutes gave optimal vertex‐wise within‐ and inter‐subject correlations of both eAV‐45 versus FDG‐PET (maximal) and eAV‐45 versus lAV‐45 (minimal) (Figure 1). Balanced accuracy of pattern overlap was globally maximal with pons scaling (Figure 2), whereas classification performance between patients’ subgroups and controls were similar across scaling regions for both eAV‐45 and FDG‐PET (Figure 3A). Finally, classification performance was significantly superior for combined early plus late AV‐45 compared to FDG‐PET alone (Figure 3B).ConclusionResults show that eAV‐45 from 0 to 4 minutes with pons scaling is an optimal surrogate of FDG‐PET in ageing and Alzheimer’s clinical syndrome. This study highlights the strong potential of optimized dual‐phase AV‐45, allowing to outperform FDG‐PET discriminative power when combining both early plus late AV‐45 information obtained from a single PET‐tracer injection. Interestingly, the use of dual‐phase AV‐45 instead of FDG‐PET plus lAV‐45 will reduce the radiation dose, total time, number of visits and costs.