bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the sociodemographic and clinical characteristics and level of care home placement in Asian and European people with moderate to severe cognitive impairment living in New Zealand
Authors: Guo Yuxuan Joyce , Rodriguez Claudia Rivera , Cheung Gary , Cullum Sarah , Kerse Ngaire , Martinez‐Ruiz Adrian 
Published: February 2022

AbstractBackgroundDue to the ageing population in New Zealand (NZ), there will be more people with dementia in need of long‐term care. As a culturally diverse country, the characteristics of different ethnicities need to be understood in order to provide culturally appropriate care. This study aims to compare: 1) the sociodemographic and clinical characteristics, and 2) the level of care home placement in Asian and NZ European people with moderate to severe cognitive impairment living in long‐term care facilities.MethodThe sample included individuals aged≥65 and self‐identified as Asian or NZ European who had received the Long‐Term Care Facility version of interRAI, a standardised and comprehensive geriatric assessment, in 2018. All participants had moderate to severe cognitive impairment defined by a score of ≥ 3 in the Cognitive Performance Scale (range 0‐6). The analysis examined the association of ethnic group with sociodemographic and clinical variables and level of care home placement.ResultThe sample included 7298 older adults (441 Asians, 6857 NZ Europeans). The average age of the sample was 84.1 SD±8.7 (Asian= 83.7 SD±7.7, European= 84.1 SD±8.8, p=0.29), and 57.5% were female (Asian=62.6%, European=57.2%, p=0.08). Logistic regression showed that, compared with NZ Europeans, Asians were more likely to have untreated diabetes (OR=2.14, 95%CI=1.55–2.96); less likely to be overweight/obese (BMI 25–29: OR=0.54, 95%CI=0.41–0.73; BMI 30–40: OR=0.25, 95%CI=0.13–0.46), have hearing loss (OR=0.55, 95%CI=0.44–0.69) and had fewer medical comorbidities (OR=0.39, 95%CI=0.24–0.65). Despite lower comorbidity, Asians with cognitive impairment were more likely to be placed in hospital level care (OR=1.60, 95%CI=1.23–2.08) and less likely to be placed in dementia level of care (OR=0.53, 95%CI=0.36–0.77).ConclusionThe study results demonstrate differences in clinical characteristics and level of care home required for Asians and NZ Europeans living in NZ. Despite lower comorbidity, Asians with cognitive impairment were more likely to be placed in hospital level of care and less likely to be placed in dementia level of care. Additional studies are needed to understand this relationship, and the results may help to generate more culturally tailored health services aimed for people with cognitive impairment.
A systematic review of progranulin concentrations in biofluids in over 7,000 people: Assessing the pathogenicity of GRN mutations and other influencing factors
Authors: Swift Imogen J. , Esteve Aitana Sogorb , Heller Carolin , Zetterberg Henrik , Rohrer Jonathan D. 
Published: February 2022

AbstractBackgroundHeterozygous mutations in the GRN gene are a major cause of genetic frontotemporal dementia (FTD), accounting for an estimated 5‐10% of all people with FTD. GRN encodes for progranulin, with mutations causing haploinsufficiency, and being associated with significantly lower concentrations of progranulin in biofluids in mutation carriers compared to controls.MethodWe performed a search of the literature (up to December 2019) looking for publications reporting progranulin concentrations within serum, plasma or CSF in any medical condition including FTD and other forms of dementia. We then contacted all authors and asked if they were able to share anonymised data from their study including progranulin concentrations and clinical data including specific mutation if present, clinical diagnosis, age at onset of dementia, sex, and GRN rs5848 polymorphism. Data from 7,071 people was collated and analysed.ResultData on plasma progranulin concentrations measured using the Adipogen assay was available from 3,265 cases. Variability in levels across 109 different GRN mutations was seen and when split into mutation groups, missense variants outside the signal peptide had significantly higher levels compared to all other groups, suggesting that these variants are unlikely to be pathogenic. We established a plasma progranulin cut‐off value of 74.8ng/µL between pathogenic GRN mutation carriers and non‐carriers. We found that the GRN rs5848 polymorphism also affected plasma progranulin levels, with the TT genotype associated with significantly lower levels than CC. Sex differences were also seen, with significantly higher progranulin levels in females than males.ConclusionTogether these findings highlight the variable pathogenicity of different GRN mutations and the importance of considering other factors such as genetic risk factors and sex differences when looking at biofluid concentrations of progranulin. This is of particular relevance in upcoming clinical trials of progranulin‐associated FTD where progranulin levels are being measured as outcome measures.
Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer’s disease
Authors: Pfeil Julia , Hönig Merle C. , Doering Elena , van Eimeren Thilo , Drzezga Alexander , Bischof Gerard N. ,   Alzheimer's Disease Neuroimaging Initiative
Published: February 2022

AbstractBackgroundRegional differences in amyloid‐beta burden were examined between healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and its prognostic value was compared to other biomarkers.MethodADNI data (http://adni.loni.usc.edu/) of four age‐matched amyloid‐beta‐positive groups were included: cognitively stables (CN‐CN, n=38), CN to MCI or AD progressors (CN‐MCI/AD, n=38), MCI stables (MCI‐MCI, n=104), and MCI to AD progressors (MCI‐AD, n=104). Baseline 18F‐florbetapir scans were pre‐processed including normalization and intensity‐standardization (reference: cerebellum). To assess regional differences in amyloid‐beta burden, voxel‐wise group‐wise comparisons (FWE‐corrected) were performed between CN‐CN vs. CN‐MCI/AD and MCI‐MCI vs. MCI‐AD, respectively. Mean amyloid‐beta burden of resulting significant regions was subsequently used in logistic regression analyses together with global amyloid, genetic risk, and CSF biomarkers to determine the best predictive biomarker for progression.ResultCN to MCI/AD progression was predicted by amyloid deposition in the precuneus, lingual and angular gyrus, pallidum, caudate, middle and superior temporal gyrus. MCI to AD progression was predicted by amyloid deposition in the anterior cingulate gyrus, medial frontal cortex, precuneus, middle and superior temporal gyrus, posterior and anterior insula.ConclusionRegional amyloid‐beta burden is a more sensitive predictor of progression to MCI or AD than global amyloid‐beta burden, pointing towards its usefulness as prognostic biomarker.
Maintaining pedagogic excellence in family carer training using online learning
Authors: de Klerk‐Rubin Victoria B 
Published: February 2022

AbstractBackgroundThe Family Caregiver Course (FCC) is an 18‐week Validation training to sensitize family carers to the psycho‐social needs of their relatives, integrate new behaviors that build relationships and specific verbal and non‐verbal techniques to increase communication. It used: 5 ‘on‐demand’ videos to deliver asynchronous learning with written assignments to process information: 9 synchronous, interactive webinars to process information, practice skills and get coaching; a two‐day in‐person training was used exclusively to practice skills and integrate new behaviors. The book, Validation Techniques for Dementia Care was sent to each participant prior to the class start and a monthly online Support Group is offered to all participants as follow‐up to the course.MethodPre‐ and Post‐Surveys of the 2019 FCC (in a partnership between the Alzheimer’s Association of Colorado and the Validation Training Institute) were compared.ResultAfter taking this course family carers: reported that they knew what to do when faced with challenging behaviors from their relative; understood that lying or pretending to agree with a disoriented person was not an effective strategy for communication; gained knowledge of the different forms of dementia and that the differences are significant; were clear about the differences between Validation and other methods.ConclusionIn 2020, VTI again partnered with the Alzheimer’s Association of Colorado for a second iteration of the FCC with 18 family caregivers. Due to COVID – 19 limitations, this course was turned into a completely digital experience. The same learning and skill development inherent in the FCC was delivered through online learning, using principles of online pedagogy. To replace the two‐day in‐person component of this course, we developed four, 4‐hour Zoom sessions that allowed participants to: practice specific Validation techniques, exercise, process and apply what was learned, role play and receive coaching to anchor skills. Important online rules were maintained, such as, offer opportunities for participant engagement every 10 minutes and create a community of inquiry. The outcomes of 2019 and 2020 Pre‐ and Post‐Survey data will be compared in the presentation.
Comparative preclinical evaluation of a microtubule PET tracer with a beta‐amyloid PET tracer in AD mice
Authors: Neelamegam Ramesh , Zhang Wei , O'Boyle Michael , Galvan Veronica , Fox Peter T. , Seshadri Sudha , Kumar J.S. Dileep 
Published: February 2022

AbstractBackgroundCurrently available PET tracers used in Alzheimer's disease (AD) have limited utility in prognosis and in revealing reliable clinicopathologic correlations of disease. Therefore, identification and validation of novel biomarkers for AD progression and preclinical disease onset through noninvasive neuroimaging is a top priority in biomedical research. We proposed to target microtubules (MTs) as an imaging target for AD in preclinical, postmortem and clinical studies that support the implication of altered regulation of MTs in AD and positively correlated with neurodegeneration process. Furthermore, MT loss in AD is contributed to a large number of mutated proteins, enzymes, and post‐translational modifications compared to other imaging targets. Therefore, targeting brain MTs may be advantageous, as cumulative loss of MTs is the final common pathway for a variety of biochemical pathologies leading to neurodegeneration in AD. [11C]MPC‐6827 is the pioneer BBB‐penetrating PET tracer available for in vivo imaging of MTs in brain.1,2 Herein, we report the comparative binding of [11C]MPC‐6827, and [11C]PiB in Aβ over expressing APP mutated transgenic J20 mice and controls.Method[11C]MPC‐6827 and [11C]PiB were synthesized using GE Tracerlab FX2 MEI and FX2N modules. Dynamic PET scans were performed for 30 min after tail vein injection of [11C]MPC‐6827 and [11C]PiB in 6‐month‐old J20 mice and littermates (n=4) using a Siemens Focus 220 microPET scanner. Image analyses were performed with Mango software on reconstructed data.ResultPET image analyses show ∼30% of reduced whole brain uptake of [11C]MPC‐6827 in J20 mice whereas, [11C]PiB exhibited modest higher binding (∼10%) in J20 than control mice. Standardized uptake values (SUVs) show similar trend of binding of tracers in prefrontal cortex (PFC) and hippocampus in J20 and control mice.ConclusionOur preliminary studies show that in J20 mice, binding of the [11C]MPC‐6827 is reduced in whole brain, hippocampus and PFC compared control mice and is inversely correlated with [11C]PiB binding. The effect size of [11C]MPC‐6827 seems higher than [11C]PiB. Therefore, [11C]MPC‐6827 could be used as a PET tracer for human brain imaging of AD and other NDs. Acknowledgement: This work was funded by Center for Biomedical Neuroscience (CBN) 2020‐2021, UT Health San Antonio, Texas, USA.
Alaska Native elders’ cultural beliefs, practices, and values: The case for culturally informed holistic dementia care
Authors: Crouch Maria Christina , Rosich Rosellen M 
Published: February 2022

AbstractBackgroundAlaska Native (AN) people are projected to experience Alzheimer’s disease and related dementias at an increasingly high rate in comparison to other US races. However, due to colonization among AN tribes and the subsequent institutionalization of modern medicine, cultural practices and values that greatly impact holistic health and dementia care have been overshadowed and in some instances eradicated. Thus, more can be known about the psychosocial factors that have and can contribute to optimal dementia care for a population that experiences health disparities (e.g., heart disease, chronic lower respiratory diseases, cerebrovascular diseases) and barriers to care (e.g., language, rurality, access to resources).MethodIn order to understand precolonial and present cultural practices that comprise optimal dementia care for AN people, a grounded theory, exploratory study was conducted. Twelve semi‐structured interviews with AN Elders assessed the etiology, course, treatment, caregiving, and the culturally derived meanings of memory function, loss, decline, and disease.ResultQualitative analyses revealed eight culturally grounded and salient themes: 1) Traditional Knowledge Systems and Values; 2) Caregiving Networks; 3) Memory Function; 4) AN Spirituality; 5) Stories, Generative Sharing, and Healing; 6) Historical Change; 7) Connection, Communication, and Compassion; and 8) Assisted Living. These themes are best understood through AN lifecycle theory, which is a holistic representation of the culturally specific psychosocial protective factors, disease preventive, and caregiving practices that comprise an AN caregiving model.ConclusionThis study highlights the overall themes of continuity, connectedness, spirituality, intergenerational transmission, history, and belief systems, which emerged as a result of investigating cultural practices that comprise optimal dementia care for AN people. The culturally adaptive and congruent representations that AN Elder’s utilize in understanding memory functioning, loss, decline, and disease (i.e., forms of dementia) both explain and transcend Western biomedical models. Further, more meaningful beliefs are the outcome of an internalization and lived expression of the AN lifecycle. This AN lifecycle theory provides proscriptions for living life holistically, with a strong connection to land, and provides a fulcrum that allows one to understand the complexity of dementia caregiving as it relates to AN culture, history, and traditions embedded within the current sociocultural context.
Longitudinal associations between racial discrimination and brain aging among black older adults
Authors: Zahodne Laura B. , Sharifian Neika , Kraal A. Zarina , Morris Emily P. , Sol Ketlyne , Zaheed Afsara B. , Meister Lindsey , Mayeux Richard , Schupf Nicole , Manly Jennifer J. , Brickman Adam M. 
Published: February 2022

AbstractBackgroundNon‐Hispanic Black older adults exhibit worse brain and cognitive health than non‐Hispanic Whites. Emerging research points to racially‐patterned social stress (e.g., discrimination) as a contributor to racial inequalities independent of socioeconomic and health status. While comparative studies show that non‐Hispanic Blacks face more discrimination than non‐Hispanic Whites, few studies focus exclusively on non‐Hispanic Black older adults in order to examine within‐group heterogeneity and clarify how the unique experiences of discrimination among Black older adults link to their brain aging.Method221 non‐Hispanic Black participants in the Washington Heights‐Inwood Columbia Aging Project completed psychosocial measures and structural magnetic resonance imaging (MRI). Experiences of discrimination were operationalized using the Everyday Discrimination and Major Experiences of Lifetime Discrimination scales. After reporting the frequency of discrimination, participants reported the attribution(s) of these experiences (e.g., race). Latent difference score models examined associations between discrimination and brain aging, operationalized as hippocampal and white matter hyperintensity (WMH) volumes measured over an average of four years. Initial models considered general discrimination (i.e., regardless of attribution), and subsequent models considered racial discrimination per sé. All models controlled for age, sex/gender, education, income, total intracranial volume, and length of follow‐up.ResultGeneral discrimination was not associated with brain aging. Lifetime racial discrimination was associated with lower initial hippocampal volume. Everyday racial discrimination was associated with faster accumulation of WMH over time.ConclusionThis longitudinal MRI study suggests that racial discrimination may be detrimental for brain aging among non‐Hispanic Black older adults, which could contribute to their disproportionate dementia burden. Disaggregating discrimination by attribution can clarify research on psychosocial contributors to racial inequalities in brain and cognitive aging, as racial discrimination appears to be particularly toxic. Future research should examine both distal (e.g., environmental exposures, life course opportunities) and proximal (e.g., physiological stress pathways, inflammation) mechanisms linking racial discrimination to worse brain aging, which may differ for institutional versus interpersonal forms of racism.
Early engagement with the wider patient community in early‐phase clinical trial design: Insights from the CareRing caregiver community in designing the Brainshuttle AD trial
Authors: Croney Ruth , Agnew David , Vogt Annamarie , Alcaraz Fabien , Svoboda Hanno , Kulic Luka , Proulx Léa 
Published: February 2022

AbstractBackgroundCaregivers and families of people with Alzheimer’s disease (AD) play a crucial role in the decision to participate in a clinical trial, and in supporting participants during the trial process. Early engagement with the wider patient community could enable the design of trials that are less burdensome for participants and caregivers. The CareRing initiative gathered caregiver insights on: participant/caregiver motivations for involvement in early phase clinical trials where no treatment benefit is expected; the role caregivers expect to play when loved ones participate in a trial; and holistic support that could help minimize the impact of trial participation on daily life.MethodSix Roche employees from different geographical regions with varying backgrounds and roles, who are caregivers for a person with AD, participated in two 60‐minute telephone calls. The calls included presentations of the Roche brain shuttle technology and draft protocol for the Phase IB/IIA Brainshuttle AD trial evaluating RO7126209 in prodromal or mild‐to‐moderate AD (NCT04639050), and allowed caregivers to provide input on the protocol and holistic support that could alleviate the burden of participation. Key insights/recommendations from caregivers were used to develop guidance on trial design and supporting materials.ResultFeedback suggested participants are motivated by being able to help others (including their families) avoid the suffering they experience, decreasing their sense of isolation, and access to state‐of‐the‐art care, testing, and neurology teams. Caregivers noted their participation goes far beyond study visits: they prepare participants for visits physically (e.g. washing, dressing) and mentally (e.g. detailing what visits will involve and supporting anxious or angry loved ones), accompany them on visits, and help participants recover from their change in schedule. Caregivers also carry the psychological burden of providing continual reassurance and being the sole person to answer participant’s questions, particularly until trust is built with the study team, and face challenges in taking time off and re‐organizing appointments where necessary.ConclusionCaregiver support and time commitments go far beyond study visits. The guidance provided by caregivers in the CareRing initiative has helped us adapt the design and holistic management of the Brainshuttle AD trial, and co‐create/refine specialized support for both caregivers and participants.
Correlation between MK‐6240 tau‐PET and CSF tau, P‐tau and amyloid proteins
Authors: Gérard Thomas , Malotaux Vincent , Ivanoiu Adrian , Lhommel Renaud , Hanseeuw Bernard J. 
Published: February 2022

AbstractBackgroundMK‐6240 is a promising second‐generation tau‐positron emission tomography (PET) tracer for evaluation of cerebral tauopathy in patients with and without cognitive impairment. To further validate the use of MK‐6240 in Memory Clinics, we aimed to evaluate the association between MK‐6240 PET results and well‐validated cerebrospinal fluid (CSF) tau and amyloid protein quantifications.MethodWe acquired MK‐6240 tau‐PET and 3D‐T1 MRI in 44 patients attending our Memory Clinic who accepted lumbar puncture. PET data were processed using PMOD 4.1 Neuro tool: we created three clusters of brain segments based on Braak pathological stages (1‐2; 3‐4 and 5‐6). Standardized uptake value ratio (SUVr) measures were calculated without partial volume correction for these three regions, using cerebellar grey matter as region of reference. SUVr measures in the three regions were correlated to CSF measures of total tau, phospho‐tau 181 (P‐tau) and amyloid (Aβ42) proteins. Linear regressions were calculated for each pair of data.ResultTable 1 provides the characteristics of the participants, as well as CSF and PET data. Fig. 1‐3 provides illustrative cases. We observed that SUVr significantly correlated with total (t‐tau) and P‐tau levels for each of the three Braak regions, but best correlated for the Braak 3‐4 region (t‐tau: r2=0.184; p=0.004 and p‐tau: r2=0.227; p=0.001, see Fig. 4). Only the Braak 1‐2 SUVr significantly correlated with CSF Aβ42 levels (r2=0.121; p=0.021, Fig. 4, line 3). The SUVr thresholds who best discriminate between CSF t‐tau positive and negative cases (based on our clinical threshold of 381pg/ml) were respectively: 1.54 SUVr (Braak1‐2), 1.35SUVr (Braak3‐4), 1.17SUVr (Braak5‐6).ConclusionAmyloid CSF levels only correlated with tau‐PET signal in the Braak 1‐2 region, suggesting an association between these two early pathological processes. In contrast, total and phosphorylated tau CSF levels best correlated with tau‐PET signal in the Braak 3‐4 region, suggesting that tau pathology has to reach the temporal neocortex prior to elevate a “global” tau‐measure such as the one measured in the CSF.