bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building a Dementia‐Capable Nursing Workforce
Authors: Vasquez Lyndsy , Schultz Melinda , Ishado Emily , Borson Soo , Sadak Tatiana 
Published: December 2022

AbstractBackgroundToday’s undergraduate nursing students will play a pivotal role in caring for the rising numbers of older adults and people living with dementia (PLWD). Because current nursing training does not require dementia care competencies, new graduates may not be adequately prepared to care for this population.ObjectiveThis study aimed to capture students’ interest and intention to work with older adults and PLWD as a career path, and elicit their feedback on how best to structure educational and clinical training offerings that would attract them to this field. Long‐Term care (LTC) settings blend clinical and residential features in a comprehensive setting uniquely suited for teaching nursing students about dementia. Hence, we evaluated students’ interest in enrolling in a new elective rotation, the LTC Externship.MethodsWe designed and administered a survey and conducted a focus group. The survey consisted of 20 questions modified from the Dementia Attitude Scale and eight questions related to respondents’ health care experience and attitudes about nursing care for older adults, comfort working with PLWD, and willingness to further develop geriatric and dementia care skills. Focus group enrollment was limited to the first 8 participants who expressed interest and completed preliminary questionnaires.ParticipantsFirst and second‐year Bachelor of Science in Nursing students at the University of Washington School of Nursing (SoN).ResultsSeventy Six of 223 (34%) students responded to the survey. The majority expressed low interest in working with older adults, as evidenced by the low survey response rate, low self‐reported knowledge of nursing care for PLWD, and a lack of desire to work with older adults after graduation. Among the eight focus group participants, six expressed interest in acquiring additional knowledge and hands‐on learning opportunities. Participants identified three specific training components that could attract students to geriatrics and LTC education: weekly structured seminars that reflect the depth of relevant scholarship; access to interactive, relevant pre‐study materials developed by clinicians; and 4‐6 hours per week of supervised paid, clinical training in hands‐on skills.ConclusionsThe findings informed the development of a LTC Externship at the UW SoN that is currently being piloted and evaluated.
Highly specific plasma β‐amyloid assays on the fully automated platform predict brain β‐amyloid pathology determined by a Centiloid threshold of amyloid PET
Authors: Yamashita Kazuto , Miura Masahiro , Watanabe Shunsuke , Ishiki Kengo , Arimatsu Yuji , Kawahira Junoko , Kubo Toshiko , Sasaki Katsutaka , Arai Takayuki , Hagino Kei , Irino Yasuhiro , Nagai Kota , Verbel David , Koyama Akihiko , Dhadda Shobha , Niiro Hayato , Iwanaga Shigeki , Sato Toshiyuki , Yoshida Tomokazu , Iwata Atsushi 
Published: December 2022

AbstractBackgroundThe U.S. Food and Drug Administration approved aducanumab for the treatment of Alzheimer’s disease (AD) under the accelerated approval pathway and several new drug candidates are currently in development or have been submitted for marketing authorization in the U.S. and other countries. Consequently, the necessity of pathological diagnosis of AD by confirming brain β‐amyloid (Aβ) pathology in routine clinical practice is increasing to ensure that appropriate AD patients can access these drugs. We reported the development of the fully automated plasma Aβ40 and Aβ42 immunoassays that showed high performance for predicting brain Aβ pathology defined by amyloid PET. Here, we present the effect of several markers on the performance of our plasma Aβ assays.MethodsPlasma Aβ40 and Aβ42 levels were measured using a fully automated platform (HISCLTM series). To assess the performance of plasma Aβ42/Aβ40 ratio for predicting brain Aβ pathology, two studies (discovery and validation studies) were performed using plasma samples obtained from the elenbecestat phase 3 program. Brain Aβ pathology was determined by amyloid PET Centiloid scale. A cut‐off of Centiloid unit was determined as 32.21 by performing a receiver operating characteristic (ROC) analysis and determination of the Youden Index using visual reads as the standard. To evaluate the clinical performance of our assays, area under the curve (AUC) was obtained by performing a ROC analysis. The model, incorporating age and APOE ε4 status, was also evaluated.ResultsPlasma Aβ42/Aβ40 ratio predicted brain Aβ pathology defined by amyloid PET with AUCs of 0.93 and 0.92 in the discovery and validation studies, respectively. The sensitivity and specificity were calculated as 97.5% and 80.8% in the discovery study and 94.5% and 78.0% in the validation study. The model incorporating age and APOE ε4 status didn’t show significant improvement for predicting brain Aβ pathology.ConclusionsPlasma Aβ42/Aβ40 ratio measured by our immunoassays achieved high accuracy to predict brain Aβ pathology, and age and APOE ε4 status didn’t contribute to improve the accuracy unlike most past reports from other groups. Our assays may contribute to a high‐throughput, less invasive diagnostic method for detecting brain Aβ pathology in routine clinical practice.
Sex and APOE‐ε4 carrier effects on early‐onset Alzheimer’s disease pathology
Authors: Logan Paige E. , Nemes Sára , Iaccarino Leonardo , Mundada Nidhi S. , La Joie Renaud , Aisen Paul , Dage Jeffrey L. , Eloyan Ani , Fagan Anne M. , Foroud Tatiana M. , Gatsonis Constantine , Hammers Dustin B. , Jack Clifford R. , Kramer Joel H. , Koeppe Robert , Saykin Andrew J. , Toga Arthur W. , Vemuri Prashanthi , Atri Alireza , Day Gregory S. , Duara Ranjan , Graff‐Radford Neill R. , Honig Lawrence S. , Jones David T. , Masdeu Joseph C. , Mendez Mario F. , Onyike Chiadi U. , Rogalski Emily J. , Sha Sharon , Turner Robert W. , Womack Kyle B. , Carrillo Maria C. , Rabinovici Gil D. , Dickerson Bradford C. , Apostolova Liana G. 
Published: December 2022

AbstractBackgroundPreviously, we found that female sex is associated with greater pathology burden in early‐onset Alzheimer’s disease (EOAD) in the Longitudinal EOAD Study (LEADS). Here, we have expanded our analyses by adding APOE‐ε4 carrier status as a further predictor of EOAD pathologic burden.MethodWe included 180 EOAD LEADS participants with available APOE genotype, Flortaucipir PET, Florbetaben PET, and MRI data. Demographic and biomarker differences were analyzed using ANOVA. EOAD participants were split by sex and APOE‐ε4 carrier status. Box plots were created in R and a voxel‐wise multiple linear regression in SPM12 yielded statistical brain maps of gray matter density (GMD), amyloid and tau burden.ResultCompared to males, EOAD females showed significantly greater global amyloid uptake (mean SUVR, p=0.002) and greater tau SUVR in the MetaROI, Braak 3&4 and 5&6 regions (p=0.0007, p=0.001, p=0.01, resp., Table 1). Female APOE‐ε4 carriers showed greater tau SUVR in Braak regions 1&2 than female non‐carriers (p<0.01, Figure 2B). Male APOE‐ε4 carriers showed trend‐level thinner entorhinal cortex than male non‐carriers (p=0.06, Figure 1). Interestingly however, femaleAPOE‐ε4 non‐carriers showed greater global amyloid SUVR than female carriers (p<0.01, Figure 2A). Further, APOE‐ε4 non‐carriers showed significantly thinner medial temporal cortices than carriers in both sexes (M, p<0.05; F, p<0.01). Male APOE‐ε4 non‐carriers also showed significantly lower mean cortical thickness than male carriers (p<0.05, Figure 1). Female APOE‐ε4 non‐carriers showed trend‐level lower mean cortical thickness than female carriers (p=0.06, Figure 1). The FWE corrected SPM12 maps showed significantly greater GM atrophy in the right temporal lobe and greater amyloid burden in a right lateralized occipitoparietal pattern in female APOE‐ε4 non‐carriers compared to female carriers. Further, male APOE‐ε4 non‐carriers showed greater tau uptake in the left frontal lobe than male carriers (Figure 3).ConclusionThese results suggest that APOE‐ε4 non‐carrier status is associated with greater atrophy, amyloid and tau deposition in EOAD. This might be due to the presence of other strong genetic drivers of disease pathology in EOAD.
The feasibility of Goal Attainment Scaling in adults with Down syndrome: early results from the LIFE‐DSR‐GAS sub‐study
Authors: Dunn Taylor , Britton Angela , Chicoine Brian , Costa Alberto , Hendrix James A , Knox Kari , Lai Florence , Mobley William C , Rockwood Kenneth , Rosas H. Diana , Network The Down Syndrome Clinical Trials 
Published: December 2022

AbstractBackgroundAdults with Down syndrome (DS) face a markedly increased risk of Alzheimer’s disease (AD). LIFE‐DSR is a 32‐month longitudinal study of adults with DS aiming to characterize and assess change in cognition, behaviour, function, and health. Goal Attainment Scaling (GAS) is a patient‐centric outcome measure. It evaluates change in goals that are meaningful to participants/caregivers and has proven a valuable and sensitive instrument in dementia clinical trials. To assess the feasibility of using GAS in the DS population and to better understand what is most important to them, the LIFE‐DSR‐GAS sub‐study is enrolling and following participants and their caregivers over 16 months.MethodParticipants with DS and their caregivers who consented to the LIFE‐DSR‐GAS sub‐study took part in an initial goal‐setting interview with a trained GAS rater to identify meaningful goal areas related to the participant’s condition. Change in these goals was then rated at two follow‐up interviews at 3 and 16 months. To aid in goal setting, a menu of 58 common DS‐AD goal areas was developed pre‐study through interviews with expert clinicians and caregivers. A secondary objective is to evaluate this menu in both its comprehensiveness and usefulness as a resource to improve GAS implementation in DS‐AD studies.ResultTo date, 31 (of 45) participants with DS and their caregivers have enrolled across three U.S. study sites. All participants have set three goals (the recommended minimum). The mean (standard deviation) time to conduct the interviews was 43.2 (7.5) minutes. 20 participants have completed a 3‐month follow‐up interview; the mean time taken was 18.2 (10.4) minutes. Most goals (83/93) set to date were selected from the DS‐AD menu. The most frequent goals concerned aspects of daily function: Household Chores (8 goals), Personal Care and Hygiene (8), and Meal‐Time Preparation and Activities (7).ConclusionEvaluating health outcomes in people with DS is challenging due to varying levels of baseline cognition and function, further complicated by the onset of dementia. There is a critical need for sensitive and valid measures that capture this heterogeneity. Our early data suggest that GAS may offer a feasible solution.
Preliminary results of computer‐based multimodal training in Alzheimer’s disease over six months – the multimodAAL study
Authors: Berger Martin , Schüssler Sandra , Zuschnegg Julia , Russegger Silvia , Paletta Lucas , Fellner Maria , Strobl Bernhard , Ploder Karin , Hofmarcher‐Holzhacker Maria , Stögerer‐Oberschmid Eva Maria , Guttmann‐Lattmanig Alexandra , Koini Marisa 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) is associated with cognitive decline and limited therapeutic interventions to maintain cognitive function. The present study investigates the effectiveness of a computer‐based cognitive and physical training (CCPT) on a tablet device in patients with AD and aims to present preliminary results of the multimodAAL project (project number: FFG 875345).MethodTwenty‐three patients were randomly assigned to intervention and control group (randomized controlled trial). The intervention group received weekly multimodal CCPT with a trainer and were encouraged to train as often as possible alone or with a caregiver over six months. At the time of data analysis 14 subjects had a 6‐month follow‐up with comprehensive pre and post neuropsychological assessment including tests on global cognitive functions (Mini Mental Status Examination, MMSE), memory, working memory, executive function and verbal fluency. Repeated measures ANOVA comparing neuropsychological test performance over time was calculated to determine the between‐group difference. Analyses were corrected for disease duration. Paired t‐test was used for post‐test analyses.ResultIn this preliminary analysis six subjects from the intervention group (4 female, age: x̅ = 75.4, disease duration: x̅ = 30.3 months) and eight subjects from the control group (7 female, age: x̅ = 74.8, disease duration: x̅ = 30.75 months) were included. The results showed a significant interaction effect considering global cognition and group with a high effect size (MMSE: F(1,11) = 7.503, p = 0.019, ηp
2 = 0.405). Post‐tests revealed a maintenance of performance in the intervention group (+0.68 points in the MMSE over 6 months, t(5) = ‐1.2, p = 0.300) and a significant decrease in the performance of the control group (‐1.34 points in the MMSE over 6 months; t(7) = 2.5, p = 0.041). The other cognitive domains did not show significant results.ConclusionThese preliminary results indicate that CCPT over six months has the potential to maintain global cognitive functions in Alzheimer patients.
Plasma ratio of phospho‐ to non‐phospho‐tau at threonine 217 identifies brain amyloid burden as measured by quantitative amyloid PET in the PARIS sub‐study of IDEAS
Authors: Meyer Matthew R. , Kirmess Kristopher M. , Wente‐Roth Traci L. , Irvin Faith , Holubasch Mary S. , Verghese Philip B. , Monane Mark , Bateman Randall J. , Holtzman David M. , Venkatesh Venky , Fogelman Ilana , Yarasheski Kevin E. , Braunstein Joel B. , West Tim 
Published: December 2022

AbstractBackgroundAccumulation of amyloid beta plaques and tau tangles in the brain are sequential pathological hallmarks of Alzheimer’s disease. Specific measurement of tau phosphorylation sites in plasma samples can be used to investigate the presence of both amyloid plaque and tau tangle brain pathology.MethodA tandem mass spectrometry assay that quantifies phosphorylation of tau at threonine residues 181 and 217 in plasma was developed. Both phosphorylated (phospho) and non‐phosphorylated (non‐phospho) peptides containing tau residues 181 and 217 as well as the ratio of phospho to non‐phospho at each of these phosphorylation sites can be calculated from a blood sample. We tested the concordance between these measures and brain amyloid burden in PARIS study participants, an IDEAS sub‐study in patients with mild cognitive impairment or dementia. K2EDTA plasma samples from PARIS participants (n=221) were analyzed for tau phosphorylation and Aβ42/40.ResultsThe amount of phosphorylation at both 181 and 217 sited were significantly higher in patients who were amyloid PET positive, while PET negative patients showed very low amounts of phosphorylation at 217 (1.2 pg/mL vs. 4.9 pg/mL; p <2e‐16). The ratio of phospho‐tau to non‐phospho‐tau 217 showed high correlation (Spearman’s rank correlation r=0.78; p <2e‐16) with quantitative amyloid PET, demonstrating that phosphorylation of tau on threonine‐217 can quantitatively identify the amount of amyloid burden. This ratio of phospho‐tau to non‐phospho‐tau also correlated better with amyloid status than the concentration of phospho‐tau alone, with area under the curve (AUC) for detecting brain amyloid burden improving from 0.74 (95%CI 0.67‐0.82) to 0.81 (95%CI 0.75‐0.88) for 181 and from 0.92 (95%CI 0.88‐0.96) to 0.95 (95%CI 0.92‐0.98) for 217. Combining the phospho‐tau‐217 with the Aβ42/40 ratios for the same sample further increased the AUC to 0.96 (95%CI 0.93‐0.99).ConclusionThis novel mass spectrometry‐based quantitative assay for plasma phospho‐tau and non‐phospho‐tau species has excellent analytical and clinical validity performance characteristics. Combining the ratio of tau phosphorylation at 217 with plasma Aβ42/40 can help identify brain amyloid pathology with a performance that rivals that of CSF or PET tests.
Human nasal beta‐amyloid 42 reflects cognition decline in Alzheimer’s disease
Authors: Jung Da Hae , Son Gowoon , Wang Shengmin , Lim Hyun Kook , Moon Cheil 
Published: December 2022

AbstractBackgroundThe key in Alzheimer’s disease (AD) therapy is a timely and accurate diagnosis for prompt drug intervention. However, due to the high cost and invasiveness of conventional biomarker analyses, including brain positron emission tomography (PET) imaging and cerebrospinal fluid (CSF)‐based assays, easy accessibility to these screening tests is often hindered. There is, therefore, a great need to develop a more accessible biomarker screening test using less invasive and cost‐effective peripheral body fluid biomarkers. Previous studies examined the non‐quantitative expression of beta‐amyloid (Aβ) in normal and AD patients' nasal discharge fluid. They identified higher expression of oligomeric Aβ in AD patients, showing a correlation with cognitive decline. However, the quantitative measurements of nasal Aβ42 levels, including the full AD continuum, remain unknown. Here, we assessed whether quantified human nasal Aβ42 levels could identify patients with AD and differentiate them from non‐AD patients.Method161 subjects (cognitively normal (CN), n=32; preclinical, n=29; mild cognitive impairment (MCI), n=73; AD, n=27) underwent neuropsychological battery tests. Their nasal discharge samples were collected, and nasal Aβ42 levels were measured via enzyme‐linked immunosorbent assay (ELISA).ResultWe found that the second‐highest quartile (Q3) group of nasal Aβ42 constituted the majority of patients with AD diagnosis (p=0.036). The Q3 group also outnumbered the other groups in the most cognitively impaired subjects in all three neuropsychological battery tests (p=0.033; p=0.0212; p=0.0147).ConclusionQuantified nasal Aβ42 is strongly associated with cognition measurements. Nasal Aβ42 suggests the possibility for discriminating AD from non‐AD.
Cell‐type Specific Effects of AD Mutations on Hippocampal Intrinsic Firing Properties in Genetically Diverse Mice
Authors: Berchulski Mariah R , Funke Jonathan R , Hadad Niran , O'Connell Kristen MS , Kaczorowski Catherine C. 
Published: December 2022

AbstractBackgroundCognitive resilience to Alzheimer’s disease (AD) is a phenomenon whereby individuals with known AD mutations or high levels of pathology exhibit better than predicted cognitive performance. Identification of the factors governing resilience may lead to novel therapeutic interventions to treat AD. Analysis of hippocampal transcriptional profiles from susceptible and resilient AD‐BXD strains indicates that transcriptomic changes in excitatory neurons in CA1 and dentate gyrus (DG) are associated with resilience and we now seek to examine physiological changes.MethodWe adapted the Patch‐Seq method (Cadwell et al., 2017) to investigate cell type‐specific transcriptional and electrophysiological changes associated with AD using the AD‐BXD genetic reference panel (Neuner et al., 2019). Whole‐cell patch clamp was used to evaluate intrinsic excitability of neurons within the DG and CA1 of 14m old mice with cognitive deficits compared to age matched controls; their cellular contents, including the nucleus, were collected after each recording to characterize the transcriptome.ResultComparison of the intrinsic properties of DG and CA1 neurons of hippocampal slices from 5XFAD mice and their non‐transgenic (Ntg) counterparts revealed that DG granule cells from 5XFAD mice have a lower input resistance and an increased sag ratio in response to hyperpolarizing current injections. Pyramidal neurons from the CA1 of 5xFAD mice exhibit significantly more depolarized action potential thresholds, a significant increase in the medium afterhyperpolarization (mAHP) and sag ratio compared to Ntg controls. While these intrinsic properties are proxy measures for neuronal excitability, we did not observe a significant effect of genotype on firing rate in response to 1s and 15s depolarizing current steps.ConclusionOur findings newly demonstrate disease related changes to intrinsic firing properties of DG granule cells at 14mo indicating that these neurons may be hypoexcitable. Also found, CA1 neurons from AD mice exhibit an increased mAHP and changes to sag ratio and AP threshold, indicating they too become less excitable. Future work will add additional AD‐BXD strains characterized as resilient or susceptible to the AD transgene to discover changes in intrinsic properties that could underlie resilience. We will also use an integrated analysis of transcriptomic and electrophysiological data to identify relevant functional targets for validation.
Multimodal Imaging Analysis for Brain Clearance: PET Imaging Based Clearance Slope, FASTT2 MRI‐based Parenchyma CSF fraction, and DTI‐based ALPS‐index
Authors: Zhou Liangdong , Nguyen Thanh D , Wegiel Jarek , de Leon Mony J. , Li Yi 
Published: December 2022

AbstractBackgroundGlymphatic clearance is important to maintain brain health, which depends on two interconnected fluid systems: the novel glymphatic system and the traditional well‐characterized CSF system1. There are several imaging tools have been developed to evaluate the glymphatic function in the human brain, however each method providing only a limited perspective into glymphatic system2. A proper imaging tool should consider both circulation pathway of the bulk CSF flow, and a complex PVS network parallel to the microvascular structure. We developed and tested an imaging package including vCSF, CSFF, and DTI‐ALPS, to investigate the ventricular CSF turnover rate, perivascular CSF flow and brain parenchymal CSF fraction.MethodA total of 23 subjects (F=16, M=7, NL=17, MCI=6) age from 63 and 82 years (mean=69.3, std=5.1). PET MK6240 was acquired for lateral ventricle CSF clearance measure3 (vCSF), and MRI FASTT2 and DTI was acquired for CSF fraction4 (CSFF) and diffusion tensor imaging along perivascular spaces5 (DTI‐ALPS) index, respectively. Precisely, vCSF was calculated as the slope of 10 to 30min lateral ventricle TAC normalized by 1‐4min whole brain AUC. CSFF was fitted using three compartment model with 6 TEs = 0, 7.5, 17.5, 67.5, 147.5, 307.5 ms. DTI‐ALPS was calculated by mean(D𝑥_𝑝𝑟𝑜𝑗,D𝑥_𝑎𝑠𝑠𝑜𝑐)/mean (D𝑦_𝑝𝑟𝑜𝑗, D𝑧_𝑎𝑠𝑠𝑜𝑐), where Dx, Dy and Dz are the diffusivity along x‐, y‐ and x‐axis, and the projection, association regions.ResultFigure 4 shows Parenchymal CSFF negative correlates with DTI‐ALPS (r = ‐.51; p=.01 n=23), suggesting link between glymphatic system dysfunction and increased cerebral CSFF. 4 NL subjects with high CSFF and low DTI‐ALPS are amyloid positive. Figure 5 shows ventricular CSF turnover rate (vCSF) negative correlates CSFF (r = ‐.53; p=.01 n=23).ConclusionOur preliminary results showed that ventricular CSF turnover rate (vCSF), perivascular CSF flow (DTI‐ALPS) and brain parenchymal CSF fraction (CSFF) are correlated to each other and indicate the connection between the glymphatic system and the traditional CSF system. The complementary imaging approaches could lead to a much greater understanding of glymphatic clearance, and facilitate a more complete perspective on both glymphatic pathology and function alterations.
Reference: 1. JM. Wardlaw,2020. 2. M. Niazi,2018. 3. Y. Li, 2022. 4. L. Zhou, 2021. 5. T. Taoka, 2017