bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mass spectrometry approaches for the selection of primary calibrators in the development of reference method
Authors: Coppens Salomé , Dubois Christelle , McCullough Bryan , Hirtz Christophe , Quaglia Milena 
Published: December 2021

AbstractBackgroundNeurofilament‐light chain (NF‐L) is a known early marker for neurodegeneration. This marker which is essential for the axonal structure, is quantifiable in biological fluids after neuronal damage but is not specific to a given pathology. Currently, the methods for detecting/quantifying this biomarker are mainly based on immunoassays. While the performance of immunoassay‐based assays is good in term of sensitivity and precision, mass spectrometry (MS) approaches are required to achieve standardisation. Those aiding to improved characterisation/quantification of the calibrator and potential for developing a reference measurement procedure traceable to the International System of Units. Furthermore MS has the potential of multiplexing NF‐L with other specific biomarkers for dementia. The characterization and quantification of a number of primary calibrators and their suitability for harmonization of immunoassay based results and development of a reference measurement procedure is here assessed.MethodMicrowaver hydrolysis and isotope dilution MS was used for quantification of NF‐L from different manufactures. An Orbitrap mass spectrometer (Q‐Exactive, Thermofischer) was used to provide high resolution intact protein analysis information. A QQQ mass spectrometer (Xevo TQ‐XS, Waters) was utilized to assess the potential of developing a reference measurement procedure for NF‐L.ResultThe quantitative analysis of the three NF‐L by amino acid analysis (AAA) showed for all samples discrepancy between the nominal concentrations and the experimental results with a general overestimation for the nominal concentration due to water and salt contents. Separation, identification and quantification of impurities present in the preparations was attempted to obtain a total protein content from the AAA and the NF‐L content from the AAA results corrected for the impurities. The sequence of NF‐L was verified by high resolution intact protein MS and tryptic digestion. A QQQ method was developed to monitor the tryptic digest peptides and assess their suitability to be used for the development of a reference measurement procedure. This was based on specificity, limits of detection and limits of quantification.ConclusionThese studies allow us to characterize three NF‐L proteins from different suppliers and to perform a first selection of the most relevant ones as primary calibrators for the development of a reference method.
“Nothing more will be changed here”: A qualitative study on the needs of people with dementia
Authors: Kowe Antonia , Panjaitan Hentry , Brokop Lisa , Teipel Stefan J. 
Published: December 2021

AbstractBackgroundTo prepare nursing students optimally for their future daily working life as formal caregivers of people with age‐related diseases such as dementia, the needs of this target group must be identified. We explored the needs of people with dementia based on Maslow’s need hierarchy theory to systematically identify requirements of nursing professionals as part of the project Digital Training of Nursing and Health Management (DigiCare).MethodWe conducted semi‐structured interviews with people with dementia (n = 10) and caregivers of people with dementia (n = 32). We asked for their daily routines, favoured living spaces, leisure activities and experience of care. We analysed the data with qualitative content analysis according to Mayring. Categories were formed deductively based on the need levels defined by Maslow.ResultsThe survey showed that the deficiency needs (physiological needs, safety and security, love and belonging) were mostly met in people with dementia, although some respondents described that social needs were not sufficiently met. People with dementia felt loneliness caused by the loss of social contacts due to disease symptoms such as language impairment. The respondents made very ambivalent statements regarding growth needs (esteem, and self‐actualization) of people with dementia. Some people with dementia and their relatives dealt openly with the disease, others described the stigmatisation of dementia and the resulting social rejection of those affected by the disease. Dementia, but also old age in general, was a barrier to cover the need of self‐actualization. The majority of people with dementia we interviewed showed little willingness to accept external help and preferred a high degree of independence. Maintaining good health was mentioned as the most important wish for the future. The identification of further wishes was challenging, as the majority of respondents wanted to continue with their usual life without any changes.ConclusionOur survey suggests that people with dementia need support in particular to cover the needs for belonging, esteem, and self‐actualization. The systematic identification of needs carried out in this study can help to inform formal caregivers to deliver demand‐oriented and person‐centred care.
LANGaware: Introducing the right solution for the early detection of neurodegenerative and psychiatric diseases
Authors: Rentoumi Vassiliki , Vassiliou Evangelos , Demiraj Admir , Pittaras Nikiforos , Mandalis Petros , Alexandridou Martha , Kemp Hollie , Eleftheriou Ioanna , Danezi Maria , Hatzopoulou Maria , Kamtsadeli Vasiliki , Paliouras George , Papatriantafyllou John D 
Published: December 2021

AbstractBackgroundThere are multiple neurodegenerative diseases that directly affect speech [1]. However, its utilization as a robust indicator for cognitive impairment is under‐investigated. In many cases, mild cognitive decline progresses to a neurodegenerative disease and its detection is of utmost importance, since it is at this stage that treatment is most effective. One of our core goals is developing techniques for differentiating between patients with cognitive decline and healthy cohorts, by utilizing only speech samples [2]. Such samples are obtained from verbal elicitation tasks designed for cognitive assessment, e.g. picture descriptions and narration of everyday activities.MethodAudio recordings from cognitive assessment tasks are fed through our platform to a Natural Language Processing and Machine Learning pipeline, employing an automatic discovery procedure of predictive salient biomarkers, to train an advanced classification system. The biomarker collection includes features that characterize voice, speech, language structure, composition and usage, and are engineered to highlight symptoms of neurodegenerative disorders. Biomarkers undergo multiple stages of filtering, processing and transformation to train and fine‐tune the final model. Diagnostic performance of the output classifier is obtained on an unseen test set, to ensure a robust generalization of the platform.ResultOur platform utilizes the set of automatically selected, cross‐linguistic digital biomarkers to obtain sensitivity and specificity scores of 81% and 84% respectively, compared against medical expert diagnosis. The most salient biomarkers with respect to identifying our pathological cohort, relate to feature categories of Syntactic Complexity, Content Word usage, Lexical Repetition, Syntactic Errors and Function Words, with weight contributions of ∼ 16%, 14%, 13%, 12% and 11% respectively. Our platform provides additional, detailed population and patient‐based descriptive analytics to enhance transparency and explainability of the results.ConclusionEarly detection of cognitive decline facilitates early intervention, treatment and proactive care, delaying disease progression and reducing symptom severity. We believe that our platform provides an effective solution for risk factor estimation and our findings incentivize further research into speech analysis techniques for the prediction of cognitive decline.[1] Boschi, Veronica, et al.,Frontiers in psychology 8 (2017): 269.[2] Vassiliki Rentoumi et al., Alzheimer's & Dementia, Wiley, volume 16, 2020.
An unexpected risk: Surgical procedures are common in patients with prion disease
Authors: Prusinski Christian C , Porter Amanda , Lazar Evelyn , Yuh Clara , Bucelli Robert C , Day Gregory S 
Published: December 2021

AbstractBackgroundPatients with prion disease commonly present with visual, sensorimotor or gait complaints that may prompt surgical interventions for related disorders (e.g., cataracts, carpal tunnel syndrome and joint disease). To prevent iatrogenic transmission of prion disease, surgical instruments used on patients with possible prion disease must be decontaminated or decommissioned. This is only done when the diagnosis of possible prion disease is recognized by the healthcare team. We considered the frequency with which patients with definite or probable prion disease underwent surgeries within one year of the symptomatic onset of prion disease diagnosed.MethodThe Mayo Clinic’s Advanced Cohort Explorer was used to identify patients with prion disease diagnostic codes assessed since 1/1/2014 (n=296). Patients with prion disease enrolled in prospective studies of rapidly progressive dementia beginning 2/14/2015 at Washington University School of Medicine (St. Louis, MO) were also included (n=14). Charts were independently reviewed by two team members, and demographic and clinical details extracted.Result108 patients with probable or definite prion disease were identified, including 62 (57%) with autopsy‐ or genetically‐proven prion disease (57 sporadic, 4 familial, 1 fatal familial insomnia). The majority of patients experienced a rapidly progressive course (mean symptom‐duration 10.0±9.7 months). Twenty‐nine patients (26.9%) underwent 36 surgeries or invasive procedures using durable instruments, including 3 high‐risk procedures directly involving the central nervous system, and 13 intermediate‐ (e.g., joint replacement) and 20 low‐risk procedures (e.g., endoscopy). Surgeries were performed a median of 10.2 months before death (range: 0.8‐62.3), with 16 (44%) performed after symptom onset. Surgical operators were unaware of the diagnosis of possible prion disease in all but one case (diagnostic brain biopsy).ConclusionSurgeries were common in patients with prion disease in this series and were commonly performed by operators who were unaware of the diagnosis. Coordinated approaches to screening and reporting may be needed to reduce the risk of iatrogenic spread of prion disease.
Clinical phenotypes of behavioral variant frontotemporal dementia by age at onset
Authors: Fieldhouse Jay L.P. 
Published: December 2021

AbstractBackgroundBehavioral variant frontotemporal dementia (bvFTD) is generally considered a young‐onset dementia, although late‐onset is not uncommon. BvFTD knows a large clinical variability and an age range varying from 21 to 85 years of age at onset. This heterogeneity challenges diagnostics, patient management and trial cohort design. While several studies indicate clinical differences regarding age at onset, no biomarker validated cohort studies with updated clinical criteria have been performed. We aimed to examine behavior, cognition and mortality over the full age spectrum in a cohort of bvFTD patients with neuroimaging, genetic or histopathological confirmation and exclusion of positive Alzheimer’s disease biomarkers.MethodIn total, 321 patients with a clinical diagnosis of probable or definite bvFTD from the Amsterdam Dementia Cohort were included and grouped into quartiles by age‐at‐diagnosis. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory and the Geriatric Depression Scale. Cognitive functioning was assessed with a neuropsychological test battery. Data on mortality was obtained from the Dutch municipal register. Continuous associations of clinical features with age‐at‐diagnosis, group differences between age quartiles, and mortality risk were examined in two models (M1: unadjusted, M2: adjusted for sex).ResultAge‐at‐diagnosis ranged between 26‐85 years and established quartiles with mean ages of 52±6, 60±2, 66±2 and 74±3 years. In the total sample, 44.2% exceeded an age of 65 years at time of diagnosis, 50% were deceased at time of analysis and mean survival time from date of diagnosis was 4±3 years. Earlier age‐at‐diagnosis was associated with more severe behavioral symptoms of primarily euphoria, apathy and depression, while later age‐at‐diagnosis was associated with more memory deficits. This was mainly explained by the youngest subgroup. Unexpectedly, mortality risk was not associated with age‐at‐diagnosis and was equal within age quartiles (Figure 1).ConclusionIn bvFTD, symptom profile is associated with age‐at‐diagnosis. This should be taken into account with regard to diagnostics, patient management and trial design. Furthermore, our findings suggest that late disease onset and memory deficits are more frequent in bvFTD than generally thought.
Associations between late‐life cardiometabolic risk factors and dementia
Authors: Ren Dianxu , Lopez Oscar L , Lingler Jennifer H , Conley Yvette 
Published: December 2021

AbstractBackgroundLate‐life cardiometabolic risk factors (overweight/obesity, hypertension, hypercholesterolemia, and diabetes) have been inconsistently reported to associate with dementia, with both increased and decreased risks. The purpose of this study was to examine such associations with incident dementia using the large national dataset from National Alzheimer’s Coordinating Center (NACC).MethodWe used NACC dataset from 2005 to December 2020 and restricted our analysis to patients who were 65 years and older at initial visit, had an APOE genotype available, first visit with dementia free and had a minimum of one follow‐up visit. The cardiometabolic risk factors were measured at initial visit. Piecewise multivariable Cox proportional hazard models accounting for non‐proportional hazards were performed to examine the associations of the 4 cardiometabolic risk factors with incident dementia, controlling for age, gender, race, education and APOE genotype. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) were reported.ResultFor the defined cohort (N=13,068), mean age at enrollment was 74.9 years, participants were more female (59%), and non‐Hispanic white (76.9%). Over an average of 4.8 years follow‐up, 2817 (21.6%) developed dementia. Both diabetics and hypertension demonstrated the increased risk of dementia compared to non‐diabetics (aHR=1.26, 95% CI (1.12, 1.41), P<0.0001), and to non‐hypertension (aHR=1.09, 95% CI (1.01, 1.19), P=0.026). However, hypercholesterolemia was not associated with dementia (aHR=1.03, 95% CI (0.95, 1.11), P=0.65). Differential BMI effects on incident dementia were observed over the length of follow‐up before dementia diagnosis. During the time of 0‐4 years and 4‐8 years before dementia, increased BMI significantly associated with reduced risk of dementia [aHR=0.96, 95% CI (0.95‐0.97), P<0.001; aHR=0.98, 95% CI (0.96‐0.99), P=0.016], and no effect during the time of 8‐12 years (aHR=0.99, 95% CI (0.96‐1.02), P=0.54). However, for the time longer than 12 years before dementia, higher BMI exhibited a trend of increased risk of dementia (aHR=1.05, 95% CI (0.99‐1.10), P=0.08).ConclusionOur analyses showed baseline diabetes and hypertension in late‐life are associated with dementia. The BMI‐dementia association likely attribute to a harmful effect of higher BMI with the onset of dementia over a long follow‐up and a potential reverse‐causation effect when the follow‐up is short.
Concordance and diagnostic accuracy between Innotest and two fully automated platforms: Elecsys and Lumipulse
Authors: Ortega Ricard López , Dakterzada Faride , Arias Alfonso , Llena Iolanda Riba , Julián Maria Ruiz , Huerto Raquel , Tahan Nuria , Piñol‐Ripoll Gerard 
Published: December 2021

AbstractBackgroundManual ELISA assays are the most commonly used methods for quantification of CSF AD biomarkers; however, they show inter‐ and intra‐laboratory variability. We compared the Innotest ELISA method with two fully automated platforms (Lumipulse and Elecsys) to determine whether these new methods can provide effective substitutes for ELISA assays.MethodWe included 149 males and females with AD (n = 34), MCI (n = 94) and non‐AD dementias (n = 21). Aβ42, T‐tau, and P‐tau were quantified using the ELISA method (Innotest, Fujirebio Europe), CLEIA method on a Lumipulse G600II, and ECLIA method on a Cobas e 601 instrument.ResultWe found a high correlation between the three methods. Both Lumipulse and Elecsys methods were highly concordant with clinical diagnoses, and the combination of Lumipulse Aβ42 and P‐tau had the highest discriminating power (AUC 0.915, 95% CI 0.822–1.000). The use of Aβ42/Aβ40 ratio instead of Aβ42 alone in AT(N) classification enhanced the diagnostic accuracy (AUC 0.798, 95% CI 0.649–0.947 vs AUC 0.778, 95% CI 0.617–0.939). Finally, the biomarker ratios (P‐tau/Aβ42 and T‐tau/Aβ42) were more consistent with the Aβ42/Aβ40 ratio for both Lumipulse and Elecsys methods, and Elecsys P‐tau/Aβ42 had the highest consistency with amyloid pathology (AUC 0.994, 95% CI 0.986–1.000 and OPA 96.4%).ConclusionThe Lumipulse and Elecsys CSF AD assays showed high analytical and clinical performances so their use is recommended for the measurement of CSF AD biomarkers compared with unstandardized manual methods.
Influencing factors and strategies to support communication between older adults with dementia and caregivers throughout the care trajectory
Authors: Zwakhalen Sandra , Bormans Kasper 
Published: December 2021

AbstractBackgroundCommunication is an essential aspect of life and caregiving. However it is often taken for granted although ccommunication between older adults with dementia and their carers is often extremely challenging. Effective communication is essential to provide relationship centered care and tailor care to patients needs.ObjectivesWe aimed to determine factors that influence communication in older adults’ with dementia and their caregivers’ and explored strategies to enhance communication that could be supportive throughout the care trajectory.Design and methodsFactors that impact communication between older adults with dementia and caregivers were determined by using a scoping review and included a thematic analysis of the literature. These determined factors were validated using a large variety of video observations and additional qualitative interviews (n=15). To determine strategies that could be beneficial to improve communication, communication strategies were determined. To determine these strategies existing literature of other expertise areas (including marketing and communication science) was used and think a‐loud sessions with experts were performed.ResultsThe scoping review revealed that factors that can affect caregivers' communication with older adults with dementia relate to the older adult, the caregiver and the context of the caregiving situation / environment, and the interactions between these factors. Observations confirmed that most influencing factors were related to the caregivers including for example non‐verbal behaviour. However contextual factors (e.g. organization of care, and care situation) were less observed although these may offer opportunities to enhance the communication. Strategies identified from other fields (f.i. social psychology and consumer behaviour research) were included for example compliance‐without‐pressure‐techniques.ConclusionsThis study gained important insight into influencing factors on communication between older adults with dementia and their caregivers. Strategies as ‘The‐foot‐in‐the‐door’, verbal mimicry and ‘The illusion of choice’ could support communication throughout the care trajectory and are provide useful insights, which are not always taken into consideration in current practice. This information can be used for developing solid interventions to support communication and enhance relationship centred care in accordance to the older adults needs.
Reaching the unengaged: Conversations about dementia risk reduction
Authors: Fair Hannah , Doherty Kathleen , Eccleston Claire , Klekociuk Shannon Z , Farrow Maree 
Published: December 2021

AbstractBackgroundThe Preventing Dementia Massive Open Online Course (PD‐MOOC) aims to increase public knowledge of dementia risk factors and promote risk‐reducing behaviour. This course attracted 147,000 enrolments from 2016 to 2020. Men and people with low levels of education are under‐represented in the PD‐MOOC. This study investigated whether members of these under‐engaged groups receive dementia risk information “second‐hand” from close contacts who undertake the PD‐MOOC.MethodIn May 2020, first time PD‐MOOC enrolees from Tasmania, Australia, provided qualitative and quantitative data about the people they felt very close or somewhat close to. Participants were retrospectively asked about conversations in which information from the PD‐MOOC was discussed. Two‐proportions z‐tests were used to determine the extent to which “second‐hand” information reached under‐engaged groups.ResultParticipants (n = 37) provided information about 799 close contacts; networks ranged in size from 8 to 45 people. Participants reported sharing dementia risk information with between 0 and 100% of their close contacts. Overall, information was shared with 437 close contacts. The proportion of men with whom dementia risk information was shared was significantly higher than the proportion of men directly receiving such information via the May 2020 PD‐MOOC (24% vs 15%, p<0.001). The proportion of people with a low level of education (less than high school completion) with whom dementia risk information was shared was significantly higher than the proportion of people with a low level of education directly receiving such information via the May 2020 PD‐MOOC (12% vs 1%, p<0.001). Some participants reported that some of the close contacts with whom they discussed dementia risk were unlikely to engage in dementia risk education themselves: “[my friend] said ‘…well you can tell me about it … after you've done it’ ‐ they weren't prepared to do the course”.ConclusionInterpersonal conversations increase the reach of dementia risk information, reaching people and demographic groups that are less likely to engage with interventions like the PD‐MOOC. Interpersonal conversations about dementia risk reduction could potentially be promoted to help reach important target populations for dementia prevention.