bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain structure and anticholinergic medication: Different results with different scales
Authors: Kilimann Ingo , Katharina Wittfeld , Wucherer Diana , Ittermann Till , Voelzke Henry , Bülow Robin , Hoffmann Wolfgang , Grabe Hans J. , Teipel Stefan J. 
Published: December 2020

AbstractBackgroundPrevious studies showed an inverse correlation between anticholinergic activity from individual medication and cognitive function. Various scales have been developed for scaling the anticholinergic effect of pharmacological substances. The Anticholinergic Cognitive Burden Scale (ACB) and the Anticholinergic Risk Scale (ARS) are the two most commonly used scales for this purpose. Our study evaluated the association of the ACB and the ARS total score with volumes of vulnerable brain structures for cognitive impairment (hippocampus [HIP] and basal forebrain [BF]) in non‐demented participants from a population‐based study.MethodsWe analyzed structural MRI and medication (n= 3,316) from participants (aged 20 to 93 years, 52.2% female) of the population‐based Study of Health in Pomerania (SHIP). Anticholinergic burden was obtained from the current medication plan using the ACB and the ARS scales, respectively. We added all scores per participant to an individual total score and evaluated the association with the volume of the HIP and the BF corrected for age, gender, education and total intracranial volume. In addition, we conducted voxel‐based morphometry analysis and compared the results to the volumetric analysis.ResultWe identified 1471 medications to be anticholinergic according to the ACB in a total of 706 participants and 446 medications according to the ARS in 188 participants. The volumetric analysis showed a statistically significant inverse association between the ACB and the volume of the HIP (left p=.0003, r=‐.54; right p=.00007, r=‐.59) but no correlation between the ACB total score and the BF volume (p=.070, r=‐.29). The analysis of the volumes of the HIP and the BF and the total ARS score did not show any statistically significant association in these structures (HIP left p=.431, r=+.12, HIP right p=.362, r=+.14, BF p=.055, r=+.28).ConclusionSeveral scores with different levels of comprehensiveness are available to calculate the individual anticholinergic burden. Our study showed that the more detailed ACB scoring revealed an association between the anticholinergic burden and the hippocampus whereas the ARS score with a limited number of substances did not show any statistically significant correlations. Further studies in independent samples and clinical follow‐up examinations are needed to better understand the potentials of the different scales.
Network electroencephalographic (EEG) measures in primary progressive apraxia of speech and aphasia
Authors: Utianski Rene L , Botha Hugo , Caviness John N , Worrell Gregory A , Duffy Joseph R , Clark Heather M , Whitwell Jennifer L , Josephs Keith A 
Published: December 2020

AbstractBackgroundPast research has demonstrated that clinical EEG is sensitive to dementia associated with Alzheimer's (AD) and Parkinson’s diseases (PD), and nonfluent/agrammatic Primary Progressive Aphasia (agPPA), but not Primary Progressive Apraxia of Speech (PPAOS). However, clinical EEG studies do not quantify interactions of multiple brain areas, or network activity. Graph theory (GT) simplifies analyzing and comparing complex brain networks. Studies have shown changes in EEG GT measures in AD and PD, but have not been studied in agPPA or PPAOS. The goal of this study was to use GT to characterize network‐level changes and associations with speech and language functioning in patients with agPPA and PPAOS.MethodsScalp EEGs of 14 agPPA and 7 PPAOS patients were collected during relaxed wakefulness (10‐20 positions, 256Hz sampling, 1–200Hz bandpass filter). Eight artifact‐free epochs were selected from non‐overlapping 1024‐point epochs. Via Brainwave software, GT weighted connectivity and minimum spanning tree (MST) measures were calculated for theta and alpha frequency bands. Differences in theta MST measures between agPPA and PPAOS were assessed with Wilcoxon rank‐sum tests. Spearman correlations were computed between behavioral and all network measures across all patients.ResultsTheta frequency MST diameter and eccentricity were significantly lower and leaf was significantly higher in agPPA compared to PPAOS patients; betweenness centrality did not differ. This indicates agPPA networks are more integrated (star‐like) than PPAOS. There were significant correlations between several network measures (e.g. kappa, lambda, PLI) and indices of speech‐language functioning.ConclusionsThe results provide EEG evidence of network alteration in agPPA and PPAOS patients. The GT measures and associations with behavioral measures provide support for reduced global efficiency, or network specificity, in these patients. The correlation of language measures with lambda (path length) in the theta frequency band suggests agPPA is associated with an inefficient path length and/or increased integration. The correlation between apraxia of speech (AOS) measures and MST eccentricity in the alpha frequency band suggests that more severe AOS is associated with reduced distance between two nodes. This study demonstrates potential for EEG GT measures to quantify network changes and distinguish network changes between related but different clinical syndromes.
Self‐perceived problems in daily activities and strategy building in people without and with mild and severe dementia
Authors: Ross Sabrina D , Rodriguez Francisca S 
Published: December 2020

AbstractBackgroundIt is well known that people with dementia experience severe problems in their daily lives. Less is known about how self‐perceived problems decline throughout the course of dementia together with their decline in memory, language, and executive functions. Hence, we wanted to assess self‐perceived problems when performing daily activities as well as possible developed strategies that help to prevent mentioned difficulties at different cognitive stages for older people.MethodTo attain our goal, we analyzed qualitative semi‐structured interviews conducted with 25 people (age (mean: 67.64; SD: 23.625), sex (f: 14 (56%); m: 17 (68%)), cognitive status (healthy: 6; mild demented: 7; severe demented: 12)) based on the Grounded Theory approach from Glaser and Strauss. The interviews further comprised a cognitive and a functioning assessment, including Montreal Cognitive Assessment (MoCa), the script generation task, and the Lawton Instrumental Activities of Daily Living Scale (IADL), that were used as a base for the qualitative questions concerning self‐perceived problems and thereupon developed strategies in daily activities.ResultThree main categories where identified, (i) disturbing factors when performing daily activities, (ii) variations in the autonomy level and (iii) self‐established daily life strategies to circumvent mentioned problems. Findings suggest that orderliness, making notes for appointments, and the usage of a shopping list help with daily activities whereas conversations, noise, and stress disturb the performance of daily activities. People who were aware of problems, reported developing strategies, while people who did not have awareness of any problems did not. Only people without and with mild dementia recognize problems and therefore develop strategies.ConclusionThis study aimed at understanding how self‐perceived problems change and get affected with increasing cognitive impairment. It turns out that a certain cognitive status is needed to develop strategies and be aware of problems. Further research is needed to establish more useful strategies that help dementia sufferers as well as older people to delay the progress or onset of the disease and make their lives longer, more independent and especially more worth living.
A systematic review of culturally tailored dementia interventions for minority ethnic groups and low‐ and middle‐income country populations: Acceptability, feasibility and outcomes
Authors: James Tiffeny , Ceballos Stefanny Guerra , Mukadam Naaheed , Livingston Gill 
Published: December 2020

AbstractBackgroundThere are more people living with dementia worldwide, particularly in low‐ and middle‐income countries (LMICs) and minority ethnic groups. In high‐income countries (HICs), evidence‐based psychosocial interventions can improve outcomes for people with dementia and family carers. To consider their efficacy in other settings, we investigated whether there are culturally tailored interventions for LMIC populations and minority ethnic groups, with tested acceptability, feasibility and efficacy.MethodWe systematically reviewed the literature on culturally tailored dementia interventions in LMICs and minority ethnic groups. We searched 11 databases for terms relating to dementia, interventions and cultural tailoring. We identified eligible papers using predefined inclusion criteria. We rated study quality using a quality checklist and prioritised those with less risk of bias when reporting results (PROSPERO: CRD42019133090).ResultWe found 22 studies out of 22,221 unique references that met criteria for inclusion. Most studies targeted family carers (n = 15) and LMICs (n = 14). Studies of interventions for family carers had mixed quality and there were no higher quality studies of people with dementia. Only three studies reported whether the adapted outcome measures used had been validated in their sample. Culturally tailored, group interventions involving a therapeutic and educational component were associated with improvements in family carers’ depressive symptoms in Egypt and Columbia, and in Latino carers in the US, reflecting findings in HICs and non‐minority groups. An individually delivered, multicomponent intervention improved carer mental health in India but not in Peru or Russia. An adapted Cognitive Stimulation Therapy appeared to be acceptable and feasible in sub‐Saharan Africa, with a full trial planned.ConclusionCulturally tailored interventions for family carers appear to be acceptable and feasible in some LMICs and minority ethnic groups as they are in HICs. Although research in these groups is increasing, studies of culturally tailored interventions were only published for 11 out of 142 LMICs, and studies of interventions for people with dementia are few and of low quality. To improve reliability and validity of future studies of culturally tailored interventions, researchers should ascertain psychometric properties of adapted and translated outcome measures before using them in a new setting.
Transitions in early‐onset dementia: A qualitative study exploring the experiences of people recently diagnosed with dementia
Authors: Aspö Malin , Cronfalk Berit Seiger , Boström Anne‐Marie , Kivipelto Miia 
Published: December 2020

AbstractBackgroundReceiving a diagnosis of dementia before the age of 65 has a considerable impact on a person’s everyday life. The social impact most likely include work and family life, as the person may be the main or sole provider for the family. During the disease there are several critical points, some may differ from those identified in late‐onset dementia. Transitions are initiated by critical points or events, followed by a period of instability and distress, in which the person is vulnerable and at risk of making unhealthy decisions. This study aims to describe transitions and identify critical points in the initial phase of early‐onset dementia.MethodParticipants younger than 65 (mean age 60), with a MMSE score greater than 24, were recruited from a specialized memory clinic in Sweden. In‐dept interviews were conducted shortly after diagnosis, focusing on the period before receiving the diagnosis, on how the diagnosis has impacted their daily life, as well as their thoughts about the future. A preliminary analysis, using qualitative content analysis, was performed on nine interviews.ResultsIn the preliminary results early (forced) retirement was identified as a main critical point, leading to both economic and psychosocial issues. The participants all knew about the later phases of dementia but had different thoughts how to approach this. Most of the participants actively searched for information about the disease and prognosis, as well as information about how to postpone decline, while others did not want any further information about the disease.ConclusionSeveral signs of transitions and critical points were identified, some of them being specific to people younger than 65. The results from this study can help professional caregivers to facilitate transitions and enhance the wellbeing and quality of life in young people living with dementia and their family.
Tau kinetics in Alzheimer disease and primary tauopathies
Authors: Sato Chihiro , Horie Kanta , Barthelemy Nicolas R. , Patterson Bruce W. , Gordon Brian A. , Benzinger Tammie L.S. , Mallipeddi Nipun , Sullivan Melissa , Li Melody , Lloyd LaKisha , Elbert Donald L. , Wright Brenton A. , Day Gregory S. , Davis Albert A. , Rohrer Jonathan D. , Paterson Ross W. , Ghoshal Nupur , Bateman Randall J. 
Published: December 2020

AbstractBackgroundUnderstanding tau kinetics in the human central nervous system is critical for evaluating the effects of tau‐targeted therapies and designing clinical trials against tau in Alzheimer disease (AD) and other primary tauopathies. We hypothesized that tau production or clearance is altered in tauopathies and measured tau kinetics in AD and in a small set of participants with Progressive Supranuclear Palsy (PSP), Corticobasal Syndrome (CBS), or from Frontotemporal Dementia (FTD)‐MAPT families.Methods
In vivo human tau Stable Isotope Labeling Kinetics (SILK) were performed in 65 participants including 10 young normal controls, 23 age‐matched controls, 16 AD and 16 primary tauopathies (2 PSP, 4 CBS, 10 MAPT mutation family). Briefly, participants received 16hr intravenous infusion of 13C6‐leucine and cerebrospinal fluid (CSF) was collected from five lumbar punctures over 120 days. Labeled tau was measured with mass spectrometry to obtain kinetic curves of tau. Production and clearance rates were calculated and compared across different tauopathies. CSF amyloid beta (Aβ), amyloid and tau Positron Emission Tomography (PET) imaging were measured in a subset of participants, and analyzed for correlation with SILK measures.ResultsFirst, we confirmed the reproducibility of previous results (Sato et al., 2018) and demonstrated that tau production rates increased with amyloid measured by PET or CSF Aβ. Second, CSF tau concentration correlated with CSF Aβ40 and Aβ42 in primary tauopathies but only with Aβ40 in those with abnormal Aβ levels. Third, 2 PSP patients had slower clearance of tau with tau half‐lives approximately 1.5‐2.5 times longer than other cohorts. Tau Fractional Synthesis Rate also negatively correlated with tau concentration in primary tauopathies, and CBS and FTD‐MAPT had different slopes, suggesting that they may have different kinetics.ConclusionsThe results from this study provide mechanistic insights into differences between AD and other primary tauopathies, which may be targeted differently when developing therapies against tau metabolism. In vivo tau kinetics can help evaluate the efficacy of tau‐targeted therapies and provide information for designing clinical trials targeting tau.
What do people write about after filling out a survey on extending assistance in dying to incompetent patients with dementia?
Authors: Bravo Gina , Arcand Marcel 
Published: December 2020

AbstractBackgroundIn December 2015, the Canadian province of Quebec legalized medical aid in dying (MAID) for competent patients who satisfy strictly defined criteria. Like the rest of Canada, Quebec is considering extending the legislation to incompetent patients under certain conditions not yet specified. With the objective of informing policy developments in this sensitive area, we recently conducted a province‐wide postal survey to assess stakeholders’ attitudes toward giving incompetent patients with dementia access to MAID in some circumstances. Objective: To describe the comments respondents left at the end of the questionnaire.MethodThe questionnaire was mailed to 2,125 randomly selected representatives of four stakeholder groups: adults 65 and over presumed free of cognitive impairment, informal caregivers of persons with dementia, and nurses and physicians who were caring for patients with dementia at the time of the survey. A total of 1,050 questionnaires were returned (49.4%), of which 420 (40%) included comments. These ranged from a few words to several pages of free text. Comments were independently coded by the two authors into themes, topics and subtopics.ResultSeven major themes were identified, under which a total of 1,148 units were classified. Respondents wrote (1) about themselves (297 units), (2) the survey and questionnaire (204), (3) patients with dementia (235), (4) their informal caregivers (97), (5) the health care system (75), (6) the MAID legislation (207), and (7) society in general (33). Each theme comprises between two and five topics. Topics include, for instance, the respondent’s personal values and beliefs, informal caregivers’ difficulty in making end‐of‐life decisions for a loved one, and health care professionals’ lack of training in caring for patients dying with dementia. Theme 6, on the MAID legislation, includes two topics (the current legislation and its extension), the second of which was subdivided into five subtopics for greater refinement: preferred alternatives to MAID, fears should it be extended to incompetent patients, advanced requests, anticipated difficulties in providing MAID to incompetent patients, and eligibility criteria.ConclusionIn their comments, respondents raised several challenges associated with the possible expansion of MAID to incompetent patients that need attention.
Antipsychotic use in dementia: The relationship between neuropsychiatric symptom profiles and adverse outcomes
Authors: Mueller Christoph , John Christeena , Perera Gayan , Aarsland Dag , Ballard Clive , Stewart Robert 
Published: December 2020

AbstractBackgroundAntipsychotic treatments are associated with safety concerns in people with dementia. The authors aimed to investigate whether risk of adverse outcomes related to antipsychotic prescribing differed according to major neuropsychiatric syndromes – specifically psychosis, agitation, or a combination – in order to inform a precision medicine approach to management of key neuropsychiatric symptoms.MethodA cohort of 10,106 patients with a diagnosis of dementia was assembled from a large dementia care database in southeast London. Neuropsychiatric symptoms closest to the time of first dementia diagnosis were determined according to Health of the Nation Outcome Scales (HoNOS) mental and behavioural problem scores and the sample was divided into four groups: ‘agitated psychosis’, ‘agitation, but no psychosis’, ‘psychosis, but no agitation’, and ‘neither psychosis nor agitation’. Antipsychotic prescription in a six‐months window around first dementia diagnosis was ascertained as exposure variable through natural language processing from free text. Cox regression models were used to analyse associations of antipsychotic prescription with all‐cause and stroke‐specific mortality, emergency hospitalisation and hospitalised stroke adjusting for sixteen potential confounders including demographics, cognition, functioning, as well as physical and mental health.ResultOnly in the group ‘psychosis, but no agitation’ (n=579), 30% of whom were prescribed an antipsychotic, a significant antipsychotic‐associated increased risk of hospitalised stroke was present after adjustment (adjusted hazard ratio (HR) 2.16; 95% confidence interval (CI) 1.09‐4.25). An increased antipsychotic‐related all‐cause (adjusted HR 1.14; 95% CI 1.04‐1.24) and stroke‐specific mortality risk (adjusted HR 1.28; 95% CI 1.01‐1.63) was detected in the whole sample, but was no interaction between the strata and antipsychotic‐related mortality.ConclusionThe adverse effects of antipsychotics in dementia are complex. Stroke risk may be highest when used in patients presenting with psychosis without agitation, indicating the need for novel interventions for this group.
Feasibility of mobile app‐based assessment of memory functions: Insights from a citizen science study
Authors: Berron David , Billette Ornella V. , Ziegler Gabriel , Güsten Jeremie , Grande Xenia , Heneka Michael T. , Schneider Anja , Teipel Stefan J. , Jessen Frank , Wagner Michael , Düzel Emrah 
Published: December 2020

AbstractBackgroundMobile app‐based, high‐frequency monitoring of cognition holds the promise to facilitate the individual detection of cognitive change. However, there are several factors in everyday life that potentially influence estimates of cognitive performance in an unsupervised remote test setting. Characterizing these factors is critical to guide the interpretation of results from mobile app‐based studies of cognitive function in the future.MethodsWe conducted a Germany wide Citizen Science Project (after accreditation with the Citizen Science Portal of the German Ministry for Science and Education) with the goal to identify everyday life factors influencing cognitive performance estimates acquired via smartphone‐based assessments. To that end, every participant was pseudo‐randomly assigned to one of three memory tests: 1) pattern separation of objects and scenes (Berron et al., 2018, 2019); 2) complex (photographic) scene recognition memory (Düzel et al., 2011, 2018); 3) pattern completion of object‐in‐scene associations. Participants were asked to perform one test per week over a period of 15 weeks.Results1765 participants (70% female) completed 7900 weekly test sessions. The age‐range of participants was between 18 and 89 years of age. Mean age was 53 (SD=15). We found significant effects of age, time of the day of test performance, time between encoding and retrieval as well as the screen size of the mobile device. Further, our results indicate minor or even no practice effects with repeated tests and indicate that between 4‐5 test sessions are sufficient in order to define a measure of baseline performance.ConclusionOur results indicate several factors influencing cognitive measures in an unsupervised setting of remote smartphone‐based assessment of memory functions. While some factors were specific to only some tests, most factors were associated to all three tests suggesting that they are of general nature. Finally, several sets of different parallel test versions for each memory test resulted in marginal practice effects with repeated assessments.