bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term safety and efficacy of lemborexant in subjects with irregular sleep‐wake rhythm disorder and Alzheimer’s disease dementia
Authors: Moline Margaret , Bsharat Mohammad , Cheng Jocelyn
Published: December 2020

Background

Irregular Sleep‐Wake Rhythm Disorder (ISWRD) is a common circadian rhythm sleep disorder among individuals with Alzheimer’s disease dementia (AD‐D). The dual orexin receptor antagonist lemborexant (LEM) is approved in the US and Japan for insomnia, and is under investigation for ISWRD. Effects of LEM on clinical measures of ISWRD were evaluated in patients with mild‐moderate AD‐D in a Phase 2 proof‐of‐concept and dose‐finding clinical study (NCT03001557; E2006‐G000‐202). LEM improved circadian variables, helped consolidate nighttime sleep, and was well tolerated, over 1 month. Safety and efficacy data over the Core and long‐term open‐label Extension Phases are reported for subjects who entered the Extension Phase.

Methods

This randomized, double‐blind, multicenter, global, placebo (PBO)‐controlled parallel group study enrolled subjects (aged 60‐90y) who met DSM‐5 criteria for ISWRD and had mild‐moderate AD‐D. In the Core Phase, subjects were randomized to PBO or LEM (2.5mg, 5mg [LEM5], 10mg [LEM10], or 15mg [LEM15]) for 28 days. During the Extension Phase, eligible subjects initially received open‐label LEM10, with option of adjusting the dose to LEM5 or LEM15. Caregivers completed the Sleep Disorders Inventory (SDI), which assesses sleep‐related disturbances. SDI total score (SDI‐ts) was derived as the product of the average of the frequency ratings and the average of the severity ratings (range: 0–12 [worst]).

Results

Twenty‐five subjects entered the Extension Phase. In these subjects, treatment emergent adverse events (TEAEs) were reported in 16(64%) subjects over the Core and Extension Phases (1‐14 months). Serious TEAEs were reported in 3(12%) subjects; no deaths were reported. TEAEs led to dose adjustment in 4(16%) subjects. The most common TEAEs (incidence >10%) were nasopharyngitis (n=4;16%), fall (n=3;12%), and somnolence (n=3;12%). In subjects who received a modal dose of LEM10 (Core and Extension Phases [n=17]), mean(SD) SDI‐ts was 0.72(0.75) at baseline (n=12). Mean(SD) change from baseline (CFB) in SDI‐ts at Day 29 (n=12) was −0.14(0.63). In the Extension Phase, mean(SD) CFB in SDI‐ts was −0.37(0.50) at Day 133 (n=14) and −0.12(0.81) at Day 223 (n=12).

Conclusions

In subjects with AD‐D and ISWRD treated with LEM10, moderate improvement in SDI‐ts continued to be observed over time. LEM was well tolerated over 1‐14 months. Support: Eisai Inc.
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

Background

Previous 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.

Methods

We 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.

Result

We 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).

Conclusion

Several 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

Background

Past 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.

Methods

Scalp 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.

Results

Theta 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.

Conclusions

The 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

Background

It 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.

Method

To 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.

Result

Three 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.

Conclusion

This 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

Background

There 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.

Method

We 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).

Result

We 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.

Conclusion

Culturally 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

Background

Receiving 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.

Method

Participants 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.

Results

In 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.

Conclusion

Several 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

Background

Understanding 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.

Results

First, 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.

Conclusions

The 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

Background

In 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.

Method

The 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.

Result

Seven 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.

Conclusion

In 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

Background

Antipsychotic 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.

Method

A 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.

Result

Only 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.

Conclusion

The 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

Background

Mobile 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.

Methods

We 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.

Results

1765 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.

Conclusion

Our 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.
Validation of a latent dementia index in the Aging, Demographics, and Memory Study
Authors: Saenz Joseph , Beam Christopher R
Published: December 2020

Background

Longitudinal studies of aging often lack clinical gold standard measures of dementia and instead rely on nondiagnostic approaches to categorizing study participants as demented or cognitively normal. Recently, latent variable models have been used to estimate latent dementia indexes (LDI) using cognitive ability, memory, and functional ability measures to distinguish dementia risk from general cognitive functioning. The LDI exhibits clinical utility and puts dementia risk on a continuous scale, to approximate the process of becoming demented. The purpose of the current study is to validate an LDI in the Aging, Demographics, and Memory Study (ADAMS) using participants’ neuropsychological assessment and functional ability scores.

Method

We evaluated the 2001‐2003 ADAMS including 856 adults age 65+ who had participated in the United States Health and Retirement Study (HRS). ADAMS respondents were given an extensive neuropsychological battery of tests spanning various cognitive domains and provided information on functional abilities. We analyzed cognitive tasks (trails A&B, digits forward/backward, Shipley VocabularyTest, delayed 10‐word recall, recognition memory, and logical memory) and functional tasks (difficulty with household tasks, using familiar appliances, shopping independently, ability with complicated tasks, and handling small sums of money). Using confirmatory factor analysis, we modeled the LDI by performance on cognitive, memory, and functional ability reports. Validation involved comparing the LDI to the diagnosis of dementia made by a consensus panel including neuropsychologists, neurologists, geropsychiatrists, and internists.

Results

A single factor LDI model fit the data well (Comparative Fit Index = .96; Root Mean Square Error of Approximation = .05, .90CI: [.03, .06]). The LDI significantly predicted clinical gold standard diagnosis (OR = .55, .95CI = [.50, .60]), with LDI scores +1 SD above the LDI mean predicting .36 times lower odds of dementia and LDI scores ‐1 SD below the mean predicting 2.78 times greater odds of dementia.

Conclusion

An LDI that does not rely on clinical gold standard dementia diagnoses has good clinical utility in the ADAMS 2001‐2003 sample. Future research includes validating LDI scores longitudinally in ADAMS and extending the LDI approach to the HRS core sample.
Community‐based participatory approach to promote convenience stores’ support for older adults with dementia in Japan
Authors: Igarashi Ayumi , Matsumoto Hiroshige , Takaoka Manami , Kugai Haruna , Suzuki Miho , Murata Satoshi , Shimada Hiromi , Kubo Tomoko , Hiratsuka Tomoyuki , Yazawa Akio , Yamamoto‐Mitani Noriko
Published: December 2020

Background

Convenience stores (CVSs), small retail chains that sell a variety of daily necessities ranging from sandwiches to shaving creams in a neighborhood, support older adults with dementia by providing them a convenient shopping place and meeting their small daily needs. Since 2017, we have conducted community‐based participatory research in Nerima City, Tokyo, to promote collaboration between CVSs and community healthcare/social care professionals and to strengthen the CVSs’ support function for community‐dwelling older adults. We evaluated the effect of our activities in the past 3 years.

Methods

In 2018, community support center (CSC) staff visited CVSs in the neighborhood to become acquainted with each other. Thereafter, the CSC staff continued to collaborate with CVSs in supporting older adults, such as by regularly asking the CVSs about difficulties in dealing with older customers. To evaluate these activities, every year from 2017 to 2019, we administered self‐report questionnaires to owners/managers of all convenience stores in Nerima City (intervention group) and two other cities (control group) in Tokyo. We analyzed the data using the difference‐in‐difference method.

Results

The participants who completed the survey were 97 (valid response rate: 17.9%; n = 37 in Nerima vs. 60 in others) in 2017, 103 (19.2%; n = 50 vs. 53) in 2018, and 108 (17.9%; n = 52 vs. 56) in 2019. Altogether, the mean age (± standard deviation) was 46.9 (±13.0) years, and 77% were men; 56% were owners of the CVSs, and they had 17.1 (±7.2) staff in their stores. The analyses showed significant improvements in “experience of emergency protection for an older adult” (p = 0.03), “knowledge of the function of the CSC” (p = 0.001), “knowing individual healthcare/social care professionals in the CSC” (p = 0.02), and “awareness of when to contact the CSC” (p = 0.002) among the subjects in Nerima City as compared to those in other cities.

Conclusion

The results suggest that these collaborative actions were effective in promoting activities to support older adults and establishing relationships between CVSs and CSCs.
Functional connectivity for discrimination between mild cognitive impairment and subjective cognitive decline in Alzheimer disease: A study on resting‐state EEG rhythms in the Peruvian population
Authors: Vilca Brenda Nadia Chino , Fernández Ricardo Bruña , Maestú Fernando , Acobo Roxana Castillo
Published: December 2020

Background

The increase in cases of dementia worldwide has promoted the development of research for its detection and early intervention. However, the strategies, procedures, and tools designed to address the problem from the international level have found significant barriers in its implementation in Latin American countries, where factors such as socio‐demographic variability and clinical techniques limit their scope in terms of identification and intervention. Under this framework, research with signals in EEG / MEG has shown that the analysis of functional connectivity can be a sensitive biomarker in neurodegenerative processes, including the analysis of pre‐symptomatic stages with subsequent conversion to Alzheimer disease. This study seeks to develop robust methods for the diagnosis and characterization of Alzheimer's disease (AD) in the phase from the analysis of 160‐channel EEG signals in the Peruvian population.

Method

500 screening evaluations were carried out, with 75 adults/seniors between 50 and 75 years of age being selected: 17 subjective cognitive declines, 24 with a family history of dementia and 31 mild cognitive impairment. The participants underwent four evaluation sessions, which included an EEG record in a state of rest (eyes closed and eyes open) and neuropsychological tests.

Result

The functional connectivity patterns are consistent with similar studies using MEG in European and North‐American population.

Conclusion

Our results demonstrate the utility of the EEG for the diagnosis and distinction of the previous stages of AD and the variation of the default mode network between QSM, DCL, and AF.
Regulation of ribosomal function by oligomeric tau
Authors: Jiang Lulu , Wolozin Benjamin
Published: December 2020

Background

Accumulation of tau pathology is a core feature of Alzheimer’s disease (AD) and related tauopathies, but tau pathology is pleiotropic. The many species of tau oligomers/aggregates has prevented elucidation of the mechanisms by which tau induces neurodegeneration. Fibrillary tau aggregates are considered to be less toxic than tau oligomers, but have received extensive attention because they are readily identifiable with pathological dyes, such as thioflavines, as well as by reagents used for diagnostic imaging. Multiple studies indicate that oligomeric tau (oTau) is the key toxic species, but the mechanism of toxicity is unknown

Methods

We applied optogenetics to induce tau oligomerization, and then used this to investigate the proteins with which oligomeric tau interacts and the mechanisms through which it regulates protein synthesis.

Results

Our results demonstrate a temporal evolution of oTau, transitioning from reversible to irreversible states. Tau oligomerization rapidly induces a translational stress response including inhibition of protein synthesis. Application of mass spectrometry identifies numerous ribosomal proteins that selectively bind to oTau. These ribosomal function appear to function in quality control of ribosome biogenesis and quality control of RNA translation.

Conclusion

oTau induces major changes in ribosomal function that alter quality control mechanisms related to ribosomal biogenesis and RNA translation.
Presentation 3: Translational dysregulation promotes pathogenic events in tauopathies
Authors: Koren Shon , Meier Shelby E , Abisambra Jose F.
Published: December 2020

Background

A major challenge in the field of tau‐associated neurodegeneration is the identification of the pathogenic mechanisms leading to disease. Tau is best known for associating and stabilizing microtubules; however, emerging results identifying alternate tau functions opens a new opportunity to understand the molecular basis of disease. Given the association of tau with ribosomes and RNA, and the enhancement of this interaction in Alzheimer’s disease, we hypothesized that the aberrant tau‐ribosome interaction impairs (increases and decreases) transcripts that are necessary for cellular homeostasis. For nearly thirty years, the consequences of tau‐ribosome complexes were unknown until now.

Methods

We used in vitro models such as GFP‐based cell‐free translation assays and surface sensing of translation (SUnSET) assays in immortalized and primary neuronal cultures. Moreover, we pioneered in vivo SUnSET in the brains of tau transgenic mice, and coupled these techniques with proteomics. We validated our results using human brain samples from AD and non‐demented controls. Finally, we performed ribosomal profiling assays using in vitro models of tauopathy.

Results

We demonstrate that pathological tau species associate robustly with ribosomes profoundly shifting the translatome. Surprisingly, a significant number of proteins whose translation was impaired corresponded to ribosomal proteins. We also identified that the ribosomal protein S6, which regulates translation of the machinery necessary for translation (ribosomal proteins as well as elongation and initiation factors), was significantly reduced in vitro, in vivo, and in human brains. Finally, we also found major shifts in the integrity of AD brain polysomes as a consequence of tau aggregation.

Conclusion

Pathological tau species negatively regulate ribosomal specificity thereby shifting the translatome.
A phase 1B open‐labelled study of sodium selenate as a disease modifying treatment for possible behavioural variant fronto‐temporal dementia
Authors: Vivash Lucy E. , Malpas Charles B. , Velakoulis Dennis , O’Brien Terence
Published: December 2020

Background

There are currently no approved disease‐modifying treatments of behavioural variant frontotemporal dementia (bvFTD), with the only treatments available providing symptomatic relief to secondary behavioural symptoms. Approximately 45% of bvFTD cases are tauopathies, with the main pathological hallmark and proposed pathogenic mechanism being the accumulation and aggregation of hyperphosphorylated tau. For this reason, hyperphosphorylated tau represents a promising target for a disease modifying treatment in this population. Sodium selenate stimulates the PP2A enzyme, which directly dephosphorylates hyperphosphorylated tau. This study investigated the use of sodium selenate as a disease‐modifying treatment for patients with bvFTD.

Method

Fifteen patients with possible bvFTD were treated with sodium selenate (15mg tds) for twelve months. Participants underwent a battery of cognitive and behavioural tests, MRI, lumbar puncture and safety assessments at screening, baseline, and at regular intervals following the commencement of treatment. Adverse events were monitored via diary cards between clinic visits.

Result

Fourteen patients are either on treatment or have completed the study. Interim safety analysis (9 completed patients, 5 on treatment) has shown that sodium selenate is safe and well tolerated, with no study withdrawals. Commonly reported adverse events are nail changes (n=5), fatigue (n=4) and nausea (n=4). No treatment related serious adverse events have occurred. An interim mixed‐effects analysis on all available neurocognitive data showed no statistically significant change in NUCOG total score (b=‐0.02, 95% CI = ‐0.18, 0.14]) or Carer Burden Scale (CBS) score (b =0.04, 95% CI = ‐0.05, 0.13]), CVLT total learning score (M diff = 5.80, 95% CI = ‐6.97, 18.57]), or NIH composite score (M diff = 4.72, 95%CI = ‐11.50, 14.70]). Percentage change in whole‐brain volume from baseline to 12 months ranged from ‐0.68% to ‐6.26% (n=5 <‐2%, n=2 ‐5‐6%).

Conclusion

The interim results have shown that sodium selenate is safe and well tolerated in patients with bvFTD. Early indications show sodium selenate may be effective in reducing atrophy and halting cognitive decline in a subset of bvFTD patients. A larger phase 2 placebo controlled study is necessary to evaluate whether sodium selenate is efficacious as a disease modifying treatment of bvFTD.
Metabolic syndrome is associated with plasma β‐amyloid levels in ApoE ε4 non‐carriers
Authors: Dang Liangjun , Gao Ling , Shang Suhang , Chen Chen , Wei Shan , Wang Jin , Huo Kang , Wang Jingyi , Qu Qiumin
Published: December 2020

Background

The relationship between metabolic syndrome (MetS) and Alzheimer’s disease (AD) is not fully understood. As Amyloid‐β (Aβ) deposition in the brain is a main pathophysiology of AD and plasma Aβ is closely related to Aβ deposition in the brain, in present study, we investigated the relationship between plasma Aβ and MetS in community population.

Method

This was a population‐based cross‐sectional study. A total of 1275 participants from a village in the suburbs of Xi’an, China were enrolled from October 2014 to March 2015. Fasting venous blood was taken in the morning and plasma Aβ levels were measured by ELISA. The ApoE genotype was detected using polymerase chain reaction and Sanger sequencing. Metabolic syndrome was diagnosed according to ATP‐III riteria, and MetS severity z scores (MetS‐Z) were calculated from waist circumference, triglycerides, HDL cholesterol, systolic blood pressure, and fasting glucose. Relationships between plasma Aβ and MetS were determined using multiple linear regressions.

Result

In the total population and the ApoE ε4 non‐carriers, MetS was associated with higher plasma Aβ40 level (51.704±8.594 pg/ml vs. 53.536±8.063pg/ml, p=0.002;51.693±8.626 pg/ml vs. 53.593±7.990 pg/ml, p=0.003) and lower Aβ42/ Aβ40 ratio(0.814±0.189 vs 0.784±0.170, p=0.018;0.813±0.189 vs. 0.778±0.172, p=0.011). In the multivariable regression analysis, plasma Aβ40 was associated with MetS in the total population and ApoE ε4 non‐carriers (β=1.711, p=0.008; β=1.661, p=0.019) and Aβ42/ Aβ40 ratio (β=‐0.031, p=0.030; β=‐0.035, p=0.024). Furthermore, plasma Aβ40 correlated positively with MetS‐Z in the total population (r=0.073, p=0.009) and the ApoE ε4 non‐carriers (r=0.074, p=0.015), while Aβ42/Aβ40 ratio was negatively related with MetS (r=‐0.064, p=0.038) in ApoE ε4 non‐carriers, but not in ApoE ε4 carriers. There was no significant correlation between MetS and plasma Aβ42.

Conclusion

Metabolic syndrome was associated with higher plasma Aβ40 level and lower Aβ42/ Aβ40 ratio in ApoE ε4 non‐carriers, but not in ApoE ε4 carriers. This indicated that the relationships between MetS and plasma Aβ may be confounded by ApoE ε4 status.
fNIRS assessment during cognitive tasks in elderly patients with depressive symptoms
Authors: Kang Min Ju , Yang Youngsoon
Published: December 2020

Background

The aim of this study was to analyze and compare the level of activation in the frontal cortex using functional near‐infrared spectroscopy (fNIRS) according to the presence of depressive symptoms, which was assessed by the Geriatric Depression Scale (GDS) in elderly participants.

Method

We investigated 204 community‐based normal participants without psychiatric disorder or dementia between the ages of 60‐80 years. GDS and fNIRS were used to assess the presence of depression in all patients, along with cognitive tasks including the digit span, Verbal Fluency Task (VFT), and Stroop test to investigate hemodynamic response in the frontal cortex.

Result

During the Stroop test, significantly reduced hemodynamics was observed in the depressive‐symptom group. Mean accΔHbO2 of all channel averages was 0.14μM in the control group and ‐0.75μM in the depressive‐symptom group (p=0.03), right hemisphere average was 0.13μM and ‐0.96μM, respectively (p=0.02), and left hemisphere average was 0.14μM and ‐0.54μM, respectively (p=0.12). There was no significant difference in hemodynamic response (mean accΔHbO2) between the two groups during the digit span backwards and VFT.

Conclusion

The hemodynamic response during fNIRS was significantly different between control and depressive‐symptom groups. Among the three tasks, the Stroop test results indicated reduced hemodynamics in the frontal cortex of the depressive‐symptom group.
Influence of sleep quality, risk of obstructive sleep apnea and sleep deprivation on cortical oxygenation in elderly individuals
Authors: Bae Heewon , Kang Min Ju , Yang Youngsoon
Published: December 2020

Background

Poor sleep quality, obstructive sleep apnea (OSA) and sleep deprivation are risk factors for cardiovascular diseases and cognitive impairment. Cerebral blood flow and its regulation are affected by pathological condition commonly observed in the elder population, such as dementia, history of stroke, diabetes mellitus and hypertension. The aim of this study was to investigate the influence of sleep quality, OSA risk and total sleep time (TST) of prior night in level of activation of the frontal cortex using functional near‐infrared spectroscopy

Method

We investigated 204 participants without cognitive impairment between the ages of 60 and 85 years. All patients functional near‐infrared spectroscopy (fNIRS) along with cognitive tasks, including digit span, semantic verbal fluency task, stroop test, to investigate hemodynamic response in the fontal cortex of patients with depression compared to a healthy elderly group. The Pittsburgh Sleep Quality Index (PSQI) for sleep quality, STOP‐BANG questionnaire for risk of OSA, and TST of prior night which reported by participants was assessed.

Result

In poor sleep quality group (PSQI<5), reduced hemodynamics during the Stroop task compared to control group in all channel average (Mean accΔHbO2 of 0.11μM in poor sleep quality group versus ‐0.12 μM in control, p<0.05) and right channel average (Mean accΔHbO2 of 0.01μM and ‐0.03 μM, p<0.05). In sleep deprived group (TST<5), reduced hemodynamics during the verbal fluency test was observed in right channel average (Mean accΔHbO2 of 0.024 in sleep deprived group versus 0.01 μM in control, p<0.05). There was no significant difference between high risk of OSA group (STOP‐BANG>5) and control group in all cognitive tasks.

Conclusion

Poor sleep quality and sleep deprivation (<5 hours) may be an important factor that influences cortical oxygenation in the elderly population.
Potentially inappropriate medication use in people with dementia in China and its associated factors
Authors: Nguyen Tuan Anh , Du Duc , Dang Thu Ha , Wang Haipeng , Qiang Sun , Roughead Elizabeth E
Published: December 2020

Background

Medicine use in people with dementia is challenging. This study was conducted to examine the use of potentially inappropriate medicines that may affect cognition (PIMcog) or reduce the effectiveness of cholinesterase inhibitors (CEIs) in people with dementia.

Method

A cross‐sectional study of people with dementia admitted to hospitals in Shandong, China between 31st Dec 2014 and 31st Dec 2016 was conducted. Patients’ medical records were reviewed and their medicine use assessed. Polypharmacy was defined as use of five or more medicines in the same hospital episode. Concomitant use of CEIs with anticholinergic medicines was assessed using a list of medicines with clinically relevant anticholinergic property based on a consensus combination of different anticholinergic scales. Use of PIMcog was assessed against a list of PIMcog developed based on relevant Beers 2012 and STOPP 2014 criteria. Variables associated with having a PIMcog were assessed using a multiple logistic regression.

Result

Of the 453 participants with a mean age of 75.9 years, 98.7% used polypharmacy, 56.1% used a PIMcog, 30.7% used CEIs concomitantly with anticholinergics, and 32.2% used antipsychotics. PIMcog use was associated with higher number of comorbidities (adjusted OR 1.14; 95% CI: 1.04 ‐ 1.33), higher number of other medicines prescribed rather than PIMcog (adjusted OR 1.07; 95% CI: 1.01 ‐ 1.13) and types of prescribers.

Conclusion

Use of polypharmacy and medicines that can further impair cognition or reduce the effectiveness of CEIs in people with dementia was prevalent. Efforts to improve quality use of medicines for this population are warranted.