bluuebunny/crossref_metadata_2025 huggingface dataset:
Tunable Carbon–CsPbI3 Quantum Dots for White LEDs
Authors: Rad Rafat Rafiei , Gualdrón‐Reyes Andrés. F. , Masi Sofia , Ganji Bahram Azizollah , Taghavinia Nima , Gené‐Marimon Santi , Palomares Emilio , Mora‐Seró Iván
Published: December 2020

In this work, a simple method to prepare white light emissive diodes based on quantum dot (QD) colloidal solutions using mixed carbon QDs (CQDs) and CsPbI3 perovskite (PQDs) is reported. The right combination generates emission across the entire visible spectrum upon ultraviolet excitation. The white light emission of the final films provides high and stable color rendering index of 92%, tuning the chromaticity coordinates of the emission through the applied voltage. By varying the CsPbI3 QD concentration, a mixture is obtained that emits the “warm”, “neutral”, and “cold” white light sought for many indoor lighting applications, or to approximate the visible region of the solar spectrum, respectively. Remarkably, the material syntheses are low cost and truly scalable. In addition, colloidal mixtures of CQDs and CsPbI3 PQDs show a facile deposition for light‐emitting diode (LED) application, showing white electroluminescence, indicating that both kinds of QDs are stable during LED operation. Last but not least, the photoluminescence quantum yield of the colloidal mixtures is higher (up to 75%) than single white emitters, showing itself as a promising system for white emission with tunable properties.
Recent Advances in Luminescent Zero‐Dimensional Organic Metal Halide Hybrids
Authors: Zhou Chenkun , Xu Liang‐Jin , Lee Sujin , Lin Haoran , Ma Biwu
Published: December 2020

Organic metal halide hybrids (OMHHs) have attracted great research attention owing to their exceptional structure and property tunability. Using appropriate organic and inorganic metal halide components, OMHHs with controlled dimensionalities at the molecular level, from 3D to 2D, 1D, and 0D structures, can be obtained. In 0D OMHHs, anionic metal halide polyhedrons are surrounded and completely isolated by organic cations to form single crystalline “host–guest” structures. These ionically bonded organic–inorganic hybrid systems often exhibit the intrinsic properties of individual metal halide species, for instance, highly efficient Stokes‐shifted broadband emissions. In this progress report, the recent advances in the development and study of luminescent 0D OMHHs are discussed: from synthetic structural control to fundamental understanding of the structure–property relationship and device integration.
Non‐Empirical Law for Nanoscale Atom‐by‐Atom Wear
Authors: Wang Yang , Xu Jingxiang , Ootani Yusuke , Ozawa Nobuki , Adachi Koshi , Kubo Momoji
Published: December 2020

Wear of contact materials results in energy loss and device failure. Conventionally, wear is described by empirical laws such as the Archard's law; however, the fundamental physical and chemical origins of the empirical law have long been elusive, and moreover empirical wear laws do not always hold for nanoscale contact, collaboratively hindering the development of high‐durable tribosystems. Here, a non‐empirical and robustly applicable wear law for nanoscale contact situations is proposed. The proposed wear law successfully unveils why the nanoscale wear behaviors do not obey the description by Archard's law in all cases although still obey it in certain experiments. The robustness and applicability of the proposed wear law is validated by atomistic simulations. This work affords a way to calculate wear at nanoscale contact robustly and theoretically, and will contribute to developing design principles for wear reduction.
Novel natural plant protein and mimetic peptides rescues aberrant brain‐energy metabolism and Alzheimer’s disease pathology
Authors: Kim Myeong Ok
Published: December 2020

Background

Extensive evidence has indicated that a high rate of cholesterol biogenesis and abnormal neuronal energy metabolism play key roles in Alzheimer’s disease (AD) pathogenesis. Here, for the first time, we used protein and peptide, a plant protein homolog of mammalian adiponectin, to determine its therapeutic efficacy in different AD models.

Method

Mice were grouped before treatment as follows: WT and Transgenic mice (APP/PS1 and Adipo‐/‐ mice) were administered via intraperitoneal injection with 3 types of solution (saline, osmotin and osmotin mimetic peptide). Mice were decapitated at the age of 5, 9, 12 or 16 months. Protein samples were analyzed by immunobloting as well as immunofluorescence. Brain sections were analyzed by immune histochemistry. LTP was measured by mEPSC.

Result

Osmotin, natural plant protein, and its mimetic peptide treatment modulated adiponectin receptor 1 (AdipoR1), significantly induced AMPK/SIRT1 activation, and reduced SREBP2 expression in both in vivo and in vitro AD and Adiponectin deficient mice. Osmotin acts Via AdipoR1/AMPK/SIRT1/SREBP2 and TNFR1 signaling pathway, Osmotin and its mimetic peptide significantly diminished amyloidogenic Aβ production, abundance and aggregation, accompanied by improved pre‐ and post‐synaptic dysfunction, cognitive impairment, memory deficits. Most importantly, it reversed the suppression of long‐term potentiation (LTP) in AD mice. Interestingly, AdipoR1, AMPK, and SIRT1 silencing not only abolished Osmotin capability but also further enhanced AD pathology by increasing SREBP2, APP, and β‐secretase (BACE1) expression and the levels of toxic Aβ production. Likewise, mimetic peptide mechanistically instigates AdipoR1/AMPK signaling and consequently suppressed the hyperactivated TNF‐α/TNFR1 signaling in both in vivo and in vitro models of AD.

Conclusion

Osmotin and its mimetic peptide mitigate aberrant brain‐energy metabolism and AD pathology in in vivo and in vitro AD models via regulating AdipoR1/AMPK/SIRT1/SREBP2/TNFR1 signaling pathway. These results suggest that Osmotin and peptide‐based mimetics can be a potential candidate for AD treatment.
Depression and anxiety are associated with decline in executive function over two years in adults 50 and over
Authors: Getaneh Mekdes Mulusew , Ballard Clive , Brooker Helen
Published: December 2020

Background

Depression and anxiety are known to be associated with a range of physical and mental health issues, including disruptions to cognitive function. This is a particularly pertinent issue in older adults where factors which increase the risk of cognitive impairment may increase the rate of cognitive decline. However, anxiety as a potential accelerator of cognitive decline has never been investigated. The Platform for Research Online to investigate Genetics and Cognition in Ageing (PROTECT) is a study being conducted in adults aged 50 and older, to identify factors which can influence cognitive aging. This particular study was done to establish the relationship between depression and anxiety and core aspects of cognitive function. We hypothesized to see an association between both depression and anxiety with accelerated cognitive decline.

Method

The volunteers were invited at study entry to perform online cognitive tests from the CogTrackTM System and the PROTECT cognitive test system. The 6 tasks from the two test systems assessed attention, information processing, reasoning, working and episodic memory over two year follow up period. The PHQ‐9 depression severity groupings analyzed were: greater than 10 was taken to indicate clinically significant depression and GAD 7 scoring of greater than 10 was taken to indicate clinically significant anxiety. We used General Linear Model (Repeated Measures) to evaluate any differences in cognitive decline between people with or without depression and anxiety respectively. For statistical analysis, Wilk’s Lambda MANOVA was used. Covariates were Age, gender, and education level.

Result

This study has identified highly significant and clinically relevant association between both depression and anxiety and decline in grammatical reasoning.

Conclusion

The result is a key finding in that executive function is what relates mostly with daily activities and that provides key insights in the types of intervention we need to maintain cognitive function in people with mood disorders. An important limitation, which will be examined as part of the final analysis, is the impact of anti‐depressants on cognitive outcome since some anti‐depressants accelerate decline in some patients, or if the mood disorder is being treated, the therapy might help slow down the cognitive decline as well.
Usage and adherence of antidementia drugs in a memory clinic cohort in Chongqing, Southwest China
Authors: Yu Xingyan , Yu Weihua , Yang Wenkai , Lü Yang
Published: December 2020

Background

To investigate the use and adherence of anti‐dementia drugs in elderly patients with dementia from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University.

Method

Patients were recruited from the Memory Clinic of The First Affiliated Hospital of Chongqing Medical University between December 2010 and December 2018. The medical chart was reviewed, including diagnosis, dosage of antidementia medicine, neuropsychological testing scores, and the further questionnaires were conducted via face‐to‐face or telephone, included duration of treatment, types of anti‐dementia drugs, and reasons for treatment discontinuation.

Result

The data from 422 patients were analyzed retrospectively for this study. 315 were diagnosed with AD, 67 with MCI, and 40 with other types of dementia. From the 422 patients, 26.8% were treated with original donepezil, 11.6% with generic donepezil, 24.6% with memantine, 13.3% with huperzine A, and 23.7% with a combination of drugs. However, 73% of patients discontinued treatment within one year of initiation. Patients with less than nine years of education were more likely to discontinue treatment than patients with more than nine years of education. Patients with elevated PSMS scores had a high risk of discontinuation. Patients had a higher risk of discontinuation when they had received treatment for less than 36 months.

Conclusion

Overall treatment compliance is relatively poor in memory clinic in Chongqing. Our study demonstrates that high education, combined medication may lead to better treatment adherence in dementia care. However, poorer PSMS is a significant risk factor for treatment discontinuation.
ENGLOBA Project — memory clinics in Spain: Patient care for those with mild cognitive impairment (MCI)
Authors: Palomo María Sagrario Manzano ,   ENGLOBA Group
Published: December 2020

Background

ENGLOBA Project is focus on knowing the reality about MCI care in Spain and building the bases to improve it, regarding expert opinions.

Method

The MC were randomized from all over the country.

The questionnaire included descriptive answers in order to obtain more information.

Part I: about the professional and the Memory Clinic (MC) where performs its activity.

Part II: about circuit of MCI care, diagnosis and treatment.

Result

20 neurologist of 19 hospitals in Spain were included, with 2‐25 years of experience in dementia field. The majority of MC involved aren´t accredited by a governmental agency. In the research unit, 70% make clinical research, 30% biomarkers and 10% clinical trials. 95% of them work in a multidisciplinary team and have the possibility to attend conferences or make publications(79%). Neuropsychologists work full time only in 37% of cases. They don´t have basic researchers(79%) or specialized nurses(100%). 74% of neurologists haven´t the possibility of a Day Hospital to implement treatments. The etiology of MCI is neurodegenerative in 60% of cases. 76 % diagnosis MCI due to Alzheimer´s Disease(AD). The delay from General Practitioner to MC is 2,5 months, but, in 78% of cases, thy have the possibility to contact with them via e‐mail or phone. Neurologists have almost 40 minutes to explore patients in the first visit. In 63% of cases they have joint interview (patient and caregiver). 63% implement biomarkers: 32% CSF, 16% FDG‐PET scans,11% amyloid PET scans. In 78% of cases the diagnosis is confessed to patients, 100% to families and in 95% they used “Cognitive Impairment (CI)” to reveal it. 21% of patients were indifferent, but 8% of relatives showed a severe emotional impact after the diagnosis.Treatment: 94% treat vascular MCI(57% citicoline;22% galantamine, EGB 761 14%). 76% use nutraceuticals to treat MCI. 76% use colinesterase inhibitors to treat MCI due to AD.

Conclusion

The neurologist who treat cognitive impairment work usually in a multidisciplinary team (95%). The majority of the MC reveals the diagnosis to the family as ”Cognitive Impairment”. They usually use biomarkers in clinical practice. CSF is the more frequent. They treat MCI in many different ways, according to the etiology.
Transcranial detection of amyloid‐beta at single plaque resolution in vivo with large‐field multifocal illumination fluorescence microscopy
Authors: Ni Ruiqing , Chen Zhenyue , Shi Gloria , Villois Alessia , Zhou Quanyu , Arosio Paolo , Nitsch Roger M. , Nilsson K. Peter R. , Klohs Jan , Razansky Daniel
Published: December 2020

Background

The abnormal deposition of beta‐amyloid proteins in the brain is one of the major histopathological hallmarks of Alzheimer’s disease. Currently available intravital microscopy techniques for high‐resolution plaque visualization commonly involve highly invasive procedures and are limited to small field‐of‐views within the rodent brain.

Method

We devised a large‐field multi‐focal illumination (LMI) fluorescence microscopy method that provides a 20 × 20 mm field‐of‐view and an axial resolution of ∼15 mm. In vivo and ex vivo transcranial LMI fluorescence microscopy and wide‐field fluorescence microscopy for amyloid deposits were performed in APP/PS1 and arcAb mouse models of Alzheimer’s disease amyloidosis using luminescent conjugated oligothiophene probe HS‐169. Immunohistochemical staining with HS‐169, anti‐Ab antibody 6E10, and conformation antibodies OC (fibrillar) of brain tissue sections

Result

LMI fluorescence microscopy detected amyloid‐beta deposits at a single plaque level in APP/PS1 and arcAb mice with high sensitivity and specificity. The contrast‐to‐noise ratio was approximately 24 times higher in LMI fluorescence microscopy of amyloid deposits compared to wide‐field fluorescence microscopy. Immunohistochemical staining showed HS‐169 co‐localized with 6E10 and OC stained compact parenchymal and vessel‐associated amyloid deposits.

Conclusion

The novel LMI in vivo amyloid imaging platform offers new prospects for studies into Alzheimer’s disease mechanisms in animal models as well as longitudinal monitoring of therapeutic responses at a single plaque level.
Companion robot for elderly residents with dementia: A cognitive behavioral analysis for neuropsychiatric symptoms
Authors: Tsoi Kelvin KF , Chan Tak Kit , Cheung Ruby SM , Wong Yuk Sheung , WAI Man Yi , Chan Lai Kok , Tan Kelvin , Lou Vivian
Published: December 2020

Background

Elderly with cognitive impairment may be benefit from interacting with companion toys. This study aims to investigate the daily living behavior of cognitive impaired elders interact with a five‐year‐old childlike companion robot under supervision of Occupational Therapist by a motion sensor installed. The active users of the robot were further evaluated for emotional and behavioral symptoms.

Method

Subjects with cognitive impairment were recruited from elderly residential care homes in Hong Kong. Each participant was assigned with the robot for eight weeks. The motion sensor captured the time and duration of interaction between the robot and the participants. The activity time was set between 7:00 am and 9:00 pm of each day. Participants were classified into active and non‐active users according to the days of interacting the robots. The time length of interacting was summarized by hours. Participants were also interviewed with questionnaires of Activity of Daily Living (ADL) Scale, Neuropsychiatric Inventory (NPI), and Geriatric Depressive Scale (GDS) before and after using robots.

Result

Forty‐eight participants with cognitive impairment were recruited from seven residential care homes, but finally only twenty‐eight participants were completed the data collection. Majority of the participants were female (82%) and aged over 80 years old(86%). There are active (57%) and non‐active (43%) groups were defined. Eleven (39%) were the long‐term active users whose had interaction until the end of the study. The interaction peak hours were at around 11:00 am and the period from 3:00 to 4:00pm. The findings showed that there is significant improvement on neuropsychiatric symptoms. (Mean change (SD) of NPI‐Behaviour and NPI‐Distress = ‐2.39 (3.56), p<0.01 and ‐2.50 (5.00), p=0.013), no significant improvement on daily living activities or depressive symptom.

Conclusion

The findings of this study confirmed that elderly residents with cognitive impairment can obtain benefits from the use of companion robots and relived from neuropsychiatric symptoms. However, almost half of the participants were inactive users which limited our analysis. Further study with a larger number of participant and more sophisticated research design is recommended.
Alteration of inflammatory factors between chronic stroke and post‐stroke dementia: A cross‐sectional study
Authors: Liu Yu‐Li , Chen Yi‐Chun , Chou Wen‐Hai , Tsou Hsiao‐Hui , Liu Tung‐Hsia , Kuo Hsiang‐Wei , Fang Chiu‐Ping , Liu Chia‐Chen
Published: December 2020

Background

Inflammation may play a role in the pathological processes of stroke and post‐stroke dementia. However, there has not been compared and discussed upon the alterations among the plasma inflammatory factors from stroke to post‐stroke dementia.

Method

In this study, an age‐ and gender‐matched normal controls and ischemic stroke patients with (PSD) or without (PSNoD) dementia had been recruited. The ischemic stroke patients had further examined the 30‐day Modified Rankin scale (MRS), stroke infarction subtypes, anti‐cholinergic treatment status and Clinical Dementia Rating (CDR). Levels of plasma inflammatory factors epidermal growth factor (EGF), growth‐regulated oncogene (GRO), soluble CD40 ligand (sCD40L), Interleukin 7 (IL‐7) and Interleukin 4 (IL‐4) were measured by Milliplex map human cytokine/chemokine magnetic bead panel assay. The butylcholinesterase (BChE) activity and plasma D‐amino acid oxidase (DAO) were also included in these analyses due to our previous published report [1, 2].

Result

The ischemic stroke patients showed significantly higher percentage of hypertension (HTN), Diabetes mellitus (DM) and self‐report smoking than normal controls (p<0.01). Normal controls had significant higher plasma EGF, GRO, sCD40L, IL‐7, but lower plasma DAO levels than the ischemic stroke patients (p<0.003). In comparisons between the PSD and PSNoD patients, the PSD showed significantly higher 30‐day MRS, CDR, percentage of anti‐cholinergic treatment than the PSNoD (p<0.014) after adjust with age. The plasma BChE activity showed lower levels in PSD than PSNoD (p=0.0002) after adjust with age.

Conclusion

The inflammatory factors of EGF, GRO, sCD40L, IL‐7 and plasma DAO levels were mainly associated with ischemic stroke. The BChE activity may be a better indicator for the post‐stroke dementia. References: (1) Chen, Y.‐C., et al., Serum level and activity of butylcholinesterase: A biomarker for post‐stroke dementia. Journal of clinical medicine, 2019. 8(11): p. 1778. (2) Chen, Y.‐C., et al., A Post‐hoc Study of D‐amino Acid Oxidase in Blood as an Indicator of Post‐stroke Dementia. Frontiers in neurology, 2019. 10: p. 402.
Path integration changes as a cognitive biomarker for vascular cognitive impairment? A pilot study
Authors: Lowry Ellen , Puthusseryppady Vaisakh , Coughlan Gillian , Jeffs Stephen , Hornberger Michael
Published: December 2020

Background

Path integration spatial navigation processes are emerging as promising cognitive biomarkers for prodromal and clinical Alzheimer’s disease (AD). However, such path integration changes have been little explored in Vascular Cognitive Impairment (VCI),despite neurovascular change being a major contributing factor to dementia and potentially AD. In particular, the sensitivity and specificity of path integration impairments in VCI compared to AD is unclear. In the current pilot study, we explore path integration performance in AD and VCI patient groups and hypothesise that i) medial parietal mediated egocentric processes will be more affected in VCI and ii) medial temporal mediated allocentric processes will be more affected in AD.

Method

The cross‐sectional study included early stage VCI patients (n=9), AD patients (n=10) and healthy age‐matched controls (n=20). All participants underwent extensive neuropsychological testing, as well as spatial navigation testing. The spatial navigation tests included the virtual reality ‘Supermarket’ task assessing egocentric (body‐based) and allocentric (map‐based) navigation as well as the ‘Clock Orientation’ test assessing egocentric and path integration processes.

Result

Findings showed that egocentric path integration processes are only impaired in VCI, potentially distinguishing it from AD. Whereas, allocentric path integration was similarly impaired for VCI and AD. Egocentric scores of Supermarket and Clock Orientation predictors explained 77% (Nagelkerke R
2
) of variance in VCI and AD patients and correctly classified 84% of patients (7 out of 9 VCI; 9 out of 10 AD) into their respective cohorts. ROC curves were computed and similarly, Area Under the Curve (AUC) values indicated that egocentric orientation in the Supermarket (AUC = .8, SE = .12; 95% CI [.56, 1]) and Clock test (AUC= .91, SE = .06, 95% CI [.8, 1]) had strong diagnostic accuracy in distinguishing VCI from AD patients.

Conclusion

These preliminary findings suggest egocentric path integration deficits emerge as more specific to VCI, potentially allowing for more specific diagnostic and treatment outcome measures for vascular impairment in dementia. By contrast, there was limited specificity of allocentric path integration deficits between VCI and AD.
AlzPED: Improving the predictive power and translational validity of preclinical testing of candidate therapeutics in Alzheimer’s disease animal models
Authors: Chakroborty Shreaya , Sharma Ali , Mancevska Katerina , Martin Zane , Yuan Jean , Sheffield Cindy , Petanceska Suzana S. , Refolo Larry
Published: December 2020

Background

AlzPED is a publicly available database created by the National Institute on Aging to address key factors contributing to poor translation of preclinical efficacy from animal models to the clinic in Alzheimer’s disease (AD) therapy development. Specifically, AlzPED is missioned to identify critical experimental design elements and methodology missing from studies that make them susceptible to misinterpretation and reduce their reproducibility and translational value, as well as serve as a platform for reporting unpublished negative findings. AlzPED provides funding agencies with a tool for enforcement of the requirements for transparent reporting and rigorous study design. Through these capabilities, AlzPED is intended to guide the development and implementation of strategies and recommendations for standardized best practices for the rigorous preclinical testing of AD candidate therapeutics and mitigate the publication bias that favors the reporting of positive findings.

Method

Using key word‐driven literature searches published studies are acquired and curated by two experts for data on authors, funding source, AD animal models, therapeutic targets and therapeutic agents, study design, and outcome measures, prior to publication in the database. Rigor in study design is evaluated with an experimental design scorecard that summarizes the elements of experimental design reported in each study in the database.

Result

AlzPED currently houses curated summaries from 917 published studies. Summaries are searchable by author, funding source, animal model, therapeutic target and therapeutic agent. At present, the database contains data on 185 animal models, 175 therapeutic targets, 804 therapeutic agents and, more than 1500 AD‐related outcome measures. Evaluation of experimental design scorecards from each study demonstrates significant under‐reporting of critical elements of methodology even in high impact factor journals and highly cited published preclinical research.

Conclusion

Analysis of curated studies demonstrates serious deficiencies in reporting critical elements of methodology such as power/sample size calculation, blinding for treatment/outcomes, randomization, balancing for sex, animal genetic background and others, irrespective of journal impact factor and number of citations. These deficiencies diminish the scientific rigor, reproducibility and translational value of the preclinical studies. Thus, it is evident that a standardized set of best practices is required for successful translation of therapeutic efficacy in AD research.
Development of international practice recommendations for the recognition and management of hearing, vision and cognitive impairment
Authors: Littlejohn Jenna Louise , Leroi Iracema ,   The International Hearing, Vision and Dementia Practice Recommendations’ Task Force
Published: December 2020

Background

Unrecognised hearing and vision impairment complicates the assessment and management of people living with dementia (PwD). Hearing and vision impairment may be more likely to go unrecognised among PwD, because PwD may be less likely to recognise and report difficulties. Communication difficulties and behaviours that challenge in PwD may be wrongly attributed to cognitive impairment by carers and clinicians, when actually they are the consequence of remediable sensory loss. Despite these issues, practice recommendations for recognition and management of hearing, vision and cognitive impairment are non‐existent. The aim was to develop internationally relevant, multi‐disciplinary practice recommendations for professionals involved in the diagnosis, care and management of older people with concurrent cognitive, hearing and/or vision impairment.

Method

The International Hearing, Vision and Dementia Practice Recommendations’ Task Force consisted of 16 interdisciplinary professionals from Europe, Australia, Canada and the USA. We adapted core elements of the Who Handbook for Guideline Development as it allows for flexibility to develop evidence‐based practice recommendations considering benefits and limitations of the existing evidence while emphasising the need for individualised professional judgement. Three phases were involved in the development of the guidance, (1) collating existing evidence; (2) filling the gaps in evidence; (3) refining the final list of recommendations. Phases 1 to 3 encompassed various methodologies including a review of existing guidelines within the three clinical domains, systematic reviews, qualitative studies, expert reference groups, clinical professional consortium, and consensus meetings. Recommendations were developed with the input of clinical and lay stakeholders.

Result

A consensus was reached on 16 recommendations, classified into six domains regarding Awareness and Knowledge, Recognition and Detection, Evaluation, Management, Support and Policy.

Conclusion

This is the first set of international, interdisciplinary practice recommendations regarding care of concurrent cognitive, hearing and/or vision impairment in older people. These recommendations may help guide development of services and policy to improve the lives of older people with dual or triple impairments.
Single‐nuclei chromatin accessibility and transcriptomics unravels altered human oligodendrocyte heterogeneity in Alzheimer’s disease
Authors: Morabito Samuel , Miyoshi Emily , Michael Neethu , Shahin Saba , Swarup Vivek
Published: December 2020

Background

Alzheimer’s disease (AD) is a devastating neurodegenerative disease, characterized by changes in cell‐type proportions and marked alterations of the epigenome and transcriptome. Recent “bulk” tissue RNA‐seq on thousands of postmortem AD brain samples by AMP‐AD consortia has shed light on new AD biology. Unfortunately, cell‐type specific disease biology is completely missed or averaged out using conventional “bulk” tissue RNA‐seq approaches. Single‐cell transcriptomics using single‐nuclei RNA‐seq (snRNA‐seq) and epigenomics (single‐nuclei ATAC‐seq) promises to capture cell‐type heterogeneity and unravel relevant biology related to cell‐to‐cell variability. Such single‐cell approaches have been recently used in psychiatric diseases through PsychENCODE consortia and integrated with bulk tissue RNA‐seq to understand cellular heterogeneity in these diseases. Our work is the first to define single‐nuclear clusters based on open‐chromatin (snATAC‐seq) and gene‐expression (snRNA‐seq) that are dysregulated during the progression of the disease.

Method

Using snATAC‐seq, we have profiled more than 150,000 single‐nuclei open chromatin profiles from normal human (n = 10) and late‐stage AD frontal cortex (n = 11) samples. We have also used same samples to further profile gene‐expression changes at single‐cell resolution using snRNA‐seq from more than 70,000 nuclei. In addition, we have performed bulk‐tissue RNA‐seq from control and AD frontal cortex (n = 50/group) samples and developed gene co‐expression methods to integrate bulk‐tissue and snRNA‐seq to unravel cell‐type specific co‐expression changes altered in AD.

Result

Our analysis has identified distinct cell‐clusters based on both open‐chromatin (snATAC‐seq) and transcriptomics (snRNA‐seq) which are altered in late‐stage AD. We have identified several oligodendrocyte cell‐clusters which are increased only during disease progression. Pseudo‐time analysis of data indicates that AD‐specific oligodendrocyte clusters have a distinct developmental trajectory that define the terminal fate of these clusters. In addition, co‐expression analysis with bulk‐tissue RNA‐seq and snRNA‐seq data has identified functional modules (groups of genes) that are dysregulated in these AD‐specific oligodendrocyte clusters. These data highlight the potential role of myelination deficits that occur during the progression of disease.

Conclusion

Our tour‐de‐force work has identified distinct oligodendrocyte cell‐clusters that are altered in late‐stage AD. We have also identified core regulatory networks in these oligodendroglia cells that promises to provide novel therapeutic targets for AD.
Clinical correlation of cerebrospinal fluid total tau levels and depression as measured by PHQ9 total in a memory clinic
Authors: Pillai Malavika , Nair Anil
Published: December 2020

Background

Tau protein levels in cerebrospinal fluid is indicative of Alzheimer's dementia. We correlated PHQ‐9 screen severity of depression to CSF tau levels in a memory clinic sample.

Method

We analyzed data from patients attending a memory clinic in the south shore of Boston from 2010 to 2019 who had a lumbar puncture to obtain CSF tau levels. We correlated depression screening data from PHQ9 scores. Univariate analyses used Spearman correlation. A multivariate regression model was created including covariates of age, sex, and race.

Results

Depression as measured by PHQ9 total was not correlated to total tau levels in CSF.

Conclusion

In a memory clinic sample, CSF tau levels did not correlate to PHQ9 scores.
Construct and validity of Persian Mini Mental Status Examination in illiterate elderly
Authors: Khodamoradi Zohre , Beheshti Maryam , Khodamoradi Mohammadreza
Published: December 2020

Background

Dementia is a health concern all over the world. The prevalence of dementia is growing due to increasing elderly population. Mini‐Mental State Examination (MMSE) is common tool for assess cognitive disorders. We aim to construct and validate the Persian version of MMSE in illiterate elderly (60 years and older) and also assign cut off point for this population in Iran.

Method

We did a cross‐sectional study on 310 elderly individuals (209 healthy participants and 101 elderlies with dementia) in teaching center in Shiraz from 2012 to 2014. Our participants categorized to different stages of dementia with Clinical Dementia Rating Scale (CDR). We used Receiver operating characteristic analysis, kappa analysis and Cronbach’s α coefficient for statistical analysis.

Result

Our results showed that MMSE score has significant association with age, marital status, living condition, occupation and CDR score (P< 0.001). The total Cronbach's alpha value for all domains of MMSE was more than 0.7. The cut‐off point of 21/5 of revised Persian MMSE for illiterate Persian elderly with 95% sensitivity and specificity rates of 72% was calculated. We showed cut off point for three age groups of elderly. We found 24.5, 21.5 and 22.5 for participants with 60‐69, 70‐80 and more than 80 years old respectively.

Conclusion

The Persian version of MMSE was found to be useful and valid instrument for the determination of dementia in the illiterate elderly population.
Amyloid precursor protein (APP) knock‐in mouse model recapitulates transciptomic signature in human late‐onset Alzheimer’s disease
Authors: De Bastiani Marco Antônio , Zimmer Eduardo R. , Forner Stefania , Martini Alessandra Cadete
Published: December 2020

Background

Over the years, improved rodent models have been generated aiming at recapitulating Alzheimer’s disease (AD) phenotype. However, the majority of these models harbor pathological mutations that are present in early‐onset AD, which represents only 5% of all cases. On the other hand, new models aiming at recapitulating late‐onset AD (LOAD) are of great interest. In this context, the knock‐in mouse model (hAβ‐KI line), in which murine amyloid precursor protein (APP) gene was humanized at the Aβ locus, was recently introduced as a potential LOAD model. Here, compare hippocampal transcriptomic profiles of human LOAD individuals and hAβ‐KI mouse model. We hypothesized that hippocampal transcriptomic profile of hAβ‐KI mouse model will be similar to the human LOAD.

Method

Publicly available human AD/cognitively unimpaired (CU) transcriptomic profiles of hippocampus were collected from GEO (https://www.ncbi.nlm.nih.gov/geo/), merged and submitted to differential expression analysis and master regulator analysis (MRA) using R. RNAseq expression profile of hAβ‐KI mouse model was obtained at the AMP‐AD Knowledge Portal (https://www.synapse.org/) and also submitted to differential expression analysis and MRA.

Result

We observed that the hippocampus of human LOAD individuals and hAβ‐KI mice model share over 100 differentially expressed genes (DEGs). Functional enrichment of Gene Ontology terms using these genes revealed several biological processes such as gliogenesis, glial cell differentiation, axon development and ensheathment of neurons. We also found shared transcription factors between human LOAD individuals and the hAβ‐KI mice model (Figure 1).

Conclusion

The novel hAβ‐KI mice, which expresses an humanized APP, has been proposed as a better model to mimic sporadic LOAD. Our early findings indicate that at the transcriptomic level the hAβ‐KI mice presents molecular alterations compatible to human LOAD condition. Thus, studies using this model may reveal important insights to understanding sporadic LOAD and lead to better translational concordance.
Age‐friendly initiative needs assessment survey: Los Angeles City and County employees
Authors: Aguilar Iris , Lloyd Donald A , Trejo Laura , Aranda Maria P
Published: December 2020

Background

The City and County of Los Angeles Age‐Friendly Cities initiative, Purposeful Aging Los Angeles (PALA), 2017 needs assessment included an online survey of the workforce expected to implement age friendly policies and programs. The aim of this study was to describe the rate and characteristics of family caregivers within in the City and County workforce (employees). The overall response rate was 6.5% (City 4.5%, County 7.5%) for a final sample size 9,330. The category of family caregiver was derived from the following survey questions: 1) Are you or someone else in your home caring for a family member or friends who are experiencing problems/thinking that is affecting their ability to work or live a normal life? and 2) Are you a family caregiver? The analysis revealed that 34% of all respondents were family caregivers with an almost even number of male to female ratio. Among all caregivers, the mean age for caregiving for someone with cognitive impairment not diagnosed dementia was 47 and diagnosed AD/Dementia was 49. The majority of caregivers (all types) were caring for either a child/children under the age of 18 (42.1%) followed by a parent(s) (23.1%). Nearly 15% of caregivers of adults with cognitive impairment reported caring for a child/children under the age of 18. When caregivers of adults with cognitive impairment were asked “what type of help might be most useful?”, a higher preference for services was indicated by those aged 45‐64 who selected all the help types as most useful (information, symptom management, someone to talk to, ID lost person, diagnosis and help with care, legal, support group, caregiving financial support, chores/respite, day care, out‐of‐home placement). The current family caregiving research literature suggests that family caregivers experience higher rates of depression, anxiety, and social isolation due to the caregiving demands. Caregiving demands have the potential to create work‐family conflicts that are important for employers to consider when designing wellness programs, and other supportive employment programs. It is critical to identify ways to address caregiving implications on social services, healthcare, and the environment.
Investigating CSF biomarker levels to predict which MCI patients will progress to AD within 5 years
Authors: Cherbuin Nicolas , Tabatabaei‐Jafari Hossein
Published: December 2020

Background

Mild cognitive impairment (MCI) is a heterogeneous condition whose progression is difficult to predict. In the population up to 60% of individuals found to have MCI revert to normal cognition at follow‐up assessments. Amongst those who do not, it is currently difficult to predict those who will progress to Alzheimer’s Disease in the next few years from those who will remain MCI in the longer term. The aim of this study was to investigate whether CSF biomarkers can help predict which individuals with MCI will convert to AD within 5 years.

Method

CSF amyloid beta 42, total and phosphorylated tau were assayed in 304 individuals with Mild Cognitive Impairment (MCI) and 103 cognitively normal participants (CN). Participants were classified into longitudinal diagnosis groups based on disease progression (reverter, stable, converter) over at least 5 years to produce five categories (CNs, CNc, MCIr, MCIs, MCIc). Baseline differences in biomarker levels across categories were tested by linear regression analyses while controlling for age and sex. The predictive value of biomarker levels was tested by logistic regression to predict AD conversion among MCI participants and future disease risk across all participants (Low risk: CNs, MCIr; high risk: CNc, MCIs, MCIc).

Result

Over the follow‐up 42 CN and 57 MCI participants remained stable, 35 MCI reverted, 61 CN converted to MCI, and 212 MCI converted to AD. Across all biomarkers progressively higher baseline pathology was detected across the diagnostic category gradient such that CNs < MCIr < CNc < MCIs < MCIc. When contrasting MCIc vs CNs, Abeta levels were 33% lower, and tTau/pTau levels were 40/52% lower in MCIc. With every 10% increase Abeta or decrease tTau/pTau CSF levels, MCI individuals were at significantly increased risk of conversion to AD within 5 years (Abeta: RR 1.77, 95%CI 1.55‐2.04; tTau: RR 0.85, 95%CI 0.80‐0.89; pTau: RR 0.29, 95%CI 0.19‐0.42).

Conclusion

MCI individuals with substantially lower Abeta or higher Tau levels are at a much higher risk of converting to AD within 5 years. CSF biomarkers may be clinically useful in identifying those with MCI at highest risk of conversion to AD.
Study on the nursing of patients with early dementia based on a hierarchical genetic algorithm (GA‐RBF) neural network system
Authors: Han Peiying
Published: December 2020

Objective

In order to improve the efficiency and prediction accuracy of BP neural network for disease diagnosis, a genetic algorithm was proposed to optimize BP neural network for the diagnosis of Alzheimer's disease to verify the more practical and dementia diagnosis. Methods: Taking the electronic medical record data mining in hospital as an example, a predictive model was established for the diagnosis of Alzheimer's disease. The method firstly uses the genetic algorithm's search optimization technology to carry out feature reduction, and then uses the reduced feature as the input variable of BP neural network to train and construct the BP neural network model. The simulation experiment was carried out on the MATLAB software platform. Results: Compared with single BP neural network, genetic algorithm optimization BP neural network can reduce the training time of the model and improve the prediction accuracy. It is a feasible auxiliary diagnosis method for Alzheimer's disease. Conclusion: The application of hierarchical genetic algorithm GA‐RBF neural network system and early prediction of senile dementia and cognitive status can help to accurately predict the cognitive status of the elderly, prevent it in advance, and improve the quality of care for patients with Alzheimer's disease clinical promotion.
Family availability and its influence on informal and formal care used by adults with dementia in the United States
Authors: Choi HwaJung , Heisler Michele , Cho Tsai‐Chin , Connell Cathleen M
Published: December 2020

Background

Potential family availability may have a profound impact on the level of informal care received by older adults with dementia and hence formal care utilization including institutional care.

Method

From a nationally representative study of older adults, the analysis sample included 4,954 adults (9,363 year‐persons) aged 55+ who had dementia during the years of 2002‐2014. We provided national estimates of the family availability of people with dementia. And, the adjusted, predicted probability of receiving informal and formal care was estimated separately by their spouse and adult child availability using multivariable, logistic regressions. Demographic, socioeconomic, and health measures were included in the adjusted models.

Result

Only 23% of adults with dementia had a non‐disabled spouse, but 66% had an adult child living less than 10 miles. There were substantial variations in family availability across demographic and socioeconomic groups. For example, 29% of non‐Hispanic blacks vs. 40% of other racial/ethnic groups (OR=0.63; 95% CI 0.53‐0.76) had a spouse. Only 16% of the bottom quartile in the wealth distribution had a spouse but 61% of the top quartile did (OR=0.13; 95% CI 0.11‐0.15). However, the greater share of non‐Hispanic blacks vs. non‐Hispanic whites had a coresident adult child (OR=2.07; 95% CI 1.70‐2.50) and a non‐employed adult child (OR=1.45; 95% CI 1.18‐1.79). Hispanics had the greatest family availability – both spouse and child availability.

Having a spouse substantially increased the adjusted probability of receiving informal care, from 47% to 64% (OR=1.96; 95% CI 1.61‐2.40), but reduced that of receiving formal care from 47% to 33% (OR=0.54; 95% CI 0.46‐0.64) including institutional care from 30% to 18% (OR=0.50; 95% CI 0.39‐0.64). Having a coresident child substantially increased the adjusted probability of receiving informal care, from 47% to 71% (OR=2.80; 95% CI 2.18‐3.59), and lowered that of receiving formal care, from 46% to 24% (OR=0.37; 95% CI 0.29‐0.48).

Conclusion

The presence of spouse and a co‐resident adult child may significantly reduce the use of formal care ‐ including institutional care ‐ by adults with dementia in the US. Intervention programs that promote family care however should consider substantial heterogeneity in potential family availability across racial/ethnic and socioeconomic groups.
Effect of matrix metalloproteinases on the longitudinal change in Alzheimer’s disease (AD) pathology and cognitive function in patients with mild cognitive impairment due to AD
Authors: Abe Kie , Chiba Yuhei , Hattori Saki , Ide Keiko , Yoshimi Asuka , Suda Akira , Hishimoto Akitoyo
Published: December 2020

Background

Matrix metalloproteinases (MMPs), endopeptidases expressed in brain and immune cells, have been implicated in the pathogenesis of Alzheimer's disease (AD). However, the longitudinal effect of MMPs on AD patients is still unclear.

Method

We used the data of the Alzheimer's Disease Neuroimaging Initiative database. We included 95 ApoE4‐positive patients with mild cognitive impairment (MCI) due to AD confirmed with low Aβ42 and/or high phosphorylated‐tau (p‐tau) in cerebrospinal fluid (CSF). We obtained baseline demographic data and plasma MMP levels including MMP‐1, MMP‐2, MMP‐7, MMP‐9, and MMP‐10, and longitudinal data of Aβ42, total tau, and p‐tau in CSF, MRI‐measured hippocampal volume, and cognitive function evaluated on Mini‐Mental State Examination (MMSE) and AD Assessment Scale‐11 (ADAS‐11) over 4 years. We investigated the effect of baseline MMP levels on longitudinal changes in CSF AD biomarkers, hippocampus volume and cognitive function.

Result

There was no significant association between the baseline MMP levels and the longitudinal change in CSF biomarkers. Baseline MMP‐9 level was associated with a longitudinal decrease of hippocampal volume and deterioration of MMSE and ADAS‐11 scores.

Conclusion

High plasma MMP‐9 level in the patients with MCI due to AD would be a risk of consequent neurodegeneration and cognitive decline.
Cognitive function has a stronger correlation with “perceived age” than “chronological age,” especially in females
Authors: Kameyama Yumi Umeda , Kameyama Masashi , Kojima Taro , Ishii Masaki , Kidana Kiwami , Yakabe Mitsutaka , Ishii Shinya , Urano Tomohiko , Ogawa Sumito , Akishita Masahiro
Published: December 2020

Background

The perceived age of older adults, as measured by their facial appearances, has been demonstrated to be a robust biomarker of aging predictive of survival, telomere length, and DNA methylation and reportedly correlates with carotid atherosclerosis and bone status. This study aims to determine whether metrics of dementia, including general cognition, vitality, depressive state, and self‐supportability, have stronger correlations with perceived age than with chronological age.

Method

Study subjects were admitted to the Department of Geriatric Medicine, The University of Tokyo Hospital, on account of being suspected of cognitive decline between April 2012 and September 2019. Participants were photographed from the front and in profile from both sides. The mini‐mental state examination (MMSE), Vitality Index, geriatric depression scale 15 (GDS15), instrumental activity of daily living (IADL), and Barthel index were performed. Five experienced geriatricians and five experienced clinical psychologists determined the perceived age of participants based on photographs.

Result

This study included 126 participants (47 male: average age 80.4±6.1, average MMSE 21.3±5.4, 79 female: average age 81.1±6.8, average MMSE 21.8±5.2 ) . The average values of the 10 raters showed excellent reliability (ICC(3,10)=0.941). Steiger's test revealed that perceived age showed a significantly better correlation with MMSE (female), vitality index (total, female), and IADL (total) than did chronological age, but not with GDS15 or the Barthel Index.

Conclusion

Perceived age was demonstrated to be a reliable biomarker for cognitive assessment especially in female.