bluuebunny/crossref_metadata_2025_split huggingface dataset:
LBE regulates the transformation of Aβ‐activated microglia from M1 state to M2
Authors: Zhongqing Sun , Chiu Kin 
Published: December 2020

AbstractBackgroundLycium barbarum is a traditional Chinese medicine herb that exhibits a wide variety of biological functions, such as antioxidation, neuroprotection and regulating inflammation. Amyloid‐β‐induced neuroinflammation is one of the key events in the pathogenesis of Alzheimer’s disease with microglia as the main participating cells. Amyloid‐β (Aβ) can activate microglia, change it from the resting state to M1 state, and promote the occurrence of inflammation. This study aims to inversigate the Lycium barbarum extract (LBE) could reverse the active status of microglia activated under Aβ challenge.MethodIMG mouse microglial cells were cultured and an LDH assay was performed to determine the toxicity of Aβ and safe dose range of LBE. The ELISA, PCR and Western Blot were used to check the inflammatory factors exposed to Aβ. Immunostaining was used to detect the changes of inflammatory factors, the M1 marker is iNOS, IL‐1β, TNF‐α, and M2 marker is Arg1, Ym1.ResultLBE had a dose‐dependent protective effect on IMG cells exposed to o‐Aβ. The ELISA results shew that LBE could decrease the expression of TNF‐α, IL‐6 and IL‐1β inflammatory factors compared with the o‐Aβ alone group in the IMG cell line. The PCR results found that LBE also could inhibit M1‐like inflammatory factors and promote M2 factors in o‐Aβ induced microglia, which is consistent with western blots (WB) results. WB result suggested that LBE suppressed the expression of iNOS, TNF‐α, IL‐6, and IL‐1β and increase the expression of Arg1 compared with the model group. LBE attenuated o‐Aβ‐induced activate microglia by modifying microglia from M1 to M2.ConclusionLBE could modulate the status of activated microglial cells induced by o‐Aβ, and reverse it from M1 to M2 under Aβ treatment.
Determining capacity for individuals with dementia to give sexual consent: A scoping review to guide best practice
Authors: Hand Michelle Danäe , Gibson Allison 
Published: December 2020

AbstractBackgroundSexual relationships in long‐term residential care facilities are common, but addressing the issue of dementia and ability to consent to sex remains unclear. Do individuals with dementia have the mental capacity to consent to sex? And how should residential facilities address the ethical dilemma of consent among individuals with dementia in consideration of their residents’ safety and right to self‐determination? The aim of this study was to review extant research on best practices for determining capacity among individuals with dementia to give consent for sexual relationships.MethodsA systematic scoping review of scholarly literature was conducted using the search words “dementia,” “Alzheimer’s,” “consent,” “sexual,” and “sex” to locate articles in Academic Search Complete, ScienceDirect, Wiley Online and PubMed databases. Scholarly articles in peer‐reviewed journals were deemed eligible if they (a) explored how the issue of consent among individuals with dementia is perceived and determined, and (b) provided recommendations for future practice and research with individuals with dementia.FindingsSeventeen articles met this criteria and were included in the systematic scoping review. Findings demonstrate that while much of the literature has highlighted the need for widely acknowledged explicit guidelines to determine capacity for persons with dementia to consent to sex as well as recommendations to inform organizational policy and best practices for confirming an individual’s ability to consent to sex in later life among persons with dementia.ImplicationsThe issue of determining capacity to consent remains a dilemma. One possible recommendation is to explore the process for determining capacity of persons with dementia to consent to other activities, such as research participation, to inform development of a protocol for professionals to evaluate capacity for consent to sexual relationships. Such an approach will be explored, along with several recommendations for future practice.
Costs of the Care for Older Persons with Dementia in their Environment (COPE) intervention when delivered through the Connecticut state Medicaid waiver program
Authors: Pizzi Laura T , Prioli Katherine M , Babcock Zachary , McAbee‐Sevick Heather , Wakefield Dorothy , Jutkowitz Eric , Fortinsky Richard H 
Published: December 2020

AbstractBackgroundThe Care of Persons with Dementia in their Environments translational study (COPE‐CT) is a Connecticut‐based randomized clinical trial conducted to evaluate the efficacy of behavioral intervention (COPE) vs. usual care (UC) for persons with dementia (PwD) and their caregivers.MethodsPwD in both groups were enrolled in the Connecticut Home Care Program for Elders (CHCPE) and received a monthly home care plan. COPE, an in‐home behavioral intervention delivered by occupational therapists and an advance practice nurse, was designed to maximize PwD physical functioning and improve caregivers’ dementia management skills. Program costs included staff training and supervision (COPE), screening for program eligibility (COPE & UC), intervention delivery (COPE), travel time and mileage (COPE), supplies (COPE & UC), lab testing (COPE), and home care plan for one year pre‐enrollment to one year post‐enrollment (COPE & UC). Mean per‐dyad cost differences at 12 months vs. baseline were calculated for each group and compared using a difference‐in‐difference approach.Result291 PwD/caregiver dyads were randomized (145 COPE, 146 UC). Mean per‐dyad cost of COPE was $1,868 vs. $6.41 for UC, yielding an incremental difference‐in‐difference cost of $1,862/dyad for COPE. COPE delivery was the largest cost driver ($623/dyad) followed by travel time ($370/dyad) and lab testing ($316/dyad). UC costs were minimal and driven by supplies ($18.45/dyad). Both groups experienced a cost savings in the care plan at $82.06/dyad for COPE vs. $15.63/dyad for UC, but this difference was not statistically significant (p=0.5253).ConclusionGiven the lack of medical treatments for dementia, in‐home programs for PwD and their caregivers are critical. COPE represents a novel approach to dementia behavioral management and caregiver support, and the intervention costs we report inform its sustainability. Future work will examine potential cost offsets in health and social service expenditures.
G Protein‐coupled receptor kinases modulate amyloid‐β generation in Alzheimer’s disease
Authors: Todd Nicholas , Huang Yunhong , Thathiah Amantha 
Published: December 2020

AbstractBackgroundOur lab previously identified the G protein‐coupled receptor (GPCR) GPR3 as a modulator of γ‐secretase activity in Alzheimer’s disease (AD)1. The GPR3‐mediated effect on γ‐secretase activity and Aβ generation requires recruitment of the GPCR adaptor protein β‐arrestin 2 (βarr2) and subsequent βarr2 interaction with the Aph1a subunit of the γ‐secretase complex2. GPCR kinases (GRKs) phosphorylate GPCRs and generate specific phosphorylation patterns that initiate βarr2 recruitment and distinct downstream signaling3–6. Despite evidence of GRK expression changes in the human AD brain7,8, the putative involvement of GRKs in modulating pathogenic GPCR signaling or directly modulating AD pathology has not been investigated.MethodWe utilize CRISPR/Cas9 genome‐editing to generate HEK293 GRK knock‐out cell lines of each GRK that is ubiquitously expressed in the brain, namely GRK2, GRK3, GRK5, and GRK6. We perform a combination of bioluminescence resonance energy transfer (BRET), co‐immunoprecipitation, and enzyme‐linked immunosorbent assays (ELISAs) to identify the specific GRK involvement in βarr2 recruitment to GPR3 and GPR3‐mediated Aβ generation. Additionally, we investigate potential mechanisms by which βarr2 regulates γ‐secretase activity by utilizing a βarr2 recruitment assay to measure βarr2 interaction with the Aph1a subunit of the γ‐secretase complex.ResultInterestingly, genetic deletion of GRKs 2, 3, 5, and 6 individually reduce βarr2 recruitment to GPR3; however, only GRK2‐induced βarr2 recruitment to GPR3 is involved in the regulation of GPR3‐mediated γ‐secretase activity and Aβ generation in a kinase‐dependent manner. Furthermore, alanine mutagenesis of two serine residues in the cytoplasmic tail of Aph1a these residues reduces the βarr2 interaction with Aph1a.ConclusionOur findings indicate that GRK2 regulates the GPR3‐mediated increase in Aβ generation and suggest that a specific GRK2 phosphorylation barcode on GPR3 modulates γ‐secretase activity. Additionally, evidence that phosphorylation of Aph1a is required for βarr2 interaction with the γ‐secretase complex suggests that GRK2, or another GRK, either directly or through activation of GPR3 may be involved in the regulation of γ‐secretase activity. Accordingly, the putative GRK2 phosphorylation barcode of GPR3 and GRK involvement in Aph1a phosphorylation are currently under investigation. These studies provide insight into the broader mechanism by which GPR3 modulates AD pathology and illuminates a novel role of GRKs AD pathogenesis.
Investigation of the effect of PGC1A gene therapy at advanced stages of Alzheimer’s disease in an animal model of amyloid pathology
Authors: Mota Bibiana Castagna , Almpani Elisavet Velentza , Nikolaou Maria Nefeli , Garcia‐Segura Monica Emili , Huang Yu‐Hsuan , Keniyopoullos Renos , Mazarakis Nicholas D , Sastre Magdalena 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is the most prevalent form of dementia in the elderly. AD has no cure but symptomatic treatment, thus, an effective therapy is urgently needed. Previously in our laboratory we have explored the potential neuroprotective effects of the coactivator for the peroxisome proliferator‐activated receptor‐γ (PPARγ), ‐PGC‐1α mainly involved in the regulation of metabolic processes and mitochondrial biogenesis. PGC‐1α has been shown to be involved in different neurodegenerative diseases and its expression is reduced in the brain of AD patients. We have previously showed that the delivery of PGC‐1α through lentiviral vectors in APP23 mice, at the preclinical stage of the disease, resulted in reduction of amyloid‐β deposition, protection against neuronal loss and improvement of cognition functions. Therefore, the aim of this study was to generate a monocistronic lentiviral vector expressing PGC‐1α to investigate whether this therapy could ameliorate the cognitive deficit ofAPP23 mouse model of AD at an advanced stage of pathology.MethodA recombinant lentiviral vector carrying human codon optimized PGC‐1αdriven by CMV promoter was constructed and produced. To determine the therapeutic effects of overexpression of PGC‐1α, we delivered the lentiviral vector carrying PGC‐1α in the frontal cortex and hippocampus of wildtype and APP23 mice at 12 months old and animals were sacrificed 3 months later. We investigated locomotor activity and anxiety (Open Field, OF), non‐spatial (Novel Object Recognition, NOR) and spatial memories (Object Location test, OLT).ResultSo far, no differences were observed in the anxiety and locomotor activity between the groups in the OF test. APP23 mice at 15 months of age showed cognitive impairment compared with controls. Interestingly, improvement in the performance in the NOR test was observed in the APP23 mice injected with PGC‐1α vector (p>0.05, two‐way ANOVA, Bonferroni post‐hoc, n=5‐10 per group). However, in the OLT test no difference was observed between the groups 3 months after the PGC‐1α delivery.ConclusionThese preliminary results support the potential therapeutic effect of PGC1alpha on cognition at late stages of the disease.
A look at possible effects of mandated COVID‐19 social isolation on orientation scores for research participants reporting mild memory concerns
Authors: Voccia Pamela , Kruczek Katherine , Kettren Joy 
Published: December 2020

AbstractBackgroundDue to mandated quarantine and social distancing in 2020, Florida residents temporarily ceased social activities outside the home, and modified activities of daily life that required leaving the home. Subjects continued to present for clinical trials in Alzheimer’s disease. The purpose of this data review is to determine the effect of social isolation on orientation to time, due to site‐level concerns that the mandated social isolation may have a negative impact on orientation scores for subjects reporting mild memory concerns.MethodData was collected for 68 subjects reporting mild memory concerns (not meeting diagnostic criteria for dementia). Orientation responses for 52 subjects evaluated prior to the social distancing mandate (January 1 – March 26, 2020), and 16 subjects evaluated post‐implementation of social distancing (April 1‐May22), were recorded for the following items: Year, Month, Date, Day of the Week. All subjects in the post‐implementation group reported that they were mostly staying home, and not participating in their typical social activities outside of the home. The means of the two groups were compared across all orientation domains.ResultA t‐test analysis reveals that following the social distancing mandate, subject performance on measures of orientation did significantly decline, overall. The mean of the pre‐social distancing group for the 4 orientation items was 3.7. The mean of the post‐social distancing group for the 4 orientation items was 3.1. (t crit = 1.67 , t stat = 2.17 , p= 0.01). Responses significantly affected by post‐social distancing were specific to Day and Date. (Correct responses for Day: 87% pre‐quarantine, 63% post‐quarantine; correct responses for Date: 90% pre‐quarantine, 69% post quarantine). Accurate Year and Month responses appeared to be consistent across both groups.ConclusionConsistent with site‐level concerns that social isolation subsequent to Covid‐19 distancing guidelines could negatively impact orientation scores for subjects reporting mild memory concerns, the data collected and analyzed from January through May 2020 indicates a slight but significant decline in orientation scores post‐quarantine. Specifically, orientation to weekday and date appears to be most affected by the change in lifestyle and activities of daily living engaged in outside of the home.
Vitamin D deficiency is associated with decreased cognition independent from the disease status and AD morphology
Authors: Dogan Melike Karacam , Özkan Esra , Karakaşlı Ahmet Alp , Zengin Hatice Yağmur , Çap Duygu , Şenol Bedirhan , Karahan Sevilay , Karaosmanoğlu Ayça , Saka Esen , Ayhan Yavuz 
Published: December 2020

AbstractBackground25(OH)D deficiency was associated with cognitive impairment and altered brain volumes, namely reduction in white matter and medial temporal lobe and enlargement of lateral ventricles. 25(OH)D deficiency was also associated with the development of Alzheimer's disease (AD). In this study, we aimed to investigate whether 25(OH)D levels are independently associated with cognitive performance and AD‐associated morphology in a mixed sample.MethodThe study was conducted at Hacettepe University Faculty of Medicine, Ankara, Turkey. The participants were chosen from our dementia research database.Demographic variables, 25(OH)D levels, standardized Modified Mini Mental Test (3MS) z‐scores, 1.5 T brain MRI, the data for comorbid medical conditions and current prescription drugs were used as pertinent variables. FreeSurfer v.6.0 was used for automated structural neuroimaging analysis. Based on the previous literature, AD cortical signature, predictive cortical thickness, medial temporal lobe gray matter and mean hippocampal volumes were calculated and used independently to assess AD‐related morphological changes. Cut‐off for 25(OH)D deficiency was accepted as 20 ng/ml. Statistical analyses were conducted using IBM SPSS Statistics 23 for Windows. To assess the predictive power of 25(OH)D, regression models were used with standardized 3MS scores and AD‐related areas as dependent variables. Statistical assumptions were met for all models presented. Funded by TUBITAK 214S048 and Hacettepe University THD 2018‐17363.ResultA total of 210 patients over 55 years of age (47 AD, 15 nonAD dementia, 74 Mild and Subjective Cognitive Impairment, 74 cognitively intact) were included. Mean 25(OH) level was 22.48 ±15.8 ng/ml. 108 participants (51.4%) had 25(OH)D deficiency (AD 57%, nonAD Dementia 60%, SCI/MCI 51%, Control 46%, p>0.5). 25(OH)D deficiency was significantly associated with 3MS scores (χ2 =5.608,df=1,p=0.018). The association was also marginally significant when adjusted for age, diagnosis and medial temporal lobe gray matter volume (Exp(β): 2.472, p=0.05). 25(OH)D levels were not associated with AD‐related morphological changes on multivariate analyses.ConclusionPlasma 25(OH)D levels are associated with cognitive performance regardless of the diagnosis. The effect seems to be independent of AD‐related brain morphological changes. Our results suggest an independent effect of 25(OH)D levels on cognition.
Depressão e ansiedade em adultos e idosos com síndrome de Down: Resultados preliminares de um estudo prospectivo no Brasil
Authors: Soares Cristiane Nogueira Rigoleto , Forlenza Orestes Vicente 
Published: December 2020

AbstractBackgroundThe study was conducted at a non‐governmental institution (APAE‐SP) dedicated to providing care and social inclusion for individuals with ID in São Paulo, Brazil.MethodTwenty‐seven physically healthy young and older adults with DS (mean age: 38; range: 24‐60 years) of both genders (44,4% of females) were evaluated between March and June 2018 by a psychogeriatric team with the aid of the Glasgow Scale for Depression and Anxiety. This instrument encompasses 20 illustrated questions addressing the presence of depression symptoms (GS‐D), and 27 addressing anxiety symptoms (GS‐A). Each question yields three possible answers which may be scored as 0 (symptom absent), 1 (possible) and 2 (present). In the GS‐D subscale, a score of 13 or higher (out of a maximum score of 60 points) indicates the presence of depression, whereas the cut‐off for suspected cases according to the GS‐A subscale is 15 points (max. 81). Overall results obtained for each participant in the Glasgow Scale were cross‐validated with the informant’s report obtained by the CAMDEX‐DS schedule, reinforcing the perception of change in behavioral patterns of subjects with DS.Results44.4% (n=12) of the GS‐D respondents had evidence of depressive symptoms (mean score 13,2; range 0 ‐60), and 53.8% (n=14) of the GS‐A respondents had anxiety symptoms (mean score 14,7; range 0‐81). The major concern in the former group was related to the fear of death of their relatives, legal guardians and/or caregivers; anxiety symptoms were associated with the perception of lack of perspectives in their lives and inability to cope with future demands.ConclusionThe present study indicates the presence of depression and anxiety symptoms in a large proportion of adults with DS, corroborating previous studies and emphasizing the need for the systematic assessment of psychiatric symptoms in this population. The relationship between psychiatric symptoms and incident cognitive decline is yet to be determined.
College students' attitudes towards physician‐assisted death for persons with dementia
Authors: Mashal Rachel , Santulli Robert B 
Published: December 2020

AbstractBackgroundThe number of persons with dementia is expected to increase by 50% in the next 10 years, yet there is still no cure for this devastating disease (World Health Organization, 2018). The Netherlands, Belgium, and Switzerland have legalized physician assisted death (PAD) for persons with dementia; however, no states in the U.S. have done so (Menzel & Steinbock, 2013). PAD is a controversial topic that has been subject to clinical, ethical and political debate (Emanuel et al., 2000). There is research investigating the fundamental consideration of whether PAD should be considered at all in cases of dementia (Tomlinson & Scott, 2014); however, there is a lack of research focused on answering the question: under what conditions is PAD deemed acceptable for persons with dementia? This study aimed to fill that gap. This study consisted of a survey that assessed students’ attitudes towards PAD across 16 different vignettes. 128 Dartmouth College undergraduate students completed the survey. An ordinal logistical regression analysis revealed that the gender and age of the person with dementia does not significantly affect attitudes towards PAD while illness severity and frequency of requesting PAD do. ANOVA analyses revealed that student gender and family history of dementia do not affect overall acceptability of PAD, but religious affiliation does. Atheists are more accepting of PAD than those who identify with a religious faith, and those identify as “very religious” are significantly less accepting of PAD than those who identify as less religious. The results of this study elucidate the factors that college students view as important in medical decision‐making for persons with dementia.
Influence of systemic immune responses in the brain after wound injury of tail amputation in zebrafish
Authors: Chen Xiang‐Ke , Ma Alvin Chun‐Hang , Chang Raymond Chuen‐Chung 
Published: December 2020

AbstractBackgroundIncreasing lines of evidence demonstrate that systemic immune responses triggered by either sterile or infectious inflammation can activate neuroimmune responses, resulting in developing Alzheimer’s pathology, such as phosphorylation of tau protein. Systemic inflammation can be a risk factor for developing cognitive dysfunctions and even Alzheimer’s disease. We have been using a laboratory murine model, laparotomy, to demonstrate that systemic immune responses stimulate production of cytokines and activation of microglia in the brain. However, it is still unclear how systemic monocytes/macrophages responses after sterile inflammation. As zebrafish embryo has transparent body that suitable for imaging monocytes/macrophages, we aim to use zebrafish and tail amputation for investigating which factor can affect the influence of systemic inflammation in the brain.MethodZebrafish was used as experimental model. Tg(coro1a:DsRed) transgenic fish was used to monitor microglia and macrophages. Tg(mpx:mCherry) was used for monitoring neutrophils, Tg(mepg1:GFP) was used for monitoring macrophages. We have used TALEN method to make knockout or mutation of IL‐1b in zebrafish. Quantitative PCR and immunohistochemical staining were used for examination. Acridine orange and TUNEL were employed for labeling apoptotic cells. Tail amputation was performed at day 3 of embryos under anesthetization with tricaine.ResultTail amputation recruited accumulation of monocytes/macrophages into the wound site in zebrafish tail. Surprisingly, increased number of macrophages and microglia were also found in the brain, which was tissue specific as no other organs showed similar phenomenon. Expression of mRNA for different cytokines was examined in the brain. Among which, IL‐1b was significantly increased. Therefore, we prepared IL‐1b knockout and mutated zebrafish. After amputation, the number of macrophages in the brain did not show any significant increase. To further understand why monocytes/macrophages migrate into the brain after peripheral wound injury, we found increased number of apoptotic cells in the brain after wound injury. IL‐1b had a key role in regulating migration of monocytes/macrophages.ConclusionOur study demonstrated that zebrafish is a good animal model to investigate how peripheral wound injury triggers neuroimmune responses. IL‐1b is a key player to regulate migration of monocytes/macrophages into the brain.