bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic oral administration of a novel estrogen receptor beta agonist enhances memory consolidation and alleviates vasomotor symptoms in a mouse model of menopause
Authors: Fleischer Aaron W , Schalk Jayson C , Wetzel Edward A , Hanson Alicia M , Sem Daniel S , Donaldson William A , Frick Karyn M 
Published: December 2020

AbstractBackgroundWomen are at greater risk of Alzheimer’s Disease (AD) than men, and symptoms associated with the menopausal loss of circulating estrogens, including hot flashes, exacerbate cognitive decline and AD risk. Although estrogen‐based therapies reduce hot flashes and mitigate AD risk early in the menopausal transition, these treatments can increase risks of cancer, among other health issues. These adverse effects are mediated by the alpha (ERα), but not beta (ERβ), estrogen receptor isoform. Moreover, activation of ERβ facilitates memory formation and reduces hot flashes. Thus, ERβ‐selective therapies may promote memory function, reduce hot flashes, and diminish AD risk without complications associated with ERa. Our goal here was to determine whether chronic treatment with EGX358, a novel highly selective ERβ agonist developed by our group, could enhance memory and reduce hot flash‐like symptoms in a mouse model of menopause.MethodsEight‐week‐old ovariectomized C57BL/6 mice were orally gavaged each day for 10 weeks with vehicle, the highly potent estrogen 17β‐estradiol (E2; equal affinity for ERα and ERβ), the commercially available ERβ agonist diarylpropionitrile (DPN), or EGX358 (∼10x greater selectivity for ERβ than DPN). Compounds were administered at doses that enhance memory when delivered acutely. After two weeks of treatment, hot flash‐like symptoms were tested after subcutaneous injection of vehicle or senktide, a tachykinin receptor 3 agonist that induces hot flash‐like symptoms. Tail skin temperature was then recorded using a thermal camera for 30 minutes as a proxy for vasodilation. Six weeks later, mice were trained in object recognition (OR) and object placement (OP) tasks to test object and spatial memory, respectively. Memory in the OR and OP tasks was tested 48 and 24 hours later, respectively.ResultsE2, DPN, or EGX358 treatment reduced the senktide‐mediated increase in tail skin temperature. Furthermore, treatment with E2, DPN, or EGX358, but not vehicle, enhanced memory in the OR and OP tasks.ConclusionsThese data suggest that chronic EGX358 treatment can reduce hot flash‐like symptoms and improve spatial and object recognition memories. Therefore, ERβ activation may be a promising avenue for reducing menopause‐related hot flashes, memory dysfunction, and AD risk.
New evidence reveals weakening of association between language and thought in aMCI versus in normal aging
Authors: Sherman Janet C. , Flynn Suzanne , Henderson Charles , Lust Barbara 
Published: December 2020

AbstractBackgroundClinical manifestation of prodromal AD is typically evaluated through measures that assess individual cognitive domains with less focus on their relationship. Further, while decades of research identify deterioration in episodic memory as well as semantic aspects of language, there has been less focus on other aspects of linguistic computation. We provide evidence that advances our understanding of how language deficits in aMCI extend to sentence production, and how relations between performances in cognitive functions, specifically language and cognition, may differ in aMCI vs. Healthy Aging (HA).MethodWe tested 24 individuals diagnosed with aMCI based on neurologic and neuropsychological evaluations, and 22 older adults with normal cognition (Healthy Aging (HA). All subjects were administered a multi‐domain cognitive screen (ACE‐R) and a psycholinguistic assessment of complex sentence production. The ACE‐R provided a Total Score and scores on attention and orientation, memory, fluency, language, and visuospatial measures (Mioshi et al 2006, Hsieh et al 2013, Monsch et al 1994).) The psycholinguistic test assessed Elicited Imitation of complex sentences with relative clauses (RC) in an experimental design varying syntactic and semantic factors (Table 1) (Lust et al 2017).ResultACE‐R Total score was significantly lower for aMCI than HA. aMCI also performed significantly worse than HA on the psycholinguistic test (Table 2). For HA, not aMCI, ACE‐R Total score significantly predicted successful sentence production on the psycholinguistic test (Table 3) (Figure 1). Similarly, for HA, not aMCI, the ACE‐R language score significantly predicted psycholinguistic test performance. In contrast, ACE‐R memory performance, which was significantly lower for aMCI than HA, did not predict linguistic performance for either group. Only ACE‐R phonemic fluency predicted linguistic performance for both groups. (Table 3).ConclusionResults suggest a weakening of associations between overall cognitive performance and performance on a linguistic measure for aMCI relative to HA suggesting that evaluation of associations between, not only within, cognitive domains strengthen detection of early changes in AD. This finding may be further expanded by linking this clinical manifestation to neuroscientific evidence of functional connectivity in AD pathophysiology and in normal aging (e.g., Brier et al 2014, Spreng and Turner 2013).
The calcium‐containing smooth endoplasmic reticulum is a focus of risk factors for early‐ and late‐onset Alzheimer’s disease
Authors: Datta Dibyadeep , Mentone SueAnn , Morozov Yury , van Dyck Christopher H , Arnsten Amy FT 
Published: December 2020

AbstractBackgroundCalcium dysregulation may be an important etiological event in Alzheimer’s Disease (AD). The presenilins (PS1/PS2) are components of the calcium‐storing smooth endoplasmic reticulum (SER), and PS1/PS2 mutations that cause autosomal dominant AD cause calcium leak from the SER. Recent studies of medial temporal lobe from animal models and patients with late‐onset AD have also found evidence of calcium leak from SER through PKA‐phosphorylated ryanodine receptors (pS2808RyR2). Thus, the SER may be a nexus for AD pathology. The current research used immunoelectron microscopy to visualize the SER in the aging rhesus monkey dorsolateral prefrontal cortex (dlPFC), a newly evolved brain region which subserves higher cognition and is vulnerable in AD. As aging increases calcium‐PKA signaling in dlPFC, we looked for evidence of pS2808RyR2, as well as PKA‐phosphorylated tau (pS214Tau), and for changes in the cAMP‐PKA regulatory protein, PDE4Ds. Finally, we examined the location of TREM2, a genetic risk factor for late‐onset AD that is linked to microglia, but was also observed on neuronal SER in the current study.MethodWe used high‐spatial resolution immunoEM to localize PDE4D, pS2808RyR2, pS214Tau and TREM2 in aging rhesus monkey dlPFC.ResultThe data show that the SER is a focus of age‐related pathology in association cortex, with loss of PDE4D from the SER in spines and dendrites, and increased PKA phosphorylation of pS2808RyR2, which causes calcium “leak”. We also find evidence of increased PKA phosphorylation of pS214tau aggregating on the SER and microtubules, an important step that causes tau to detach from microtubules and aggregate, and primes tau for hyperphosphorylation and neurofibrillary tangle formation. Finally, we found TREM2 focused on the SER in spines and dendrites in neurons in addition to its expected location in glia. Thus, early‐onset (PS1/PS2), late‐onset (TREM2) and aging, all target the SER in the association cortical synapses most vulnerable to AD pathology.ConclusionThis nexus of genetic risks supports the hypothesis that calcium dysregulation is a key factor in AD neurodegeneration, an underappreciated mechanism in the AD field. Regulating internal calcium signaling in the aging cortex may provide an opportunity for therapeutic intervention at early stages of pathology.
Public, family and health staff dementia knowledge: A multicentric study
Authors: Gallo Maria Fernanda , Deschle Florencia , Berrios Waleska , Tabernero Maria Eugenia , Cores Evangelina Valeria , Peiretti Ursula , Ramirez Linda Calderon , Bustos Claudia 
Published: December 2020

AbstractBackgroundThere are currently no studies in Argentina that measures the knowledge of all types of dementia. Given the increasing prevalence of this disease, knowing the level of knowledge could be useful to provide psychoeducation tools, allowing better understanding, objetive setting and daily managment of dementia. The aim of this study is to evaluate dementia knowledge among general population, families and health staff.MethodDementia knowledge will be assessed whith the Dementia Knowledge Assessment Tool 2 (DKAT‐2), validated in Spanish by Parra‐Anguita et al. (2018). DKAT‐2‐Sp has 21 items, with three response optiones (Yes, No, I don’t know). The questionnaire will be distributed in form throught virtual platforms. Statistic data will be analyzed with SPSS.ResultWe expect a participation of no less than 300 respondents. Toye et. al (2013) administered DKAT‐2 in familiies and care staff, obteining a median of 14 correct responses for familires, and 16 for the staff. In 2018, Parra‐Anguita et. al evaluated dementia knowledge with DKAT‐2‐ Sp in nursing professionals and students, obtaining a mean of 15.57 in staff versus 12.85 in students, with very significant differences in incontinence, visual perception, distressing behaviors and swallowing difficulties items. For the current study, we will include general population, predicting similar results, with highest scores to be obtained by health care professionals, comparatively lower scores by family carers and lowest scores among the general population.Conclusionthe results could be usefull to detect areas of intervention and provide psychoeducations tools for better understanding dementia.
Effects of art therapy on agitation in elderly people with dementia: An integrative review
Authors: Laranjeira Carlos 
Published: December 2020

AbstractBackgroundThe agitation behaviors manifested by the elderly are, in most cases, controlled by antipsychotic medication. However, there are several associated side effects such as: increased cognitive decline, increased risk of a stroke and even death. In terms of cognitive functions and behavioral problems, pharmacological interventions have minimal benefits and concerns about the harmful side effects caused by these antipsychotic drugs have made non‐pharmacological interventions take on a very important role. Thus, in the search for non‐pharmacological interventions to alleviate behavioral problems, special attention was paid to art therapy, which is one of the most recommended interventions.MethodThis integrative review was aimed to systematize the available evidence about the effects of art therapy on agitation in elderly people with dementia in the period from 2010 to 2020. The final sample comprised 10 studies after research at Pubmed, ISI Web and Scopus. This review included experimental, randomized and non‐randomized studies, pre‐experimental studies and case studies. The Joanna Briggs Institute (JBI) checklist was used to assess methodological quality of papers.ResultMost studies enrolled found that art therapy was effective in improving at least one parameter of agitation in elderly people with dementia. However, 6 studies have found that art therapy has shown no benefit in terms of agitation in people with dementia. The interventions used in the various studies varied widely, both in terms of how the technique was applied and in terms of duration. The measures used to assess the results of the interventions were, for the most part, subjective and, in some cases, the instruments were not validated for the population.ConclusionStill there is some evidence that seems to indicate some efficacy in the use of therapy by art as treatment of agitation in elderly people with dementia, the quality and heterogeneity of existing studies is limited, so it cannot be assumed that the use of a intervention using art therapy is effective in reducing agitation.
Role of mosaic aneuploidy in the development and progression of Huntington's disease
Authors: Elos Mihret , Caneus Julbert , Ahmed Md Mahiuddin , Markham Neil , Chial Heidi J , Potter Huntington 
Published: December 2020

AbstractBackgroundHuntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion mutation in the huntingtin (HTT) gene. HTT encodes the huntingtin protein, which has been shown to localize to spindle poles and is required for proper mitotic spindle orientation, chromosome segregation, and cell cycle regulation. Mutations in HTT lead to the production of a mature huntingtin protein with an expanded polyglutamine region (>35 repeats) at its N terminus. Previous studies have shown that mouse models of HD exhibit defects in microtubule function and in cell cycle regulation. HD is a progressive condition characterized by decline in cognitive and executive functions. Over the years, studies from our laboratory and others have shown elevated levels of aneuploidy in many neurodegenerative disorders that are characterized by cognitive deficits, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). Here, we investigated whether chromosome segregation defects that lead to mosaic aneuploidy and consequent apoptosis may also contribute to neuronal loss in HD.MethodSingle cell suspensions were prepared from human brain samples (cortex and cerebellum) and fibroblast cell lines from HD donors and age‐matched controls and were processed for FISH analysis of human chromosome 21, NeuN immunostaining, and/or TUNEL staining. Single cell suspensions from cerebellum were prepared from mouse models of HD and age‐matched controls for FISH analysis of mouse chromosome 5 or 16, which is syntenic to human chromosome 21.ResultWe observed increased levels of mosaic aneuploidy and associated apoptosis in brain tissues and in cultured fibroblasts from HD donors compared to age‐matched controls. We also observed increased levels of mosaic aneuploidy in brain tissue from HD mice compared to age‐matched controls.ConclusionTogether with our previous studies of AD and FTLD, these data provide evidence that chromosome segregation defects that lead to genomic instability may serve as a shared mechanism underlying many neurodegenerative disorders. Our findings highlight the need to further investigate the biological mechanism(s) underlying HD pathology and set the stage for novel therapeutic approaches to HD that may also be applied to other neurodegenerative disorders.
Effect of an art therapy and cognitive stimulation program in older adults with indicators of cognitive impairment
Authors: Lajo‐Alvarez Ricardo , Herrera‐Arias Leslie , Soto Marcio 
Published: December 2020

AbstractBackgroundNeurodegenerative disease affects the cognitive, behavioral and functional status in older people. Non pharmacological interventions has shown improvement in cognitive, emotional and functional performance. For this reason, we set out to analyze the effect of a combined nonpharmacological intervention program of cognitive stimulation (CS) and art therapy (AT).MethodA mixed factorial quasi‐experimental repeated measures design was used. 127 older adults were evaluated with clinical screening tests. Twenty‐seven participants were selected to whom a neuropsychological battery composed of measures of memory, executive function, verbal fluency and attention. The final group was made up of 13 participants who were divided into two homogeneous groups (Group 1, n = 6 and Group 2, n = 7). The treatment was applied to each group in parallel with 18 sessions (G1 = CS, G2 = AT), after which an intermediate neuropsychological evaluation was carried out. Later the treatments were changed (G1 = AT, G2 = CS). Finally, a cognitive evaluation was carried out in both groups.ResultThe results show that both groups had a significant improvement in working memory and semantic and phonological fluency tasks after cognitive and art therapy intervention. These improvements were maintained after the second treatment, being more noticeable in the group that started with CS and continued with art therapy.ConclusionThese results show us the importance of working with non‐pharmacological strategies for the treatment of patients with indicators of cognitive impairment and the importance of working on combined interventions to improve the cognitive and functional status.
Potential drug interactions between hydroxychloroquine and anticholinesterase drugs
Authors: Santos Gustavo AA 
Published: December 2020

AbstractBackgroundOne of the main aggravating factors in the Covid‐19 pandemic is the lack of effective treatments capable of promoting a cure to date. Unfortunately, contrary to the recommendations of WHO and health authorities, in Brazil the use of Hydroxychloroquine in the treatment of SarsCov‐2 has been approved.MethodWe selected guidelines with recommendations for treatment of Covid 19, with an emphasis on the proposed treatments. Then we evaluate the main drug interactions and their potential risks.ResultThe risk of using Hydroxychloroquine in patients with Alzheimer's Disease is high, both due to the aspect of the disease itself, but also due to the drug interactions found.ConclusionHydroxychloroquine is not recommended for patients with Alzheimer's Disease.
Pathological correlates of impaired self‐awareness of memory function in dementia
Authors: Gagliardi Geoffroy Pierre , Kuppe Madeline , Hanseeuw Bernard , Lois Cristina , Vannini Patrizia ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2020

AbstractBackgroundImpaired self‐awareness of memory function (a.k.a. anosognosia) is a common symptom observed in Alzheimer’s disease (AD), however it’s pathological correlates remain unclear. Here we investigated the impact of amyloid and tau on memory self‐awareness in a cohort of clinically normal or impaired participants.MethodThis study included 216 clinically normal (CDR=0) and 156 clinically impaired (CDR≥0.5) participants part of the Alzheimer's Disease Neuroimaging Initiative (ADNI) project. Using the E‐Cog memory subscale, a participant‐informant discrepancy index was computed such that a negative score indicates a participant’s underestimation of difficulties as compared to the partner. Linear models were performed with discrepancy as the dependent variable, and amyloid (Florbetapir) from global region of interest (ROI) and tau (Flortaucipir) from two ROI (i.e. inferior temporal and entorhinal cortices in two separate models) as independent variables. Demographics (i.e. Age, Gender, Years of Education) were added as covariates.ResultWe found that clinically impaired individuals were significantly older (p = 0.01), more educated (p < 0.001), and included more women (p = 0.01) as compared to the clinically normal group. In general, clinically impaired individuals had lower awareness scores as compared to clinically normal individuals (p < 0.001). A significant three‐way interaction was observed between clinical status and biomarkers (i.e., amyloid and tau burden, p = 0.009 and 0.033 for entorhinal and inferior temporal cortices, respectively). Post hoc analyses revealed no significant difference between groups in individuals at low levels of pathology (p > 0.05; Figures A and B, right panels). However, at higher levels of pathology (i.e., both amyloid and tau), clinically impaired individuals demonstrated significantly lower awareness scores as compared to clinically normal participants (Figures A and B, left panels).ConclusionThese findings better characterize the evolution of anosognosia in AD. Specifically, data suggest that impaired self‐awareness of memory function is associated with higher levels of amyloid and tau, providing further support that discordant subjective and objective measures may be important for clinical consideration.
Hippocampal subfield bold signal and mnemonic discrimination task performance in cognitive aging
Authors: Kern Kathryn L , Wehr Rachel K Nauer , Storer Thomas W , Schon Karin 
Published: December 2020

AbstractBackgroundCognitive aging is associated with impaired episodic memory formation (Small et al., 1999), which requires the neurocomputational process of pattern separation to disambiguate similar stimulus input. Pattern separation relies on the dentate gyrus (DG) (Yassa & Stark, 2011), a hippocampal subfield that is susceptible to age‐related change (Small et al., 2011). Cognitive aging is also associated with impaired performance on putative measures of behavioral pattern separation (Yassa et al., 2010), called mnemonic discrimination tasks in humans. Prior work using high‐resolution fMRI suggests that age‐related impairments in mnemonic discrimination are linked to aberrant activation patterns in the DG/CA3 (Yassa et al., 2010). Whereas aging is associated with impaired DG integrity and mnemonic discrimination ability, cardiorespiratory fitness is associated with enhanced DG integrity and improved mnemonic discrimination ability. Given that cardiorespiratory fitness has been positively linked to DG/CA3 integrity in young adults (Nauer et al., 2019), it is conceivable that in older adults, cardiorespiratory fitness will modulate age‐related changes in DG/CA3 activation, which in turn, will dampen age‐related impairments in mnemonic discrimination.Methods18 older adults (55‐85 years) and 18 young adults (18‐35 years) underwent a submaximal treadmill test to estimate cardiorespiratory fitness and high‐resolution fMRI to examine hippocampal subfield BOLD signal during encoding and retrieval of a mnemonic discrimination task (MDT).ResultsIn older adults, we found increased right DG/CA3 BOLD signal in incorrect mnemonic discrimination trials contrasted with correct mnemonic discrimination trials, specifically during stimulus retrieval. Additionally, in both young and older adults, we found that right DG/CA3 BOLD signal in the mnemonic discrimination fMRI contrast during stimulus encoding marginally significantly predicted MDT corrected accuracy. Finally, in both young and older adults, fitness significantly negatively predicted left DG/CA3 BOLD signal in the mnemonic discrimination fMRI contrast during stimulus retrieval.ConclusionsThese results suggest that DG/CA3 BOLD signal relates to performance on a MDT designed to tax pattern separation, and that cardiorespiratory fitness modulates BOLD signal in these subregions. Altogether, these results suggest a link between fitness, DG/CA3 functional integrity, and mnemonic discrimination that may be critical to understanding how to dampen age‐related impairments in episodic memory.