bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial autophagy‐mediated clearance of amyloid‐beta plaques is dysfunctional in Alzheimer’s disease mice
Authors: Daily Kylene P. , Amer Amal 
Published: December 2020

AbstractBackgroundAutophagy is a conserved homeostatic cellular process for clearing dysfunctional organelles, pathogens, and protein aggregates. Neurons in patients with Alzheimer’s disease (AD) exhibit accumulation of immature autophagic vacuoles, which is thought to contribute to amyloid‐beta (Aβ) plaque build‐up and neurotoxicity. However, it is still unclear what causes autophagic dysfunction in neurons and how it contributes to disease progression. Moreover, the role of autophagy in microglia, the innate immune cell and phagocyte of the CNS, has not been explored. We hypothesized that autophagy in microglia in AD is dysfunctional, leading to the inability of microglia to effectively clear Aβ plaque protein aggregates.MethodWe purify microglia from adult mice of an AD mouse model (5xFAD – 5 familial mutations of AD). We are utilizing a novel method developed in our lab to quantify Aβ internalization and degradation which does not require radioactive or fluorophore labeling. Additionally, we are able to visualize Aβ autophagic trafficking utilizing microglia from a mouse with GFP+ LC3, a key autophagy protein involved in the elongation of the autophagosome. Lastly, to understand the components at play in autophagy processing of Aβ in microglia, we are able to reduce expression of various autophagy proteins and microRNAs which target autophagy utilizing a magnetic nanoparticle transfection reagent.ResultMicroglia from AD mice and age‐matched wild‐type littermates internalize the same amount of Aβ, but AD microglia do not efficiently degrade Aβ in vitro. When stimulating autophagy using rapamycin, degradation of Aβ in AD microglia improves. We are able to see that microglia traffic Aβ to an LC3+ autophagosome, and that this trafficking and subsequent Aβ‐degradation is dependent on the expression of various autophagy molecules. Furthermore, we have reduced expression of microRNAs which downregulate autophagy and are overexpressed in AD, and recovered the degradative capacity of AD microglia in vitro.ConclusionTogether these results indicate that Aβ is degraded via autophagy and that autophagy is defective in AD microglia. Our projects in the lab are seeking to establish additional consequences beyond failure of Aβ‐clearance, such as inability to regulate expression of inflammatory cytokines, and mechanisms behind dysregulated autophagy, such as epigenetic changes.
2020 annual report of Japanese brain bank network for neuroscience research
Authors: Murayama Shigeo , Saito Yuko 
Published: December 2020

AbstractBackgroundThe Japanese Society of Neuropathology (JSNP) stared the Brain Bank Committee in 1986 and has made continuous effort to establish all Japan Brain Bank Network.MethodThe Brain Bank for Aging Research was established in 1999, including 1,200 frozen brain and peripheral tissues from cohort of aging community and 130 neurodegenerative disorders from all over Japan. BBAR invited members of JSNP to form a brain bank network of Western style, consisting of brain donation, open resource, quality control including neuropathological diagnostic criteria in 2010.ResultThree brain banks: National Center of Neurology and Psychiatry (NCNP), Mihara Memorial Hospital (MMH) and Fukushimura Hospital (FH) participated the Japanese Brain Bank Network for Neuroscience Research (JBBNNR) and received funding of Ministry of Education, Culture, Sports and Technology, Japan. All resources were from general autopsy and had clinical and radiological information. NCNP was for neurodegenerative and muscle disorders, MMH for ALS, cerebrovascular disorders and prion disease and FH for terminal cases of dementia and aging. In 2020, the Graduate School of Medicine, Osaka University will participate the network for developmental disorders. In japan, autopsy was the main source of human research and our project will be effective for ADNI‐ type clinical study constructing bioresource as well as postmortem human tissue.ConclusionOur brain bank project contributes to establish neurobiobank in Japan, bridging genome, bioresource, neuroimages and postmortem human tissue. The main target is human aging and the next step will be human development.
Integrated memory care clinic: Primary care for people living with dementia
Authors: Clevenger Carolyn K , Medders Laura J 
Published: December 2020

AbstractBackgroundThe Integrated Memory Clinic (IMCC) serves individuals with a dementia diagnosis, such as Alzheimer’s disease or a related disorder, and their care partners who reside in a community setting. The IMCC is America’s first and only comprehensive primary and dementia care practice. The IMCC addresses a primary concern for nearly 6 million Americans living with dementia: How to identify a primary care practice that is knowledgeable about, and sensitive to, the complex medical and social issues associated with a dementia diagnosis and also that can manage the co‐morbidities common in aging. The model takes a primary palliative care perspective, emphasizing aggressive symptom management, advance care planning, and holistic care that focuses on improving the quality of life for the person living with dementia and their care partner. The IMCC’s patient‐centered approach allows patients to receive a broad array of health care services in a single visit from an interdisciplinary team. The IMCC team supports families living with dementia by focusing on the care recipient and care partner well‐being and quality of life, by processes designed to avoid inappropriate acute and emergency care utilization, and through stage‐based support and psychoeducational programs. The IMCC launched a Patient Family Advisory Council simultaneously with enrolling its first patient. The Council meets monthly to review and advise health care providers about clinic operations, communications, billing practices, and sustainability. Currently, four nurse practitioners deliver care to approximately 550 patients. The average age of the patient population is 78 years; 65% of patients are female; 42% of patients are non‐white. The ambulatory care sensitive admission rate ranges from 1.56% to 2.87% for the past 12 months. Performance in hypertension and diabetes management outperforms health system benchmark goals for primary care practices. The IMCC nurse practitioners’ overall patient experience scores are at 97th percentile, representing a meaningful and positive caregiver experience. The IMCC has earned national recognition as a patient‐centered medical home from the National Commission on Quality Assurance. The IMCC represents a novel model of care for people living with dementia and their caregivers and may be a more sustainable model for this growing vulnerable population.
Daily functioning and cognition: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA)
Authors: Stickel Ariana , Tarraf Wassim , Wu Benson , Marquine Maria J , Vasquez Priscilla M , Daviglus Martha , Estrella Mayra L , Perreira Krista , Gallo Linda , Lipton Richard B , Isasi Carmen R , Kaplan Robert , Zeng Donglin , Schneiderman Neil , Gonzalez Hector M 
Published: December 2020

AbstractBackgroundHispanics/Latinos are at increased risk for Alzheimer’s disease and related dementias (ADRD). Impairments in both cognition and daily functioning are required to meet clinical criteria for ADRD. Poorer cognition and female sex have been associated with greater declines in daily functioning with age. However, predictors of daily functioning among older Hispanics/Latinos are seldom investigated.MethodParticipants included 6292 cognitively healthy adults from the Study of Latinos ‐ Investigation of Neurocognitive Aging (SOL‐INCA), an ancillary study of a subset of participants 50+ years old in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Cognitive data (learning and memory, executive functioning, processing speed) were collected at Visit 1 (HCHS/SOL). Daily functioning was assessed using the self‐rated version of the Instrumental Activities of Daily Living (IADL) questionnaire at Visit 2 (SOL‐INCA), an average of 7 years later. We used survey two‐part models (mixture of logit and generalized linear model with Gaussian distribution) and ordered logistic regression to examine whether cognitive performance (on individual tests and a cognitive composite z‐score) was associated with later functioning (risk of any impairment and degree of impairment) and tested for modifications by age (50‐59/60‐69/70+ years: Unweighted ns =2,659, 2,576, 1,057) and sex (male/female: Unweighted ns = 2239, 4053).ResultAfter covariates adjustment, higher Visit 1 global cognitive (z‐score units) performance (OR= 0.56; 95% CI=[0.47;0.67]; p<0.001), as well as higher domain specific cognitive function, were associated with lower risk of any IADL dysfunction at Visit 2. Associations were stronger for the oldest group (70+ years) relative to the youngest group (50‐59 years), and this was consistent for all measures, except word fluency. Sex did not modify any associations between cognition and later functioning. Across the full sample, higher scores on learning, memory, and the cognitive composite were also associated with lower degree of IADL impairment.ConclusionOur findings confirm that cognitive health is an important predictor of everyday functioning among Hispanics/Latinos 7‐years later, especially in older adulthood. Additionally, IADL functioning among female Hispanics/Latinas was no more or less impacted by cognition as compared to their male counterparts.
Preventive strategy against PM2.5‐induced neuronal cell death
Authors: Kwon Kyoung J.A. , Kim Ryeung‐Eun , Han Seol‐Heui 
Published: December 2020

AbstractBackgroundParticulate matter 2.5 (PM2.5) can gain access to the lungs and the circulatory system and may sequentially cross the blood brain barrier (BBB). Recent data suggested that these particles reaching the brain may cause neurological disorders including AD and PD. However, there is no study on how to prevent PM2.5‐induced inflammation and neurotoxicity.ObjectiveIn this study, we have demonstrated that PM2.5 increases the neuroinflammation and neuronal cell death, and that natural products such as astaxanthin and chlorophyll can prevent the subsequent neurotoxicity, mainly based on its anti‐oxidative and anti‐inflammatory properties. In this study, we have demonstrated that PM2.5 increases the neuroinflammation and neuronal cell death, and that natural products such as astaxanthin and chlorophyll can prevent the subsequent neurotoxicity, mainly based on its anti‐oxidative and anti‐inflammatory properties.MethodIn this regard, we measured 1) the mRNA expression of inflammatory mediators including iNOS, IL‐1b, and IL‐6, 2) the nitric oxide and reactive oxygen species production, 3) signaling molecules such as MAPKs and PI3K, 4) neurite extension and neuronal cell death using the immunocytochemistry and MTT assay. We used a well‐characterized Diesel particulate matter, PM2.5, from SIGMA‐Aldrich.ResultPM2.5 increased inflammatory cytokines such as IL‐6 and IL‐1b production in rat astrocytes and microglia. Natural products including astaxanthin, chlorophyll and olive oil components attenuated PM2.5‐induced increased NO and other inflammatory cytokines expressions and prevented neuronal cell death in rat primary cortical neurons.ConclusionOur results show that PM2.5 activates the glia through inflammation leading to neurotoxicity, and natural products we tested can prevent this through the inhibition of glial activation. These results demonstrate natural products such as astaxanthin, chlorophyll and olive oil components as the candidate against air pollution exposure such as PM2.5.
The Digital Choice Anxiety Survey (DCAS): Initial development and validation
Authors: Hall Aidan , Mak‐McCully Rachel , Glenn Jordan M. , Madero Erica N. , Fuseya Nami , Gills Joshua L. , Gray Michelle , Bott Nick 
Published: December 2020

AbstractBackgroundPsychiatric symptomatology, including anxiety, partially comprise the clinical prodrome of dementia. Moreover, increased anxiety may represent a risk factor associated with neurodegenerative disease. Efficient, longitudinal measurement of anxiety remains difficult with traditional paper‐pencil measures. As few digital measures of anxiety symptomatology exist, we aimed to develop and validate a digitally native, efficient and repeatable, anxiety survey to measure self‐reported anxiety in adults: the Digital Choice Anxiety Survey (DCAS).MethodDevelopment of the DCAS included three studies: Study one included adult participants (n=407) who completed a larger set of anxiety questions, alongside the Penn State Worry Questionnaire (PSWQ) and General Anxiety Disorder 7‐item (GAD‐7) survey. Factor analysis then reduced the larger set of DCAS questions and investigated convergent validity and accuracy of the DCAS. Study two recruited a sub‐sample of the original cohort (n=70) who completed the reduced DCAS survey to investigate convergent validity with the Geriatric Depression Scale (GDS). Study three recruited a separate sample of adults (n =58), who were administered the DCAS at baseline and again approximately two weeks after initial administration to examine test‐retest reliability.ResultStudy one: Mean participant age was 42.92±12.86 years. After removing questions with a Spearman’s correlation greater than or equal to 0.6, DCAS was shortened from 20 to 7 items. The 7 items showed strong internal reliability (Cronbach’s α=0.86), with a one factor solution found utilizing factor analysis (all factors r>0.56). There were positive associations with the PSWQ and GAD‐7 (r=0.82 & r=0.85), with overall accuracy of 0.93 for moderate anxiety on both PSWQ & GAD‐7. Study two: Mean participant age was 48.94±14.63 years. A positive association was found between the 7‐item DCAS and the GDS‐15 (r=0.58, p<0.01). Study three: Mean participant age was 54.79±12.53 years. Participants completed the DCAS an average of 11.7 days apart (SD=1.2) and showed robust test‐retest reliability (Pearson’s r=0.81).ConclusionThis study provides evidence for psychometric validity and reliability of the DCAS. Follow‐up studies will investigate performance of the DCAS on clinically characterized populations and examine participant‐associated meta‐data.
Cognitive and physical functioning as predictors of everyday functioning
Authors: Chan Michelle L. , Eng Chloe W. , Farias Sarah Tomaszewski , Gilsanz Paola , Whitmer Rachel A. 
Published: December 2020

AbstractBackgroundAlzheimer’s disease and associated cognitive impairments are major contributors to functional declines and difficulties with instrumental activities of daily living (IADL); however, it is postulated that functional decline is likely a product of multiple factors. Higher prevalence of cardiovascular conditions has been associated with greater vascular brain injury that can result in greater physical impairments (slower gait speed and reduced grip strength). Thus, physical functioning can also contribute to IADL disability. The current study examined how cognitive and physical functioning contribute to IADL functioning among a diverse ethnoracial sample.MethodThe Kaiser Healthy Aging and Diverse Life Experience (KHANDLE) cohort is comprised of Kaiser Permanente Northern California members who are age ≥65, without a diagnosis of cognitive impairment or dementia, and who participated in Multiphasic Health Checkups between 1964‐1977. At enrollment, participants completed a self‐report measure of IADLs, neuropsychological testing measuring memory and executive functioning, and physical functioning assessment (grip strength and walk speed). Analyses include 1,260 participants (401 Caucasian (32%), 339 African American (27%), 292 Asian (23%), and 228 Latino (18%)).ResultThe sample was comprised of 59.05% females and average baseline age was 75.5 ± 6.8 years. When examined individually, executive functioning (p=0.0466), grip strength (p=0.0005), and walking speed (p<.0001) were significant predictors of IADL functioning after controlling for demographics (age, education, gender, self‐rated health). Memory (p=0.4468) was not a significant predictor. When considering all 4 of these predictors in a combined model, walk speed remained the only significant predictor of IADL performance (p<.000) with slower walking speed being associated with poorer IADL performance. This relationship also differed by race (p=0.0011), with slower walk speed having the greatest negative impact in Asians.ConclusionThere are limited studies examining how both cognitive and physical functioning predicts everyday functioning, particularly among a diverse ethnoracial sample. Our results indicate that among a cohort of older adults without a formal diagnosis of cognitive impairment or dementia, physical functioning, specifically walking speed, plays an important role in IADL difficulties. Importantly, when considering walking speed, executive functioning was no longer independently associated with IADL performance. Such findings have important implications in terms of screening older persons at risk for IADL disability.
To be alive vs. to live: Filipino elderly, nasogastric tubes, and the issue of artificial feeding in dementia
Authors: Cuadro Carla Krishan A , Herrera Janel Alexis O , Quiros Thomas L 
Published: December 2020

AbstractBackgroundNasogastric tubes (NGTs) are part of the nutritional intervention of patients who present with dysphagia. While NGTs guarantee the unimpeded delivery of nutrients into a body, complaints about its discomfort and aftercare are rife. The provision of continuous nutritional support takes precedence over the NGTs’ infection and aspiration risks. The issue of artificial feeding takes a more urgent turn among individuals with dementia, where frequent pull‐outs and physical resistance are common. Using percutaneous endoscopic gastrostomy (PEG) tubes relieve one of NGT discomfort. However, research had questioned PEG tubes’ ability to improve patients’ nutritional status. For those who do use it, maintenance issues, pull‐outs, and cultural beliefs on ‘holes’ on the abdomen prevail. While most societies equate food intake as supportive of life, risking the use of feeding tubes with those with neurodegenerative conditions remains debatable. There is a paucity of research that investigate the lived experiences of elderly who wore NGTs. Using illness narratives of cognitively‐intact, verbal Filipino elderly, this project interrogated NGT insertion processes, living with the tube, bodily integrity, fullness vs. satiety, and what is amiss such that to be alive is discrepant from to live.
MethodIn‐depth episodic interviews were held among 10 older Filipinos aged 60+ years who were using or had used NGTs. These personal narratives were audio‐recorded, transcribed verbatim, and subjected to Burnard’s (1991) qualitative data analysis. The data was coded, categorized, underwent reordering and clustering to identify patterns or recurrent themes.ResultThemes on NGT as an obstruction but necessary to ‘eat,’ sensation of an NGT in one’s body, and insertion/reinsertion issues dominated these narratives. Recurring themes included NGT feeding as redefining what is gutom (hunger) to the patient, how taste contributed to satiation, and the disparity between napuno (filled up) vs. nabusog (satiated).ConclusionConcepts about the NGT as necessary but dissociates fullness from satiation, as being filled up yet never ‘eating’ may be common among older Filipinos on the tube. Understanding these perspectives may guide healthcare professionals on how individuals with dementia understand life on the tube, lending further scholarly insight on the tube‐feeding quality of life of this population.
Boot camp translation of Alzheimer’s disease and the Engaging Communities of Hispanics for Aging Research (ECHAR) Network
Authors: Medina Luis D , Mullen Rebecca , Pressman Peter S , Woods Steven P 
Published: December 2020

AbstractBackgroundHispanics/Latinos (H/Ls), the largest ethnic minority in the U.S., are 50% likelier than non‐Hispanic whites to develop Alzheimer’s disease‐related dementias (ADRD). Despite comprising 18% of the U.S. population, H/Ls represent less than 1% of participants in NIH‐funded clinical trials and less than 8% of NIH AD Research Centers, greatly limiting understanding of underlying causes of disparities. However, health literacy gaps may impact research participation. We introduce here the Engaging Communities of Hispanics for Aging Research (ECHAR) Network. The overall objective of this collaborative, transdisciplinary network is to engage, educate, and motivate H/L community members for participation in ADRD research by addressing ADRD‐related communication through use of a novel community‐based participatory method – Boot Camp Translation (BCT).MethodBCT is a manualized, robust six‐to‐eight‐month program designed to translate medical jargon into action‐based messages that are more effectively consumed by local communities. It fosters engagement between clinical experts and patients as well as community members with the overarching goal of helping to make medical evidence and guidelines locally relevant and accessible. We completed the first known BCT on ADRD with 15 community stakeholders in the Denver metropolitan area over 6 months.ResultWe had 0% attrition. Group members saw a significant (p<0.05) improvement in both subjective understanding and objective knowledge of ADRD. Four main themes were perceived as most relevant to their community: the importance of brain health, a call for self‐advocacy in medical settings and with providers, the need to learn more through research, and awareness of basic targets of cognitive changes that may be associated with ADRD. These themes were structured into a dissemination plan that included both printed and digital materials in addition to oral presentations shared with community organizations.ConclusionThe ECHAR Network aims to expand these initial findings. By the end of this project, ECHAR will have: (1) established and trained community advisory committees on ADRD in at least three cities; (2) developed key, culturally‐informed, ADRD‐related materials as well as dissemination and evaluation strategies for H/L recruitment; and (3) developed sustainable research infrastructure to enhance outreach by supporting health disparities investigators and pilot grants.