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AGEs and dementia

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https://www.readbyqxmd.com/read/28453791/progranulin-functions-as-a-cathepsin-d-chaperone-to-stimulate-axonal-outgrowth-in-vivo
#1
Sander Beel, Matthieu Moisse, Markus Damme, Louis De Muynck, Wim Robberecht, Ludo Van Den Bosch, Paul Saftig, Philip Van Damme
Loss of function mutations in progranulin (GRN) cause frontotemporal dementia, but how GRN haploinsufficiency causes neuronal dysfunction remains unclear. We previously showed that GRN is neurotrophic in vitro. Here, we used an in vivo axonal outgrowth system and observed a delayed recovery in GRN-/- mice after facial nerve injury. This deficit was rescued by reintroduction of human GRN and relied on its C-terminus and on neuronal GRN production. Transcriptome analysis of the facial motor nucleus post injury identified cathepsin D (CTSD) as the most upregulated gene...
April 26, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28449471/one-year-and-long-term-mortality-in-patients-hospitalized-for-chronic-obstructive-pulmonary-disease
#2
María-Teresa García-Sanz, Juan-Carlos Cánive-Gómez, Laura Senín-Rial, Jorge Aboal-Viñas, Alejandra Barreiro-García, Eva López-Val, Francisco-Javier González-Barcala
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Identifying potentially-modifiable predictors of mortality could help optimize COPD patient management. The aim of this study is to determine long-term mortality following hospitalization due to acute exacerbations of COPD (AECOPD), as well as AECOPD mortality predictors. METHODS: We conducted a retrospective study by reviewing the medical records of all patients admitted with AECOPD in the University Hospital Complex of Santiago de Compostela in 2007 and 2008...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28449347/caregiving-for-older-adults-with-obesity-in-the-united-states
#3
Claire K Ankuda, John Harris, Katherine Ornstein, Deborah A Levine, Kenneth M Langa, Amy S Kelley
OBJECTIVES: To determine the difference in receipt of activity of daily living (ADL) assistance between obese and normal-weight older adults. DESIGN: Retrospective cohort study. SETTING: National Health and Aging Trends Study, 2011-2015. PARTICIPANTS: U.S. adults aged 65 and older with ADL disability and a body mass index (BMI) of 18.5 kg/m(2) or greater (N = 5,612) MEASUREMENTS: BMI was classified as normal weight (18...
April 27, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28448998/efficacy-safety-and-tolerability-of-armodafinil-therapy-for-hypersomnia-associated-with-dementia-with-lewy-bodies-a-pilot-study
#4
Maria I Lapid, Karen M Kuntz, Sara S Mason, Jeremiah A Aakre, Emily S Lundt, Walter Kremers, Laura A Allen, Daniel A Drubach, Bradley F Boeve
BACKGROUND/AIMS: Hypersomnia is common in dementia with Lewy bodies (DLB). We assessed the efficacy, safety, and tolerability of armodafinil for hypersomnia associated with DLB. METHODS: We performed a 12-week pilot trial of armodafinil therapy (125-250 mg orally daily) in DLB outpatients with hypersomnia. The patients underwent neurologic examinations, a neuropsychological battery, laboratory testing, electrocardiography, and polysomnography. Efficacy was assessed at 2, 4, 8, and 12 weeks...
April 28, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28448971/pre-esrd-dementia-and-post-esrd-mortality-in-a-large-cohort-of-incident-dialysis-patients
#5
Miklos Z Molnar, Keiichi Sumida, Abduzhappar Gaipov, Praveen K Potukuchi, Tibor Fülöp, Kiran Joglekar, Jun Ling Lu, Elani Streja, Kamyar Kalantar-Zadeh, Csaba P Kovesdy
BACKGROUND: Conservative management may be a desirable option for elderly, fragile, or demented patients who reach end-stage renal disease (ESRD), yet some patients with dementia are placed on renal replacement therapy nonetheless. METHODS: From a nationwide cohort of 45,076 US veterans who transitioned to ESRD over 4 contemporary years (October 1, 2007 to September 30, 2011), we identified 1,336 (3.0%) patients with International Classification of Diseases, Ninth Revision, Clinical Modification code-based dementia diagnosis during the prelude (predialysis) period...
April 28, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28448676/-i-m-still-here-personhood-and-the-early-onset-dementia-experience
#6
Mariko L Sakamoto, Sharon L Moore, Steven T Johnson
Early-onset dementia (EOD) occurs before age 65. The current study examined the lived experience from the point of view of four adults younger than 65 with dementia, particularly how they perceive their personhood. Using interpretative phenomenological analysis as the research approach, findings revealed that the EOD experience can be incorporated into six themes: (a) A Personal Journey, (b) Navigating the System, (c) The Stigma of Dementia, (d) Connecting to the World, (e) A Story Worth Telling, and (f) I'm Still Here...
May 1, 2017: Journal of Gerontological Nursing
https://www.readbyqxmd.com/read/28448628/determinants-of-formal-care-use-and-expenses-among-in-home-elderly-in-jing-an-district-shanghai-china
#7
Fen Li, Xinye Fang, Jiechun Gao, Hansheng Ding, Changying Wang, Chunyan Xie, Yitong Yang, Chunlin Jin
The need for formal care among the elderly population has been increasing due to their greater longevity and the evolution of family structure. We examined the determinants of the use and expenses of formal care among in-home elderly adults in Shanghai. A two-part model based on the data from the Shanghai Long-Term Care Needs Assessment Questionnaire was applied. A total of 8428 participants responded in 2014 and 7100 were followed up in 2015. The determinants of the probability of using formal care were analyzed in the first part of the model and the determinants of formal care expenses were analyzed in the second part...
2017: PloS One
https://www.readbyqxmd.com/read/28448092/handgrip-strength-predicts-longitudinal-changes-in-clock-drawing-test-performance-an-observational-study-in-a-sample-of-older-non-demented-adults
#8
G Viscogliosi, M G Di Bernardo, E Ettorre, I M Chiriac
OBJECTIVE: Impairment of physical performance might identify older people at higher risk of dementia over time. The present study evaluated handgrip strength as independent predictor of cognitive decline. DESIGN: Observational, prospective. Follow-up duration: 11.2 ± 0.8 months. SETTING AND PARTICIPANTS: Geriatric outpatients center. 104 consecutive stroke- and dementia-free older adults (44% men, ages 80.2 ± 5.4 years). METHODS: The Clinical Dementia Rating scale and the Clock Drawing Test (CDT) were administered...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28448085/obesity-and-cognitive-decline-in-adults-effect-of-methodological-choices-and-confounding-by-age-in-a-longitudinal-study
#9
K Deckers, M P J Van Boxtel, F R J Verhey, S Köhler
BACKGROUND AND OBJECTIVES: Obesity has been associated with increased risk of cognitive impairment or dementia, but recent findings are contradictory, possibly due to methodological differences. The present study tries to clarify these inconsistencies by following the cognitive trajectories of individuals with obesity over 12 years and studying the effect of obesity status (obesity at baseline versus incident obesity at follow-up), chronicity, definition, potential confounding (e.g. age, cardiovascular factors), and non-linear associations...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28447221/deleterious-abca7-mutations-and-transcript-rescue-mechanisms-in-early-onset-alzheimer-s-disease
#10
Arne De Roeck, Tobi Van den Bossche, Julie van der Zee, Jan Verheijen, Wouter De Coster, Jasper Van Dongen, Lubina Dillen, Yalda Baradaran-Heravi, Bavo Heeman, Raquel Sanchez-Valle, Albert Lladó, Benedetta Nacmias, Sandro Sorbi, Ellen Gelpi, Oriol Grau-Rivera, Estrella Gómez-Tortosa, Pau Pastor, Sara Ortega-Cubero, Maria A Pastor, Caroline Graff, Håkan Thonberg, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Alexandre de Mendonça, Madalena Martins, Barbara Borroni, Alessandro Padovani, Maria Rosário Almeida, Isabel Santana, Janine Diehl-Schmid, Panagiotis Alexopoulos, Jordi Clarimon, Alberto Lleó, Juan Fortea, Magda Tsolaki, Maria Koutroumani, Radoslav Matěj, Zdenek Rohan, Peter De Deyn, Sebastiaan Engelborghs, Patrick Cras, Christine Van Broeckhoven, Kristel Sleegers
Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing...
April 27, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28446656/effect-of-a-long-term-intensive-lifestyle-intervention-on-prevalence-of-cognitive-impairment
#11
Mark A Espeland, José A Luchsinger, Laura D Baker, Rebecca Neiberg, Steven E Kahn, Steven E Arnold, Rena R Wing, George L Blackburn, George Bray, Mary Evans, Helen P Hazuda, Robert W Jeffery, Valerie M Wilson, Jeanne M Clark, Mace Coday, Kathryn Demos-McDermott, John P Foreyt, Frank Greenway, James O Hill, Edward S Horton, John M Jakicic, Karen C Johnson, William C Knowler, Cora E Lewis, David M Nathan, Anne Peters, Xavier Pi-Sunyer, Henry Pownall, Thomas A Wadden, Stephen R Rapp
OBJECTIVE: To assess whether an average of 10 years of lifestyle intervention designed to reduce weight and increase physical activity lowers the prevalence of cognitive impairment among adults at increased risk due to type 2 diabetes and obesity or overweight. METHODS: Central adjudication of mild cognitive impairment and probable dementia was based on standardized cognitive test battery scores administered to 3,802 individuals who had been randomly assigned, with equal probability, to either the lifestyle intervention or the diabetes support and education control...
April 26, 2017: Neurology
https://www.readbyqxmd.com/read/28446209/antipsychotic-prescribing-for-alzheimer-s-disease-and-related-disorders-in-specialized-settings-from-2010-to-2014-in-france-a-repeated-cross-sectional-study
#12
Karim Tifratene, Valeria Manera, Roxane Fabre, Auriane Gros, Susanne Thummler, Christian Pradier, Philippe Robert, Renaud David
BACKGROUND: Safety warnings from health authorities are currently intended to limit the use of antipsychotics (APs) in dementia-related conditions to treat neuropsychiatric symptoms, such as disturbing and/or delusional behaviors. The aim of this study is to investigate prevalence, correlates and trends of AP prescribing among people with dementia between 2010 and 2014 in the French population. METHODS: AP prescribing and associated factors among individuals with AD, mixed dementia and vascular dementia in the French National Alzheimer Database between 2010 and 2014 were analyzed using multivariate generalized estimating equations models (n = 199,549)...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28444124/predicting-discharge-to-institutional-long-term-care-following-acute-hospitalisation-a-systematic-review-and-meta-analysis
#13
Jennifer Kirsty Harrison, Katherine E Walesby, Lorna Hamilton, Carolyn Armstrong, John M Starr, Emma L Reynish, Alasdair M J MacLullich, Terry J Quinn, Susan D Shenkin
Background: moving into long-term institutional care is a significant life event for any individual. Predictors of institutional care admission from community-dwellers and people with dementia have been described, but those from the acute hospital setting have not been systematically reviewed. Our aim was to establish predictive factors for discharge to institutional care following acute hospitalisation. Methods: we registered and conducted a systematic review (PROSPERO: CRD42015023497)...
April 21, 2017: Age and Ageing
https://www.readbyqxmd.com/read/28443508/nutritional-deficiency-in-early-life-facilitates-aging-associated-cognitive-decline
#14
Yu Kang, Yun Zhang, Zijuan Feng, Mingjing Liu, Yanhua Li, Huan Yang, Dan Wang, Lingling Zheng, Dandan Lou, Liangping Cheng, Chunjiang Chen, Weitao Zhou, Yi Feng, Xiaoyong Li, Jianzhong Duan, Mengjiao Yu, Shou Yang, Yuhang Liu, Xin Wang, Bo Deng, Chenghui Liu, Xiuqing Yao, Chi Zhu, Chunrong Liang, Xiaolong Zeng, Sisi Ren, Qunying Li, Yin Zhong, Yong Zhang, Jun Kang, Yong Yan, Huaqing Meng, Zhaohui Zhong, Weihui Zhou, Yanjiang Wang, Tingyu Li, Weihong Song
BACKGROUND: Nutrition is important for the fetal developmental programming. Nutritional deficiency in early life could increase the susceptibility to many aging-related disorders including cognitive decline. OBJECTIVE: Our study aims to investigate the effect of early famine exposure on aging-associated cognitive function. METHODS: We recruited 6790 subjects born between 1956 to 1964 during which the Great Chinese Famine occurred (1959-1961)...
April 24, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28442895/oral-health-related-quality-of-life-and-prosthetic-status-of-nursing-home-residents-with-or-without-dementia
#15
Anna-Luisa Klotz, Alexander Jochen Hassel, Johannes Schröder, Peter Rammelsberg, Andreas Zenthöfer
PURPOSE: The objective of this cross-sectional study was to evaluate the effect of prosthetic status on the oral health-related quality of life (OHRQoL) of nursing home residents with or without dementia. METHODS: The study was performed in 14 nursing homes across the federal state of Baden-Württemberg, Germany. All eligible participants were included, and general and medical information and information about their dental and prosthetic statuses were collected...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28442216/trem2-microglia-and-neurodegenerative-diseases
#16
REVIEW
Felix L Yeh, David V Hansen, Morgan Sheng
Alzheimer's disease (AD) is the most common form of dementia and the 6th leading cause of death in the US. The neuropathological hallmarks of the disease are extracellular amyloid-β (Aβ) plaques and intraneuronal hyperphosphorylated tau aggregates. Genetic variants of TREM2 (triggering receptor expressed on myeloid cells 2), a cell-surface receptor expressed selectively in myeloid cells, greatly increase the risk of AD, implicating microglia and the innate immune system as pivotal factors in AD pathogenesis...
April 22, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#17
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28439722/dna-methylation-age-acceleration-is-associated-with-disease-duration-and-age-at-onset-in-c9orf72-patients
#18
Ming Zhang, Maria Carmela Tartaglia, Danielle Moreno, Christine Sato, Paul McKeever, Anna Weichert, Julia Keith, Janice Robertson, Lorne Zinman, Ekaterina Rogaeva
The repeat expansion in C9orf72 is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. C9orf72 patients present with a wide range in disease duration and age of onset. The strongest risk factor for both syndromes is aging, which was linked to DNA methylation (DNAm) age based on the cumulative assessment of the methylation levels of 353 CpGs included on the genome-wide 450k BeadChip. DNAm age may reflect biological age better than chronological age. We conducted a genome-wide blood DNA methylation study of 46 unrelated C9orf72 patients...
April 24, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28439716/antipsychotic-prescribing-to-patients-diagnosed-with-dementia-without-a-diagnosis-of-psychosis-in-the-context-of-national-guidance-and-drug-safety-warnings-longitudinal-study-in-uk-general-practice
#19
S Jill Stocks, Evangelos Kontopantelis, Roger T Webb, Anthony J Avery, Alistair Burns, Darren M Ashcroft
INTRODUCTION: Policy interventions to address inappropriate prescribing of antipsychotic drugs to older people diagnosed with dementia are commonplace. In the UK, warnings were issued by the Medicines Healthcare products Regulatory Agency in 2004, 2009 and 2012 and the National Institute for Health and Care Excellence guidance was published in 2006. It is important to evaluate the impact of such interventions. METHODS: We analysed routinely collected primary-care data from 111,346 patients attending one of 689 general practices contributing to the Clinical Practice Research Datalink to describe the temporal changes in the prescribing of antipsychotic drugs to patients aged 65 years or over diagnosed with dementia without a concomitant psychosis diagnosis from 2001 to 2014 using an interrupted time series and a before-and-after design...
April 24, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28438992/microglial-nf%C3%AE%C2%BAb-tnf%C3%AE-hyperactivation-induces-obsessive-compulsive-behavior-in-mouse-models-of-progranulin-deficient-frontotemporal-dementia
#20
Grietje Krabbe, S Sakura Minami, Jon I Etchegaray, Praveen Taneja, Biljana Djukic, Dimitrios Davalos, David Le, Iris Lo, Lihong Zhan, Meredith C Reichert, Faten Sayed, Mario Merlini, Michael E Ward, David C Perry, Suzee E Lee, Ana Sias, Christopher N Parkhurst, Wen-Biao Gan, Katerina Akassoglou, Bruce L Miller, Robert V Farese, Li Gan
Frontotemporal dementia (FTD) is the second most common dementia before 65 years of age. Haploinsufficiency in the progranulin (GRN) gene accounts for 10% of all cases of familial FTD. GRN mutation carriers have an increased risk of autoimmune disorders, accompanied by elevated levels of tissue necrosis factor (TNF) α. We examined behavioral alterations related to obsessive-compulsive disorder (OCD) and the role of TNFα and related signaling pathways in FTD patients with GRN mutations and in mice lacking progranulin (PGRN)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
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