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Drugs on Dementia

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https://www.readbyqxmd.com/read/28733961/a-review-of-biomarkers-for-neurodegenerative-disease-will-they-swing-us-across-the-valley
#1
REVIEW
Thomas G Beach
Measures of the severity of cognitive impairment or parkinsonism are the usual endpoints in clinical trials for Alzheimer's disease (AD) and Parkinson's disease (PD), but are critically hampered by their lack of disease sensitivity and specificity. Due to the high failure rate of clinical trials, the rate of regulatory approval for efficacious new drugs has stagnated in the past few decades, with the gap between basic science discovery and clinical application metaphorically termed the "Valley of Death". While the causes for this are probably multiple and complex, the usage of biomarkers as surrogate endpoints, particularly when they are molecularly-specific for the disease, has achieved some success in cancer trials, and it is likely that neurodegenerative disease trials would benefit from the same approach...
July 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28729367/dementia-research-focuses-on-prevention-as-drugs-fail-to-deliver
#2
Jacqui Wise
No abstract text is available yet for this article.
July 20, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28726490/psychotropic-drug-prescription-for-nursing-home-residents-with-dementia-prevalence-and-associations-with-non-resident-related-factors
#3
Claudia H W Smeets, Debby L Gerritsen, Sytse U Zuidema, Steven Teerenstra, Klaas van der Spek, Martin Smalbrugge, Raymond T C M Koopmans
OBJECTIVES: To determine psychotropic drug prescription rates in nursing home residents with dementia and to identify associations with the so far understudied psychosocial non-resident-related factors. METHOD: A cross-sectional, observational, exploratory design as part of PROPER I (PRescription Optimization of Psychotropic drugs in Elderly nuRsing home patients with dementia). Participants were 559 nursing home residents with dementia, 25 physicians, and 112 nurses in the Netherlands...
July 20, 2017: Aging & Mental Health
https://www.readbyqxmd.com/read/28721544/sleep-in-older-adults-and-in-subjects-with-dementia
#4
REVIEW
Helmut Frohnhofen, Jeanina Schlitzer, Nikolaus Netzer
The neuronal structures for the regulation of sleep and wakefulness are located in the brain. This complex network is vulnerable to numerous factors, most importantly neurodegenerative diseases and drugs. The macrostructure and microstructure of sleep change with age. These changes are more pronounced in subjects with dementia. Sleep disorders in subjects with dementia may be independent of dementia or caused by dementia. Furthermore, epidemiological studies reveal that sleep disorders per se may induce dementia by reduction of cerebral clearance of beta-amyloids...
July 18, 2017: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/28720101/drug-candidates-in-clinical-trials-for-alzheimer-s-disease
#5
REVIEW
Shih-Ya Hung, Wen-Mei Fu
Alzheimer's disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation...
July 19, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28719360/alzheimer-s-disease-dawn-of-a-new-era
#6
Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Huong V Nguyen, Hamidreza Montazeri Aliabadi
Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique drug development issues associated with this disease...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28716141/the-german-day-care-study-multicomponent-non-drug-therapy-for-people-with-cognitive-impairment-in-day-care-centres-supplemented-with-caregiver-counselling-detamaks-study-protocol-of-a-cluster-randomised-controlled-trial
#7
Elisa-Marie Behrndt, Melanie Straubmeier, Hildegard Seidl, Stephanie Book, Elmar Graessel, Katharina Luttenberger
BACKGROUND: It is the wish of both people with cognitive impairment and their informal caregivers for the impaired person to live at home for as long as possible. This is also in line with economic arguments about health. The existing structure of day-care services for the elderly can be used to achieve this. Due to the current lack of empirical evidence in this field, most day-care centres do not offer a scientifically evaluated, structured intervention, but instead offer a mixture of individual activities whose efficacy has not yet been established...
July 17, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28714419/design-of-multi-target-agents-for-the-treatment-of-alzheimer-s-disease-based-on-tacrine
#8
Hongzhi Lin, Qi Li, Kai Gu, Jie Zhu, Xueyang Jiang, Yao Chen, Haopeng Sun
Alzheimer's disease (AD) is one of the most common forms of dementia in elderly people. To date, efficacious therapeutic agent for the treatment of AD is still very limited, so it has long been a challenging and attractive task to discover new anti-AD drugs. Considering the multifactorial nature of AD, recently, the concept of multi-target-directed ligands (MTDLs) has emerged as a new strategy for designing therapeutic agents on AD. MTDLs are believed to exert their effects through simultaneously affecting multiple targets which contribute to etiology of AD...
July 17, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28714389/a-peptide-based-pro-drug-ameliorates-amyloid-%C3%AE-induced-neuronal-apoptosis-in-in-vitro-sh-sy5y-cells
#9
Sourav Kumar, Ashim Paul, Sourav Kalita, Awanish Kumar, Saurabh Srivastav, Somoday Hazra, Anup Kumar Ghosh, Bhubaneswar Mandal, Amal Chandra Mondal
BACKGROUND: Alzheimer's disease (AD), a common protein misfolding neurodegenerative disorder, is one of the most common forms of dementia. Amyloid precursor protein (APP) derived amyloid-β (Aβ) proteins accumulated into interneuronal spaces and plays a crucial role in the disease progression and its pathology. The aggregated Aβ exerts its neurotoxic effects by inducing apoptosis and oxidative damage in neuronal cells. OBJECTIVES: We have investigated the effects of a synthesized Pro-Drug peptide (PDp) on Aβ1-40 induced cytotoxicity in human neuroblastoma SH-SY5Y cells, represents one of the most effective strategies in combating human AD...
July 13, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28713158/amyloid-beta-structure-biology-and-structure-based-therapeutic-development
#10
REVIEW
Guo-Fang Chen, Ting-Hai Xu, Yan Yan, Yu-Ren Zhou, Yi Jiang, Karsten Melcher, H Eric Xu
Amyloid beta peptide (Aβ) is produced through the proteolytic processing of a transmembrane protein, amyloid precursor protein (APP), by β- and γ-secretases. Aβ accumulation in the brain is proposed to be an early toxic event in the pathogenesis of Alzheimer's disease, which is the most common form of dementia associated with plaques and tangles in the brain. Currently, it is unclear what the physiological and pathological forms of Aβ are and by what mechanism Aβ causes dementia. Moreover, there are no efficient drugs to stop or reverse the progression of Alzheimer's disease...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28707586/an-overview-of-new-possible-treatments-of-alzheimer-s-disease-based-on-natural-products-and-semi-synthetic-compounds
#11
Enrico Zanforlin, Giuseppe Zagotto, Giovanni Ribaud
BACKGROUND: Dementias and all related neurodegenerative diseases of the Central Nervous System (CNS) are a current issue arousing a great deal of interest in the international scientific community. This is due to the increasing number of patients suffering from these diseases. These pathologies represent a serious problem, not only concerning the quality of life of the patient, but in addition, the enormous economic efforts that society has to do for their treatment. There are currently a few strategies that are available in order to prevent the progression or to mitigate symptoms of the aforementioned diseases...
July 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28705297/the-diagnosis-and-treatment-of-behavioral-disorders-in-dementia
#12
Torsten Kratz
BACKGROUND: Behavioral disorders such as aggressiveness, agitation, delusions, disinhibition, affect lability, and apathy arise in more than 90% of patients with dementia. Behavioral disorders are a major challenge and the greatest stress factor in everyday life for nursing personnel and for family members caring for the patient. METHODS: This review is based on relevant publications retrieved by a selective literature search in the PubMed, Cochrane Library, and German S3 guideline databases with the search terms "behavioral disorders," "non-cognitive disorders," and "challenging behavior," in conjunction with "dementia" and "behavioral and psychological symptoms of dementia...
June 30, 2017: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/28705243/trends-in-treatment-with-antipsychotic-medication-in-relation-to-national-directives-in-people-with-dementia-a-review-of-the-swedish-context
#13
Staffan Karlsson, Ingalill Rahm Hallberg, Patrik Midlöv, Cecilia Fagerström
BACKGROUND: The aim of this study was to explore trends in treatment with antipsychotic medication in Swedish dementia care in nursing homes as reported in the most recent empirical studies on the topic, and to relate these trends to directives from the national authorities. METHODS: The study included two scoping review studies based on searches of electronic databases as well as the Swedish directives in the field. RESULTS: During the past decade, directives have been developed for antipsychotic medication in Sweden...
July 14, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28701380/prediction-of-intracellular-exposure-bridges-the-gap-between-target-and-cell-based-drug-discovery
#14
André Mateus, Laurie J Gordon, Gareth J Wayne, Helena Almqvist, Hanna Axelsson, Brinton Seashore-Ludlow, Andrea Treyer, Pär Matsson, Thomas Lundbäck, Andy West, Michael M Hann, Per Artursson
Inadequate target exposure is a major cause of high attrition in drug discovery. Here, we show that a label-free method for quantifying the intracellular bioavailability (Fic) of drug molecules predicts drug access to intracellular targets and hence, pharmacological effect. We determined Fic in multiple cellular assays and cell types representing different targets from a number of therapeutic areas, including cancer, inflammation, and dementia. Both cytosolic targets and targets localized in subcellular compartments were investigated...
July 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28701239/the-role-of-primary-care-in-identification-and-ongoing-management-of-dementia-a-time-of-transition
#15
Constance Dimity Pond
In this edition of International Psychogeriatrics, Pertrazzuoli et al. (2017) address attitudes to dementia by primary care physicians (PCPs) across a range of European countries. The article focusses on diagnosis, screening instruments and drug treatment, and finds a wide range of approaches to the PCPs' role in referral for diagnosis and medication prescription. The findings include that PCPs who are allowed to prescribe dementia drugs, engage in higher levels of diagnostic work up, despite all the barriers to identification ably summarized in the paper...
July 13, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/28690633/how-do-community-dwelling-persons-with-alzheimer-disease-fall-falls-in-the-finalex-study
#16
Niko M Perttila, Hannareeta Öhman, Timo E Strandberg, Hannu Kautiainen, Minna Raivio, Marja-Liisa Laakkonen, Niina Savikko, Reijo S Tilvis, Kaisu H Pitkala
BACKGROUND: People with dementia are at high risk for falls. However, little is known of the features causing falls in Alzheimer disease (AD). Our aim was to investigate how participants with AD fall. METHODS: In the FINALEX (Finnish Alzheimer Disease Exercise Trial) study, participants' (n = 194) falls were followed up for 1 year by diaries kept by their spouses. RESULTS: The most common reason for falls (n = 355) was stumbling (n = 61). Of the falls, 123 led to injuries, 50 to emergency department visits, and 13 to fractures...
May 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/28688072/-a%C3%A2-qualitative-exploration-of-the-chronic-use-of-psychotropic-drugs-in-nursing-homes
#17
Lukas Leten, Majda Azermai, Maarten Wauters, Jan De Lepeleire
BACKGROUND: Although guidelines put forward non-pharmacological therapies and advise against the chronic use of psychotropic drugs, these are still being prescribed regularly in Belgian nursing homes. GOAL: To explore the reasons for initiation, continuation and cessation of psychotropic drug treatment of elderly with dementia and behavioral problems, residing in the nursing home. METHOD: Twenty-seven interviews from an earlier project were used, in which a semi-structured interview was conducted with the nursing staff, the physicians and the caretakers of eleven randomly selected residents from three nursing homes...
July 7, 2017: Tijdschrift Voor Gerontologie en Geriatrie
https://www.readbyqxmd.com/read/28687725/design-and-development-of-a-novel-chalcone-derivative-as-an-anticholinesterase-inhibitor-for-possible-treatment-of-dementia
#18
Fu-Chun Zhao, Yan Wu, Xiao-Jie Song
BACKGROUND Cognitive decline (e.g., memory loss), which mainly occurs in the elderly, is termed dementia. In the present study, we intended to explore the cholinesterase inhibitory activity of some novel synthesized chalcones, together with their effect on β-amyloid anti-aggregation. MATERIAL AND METHODS A novel class of chalcone derivatives have been synthesized and characterized by FT-IR, ¹H-NMR, ¹³C-NMR, and mass and elemental analysis. These derivatives were later used for the determination of acetylcholinesterase (AChE) inhibitory and b-amyloid anti-aggregation activity...
July 8, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28685694/multi-targeting-strategies-for-alzheimer-s-disease-therapeutics-pros-and-cons
#19
Sucharita Das, Soumalee Basu
Alzheimer's disease (AD) is a single major cause of dementia in middle to old age individuals involving several different etiopathological mechanisms that are yet to be properly characterized. Major invariant and characteristic features consist of the progressive cerebral deposition of the amyloid β-protein (Aβ) and the neurofibrillary degeneration through neurofibrillary tangles (NFT) formed by hyperphosphorylation of the tau proteins in the regions of the brain that deal with memory and cognition. There are at least five subgroups of AD that can be identified by determining cerebro-spinal fluid (CSF) levels of Aβ1-42, tau and ubiquitin...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28684681/interplay-between-autophagy-exosomes-and-hiv-1-associated-neurological-disorders-new-insights-for-diagnosis-and-therapeutic-applications
#20
REVIEW
Chet Raj Ojha, Jessica Lapierre, Myosotys Rodriguez, Seth M Dever, Mohammad Asad Zadeh, Catherine DeMarino, Michelle L Pleet, Fatah Kashanchi, Nazira El-Hage
The autophagy-lysosomal pathway mediates a degradative process critical in the maintenance of cellular homeostasis as well as the preservation of proper organelle function by selective removal of damaged proteins and organelles. In some situations, cells remove unwanted or damaged proteins and RNAs through the release to the extracellular environment of exosomes. Since exosomes can be transferred from one cell to another, secretion of unwanted material to the extracellular environment in exosomes may have an impact, which can be beneficial or detrimental, in neighboring cells...
July 6, 2017: Viruses
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