scholarly journals Study Design in Dementia Drug Trials

2007 ◽  
Vol 34 (S1) ◽  
pp. S19-S22
Author(s):  
Chris MacKnight
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Study Design ◽  
Biological Markers ◽  
Biological Marker ◽  
Convincing Evidence ◽  
Drug Trials ◽  
Disease Modification ◽  
The Past ◽  
Made In

A great deal of progress has been made in the management of Alzheimer's disease and other dementias over the past 25 years. Much remains to be achieved, however. This article discusses some of the issues surrounding study design. In the absence of an accepted biological marker of progression, it is unlikely that a novel study design, such as randomized start or withdrawal, in itself could provide convincing evidence of disease modification. Biological markers will also be crucial in the development of therapies aimed at specific processes, and of immunotherapies.

Current state and future directions of neurochemical biomarkers for Alzheimer's disease

2007 ◽  
Vol 45 (11) ◽  
Author(s):  
Daniëlle de Jong ◽  
Berry P.H. Kremer ◽  
Marcel G.M. Olde Rikkert ◽  
Marcel M. Verbeek
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Future Directions ◽  
The Past ◽  
Current State ◽  
Β Protein ◽  
Cerebrospinal Fluid Biomarkers ◽  
Made In

AbstractIn this comprehensive review, we summarize the current state-of-the-art of neurochemical biomarkers for Alzheimer's disease. Predominantly, these biomarkers comprise cerebrospinal fluid biomarkers directly related to the pathophysiology of this disorder (such as amyloid β protein, tau protein). We particularly pay attention to the innovations in this area that have been made in technological aspects during the past 5 years (e.g., multiplex analysis of biomarkers, proteomics), to the discovery of novel, potential biomarkers (e.g., amyloid β oligomers, isoprostanes), and to the extension of this research towards identification of biomarkers in plasma.Clin Chem Lab Med 2007;45:1421–34.

Alzheimer's Disease: Will Advances Made in the Past Turn the Tide?

2007 ◽  
Vol 41 (9) ◽  
pp. 1494-1496 ◽  
Author(s):  
Todd P Semla
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Pharmacy ◽  
Early History ◽  
The Past ◽  
History Of ◽  
Made In

2006 marked the 40th year of publication for The Annals. Throughout its history, The Annals has provided important contributions to the development of clinical pharmacy. In 2007, we are continuing to publish articles reflecting on the history of clinical pharmacy through the eyes of practitioners, including those pioneering clinical pharmacy, as well as those who have more recently entered the profession and a well-established specialty. In addition, we are presenting articles and editorials from the early history of The Annals that have given direction and shape to the practice of clinical pharmacy (see page 1499).

scholarly journals Trial Designs Likely to Meet Valid Long-Term Alzheimer's Disease Progression Effects: Learning from the Past, Preparing for the Future

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Aaron S. Kemp ◽  
George T. Grossberg ◽  
Steven J. Romano ◽  
Douglas L. Arnold ◽  
J. Michael Ryan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Disease Progression ◽  
Present Report ◽  
Disease Modification ◽  
The Past ◽  
Statistical Issues ◽  
New Treatments

The International Society for CNS Clinical Trials and Methodology (ISCTM) held its 4th Annual Autumn Conference in Toronto, Ontario, October 6-7, 2008. The purpose of the present report is to provide an overview of one of the sessions at the conference which focused on the designs and methodologies to be applied in clinical trials of new treatments for Alzheimer's disease (AD) with purported “disease-modifying” effects. The session began with a discussion of how neuroimaging has been applied in multiple sclerosis clinical trials (another condition for which disease modification claims have been achieved). The next two lectures provided a pharmaceutical industry perspective on some of the specific challenges and possible solutions for designing trials to measure disease progression and/or modification. The final lecture provided an academic viewpoint and the closing discussion included additional academic and regulatory perspectives on trial designs, methodologies, and statistical issues relevant to the disease modification concept.

scholarly journals Az Alzheimer-kór heterogenitása

2021 ◽  
Vol 162 (25) ◽  
pp. 970-977 ◽  
Author(s):  
Nóra Balázs ◽  
Tibor Kovács
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Clinical Manifestations ◽  
Symptomatic Therapy ◽  
Significant Progress ◽  
The Past ◽  
Atypical Manifestations ◽  
Recent Classification ◽  
Made In

Összefoglaló. A neurodegeneratív betegségek között az Alzheimer-kór a leggyakoribb kórforma. Morbiditása és mortalitása világszerte egyre gyorsabb ütemben növekszik, ezáltal szociális és gazdasági hatása is folyamatosan fokozódó terhet jelent a társadalomra. Az elmúlt néhány évtizedben jelentős előrelépés történt az Alzheimer-kór megismerésében, számos biomarker támogatja a diagnózis felállítását, tüneti terápiát szolgáló gyógyszerek kerültek bevezetésre. Az Alzheimer-kór klinikai megjelenése, lefolyása, viselkedése rendkívül változatos képet mutat, felismerése a rendelkezésre álló eszközök ellenére is kihívást jelenthet a nagy tapasztalattal bíró klinikusok számára is. Munkánk céljául tűztük ki, hogy összefoglaljuk az Alzheimer-kór genetikai, patológiai és klinikai jellemzőit, segítve ezzel a betegség jobb meg- és felismerését. Bemutatjuk a jelenleg érvényben lévő patológiai és klinikai irányelvek kritériumrendszereit, az újabb klasszifikációs szemléleteket. Részletesen ismertetjük az Alzheimer-kór heterogenitását genotípus és fenotípus szintjén egyaránt. Elemezzük a típusos és atípusos megjelenési formák jellemzőit, a társuló kórállapotoknak a megjelenésre és a progresszióra gyakorolt hatását. Orv Hetil. 2021; 162(25): 970–977. Summary. Alzheimer’s disease is the most prevalent neurodegenerative disorder. Morbidity and mortality of Alzheimer’s disease are increasing worldwide causing important social and economic burden on the society. Over the past few decades, significant progress has been made in the understanding of the pathogenesis of Alzheimer’s disease, several biomarkers support the diagnosis and drugs for symptomatic therapy had been introduced. The clinical manifestations and the course of Alzheimer’s disease have a variable picture, so – despite the diagnostic opportunities – its diagnosis could be a challenge for highly experienced clinicians as well. The aim of our work was to summarize the genetic, pathological and clinical characteristics of Alzheimer’s disease, thus helping to better understand and recognize the disease. We present the criteria systems of the currently valid pathological and clinical guidelines with the most recent classification approaches. The heterogeneity of Alzheimer’s disease at both genotype and phenotype levels is described in detail. The characteristics of typical and atypical manifestations and the effect of co-pathologies on the appearance and progression of Alzheimer’s disease are also discussed. Orv Hetil. 2021; 162(25): 970–977.

Biological markers as outcome measures for Alzheimer's disease interventions – real problems and future possibilities

2007 ◽  
Vol 19 (3) ◽  
pp. 391-400 ◽  
Author(s):  
Masatoshi Takeda ◽  
Masayasu Okochi ◽  
Shinji Tagami ◽  
Toshihisa Tanaka ◽  
Takashi Kudo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Diagnosis ◽  
Biological Markers ◽  
Surrogate Marker ◽  
Biological Marker ◽  
Pathological Process ◽  
Clinical Onset ◽  
Diagnosis Of Dementia ◽  
And Biological Markers

Because the biological pathological process is observed decades years before the clinical onset of Alzheimer's disease (AD), there is a theoretical ad-vantage in using biological markers for the early diagnosis of AD. Neuro-psychological test batteries, brain imaging and biological markers are expected to be used for screening and differential diagnosis of dementia and also for evaluation of the efficacy of early intervention.No single biological marker can serve all the purposes of screening, differential diagnosis and measurement of severity. Biological markers that reflect molecular stress, such as oxidative, ribotoxic, and nitroso stress, need to be developed, particularly for measuring the clinical outcomes of interventions. As well as providing a better understanding of the molecular pathogenesis of AD, there is a possibility of finding a surrogate marker of AD, which might fulfill the requirement of sufficient sensitivity and specificity for AD diagnosis, as well as indicating the disease-modifying activity of interventions. In this study we examine whether the mechanism of secretase activity will offer a new surrogate marker of AD.

Nanotechnology Based Delivery Systems of Drugs Currently Used to Treat Alzheimer’s Disease

2020 ◽  
Vol 10 (3) ◽  
pp. 228-247
Author(s):  
Niloufar Choubdar ◽  
Sara Avizheh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Polymeric Nanoparticles ◽  
Biological Fluids ◽  
Delivery Systems ◽  
Original Research ◽  
Sustained Drug Release ◽  
The Past ◽  
Site Of Action ◽  
Therapeutic Compound

Alzheimer’s Disease (AD) is one of the most common forms of dementia affecting over 46 million people, according to AD International. Over the past few decades, there has been considerable interest in developing nanomedicines. Using nanocarriers, the therapeutic compound could be delivered to the site of action where it gets accumulated. This accumulation, therefore, reduces the required doses for therapy. Alternatively, using nanocarriers decreases the side effects. Nanotechnology has had a great contribution in developing Drug Delivery Systems (DDS). These DDS could function as reservoirs for sustained drug release or control the pharmacokinetics and biodistribution of the drugs. In the current review, we have collected 38 original research articles using nanotechnology as DDS for the clinically used cholinesterase inhibitor drugs donepezil (DPZ), Rivastigmine (Riv), and galantamine (Gal) used for AD treatment from 2002 to 2017 from Scopus and PubMed databases. Regarding DDS used for DPZ, most of the research in recent years dealt with polymeric nanoparticles (NPs) including Poly-D, L-Lactide-Co-Glycolide (PLGA), and chitosans (CHs), then Liposomes (LPs), nanogels, and natural products, respectively. In terms of Riv most of the research performed was focused on polymeric NPs including PLGA, polylactic acid (PLA), Poly-Ε-Caprolactone (PCL), poly-alkyl-cyanoacrylates, CH, gelatin and then LPs. The highest application of NPs in regard to Gal was related to modified LPs and polymeric NPs. Polymeric NPs demonstrate safety, higher stability in biological fluids and against enzymatic metabolism, biocompatibility, bioavailability, and improved encapsulation efficacy. LPs, another major delivery system used, demonstrate biocompatibility, ease of surface modification, and amphiphilic nature.

Measuring Disease Modification in Alzheimer's Disease

CNS Spectrums ◽  
2007 ◽  
Vol 12 (S1) ◽  
pp. 11-14
Author(s):  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immunoglobulin A ◽  
Disease Process ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Disease Modification ◽  
Amyloid Disease ◽  
Therapeutic Modalities ◽  
Disease Modifying

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β -amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.

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