Experimental and clinical methods in the development of anti‐Alzheimer drugs

Allain, H.; Bentué-Ferrer, Danièle; Zékri, Oussama; Schück, Stéphane; Lebreton, Sophie; Reymann, Jean-Michel

doi:10.1111/j.1472-8206.1998.tb00919.x

Cited by 14 publications

(6 citation statements)

References 114 publications

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“…It is quite difficult to determine the effect of cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine) (Bentué-Ferrer et al 2001) on language and linguistics among the results of phase III trials in dementia that contributed to their marketing approval. Regulatory guidelines were very strict (Allain et al 1998) and the “cognitive” scales (ADAS-Cog, MMS, CGI, GDS) used for assessment contained few linguistic items, despite the frequency and importance of disorders of language comprehension and expression in patients with AD (Grossman et al 1996; Grossman et al 1998). …”

Section: Drugs and Languagementioning

confidence: 99%

Impaired cognition and attention in adults: pharmacological management strategies

Allain¹,

Akwa²,

Lacomblez³

et al. 2007

Neuropsychiatric Disease and Treatment

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Abstract:Cognitive psychology has provided clinicians with specific tools for analyzing the processes of cognition (memory, language) and executive functions (attention-concentration, abstract reasoning, planning). Neuropsychology, coupled with the neurosciences (including neuroimaging techniques), has authenticated the existence of early disorders affecting the "superior or intellectual" functions of the human brain. The prevalence of cognitive and attention disorders is high in adults because all the diseases implicating the central nervous system are associated with cognitive correlates of variable intensity depending on the disease process and the age of the patient. In some pathologies, cognitive impairment can be a leading symptom such as in schizophrenia, posttraumatic stress disorder or an emblematic stigmata as in dementia including Alzheimer's disease. Paradoxically, public health authorities have only recognized as medications for improving cognitive symptoms those with proven efficacy in the symptomatic treatment of patients with Alzheimer's disease; the other cognitive impairments are relegated to the orphanage of syndromes and symptoms dispossessed of medication. The purpose of this review is to promote a true "pharmacology of cognition" based on the recent knowledge in neurosciences. Data from adult human beings, mainly concerning memory, language, and attention processes, will be reported. "Drug therapeutic strategies" for improving cognition (except for memory function) are currently rather scarce, but promising perspectives for a new neurobiological approach to cognitive pharmacology will be highlighted.

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Section: Drugs and Languagementioning

confidence: 99%

Impaired cognition and attention in adults: pharmacological management strategies

Allain¹,

Akwa²,

Lacomblez³

et al. 2007

Neuropsychiatric Disease and Treatment

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“…To our knowledge, few consensus meetings or guidelines have been published on the management of BPSD further to those of the Canadian Medical Association [56] and the group of experts presided by Alexopoulos et al [2]. On the other hand, the recent history of the development of drugs for Alzheimer's disease illustrates the focalization of the specialists on the pure cognitive disorders and notably memory [3,4], even though the articles recommending new therapeutic strategies for dementia discuss the question and widen the drug targets to behaviour and non-cognitive signs of dementia according to the rules of 'disease management' [18,25,53,59,63].…”

Section: Practical Approachmentioning

confidence: 99%

Comparative effects of pharmacotherapy on the maintenance of cognitive function

et al. 2001

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The quality of human cognitive performance appears today as one of the main components of quality of life, whatever the age. Ageing by itself and most of the diseases affecting the central nervous system alter higher brain functions such as memory, vigilance and attention. Dementia is the most acute example, with a cascade of behavioral and psychological consequences (BPSD), which are the main cause of the caregiver's burden and need specific pharmacotherapy. In this respect, the problem will be the choice of the best drug in situations such as wandering, agitation, violence, and screaming. The psychotropics, however, should not deteriorate the already disturbed cognition of the patients. This is the reason why we propose to establish for each drug, and notably for the antipsychotics, a precise and exact "cognitive mapping"; in other words, to measure the effects of drugs on the different components of cognition. The results of such studies will be predictive of the future phase III clinical trials and therapeutic responses. As an illustration of this approach we shall relate two studies, TIATEM (phase I) and TIAGE (phase III/IV), leading to the determination of a good cognitive safety profile of an atypical neuroleptic drug, tiapride.

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“…▶ assessing the effects of putative neuroprotective, anti-degenerative, revalidation-supporting, mental health promoting, and/or cognition-enhancing compounds or treatments [ 27 , 41 - 44 ], and assessing risks (safety, teratology, toxicology) associated with these treatments [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of animal models of neurobehavioral disorders

2009

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Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s) of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration.Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended) replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result.Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia.In a manner congruent to that for improving animal models, guided by the procedure expounded upon in this paper, the developmental and evaluation procedure itself may be improved by careful definition of the purpose(s) of a model and by defining better evaluation criteria, based on the proposed use of the model.

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Experimental and clinical methods in the development of anti‐Alzheimer drugs

Cited by 14 publications

References 114 publications

Impaired cognition and attention in adults: pharmacological management strategies

Impaired cognition and attention in adults: pharmacological management strategies

Comparative effects of pharmacotherapy on the maintenance of cognitive function

Evaluation of animal models of neurobehavioral disorders

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