Cognitive Rehabilitation in Alzheimer's Disease - A Conceptual and Methodological Review.

Within the last 20 years, several standardized cognitive trainings have been developed aiming at the delay of cognitive decline in older people who are at risk of Alzheimer's Disease (AD) or in mild stages of dementia. The transfer of cognitive training effects into activities of daily living was very limited in most previous studies. Therefore, multimodal Cognitive Rehabilitation approaches have been designed that aim to improve the activities of daily living. These approaches also attempt to integrate the patient's psychopathological and behavioral status as well as social relationships into the treatment plan. Contrary to other approaches, CR mainly focuses on compensation rather than restoration of impaired functionality. In this review, we define CR conceptually, and derive specific criteria to evaluate current CR approaches for individuals with mild cognitive impairment (MCI) and AD dementia. In addition, we perform a critical, methodical analysis of available CR studies, reviewing their short- and long-term treatment effects. Findings suggest that CR approaches improve memory performance and competence of activity of daily living (ADL) in mildly cognitively impaired subjects (MCI), when compensatory, integrative, as well as interactive elements and domain specificity are taken into account. Interactive and individual aspects also appear to be relevant to sustain long-term effects. In AD dementia, similar results emerged, although with smaller effect sizes. The efficacy of individualized CR approaches was comparable with theory-based, manual-guided concepts as long as promoting interaction was part of the treatment. So far, only few randomized controlled studies of sufficient sample size are available. Future systematic efficacy studies need to consider precisely defined outcome variables. This is necessary before one can draw conclusions of how CR can be used for secondary prevention of AD dementia as well as AD treatment.

[Regulatory aspects of clinical trials with emphasis on biologicals]. / Regulatorische Aspekte klinischer Prüfungen unter besonderer Berücksichtigung biologischer Arzneimittel.

Clinical trials play a central role in clinical development for achieving marketing authorization for a drug. Carefully planned and carried out clinical trials allow for valid conclusions on the efficacy and/or safety of a drug. In order to do so, various requirements have to be fulfilled: clinical studies are to be planned and conducted in accordance with Good Clinical Practice, scientifically sound methods have to be applied, the patients' safety has to be ensured, trial objectives and results have to be clinically relevant, quality and transparency of all steps from planning to reporting a clinical study have to be ensured. For biologicals, special attention has to be paid to specific aspects, such as their mode of action or possible impact on the environment. Various guidelines reflecting regulatory aspects are available to support drug development. In addition, specific questions on drug development might be discussed directly between study sponsors and regulatory agencies. Due to the changes imposed by the 12th law amending the German Drug Law (Arzneimittelgesetz), the relevant German authorities will be more involved in the planning and conduct of clinical trials.