Maladie d'Alzheimer: de la pathogénie aux perspectives cliniques [Alzheimer disease: from pathogenetic issues to clinical perspectives].

The aim of this article is a critical review of the main pathogenetic issues debated in Alzheimer disease, with a focus on the clinical perspectives that could derive from. The pertinence of the amyloid cascade hypothesis as a unique and causal explanation of cognitive deterioration is challenged in the light of recent therapeutic failures of clinical trials and increasing role of tau protein in clinical expression. The detection of very early and possibly preclinical stages of the disease emerges as a necessary condition for the efficacy of future amyloid or tau-oriented curative strategies. In this respect, the possibility of finding individual vulnerability markers--in the group of patients with "mild cognitive impairment" or even in cognitively intact subjects--represents a major challenge of the clinical research in this field.

Traitements des facteurs de risque cardiovasculaire et dépistage de la maladie coronarienne dans le diabète de type 2 [Treatments for cardiovascular risk factors and screening for coronary artery disease in type 2 diabetes mellitus]

The recent ACCORD and DIAD studies revealed results which could modify treatments and the screening of diabetes vascular complications. Indeed, ACCORD shows no benefit on the prevention of diabetes vascular complications by aggressive treatment of hypertension or the combined treatment of the dyslipidemia. The intensive treatment of the blood glucose, if associated with severe hypoglycemias, increases mortality. DIAD revealed 20% of silent myocardial ischaemia in diabetic patients but no beneficial effect on the cardiovascular mortality. A careful reading of these studies in the light of long term studies such as UKPDS and STENO reveals that these negative results are generated by a too short follow-up and too aggressive objectives. The long term studies reveal that more realistic objectives remain beneficial.

Perception et communication du risque: du diabète à la maladie cardiovasculaire [Risk perception and communication: from diabetes to cardiovascular diseases].

Evidence-based medicine has enabled to approach disease in a more rational and scientific way. Clinical research has identified behaviours and risk factors that could cause disease often "silent" at the beginning, such as diabetes. Despite the clear impact of these evidences on public health, it seems that the individual risk perception level remains weak. To mention as well, the health professionals very often have a different views, which makes it difficult to communicate the risk with patients. In this article we describe the principles of risk perception, the diabetes related risk perception concerning cardiovascular complications, and suggest some practical strategies and tools which could improve risk communication in the everyday practice.

Maladie de Fabry. Analyse sémiologique de 17 familles en France et en Suisse

Etude de cohorte en France et en Suisse (7 centres). Analyse sémiologique des cas de maladie de Fabry (MF). Les cas index étaient 12 H, 5 F : âgemoyen au diagnostic 30 (9-58) et 34 ans (10-49), resp. Chez les H, le 1er symptôme était : acroparesthésies (acroP) (n=9) en moyenne à 8 ans (4-19). Le délai moyen premier symptôme-MF était de 17 ans (0-51), plus court en cas d'acroP qu'en cas d'autre symptôme révélateur (12.3 vs 19.6 ans). Les acroP « négligées » retardaient le diagnostic : angiokératomes (n=1, délai 28 ans), AVC du sujet jeune (n=2, délais 20 et 24 ans), insuffisance rénale terminale (n=1, délai 51 ans). Deux patients avaient une sémiologie complète : acroP, angiokératomes, hypohidrose, cornée verticillée, atteinte cérébrale, rénale (2 transplantations), cardiaque. Une hypoacousie était fréquente (n=6). Les errances diagnostiques ont été : SEP, neurobrucellose, PAN, cardiomyopathie hypertensive malgré l'absence d'HTA. Chez les F, le 1er symptôme était : acroP (n=3), cornée verticillée (n=1), angiokératomes (n=1). Le délai premier symptôme-MF était en moyenne de 15.6 ans (0-37). Tous les patients, à l'exception d'1 F, sont sous traitement enzymatique. Dans leurs familles, 47 autres cas (27H/20F) ont été diagnostiqués. La MF est à transmission dominante liée à l'X, avec expressivité variable. Elle atteint l'homme et la femme. Le diagnostic est trop tardif : l'interniste doit connaître la MF pour laquelle existe un traitement par alpha-galactosidase.