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Les traitements de la maladie d’Alzheimer (MA) actuellement disponibles ont des effets cliniques modestes et n’interferent pas dans la cascade physiopathologique presumee de cette pathologie. La recherche de nouvelles molecules ciblant les mecanismes etiologiques de la maladie est aujourd’hui au premier plan. Les agents anti-amy-loides representent la majorite des produits en cours d’evaluation. Ceux ciblant la proteine Tau et d’autres therapeutiques alternatives sont egalement en cours de developpement. Ces nouveaux agents [1] potentiellement « disease modifying » ont cependant parfois dans le passe etaient responsables d’effets indesirables graves necessitant donc actuellement une evaluation precise et complete du profil de tolerance lors des phases de developpement precoce et notamment en phase I qui constitue la premiere administration chez l’Homme.

Objectives: To describe the design and baseline patient characteristics of a multicomponent specific care and assistance plan (PLASA) study in Alzheimer’s Disease (AD). The study is designed to evaluate the effect of PLASA in AD primarily looking at change in functional capacity.Design: Two-years prospective cluster randomized controlled trial comparing PLASA and usual care. Setting: Forty-nine hospitals in France.Participants: 1120 community-dwelling AD.Intervention: Patients in the intervention group are evaluated bi-annually using a standardized comprehensive global assessment. In the case of decline in any one domain a standardized study protocol recommends specific physician directed intervention in addition to information and training for the caregiver.Measurements: Alzheimer Disease Cooperative Study-Activities of Daily Living scale, Resource Utilization in Dementia scale, Clinical Global Impression of Change.Results: At baseline, the two groups were similar regarding patient and caregiver characteristics. The mean patient age was 79.61 + 5.72 years and the mean MMSE 19.73 + 4.01 for the whole cohort. Time since dementia diagnosis was about 1.37 + 1.65 years in the whole cohort. Almost a third of the patients lived alone at baseline. Mean monthly time spent in caregiving in the whole cohort was 52.70 + 71.83 hours for instrumental activities and 17.73 + 51.38 hours for basic activities.Conclusion: Persons with dementia suffer different losses at different stages of the disease and therefore accurate assessment of abilities and losses is critical to assist the person in planning for their future and for care needs. The PLASA intervention study is ongoing with 2 year follow-up to be completed in 2007.

The long-term objective of the ICTUS study is to identify milestones in Alzheimer's disease (AD) progression and to develop a model to predict disease course in individual AD patients in Europe. The secondary objectives are to describe the patterns of prescribing, and the socioeconomic impact of AD in Europe. Between 2003 and 2005 1,380 patients with probable AD were recruited in specialised (secondary care) clinics in 12 European countries. Their mean age was 76 years and they had a mean of 8.0 +/- (SD) 4.6 years of education. Thirty-five percent were male. The mean MMSE score was 20.4 +/- (SD) 4.0. Forty-three percent had very mild dementia (CDR 0.5) and 44% had mild dementia (CDR 1). All patients completed baseline evaluation and biannual follow-up is ongoing. The goals of the current study are to describe the specific methods for recruitment in this crosscultural setting and the characteristics of the inception ICTUS cohort, including clinical features, co-morbidity, neuropsychological performance, neuropsychiatric symptoms, functional impairment and social burden.

Weight loss is frequently observed in patients with Alzheimer's disease (AD), as observed in clinical practice and reported in the literature. However, information on the evolution of nutritional status and its impact on the prognosis of AD is still scarce.Our aim was to determine the impact of nutritional status on the evolution of AD and on the response to treatment with acetylcholinesterase inhibitors (AChEI) by prospective one-year follow-up of AD patients living at home.We studied a cohort of 523 patients with Alzheimer's disease referred from 1994 to 2002 to an Alzheimer centre. After diagnosis, they were followed for one year in a prospective observational study in clinical practice. At entry and every 6 months, patients underwent standardised neurocognitive and geriatric evaluation (MMSE, ADAS-cog, IADL, MNA, caregiver burden). These evaluations were accompanied by complete clinical examination, standard paraclinical investigations and recording of treatment received.Of our patients, 25.8% presented at inclusion a risk of undernutrition with an MNA score of 23.5 or less. During follow-up, the number of patients with rapid loss on the MMSE (3 points or more in one year) was higher in subjects who presented a risk of undernutrition at inclusion (53.6%) than in well-nourished subjects (43.2%) (P = 0.07). Similarly, increased dependence at one year was more frequent in subjects at risk of undernutrition at inclusion (57.7% versus 44.4%, P = 0.0219). The beneficial effect of AChEI treatment on cognitive function was not influenced by initial nutritional status; on the contrary, among the subjects at risk of undernutrition at inclusion, the risk of rapid loss on the MMSE in one year was decreased in subjects treated during follow-up compared with untreated subjects (43.9% versus 73.1% ; OR = 0.29; 95% CI = 0.10-0.83; P = 0.0219). This relationship was not found in subjects whose initial MNA score was greater than 23.5.Our work indicates that AD patients living at home with a caregiver are frequently at risk of undernutrition. Undernourished patients seem to present more rapid aggravation of the disease, but paradoxically, these patients appear to be those who best respond to AChEI treatment.

Amongst factors associated with the institutional placement of elderly people with dementia, there has been little study of those related to malnutrition. We followed a cohort of 318 individuals with Alzheimer's disease (AD). Patients, who were all living at home at the start of the study were recruited from the outpatient service of a hospital unit specialising in AD. After one year, 20% of the patients had moved into institutional care. Multivariate analysis showed that a Mini nutritional Assessment score (MNA) of less than 25.5 (median score of the sample) and overeating behavioural problems (p=0.006) were risk factors for institutional placement. Nutritional problems are reversible and patients with a low MNA score could benefit from a thorough geriatric assessment, in order to slow or prevent institutional placement.

Large numbers of elderly patients, suspected of having dementia, need medical evaluation, often in early phases of their illness. A complete outpatient assessment clearly could be advantageous. Thirty-five centers from 15 European countries, known to their scientific gerontological and geriatric societies to have experience in outpatient care for elderly patients with dementia, participated in an effort to develop a consensus statement for the assessment needs of these patients. The comparison of the centers showed that a wide variety of approaches was currently in practice. Differences appeared to be mainly based on local facilities and organization. A consensus for diagnostic outpatient assessment was easily reached. Diagnosis should be based on DSM-IV criteria, which requires a standardized assessment (including neuropsychological, functional and technical evaluation) and should be multidisciplinary. An assessment of dementia of elderly outpatients appears to be very feasible - a consensus approach with minimum diagnostic requirements is presented.

The revised French version of the Hierarchic Dementia Scale (HDS) was assessed in 88 DAT patients (30 men, 58 women, mean age: 70, MMS from 0 to 26). The HDS consisted of 20 subtests which covered the entire range of cognitive functions; each subtest was hierarchically organized. This scale has been validated by the authors in 149 control subjects (Démonet et al., 1990). The goals of the present study were to validate this scale in DAT patients in comparison with the MMS scores and to specify the cognitive impairments of our pathologic population. Results showed that the scores on the HDS were highly correlated with the MMS scores (p.0001). Some subtests of the HDS (memory subtests and mental control) allow good discrimination between mild demented patients and controls (sensibility = 80.8 p. 100, specificity = 96 p. 100). Conversely some subtests allowed a cognitive follow-up of patients for whom the MMS was no longer useful (MMS scores from 0 to 10). In conclusion, it appears that this scale is useful for drawing cognitive profile of DAT patients and to approach the heterogeneity of dementia.