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International audience; The EU/US/CTAD Task Force, an international collaboration of AD investigators from industry and academia, met in Barcelona, Spain, on November 4th, 2015, to explore existing and planned patient registries and other clinical trial infrastructure meant to expedite recruitment of large numbers of participants into clinical trials and improve their productivity. The Task Force identified a number of approaches currently being tested around the world, including the use of predictive algorithms to identify individuals likely to have prodromal or preclinical AD, the establishment of clinical trial networks to streamline trials, and reforming the informed consent process to make it less burdensome to both investigators and trial participants. Multi-national systems such as the European Prevention of Alzheimer's Dementia (EPAD) and the Global Alzheimer's Platform (GAP) offer value for sponsors, trial sites, and patients by optimizing efforts to find effective disease-modifying and symptomatic treatments.

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.

Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary group of experts, including geriatricians, neurologists, epidemiologists, psychiatrists, pharmacologists, and public health specialists developed consensus recommendations about care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians, and specialists, based on the knowledge currently available (2005). The aim of care at all stages is to mitigate the quality-of-life of patient, caregiver, and family insofar as possible, combining care and future planning until the end of life. Management, to take into account problems including nutritional status, behavior disorders, and ability (or inability) to perform activities of daily living, must be global, multidisciplinary, and coordinated and must optimize use of local medical and social resources. The group also stressed the importance of clinical research to improve knowledge of disease course and assess management strategies and recommended specific area for research.

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.

Alzheimer's disease is a chronic pathology requiring regular follow-up. The predictive factors of rapid cognitive decline remain unclear.To analyse the baselines characteristics of patients at increased risk of rapid cognitive decline.This study presents transversal data on a community-based sample of 340 patients diagnosed with probable Alzheimer's disease and followed by REAL.FR group. Rapid cognitive decline was defined as a 3-points or greater loss on the Mini Mental State Examination (MMSE) within six months.54% of patients presented a rapid cognitive decline. Logistic regression analysis showed a positive association between rapid cognitive decline and a MMSEor = 20 (p0.003) or a greater BMI (p0.02) and a tendency towards a negative correlation with anxiety (p = 0.06) and negative correlation with the burden severity (p0.05).Patients with a worse cognitive status, a greater BMI and less anxiety or burden were at increased risk of rapid cognitive decline. Future studies should focus on determining etiologies for patients with rapid cognitive loss and help clinicians target these patients for interventions aiming to delay or stabilise the course of this disease.

We present in this article the REAL.FR research program on Alzheimer disease (AD) and its management. This is a French multicenter prospective study whose objectives are to study the natural history of AD and the modalities of its management. In order to pursue these aims, we set up a cohort of 700 AD patients in France. They entered the study in year 2000 and will be followed for at least four years. The study population consists of AD patients, living in the community at the time of enrollment and looked after by an informal caregiver. On inclusion, each patient underwent a full investigation which included gerontological and social evaluation. Patients will be seen every six months for at least four years. During follow-up, events which have occurred during the previous six months are noted (i.e. admissions to hospital or to an institution, use of new in-home help services...). To date, 577 patients have been reviewed at 6 month, 489 at 12 month, 358 at 18 month, 266 at 24 month, 178 at 30 month and 31 at 36 month. 48 death have been registered, 42 patients have been institutionalised and 124 have been dropped out. Mean age of patients on inclusion was 77.4 +/- 7 years. Nearly one-third of patients were living at home when they were enrolled in the study. Our preliminary results are encouraging regarding the feasibility of patients follow-up. The satisfactory participation of patients and their families in the later evaluations which have already been carried out also seem promising for the continuation of follow-up.

A reliable global rating of dementia severity in Alzheimer's disease is critical both in clinical and research practice. In this paper, we present the results of the assessment of a cohort of 358 patients using the French version of the Clinical Dementia Rating Scale (CDR).358 patients from a multicentric cohort were assessed in a comprehensive way: cognitive (Mini Mental Status Examination), functional (Activities of Daily Living), behavioural (Neuro Psychiatric Inventory) and global (Global Dementia Scale). CDR staging was performed after both patient and caregiver interview.27.6% of the patient had a CDR 0.5 (questionable dementia), 43% CDR 1 (mild dementia), 24.9% CDR 2 (moderate dementia) and 4.5% CDR 3 (severe dementia). All the rating scales were highly correlated with CDR stages (p0.0001). The CDR was also correlated with the Global Dementia Scale (p0.0001), but a perfect overlap of individual stages was not achieved.CDR staging takes into account the major domains of dementia assessment: cognition, function and behaviour. Staging Alzheimer's patients as CDR 0.5 arises the issue of the relationship between very mild dementia and Mild Cognitive Impairment. This study represents the first step of the CDR (French version) validation which is underway in this cohort.

Wandering is a common problem among patients with Alzheimer's disease. Few studies have examined this problematic behaviour in the community. The aim of the present study was to increase our understanding of wandering during Alzheimer's disease in subjects living in the community.We studied 571 patients with Alzheimer's disease living in the community. Objective cognitive status was assessed using a series of standardized neuropsychological tests. Nutritional assessment, risk of fall, autonomy were assessed as well as the burden of their family. The behavioural abnormalities of patients were assessed with their caregiver using the Neuro-Psychiatric Inventory. Patients with or without wandering were described.Prevalence of wandering was 12.6%. Patients with wandering appeared to have more severe cognitive impairment, less autonomy and were undernourished. Behavioural and psychological signs significantly associated with wandering were delirium, aggressiveness, irritability, depression, anxiety, euphoria, apathy, desinhibition and eating behaviour disorder. Subtype of Alzheimer's disease patients seemed to have frontal release behaviour.Wandering is a common behaviour in Alzheimer's disease patients living in the community. Special care must be organized to help those frail patients and their caregivers.

Alzheimer's disease (AD) is under-diagnosed in France. Today only an estimated 50% of patients are identified. Diagnosis of AD is particularly difficult because the amnesic syndrome, characteristic of the disease, is often confused with memory dysfunction that is frequent during the process of aging. The improvement in the diagnostic conditions of AD relies on the availability of a simple and reliable tool for screening memory disorders of organic origin.The 5-word test studies the recall of a short list, which the physician ensures the patient has registered. Its construction permits the identification of patients exhibiting objective memory disorders. A validation study has been conducted in 86 patients suffering from AD and 126 persons complaining of functional memory disorders.The study has shown the sensitivity (91%) and specificity (87%) of the 5-word test in identifying patients with AD.This is a rapid (2 minutes) and simple test that is easy to use in medical practice for the screening of AD.

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.

Elderly people can be subdivided into three groups: healthy elderly persons (65-70% of the population), elderly subjects with diseases (about 5%) and frail old people. Frailty represents "age-related physiologic vulnerability resulting from impaired homeotasic stock and a reduced capacity of the organism to withstand stress". It could lead elderly subjects to pathological, barely reversible, ageing.One of the main objective of geriatricians is to develop useful screening tools to identify people at high risk, thus allowing them to benefit from preventive interventions as early as possible. It has been suggested that the decline in homeostatic stock involves numerous physiological systems. Those at the core of frailty would be neuromuscular changes resulting in sarcopenia, neuroendocrine dysregulation, and immune disorders. A recent study has shown that increased levels of interleukin 6 is a risk factor for frailty.Work in progress aimed at identification of at-risk patients should: lead to early detection; draw attention on underestimated fields such as the nutritional status, sarcopenia, or gait disorders; promote the development of the standardized gerontological evaluation in order to identify the different components of frailty; and promote the development of non-pharmacological programmes including physical training, nutritional managing, and optimal social life.

Sporadic Alzheimer's disease is the most frequent form of dementia and appears to be associated with increasing age and certain genetic and environmental factors. Some studies have recently been published on potential protective factors.Several genes appear to be involved; one of the most common is the ApoE4 allele on chromosome 19. The physiopathology is not elucidated, but recent studies have shown a protective effect for NSAIDs, estrogen, nutritional factors (vitamins E, B6 and B12) as well as some biochemical amino acids (homocysteine).Interventional studies are now in progress and some preventive approaches will soon be available.

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.

Cognitive features in dementia of the Alzheimer's type (DAT) appear highly heterogeneous. Neuropsychological models seem useful to characterize the cognitive decline. Functional imaging may identify anatomoclinical correlations. Memory impairment is the major symptom in DAT, associated with cortical dysfunctions (aphasia, apraxia, agnosia) and deficits in executive functions. Various evolutive profiles increase this clinical heterogeneity. The use of standardized and validated psychometrical tools appears very important for diagnosis and follow-up of cognitive decline. The MMSE, for example, deserves to be included in the everyday clinical practice.

The day hospital appears to be highly suitable for a memory clinic, not only as a complementary service, but also for teaching and clinical or epidemiologic research purposes. As regards diagnostic procedures, the possibility of doing tests and assessments in the same place and in a short time is a clear advantage for these often fragile patients. In the day hospital, clinical assessments can be coupled with the paraclinical tests required to make a diagnosis, with efficient technical resources on hand. Multidisciplinarity and close collaboration between the different specialists are the key elements in the diagnosis and long-term management of these patients, who also find the premises less worrisome than the hospital environment. The day hospital appears to be the ideal setting for monitoring and therapeutic management, being situated at the interface between hospital and community physicians.

This paper reports our 2-year experience in a memory clinic practice at a University Hospital. During these 2 years, 128 patients with memory complaints were evaluated by a neurologist, a psychiatrist, a geriatrist and a neuropsychologist using a standardized test battery; only 58 of these patients actually presented with objective memory deficits. These memory impairments were mainly observed in patients with neurologic disorders (principally dementia) and in patients with psychiatric disorders (principally depression, major anxiety and psychiatric diseases with troubles of personality). The aim of this memory clinic is to identify the origin of memory disorders, provide a pharmacological treatment when required, propose appropriate assessment and follow up, and diagnose early symptoms of dementia.

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.