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Objectives: To explore associations between carer burden and characteristics of (1) the informal carer, (2) the person with dementia, and (3) the care support network in 8 European countries.Design: Cross-sectional study.Setting: People with dementia judged at risk of admission to long-term care (LTC) facilities in 8 European countries (Estonia, Finland, France, Germany, Netherlands, Spain, Sweden, United Kingdom).Participants: A total of 1223 people with dementia supported by community services at home or receiving day care or respite care and their informal carers.Measurements: Variables regarding the informal carer included familial relationship and living situation. Variables relating to the person with dementia included cognitive functioning (S-MMSE), neuropsychiatric symptoms (NPI-Q), depressive symptoms (Cornell depression scale), comorbidity (Charlson Comorbidity Index), and physical functioning (Katz Activity of Daily Living [ADL] Index). The care support network was measured using hours of caregiving (ADLs, instrumental ADLs [IADLs], supervision), additional informal care support, and service receipt (home care, day care). Experience of carer burden was recorded using the Zarit Burden Interview. Logistic regression analysis was used to determine factors associated with high carer burden.Results: Carer burden was highest in Estonia (mean 39.7/88) and lowest in the Netherlands (mean 26.5/88). High burden was significantly associated with characteristics of the informal carer (family relationship, specifically wives or daughters), of the person with dementia (physical dependency in ADLs; neuropsychiatric symptoms, in particular night time behaviors and irritability), the care support network (hours of caregiving supervision; receipt of other informal care support) and country of residence.Conclusion: A range of factors are associated with burden in informal carers of people with dementia judged to be on the margins of LTC. Support for informal carers needs to take account of gender differences. The dual challenges of distressed behaviors and difficulties in ADLs by the person with dementia may be addressed by specific nonpharmacological interventions focusing on both elements. The potential protective effect of additional informal support to carers highlights the importance of peer support or better targeted home support services. The implementation of appropriate and tailored interventions to reduce burden by supporting informal carers may enable people with dementia to remain at home for longer. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Despite good to excellent inter-reader agreement in the evaluation of amyloid load on PET scans in subjects with Alzheimer's disease, some equivocal findings have been reported in the literature. We aimed to describe the clinical characteristics of subjects with equivocal PET images. Nondemented subjects aged 70 years or more were enrolled from the MAPT trial. Cognitive and functional assessments were conducted at baseline, at 6 months, and annually for 3 years. During the follow-up period, 271 subjects had 18F-AV45 PET scans. Images were visually assessed by three observers and classified as positive, negative or equivocal (if one observer disagreed). After debate, equivocal images were reclassified as positive (EP+) or negative (EP−). Scans were also classified by semiautomated quantitative analysis using mean amyloid uptake of cortical regions. We evaluated agreement among the observers, and between visual and quantitative assessments using kappa coefficients, and compared the clinical characteristics of the subjects according to their PET results. In 158 subjects (58.30 %) the PET scan was negative for amyloid, in 77 (28.41 %) the scan was positive and in 36 (13.28 %) the scan was equivocal. Agreement among the three observers was excellent (kappa 0.80). Subjects with equivocal images were more frequently men (58 % vs. 37 %) and exhibited intermediate scores on cognitive and functional scales between those of subjects with positive and negative scans. Amyloid load differed between the EP− and negative groups and between the EP+ and positive groups after reclassification. Equivocal amyloid PET images could represent a neuroimaging entity with intermediate amyloid load but without a specific neuropsychological pattern. Clinical follow-up to assess cognitive evolution in subjects with equivocal scans is needed.

Objectives To examine whether living alone predicted hospitalizations, nursing home admission, weight loss, and death in individuals with mild to moderate Alzheimer's disease (AD) over 2 years of follow-up. Design Data are from the Plan de Soin et d'Aide dans la maladie d'Alzheimer study, a 24-month trial with a cluster randomization of memory clinics in two arms: a multidomain intervention and usual care. Setting Memory clinics in France (N = 50). Participants Community-dwelling individuals with AD with a Mini-Mental State Examination score between 12 and 26 and an identified caregiver. Measurements A neurogeriatric evaluation was conducted twice a year in the intervention group and annually in the control group. Hospitalizations, nursing home admission, weight loss, and death occurring during the past year were recorded. Information on sociodemographic characteristics, clinical conditions, therapy, and physical and cognitive status was recorded. Results At inclusion, 348 (30.8%) of the 1,131 participants lived alone. Living alone did not increase the risk of mortality or weight loss in individuals with mild to moderate AD, but significant associations with risk of hospitalization (hazard ratio (HR) = 1.33, 95% confidence interval (CI) = 1.01–1.74) and institutionalization (HR = 2.53, 95% CI = 1.84–3.47) were reported. A protective effect of physical function on institutionalization and mortality was found. Conclusion These results might support clinicians in making decisions about institutionalization of individuals with AD living alone or improving home health care, such as increasing screening and managing functional impairment in this complex population.

Objectives: To determine factors associated with the antipsychotic (AP) prescription for people with dementia (PwD) recently admitted to institutional long-term care facilities (LTCFs) and to ascertain differences in the use of this medication in 8 European countries.Design: An exploratory cross-sectional study. Setting: LTCFs from 8 European countries (Estonia, Finland, France, Germany, The Netherlands, Spain, Sweden, and England).Participants: A total of 791 PwD recently admitted to an LTCF and their caregivers.Measurements: Baseline data from RightTimePlaceCare survey was used. Patients' medical conditions, neuropsychiatric symptoms, physical and cognitive status, and medications were recorded. Multiple logistic regression models were used to assess associations with the AP use.Results: A group of 296 patients (37.4%) of 791 patients recently admitted received AP medication. The prevalence of the use of 1 or more APs varied between study countries, ranging from 12% in Sweden to 54% in Spain. Factors independently associated with the AP use were living in Sweden [odds ratio (OR) 0.12, 95% confidence interval (CI) 0.05-0.30], Finland (OR 0.26, 95% CI 0.14-0.48), Germany (OR 2.75, 95% CI 1.55-4.86) and Estonia (OR 6.79, 95% CI 3.84-12.0). The odds of AP use decreased with the presence of a dementia specific unit in the LTCF (OR 0.60, 95% CI 0.39-0.92), but was higher among residents with a hyperactivity behavior (OR 2.12, 95% CI 1.41-3.18).Conclusion: The current study shows that more than one-third of the residents recently admitted received APs and that prescription frequency across countries varied significantly. This study raises the possibility that the presence of a dementia-specific unit might play a role in the AP use. Further studies should investigate this association and seek better understanding of what will achieve optimal quality of AP use among newly admitted residents in LTCF. (C) 2014 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

Objective: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). Design, patients: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). Interventions: 1/ Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6–8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. Baseline population: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. Discussion: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

Background Cognitive dysfunction and changes in body composition share common pathophysiological pathways. The aim of the present paper was to evaluate whether changes in appendicular muscle mass (AMM) and fat mass (FM) are associated factors with an increased risk of cognitive dysfunction in community-dwelling older women. Methods A nested case–control study was performed in 181 women aged 75 years and older from a subsample of the Epidemiologie de l'Osteoporose participants from Toulouse. Body composition parameters at inclusion and 7 years later (assessed by dual energy X-ray absorptiometry), and the presence of cognitive dysfunction (dementia and mild cognitive impairment) at 7 years of follow-up, assured by two memory experts based on best clinical practice and validated criteria, were obtained. Multivariate logistic regression models assessed the association of percent change in AMM and FM with risk of cognitive dysfunction. Results At 7 years of follow-up, 15 participants suffered from dementia, 6 suffered from mild cognitive impairment, and 160 were cognitively normal. Neither body composition changes nor gait speed was found to be statistically associated with cognitive dysfunction after controlling for potential confounders. Only age, over 85 years, was associated with an increased risk of subsequent cognitive impairment (odds ratio 3.10; 95 % confidence interval 1.07–8.87). Conclusions No significant association could be evidenced between changes in body composition and cognitive dysfunction. Due to the small sample size, statistical power could be an issue. The study could also suggest the possibility that the risk of cognitive dysfunction is not mediated by changes in body composition.

The prevention of dementias, such as Alzheimer's disease (AD), is a growing public health concern, due to a lack of effective curative treatment options and a rising global prevalence. Various potential risk or preventive factors have been suggested by epidemiological research, including modifiable lifestyle factors such as diet. Current epidemiological data are in favour of a protective role of certain micronutrients (B vitamins related to homocysteine metabolism, the anti-oxidant vitamins C and E, flavonoids, polyunsatured omega-3 fatty acids, vitamin D) and macronutrients (fish) in the prevention of cognitive decline and dementia/AD. Some factors have been targeted by interventions tested in randomized controlled trials (RCTs), but many of the results are conflicting with observational evidence. Epidemiological analysis of the relations between nutrient consumption and cognitive decline is complex and it is highly unlikely that a single component plays a major role. In addition, since multiple factors across the life course influence brain function in late life, multidomain interventions might be more promising in the prevention of cognitive decline and dementia/AD. Designing such trials remains very challenging for researchers. The main objective of this paper is to review the epidemiologic data linking potential protective factors to cognitive decline or dementia/AD, focusing particularly on the roles of adiposity, caloric restriction, micro (group B vitamins related to homocysteine metabolism, the anti-oxidant vitamins C and E, flavonoids, polyunsatured omega-3 fatty acids, vitamin D) and macronutrients (fish). Limitations of the current data, divergence with results of interventional prevention studies and challenges for future research are discussed.

Objective Weight loss and behavioral disturbances are frequent over the course of Alzheimer's disease (AD) and are risk factors for poor outcome. We investigated the impact of aberrant motor behavior (AMB) on weight changes in older adults with AD. The hypothesis that patients with AMB are more likely to lose weight than patients without AMB was assessed. Methods A prospective study of 686 patients with moderate AD from the REAL.FR cohort was assessed. The AMB at baseline was defined by the item 10 from the Neuropsychiatric Inventory scale (NPI-10). Patients were classified as “no or light AMB” (NPI-10

Objectives: An international group proposed the existence of “cognitive frailty”, a condition defined by simultaneous presence of physical frailty and cognitive impairment in the absence of dementia. The objective was to compare the neuropsychological profiles in subgroups of elders differentiated across their physical frailty (Fried phenotype) and cognitive status (Clinical Dementia Rating score) to characterize the “cognitive frailty” entity. Method: We studied baseline characteristics of 1,617 subjects enrolled in Multidomain Alzheimer Disease Preventive Trial (MAPT). Included subjects were aged 70 years or older and presented at least 1 of the 3 following clinical criteria: (1) Memory complaint spontaneously reported to a general practitioner, (2) limitation in one instrumental activity of daily living, (3) slow gait speed. Subjects with dementia were not included in the trial. Results: “Cognitive frailty individuals” significantly differed from “individuals with cognitive impairment and without physical frailty”, scoring worse at executive, and attention tests. They presented subcortico-frontal cognitive pattern different of Alzheimer Disease. Cognitive performance of subjects with 3 criteria or more of the frailty phenotype are cognitively more impaired than subjects with only one. Discusion: The characterization of “cognitive frailty” must be done in frail subjects to set up specific preventive clinical trials for this population.

Disability is commonly considered as an irreversible condition of advanced age. Therefore, preventive actions need to be taken before the disabling cascade is fully established, that is in the pre-disability phase defined "frailty syndrome". The complexity and heterogeneity of frailty requires a clinical approach based on multidimensionality and multidisciplinary. In this paper, we present the main characteristics of the newborn Platform for Evaluation of Frailty and Prevention of Disability (Toulouse, France).Persons aged 65 years and older screened for frailty by general practitioners in the Toulouse area are invited to undergo a multidisciplinary evaluation at the Platform. Here, the individual is multidimensionality assessed in order to preventively detect potential risk factors for disability. At the end of the comprehensive evaluation, the team members propose the patient (in agreement with the general practitioner) a preventive intervention program specifically tailored to the his/her needs and resources.Mean age of our population is 82.7 years, with a large majority aged 75 years and older. Most patients are women (61.9%) Approximately two thirds of patients received any kind of regular help. Regarding level of frailty, 65 patients (41.4%) were pre-frail, and 83 (52.9%) frail. For what concerns the functional status, 83.9% of patients presented slow gait speed, 53.8% were sedentary, and 57.7% had poor muscle strength. Only 27.2% of patients had a SPPB score equal to or higher than 10. Autonomy in ADL was quite well preserved (mean ADL score 5.6 ± 0.8) as expected, suggesting that the patients of the platform have not yet developed disability. Consistently, IADL showed a marginal loss of autonomy reporting a mean score of 6.0 ± 2.3. About one third of patients (33.1%) presented a MMSE score lower than 25. Dementia (measured by the CDR scale) was observed in 11.6% of the platform population, whereas subjects with mild cognitive impairment (that is CDR equal to 0.5) were 65.8%. New diagnosed depressive disorders were relatively rare with only 3.2% of patients showing signs of depression but some people were already treated. Numerous patients presented vision problems with 10.4% having abnormal findings at the Amsler grid. Finally, it is noteworthy that 9% of the platform population presented an objective state of protein-energy malnutrition, 34% an early alteration of nutritional status, while almost everyone (94.9%) had a vitamin D deficiency (partially explained by the period of the year, that is winter-spring, of most of the measurements).The Platform clinically evaluates and intervenes on frailty for the first time at the general population-level. This model may serve as preliminary step towards a wider identification of early signs of the disabling cascade in order to develop more effective preventive interventions.

Weight loss is a frequent complication of Alzheimer's disease (AD) and a strong predictor of adverse outcomes in patients suffering from this disease. The aim of this study was to determine whether weight loss was a predictor of rapid cognitive decline (RCD) in AD. Four hundred fourteen community-dwelling ambulatory patients with a diagnosis of probable AD and a Mini-Mental State Examination (MMSE) score between 10 and 26 from the REAL.FR (REseau sur la maladie d'ALzheimer FRançais) cohort were studied and followed up during 4 years. Patients were classified in 2 groups according to weight loss defined by a loss of 4% or more during the first year of follow-up. RCD was defined as the loss of 3 points or more in MMSE over 6 months. The incidence of RCD was determined among both groups over the last 3 years of follow-up. MMSE, Katz's Activity of Daily Living scale, Mini-Nutritional Assessment scale, co-morbidities, behavioral and psychological symptoms of dementia, medication, level of education, living arrangement, and caregiver's burden were assessed every 6 months. Eighty-seven patients (21.0%) lost 4% or more of their initial weight during the first year. The incidence of RCD for all patients was 57.6 (95% confidence interval (CI) = 51.6-64.8) per 100 person-year (median follow-up of 15.1 months). In Cox proportional hazards models, after controlling for potential confounders, weight loss was a significant predictor factor of RCD (adjusted hazard ratio (HR) = 1.50, 95% CI = 1.04-2.17). In conclusion, weight loss predicted RCD in this cohort. Whether the prevention of weight loss (by improving nutritional status) impacts cognitive decline remains an open question.

Resume L’alteration des fonctions cognitives, en particulier la maladie d’Alzheimer (MA), a un impact majeur sur la qualite de vie du patient mais aussi de son entourage. Les changements recents de la pyramide des âges en font une des premieres preoccupations de sante des societes dites modernes. Parmi les complications non cognitives les plus frequentes de la maladie, il faut citer la perte de poids qui est associee a une plus grande mortalite et morbidite ainsi qu’une plus mauvaise qualite de vie. L’objectif de cet article est : (1) d’analyser les problemes nutritionnels les plus frequents qui surviennent au cours de la maladie et (2) d’evoquer les travaux qui se sont interesses aux facteurs nutritionnels en tant que facteurs de risque de la maladie.

Phase 3 trials estimate the effectiveness of an intervention to prevent, delay the onset of, or treat sarcopenia. Participants should have sarcopenia or present a sarcopenia risk profile. Control group should be characterized by the best standard of clinical care. This article further develops issues on sarcopenia definition, target population, primary and secondary end points, duration of the trials, muscle mass assessment, strength and physical performance assessment, and control of possible confounders. The challenges to conduct phase 3 trials in the elderly should not offset the opportunities for the development of new strategies to counteract sarcopenia and prevent late-life disability.

IAGG, WHO, and SFGG organized a international workshop on Health promotion programs on prevention of late on-set dementia. Thirty world specialists coming from Europe, North America, Asia, South America, Africa and Australia, shared their experience on methods and results of large epidemiological interventions to reduce incidents of dementia or delay its on-set. Chaired by Laura FRATIGLIONI, an expert in Epidemiological studies on dementia issues, the workshop gave opportunity for discussions and controversies about the state-of-the-art. Based on different national and international trials (ADAPT, MAPT, FINGER, GUDIAGE, GEM etc) the questions remained opened for different aspects of methodology, the choice of domain or multi domain intervention, the choice and the definition of the target populations, the best age of candidates, the issues related to the discrepancy between late effects, and interventions' duration. We are please to publish in the Journal, the presentations presented to this workshop. These publications will complete previously task force published in the journal in the last two years on methodological issues for Alzheimer's trials including end point, biomarkers, and the experience of past therapeutic trials.

L’importance de la vitamine D dans le metabolisme osseux est etablie de longue date mais il existe actuellement un regain d’interet pour cette vitamine en raison de son role eventuel dans un certain nombre d’evenements cliniques comme les chutes, les fractures, la force, l’equilibre, les troubles cognitifs, et la survenue de certains cancers et de certaines maladies inflammatoires au cours du vieillissement. La plupart des donnees de la litterature rapportent une insuffisance en vitamine D definie par une concentration en 25 (OH) D inferieure a 20 a 30 ng/ml et une carence definie par une concentration inferieure a 10 ng/ml. La prevalence de l’insuffisance ou de la carence en vitamine D est donc importante dans la population de personnes âgees ; elle reste cependant variable d’une etude a l’autre (de 16 a 78%) probablement du fait de l’utilisation de definitions differentes pour identifier les sujets en insuffisance ou carences, de l’âge de la population etudiee et du sexe (analyses realisees conjointement chez les hommes et les femmes, ou par sexe). Seule la double supplementation calcium + vitamine D parait efficace dans la prevention des fractures osteoporotiques chez les sujets âges. Les recommandations actuelles dans le traitement de l’osteoporose suggerent une supplementation calcique de 1200 mg a 1500 mg/j associee a une supplementation en vitamine D3 de 800 UI/j (Grade 2B). Il semble que les produits alimentaires fortifies (lait, jus d’orange, pain) permettraient de garantir un apport minimum supplementaire en vitamine D et en calcium.

Introduction Le recours a un outil d’evaluation simple et rapide pour reperer les personnes âgees fragiles vivant a domicile serait une aide precieuse en geriatrie. L’objectif de cet article est de rapporter les conclusions d’un groupe de travail (forme au sein de l’International Academy on Nutrition and Aging) sur la vitesse de marche en tant qu’outil de reperage de la fragilite.

Alzheimer's disease begins with cognitive deficiencies that gradually become worse with the extension of cerebral lesions. Other troubles arise such as loss of independence, orientation impairments, disordered eating behavior, and weight loss. This weight loss increases the risk of infections, skin ulcers, and falls and consequently decreases quality of life in Alzheimer's patients. Various hypotheses (increased energy expenditure, mesial temporal cortex atrophy) were suggested to explain weight loss. We set up a Health Promotion Program that aims to prevent weight loss in patients with Alzheimer's disease. This program uses various tools (nutrition calendar, Mini Nutritional Assessment, nutrition education sessions) described in this article.

Background: Comprehensive geriatric assessments of patients entering the severe stage of Alzheimer’s disease (AD) are scarce. Methods: Cross-sectional study of 126 patients entering the severe stage of AD in the longitudinal study of REAL.FR cohort. Patients who had a first MMSE score Results: The best-preserved cognitive abilities were social interaction and response to own name, while praxis, orientation, memory and language showed the largest declines. Regarding independence in daily living, locomotion was best preserved (71% of patients independent) while personal hygiene deteriorated most (15.5%). Behavioral disorders were frequent, and consisted principally of apathy, aberrant motor behavior, and agitation. The Mini Nutritional Assessment showed that 68.5% of patients were malnourished or at risk of malnutrition. Caregiver burden remained mild to moderate in 69.8% of cases. In addition, 80% of patients still lived at home and 71.6% used at least 2 support services, consisting mainly of physician visits and home help. Conclusion: Assessment of remaining cognitive, functional abilities and behavioral disorders at entry to severe AD should help to improve targeted management aimed at preserving these abilities and treating complications, thereby optimizing these patients’ quality of life.

In addition to extending lifespan, animal research shows that specific diets benefit brain functioning. Indeed, it has been proven that caloric restriction prevents age-related neuronal damage. What are those mechanisms involved in the effects of caloric restriction on brain functioning? Could caloric restriction be proposed in the future to prevent or treat neurodegenerative disorders such as Alzheimer's disease? Is there a future for caloric restriction interventions in adults?Hypotheses linking caloric restriction to cognitive capability include anti-inflammatory mechanisms, reduction of neural oxidative stress, promotion of synaptic plasticity, induction of various stress and neurotrophic/neuroprotective factors. Caloric restriction may also prevent beta-amyloid neuropathology in Alzheimer transgenic models. Finally, both exercise and caloric restriction enhance neurogenesis via different mechanisms suggesting that their combination may decrease the risk of neurodegenerative disease.It is now well established that caloric restriction could be used to promote successful brain aging. Data from randomized controlled trials in humans are limited. No positive effect on cognitive impairment was found probably due to methodological limitations. The long-term effects of caloric restriction in adults must be clarified before engaging in such preventive strategy. Additional animal studies must be conducted in the future to test the effects of 'multidomain' interventions (caloric restriction plus regular exercise) on age-related cognitive decline.

Resume L'effet potentiel de la nutrition est devenu d'un interet notoire pour la communaute scientifique et le grand public. Il existe en particulier des arguments qui suggerent que les nutriments (apport et/ou supplementation alimentaire) tels que les vitamines, les oligo-elements, et les lipides peuvent modifier le risque de declin cognitif et de demence, particulierement chez les sujets âges, fragiles, a risque de carences. Nous faisons dans cet article une revue de la litterature a partir des donnees des etudes prospectives et des essais cliniques randomises etudiant la relation entre l'alimentation et le risque de declin cognitif et de demence. Nous avons choisi de nous interesser specifiquement aux vitamines du groupe B en relation avec le metabolisme de l'homocysteine (Hcy), aux nutriments antioxydants (vitamines C et E, carotenoides, flavonoides, co-facteurs enzymatiques) et aux acides gras. Les resultats des etudes prospectives sont contradictoires et accentuent le besoin de developper d'autres etudes, incluant des patients a un stade suffisamment precoce ou au moins avant que ne se declare la maladie ou le declin cognitif. Les differences observees entre les etudes prospectives et les essais randomises peuvent s'expliquer par le fait que les doses utilisees dans les essais sont generalement plus elevees que les valeurs qui ont ete associees au declin cognitif dans les etudes d'observation. Plus d'essais randomises doivent etres conduits dans l'objectif de categories de patients specifiques (âge moyen et population vieillissante, sujet avec carence vitaminique, taux vitaminiques normaux ou eleves). De telles recherches identifiant le role de certains nutriments ou aliments ou de certains comportements alimentaires sont des etapes indispensables pour pouvoir proposer des recommandations specifiques dans le futur.

Background: Attrition, i.e. patient dropout, can threaten the validity of results in longitudinal studies. The aim of this study was to identify patient and caregiver factors predictive of attrition in a cohort of Alzheimer disease (AD) patients. Methods: 686 patients with mild to moderate AD were included in the multicenter prospective REAL.FR study. Standardized gerontological evaluations were carried out twice yearly. Factors associated with attrition were assessed by survival analysis using a Cox proportional hazard model. Results: After 2 years, 278 (40.5%) patients had dropped out. Causes of attrition included refusal (20.9%), death (20.1%), institutionalization (19.8%), and loss to follow-up (19.8%). Attrition rates between each 6-month wave were constant at 12%. After adjustment, several independent factors remained associated with attrition: patients cared for by an unrelated caregiver [HR 1.7; 95% CI (1.08–2.59)], loss of autonomy [HR = 1.37; (1.03–1.82)], increasing caregiver burden [HR = 1.014; (1.005–1.022)], use of cholinesterase inhibitors [HR = 0.40; (0.27–0.59)], use of 1 to 3 other types of medication [HR = 0.57; (0.36–0.89)]. Conclusions: The identification of both patient and caregiver factors predictive of attrition is of particular interest for the development and targeting of attrition prevention strategies. In patients with chronic diseases, particular attention should be paid to caregiver well-being to limit attrition.

Objectives Making an early diagnosis of Alzheimer's Disease (AD) is becoming increasingly important. The Clinical Dementia Rating scale (CDR), a semi-structured interview with patient and caregiver, is a global rating scale designed for use in staging dementia. The primary objective of our study was to examine the evolution of AD in individuals with very mild AD (CDR 0.5) across a 2-year follow up. Methods A cohort of AD patients (n = 682) living in the community were followed during 2 years in 16 centres of the French AD network. Each subject underwent extensive medical examination including the MMSE and CDR every 6 months. Results Two hundred and thirty-three AD patients were rated CDR 0.5 at baseline (mean MMSE score: 23.15 ± 2.57). They were younger and reported an average duration of symptoms of approximately 0.8 years less than patients with CDR ≥ 1. During the 2-year follow-up, none of the AD CDR 0.5 subjects improved; 65% of them showed an increase in the CDR score. The rate of cognitive decline was similar between the AD CDR 0.5 and CDR ≥ 1 groups. The ADL decline was more significant in patients with CDR ≥ 1 at inclusion. Conclusions It is certainly possible to identify AD at a very early stage focusing on intra individual change in cognitive and functional impairment. Criteria with a high sensitivity and specificity for detecting AD at an early stage will help to further develop effective pharmacological and behavioural interventions for delaying the onset and progression of the disease. Copyright © 2007 John Wiley & Sons, Ltd.

Background: Given the poorer prognosis of Alzheimer’s disease (AD) patients with rapid cognitive decline (RCD), there is a need for a clinical assessment tool to detect these patients. Objective: To investigate if there is a Mini Mental State Examination (MMSE) threshold of decline during 6 months of follow-up which predicts a worse disease progression at the 2-year follow-up. Then, to propose a feasible definition of RCD for routine clinical practice. Methods: Data from 565 community-dwelling AD patients recruited in a multi-centre prospective observational study were assessed. All patients had MMSE scores between 10 and 26 at inclusion and were followed up 6-monthly using a standardised clinical assessment. Patients were classified as rapid and non-rapid decliners according to 2 MMSE decline thresholds tested: ≧3 points and ≧4 points for decline over the first 6 months of the study. Worse disease outcome was defined as attainment of 1 of 4 clinical end points 18 months later: institutionalisation, death, increased physical dependence or worsening of behavioural and psychological symptoms. Results: 135 patients (23.9%) lost ≧3 points during the first 6 months of follow-up in the MMSE score and 77 patients (13.6%) lost ≧4 points. Patients with moderate disease and a loss of ≧4 points showed a significantly increased risk of mortality (HR = 5.6, 95% CI 2.0–15.9) and institutionalisation (HR = 3.8, 95% CI 1.8–8.1) at the 2-year follow-up. The same MMSE threshold was associated with a higher risk of physical decline (HR = 1.6, 95% CI 1.2–2.3). Conclusion: The loss of ≧4 points in MMSE during the first 6 months of follow-up seems to be a predictor of worse clinical course, and thus it could be used to define the category of AD patients presenting a RCD.

The aim of the present study was to describe the long-term evolution of Alzheimer's disease (AD) in a prospective cohort of patients under treatment with a close follow-up.Six hundred eighty-six AD patients from the French Network on AD (REAL-FR) were followed up and assessed every 6 months for 2 years. Cognitive, functional, behavioral, nutritional, and global status were evaluated by using Mini-Mental State Examination (MMSE), cognitive subscale of AD Assessment Scale (ADAS-cog), Activities of Daily Living scale (ADL), Neuropsychiatric Inventory (NPI), Mini-Nutritional Assessment (MNA), and Clinical Dementia Rating (CDR).There were 85.13% of patients who were specifically treated for AD during their participation in the study. We observed significant changes (P.0001) on MMSE, -4.57 +/- 0.23; ADAS-cog, 7.11 +/- 0.41; ADL, -1.32 +/- 0.07; NPI, 2.94 +/- 0.77; MNA, -0.81 +/- 0.17; and sum of boxes of the CDR (CDR-SB), 4.17 +/- 0.17. After 2 years, 10.79% (95% confidence interval [CI], 8.47 to 13.11) of the patients evolved twice as rapidly as the mean of the whole cohort on MMSE (loss,or =9 points), 65.89% (95% CI, 62.34 to 69.44) reported a loss of 3 to 9 points, and 23.32% (95% CI, 20.16 to 26.46) were stable or improved (loss of -2 points maximum). Annual incidences for institutionalization, hospitalization, and death were 11.84% (95% CI, 9.76 to 13.92), 26.13% (95% CI, 22.52 to 29.74), and 5.95% (95% CI, 4.56 to 7.34), respectively.In a recent large AD cohort mostly under treatment, AD evolution appeared to be variable, with high incidences for death or institutionalization and with 11.84% of the patients exhibiting a rapid cognitive decline, whereas one fourth of the cohort appeared in relatively stable condition, and two thirds had a moderate but significant evolution of the disease. More studies are needed to better understand these variations in patients' evolution.

Background: The concentration of aluminum or silica in drinking water may be a potential environmental risk factor for Alzheimer disease (AD). Objectives: The objective was to investigate at baseline the potential association between the composition of drinking water and the level of cognitive function in women taking part in the Epidemiology of Osteoporosis (EPIDOS) Study and to determine during follow-up the effects of the composition of drinking water on the risk of AD. Design: Women aged greater than or equal to 75 y (n = 7598) were recruited between 1992 and 1994 in 5 geographic areas of France. The participants from one center (n = 1462) were followed for less than or equal to 7 y; during this time, an active search for incident cases of AD was conducted. The initial questionnaire comprised a food consumption survey with specific questions about the daily consumption of tap and mineral water. The evaluation of cognitive function was based on the Short Portable Mental Status Questionnaire. During follow-up, the diagnosis of dementia was made by a geriatrician and a neurologist. Results: A low silica concentration was associated with low cognitive performance at baseline. Compared with the nondemented subjects, the women with a diagnosis of AD during follow-up were older at inclusion, had a lower financial status and educational level, had a poorer perception of their own health, and had a more difficult time performing activities of daily living. A multivariate analysis including potential confounding factors showed that women with AD appeared to have been exposed to lower amounts of silica at baseline. Conclusions: Silica in drinking water may reduce the risk of developing AD in elderly women. The results corroborate those of another epidemiologic study carried out in France. The potential effect of silica needs to be confirmed in additional investigations.

The frailty syndrome is a pre-disability condition suitable to be targeted by preventive interventions against disability. In order to identify frail older persons at risk of negative outcomes, general practitioners must be provided with an easy and quick screening tool for detecting frailty without special effort. In the present paper, we present the screening tool for frailty that the Gérontopôle of Toulouse (France) has developed and implemented in primary care in the region with the collaboration of the Department of Family Medicine of the University of Toulouse. The Gérontopôle Frailty Screening Tool (GFST) is designed to be administered to persons aged ≥65 years with no physical disability and acute clinical disease. It is composed by an initial questionnaire aimed at attracting the general practitioner's attention to very general signs and/or symptoms suggesting the presence of an underlying frailty status. Then, in a second section, the general practitioner expresses his/her own view about the frailty status of the individual. The clinical judgment of the general practitioner is finally retained for determining the eventual presence of frailty. Preliminary data document that almost everyone (95.2%) of the 442 patients referred to the Gérontopôle frailty clinic by general practitioners using the GFST indeed presents a condition of (pre-)frailty according to the criteria proposed by Fried and colleagues in the Cardiovascular Health Study. The use of the GFST may help at raising awareness about the importance of identifying frailty, training healthcare professionals at the detection of the syndrome, and developing preventive interventions against disabling conditions.

OBJECTIVES: To study the effects of oral nutritional supplements (OS) on body weight, body composition, nutritional status, and cognition in elderly patients with Alzheimer's disease (AD). DESIGN: Prospective, randomized, controlled study. SETTING: Geriatric wards and day care centers in the Toulouse area, France. PARTICIPANTS: Ninety-one subjects with AD aged 65 and older at risk of undernutrition as evaluated using the Mini Nutritional Assessment. INTERVENTION: After randomization, 46 patients (intervention group) received 3-month OS. The other 45 patients (control group) received usual care. MEASUREMENTS: Weight, body composition (evaluated using dual-energy x-ray absorptiometry), cognitive function, activities of daily living, eating behavior, and dietary intakes were evaluated at the beginning of the study and at 3 months and 6 months. Supplement compliance was recorded each day. RESULTS: Between baseline and 3 months, energy and protein intakes significantly improved in the intervention group, resulting in a significant increase in weight and fat-free mass, but no significant changes were found for dependence, cognitive function, or biological markers. The nutritional benefit was maintained in the intervention group after discontinuation of OS at 3 months. CONCLUSION: Three-month daily OS significantly improves body weight. It is practicable and effective, and the patients accepted it well. The improvement that was observed even in the control group showed that caregiver education is an important factor in maintaining the nutritional status of patients with AD. Moreover, regular courses of OS may help to maintain the increase in fat-free mass and improve the nutritional status of these patients.

Resume Nous presentons dans cet article l'etude REAL.FR (Reseau sur la maladie d'Alzheimer Francais). Il s'agit d'une etude prospectivemulticentrique dont les objectifs sont d'etudier l'histoire naturelle de la maladie et les modalites de prise en charge de la personne âgee atteinte de la maladie d'Alzheimer (MA) dans des contextes diversifies. Pour repondre a ces objectifs, une cohorte de patients atteints d'une MA, recrutes a partir de 16 centres hospitaliers universitaires en France, a ete mise en place. Il s'agit de patients presentant au moment de leur inclusion une demence legere a moderee, vivant au domicile et pris en charge par un aidant informel. Ces patients beneficient a l'inclusion et tous les six mois d'une evaluation gerontologique standardisee (autonomie, fonctions cognitives, troubles du comportement, statut nutritionnel) et d'une evaluation sociale (niveau d'education, mode d'habitation, recours aux services d'aide et de soins a domicile, allocations percues, revenus). La charge des aidants est egalement mesuree par le questionnaire de Zarit. Au cours du suivi, les evenements survenus au cours des six derniers mois sont releves, en particulier les hospitalisations, les placements en institution, le recours a de nouveaux services et les changements survenus dans l'entourage de la personne âgee. Au total, 700 patients ont ete inclus dans cette cohorte depuis avril 2000 et seront suivis durant au moins 4 ans. A ce jour, 577 patients ont ete revus a 6 mois, 489 a 12 mois, 358 a 18 mois, 266 a 24 mois, 176 a 30 mois et 31 a 36 mois. On enregistre 48 deces, 42 placements en institution et 124 sorties d'etude (predus de vue n = 35 ; desir de la famille n = 53 ; probleme medical n = 6 ; autres n = 30). L'âge moyen des patients a l'inclusion etait de 77,4 ± 7 ans. Pres d'un tiers des patients vivent seuls a leur domicile au moment de leur recrutement. L'etude REAL.FR constitue un observatoire unique en France des patients atteints d'une MA. L'etat d'avancement actuel est tres encourageant quant a la faisabilite du suivi des patients. La bonne participation des patients et de leur famille aux evaluations ulterieures deja realisees nous parait egalement de bon augure pour la poursuite de ce suivi.

Resume La deambulation est un probleme frequent au cours de la maladie de type Alzheimer. Peu d'etudes se sont interessees a cetrouble du comportement chez les sujets vivant a domicile. L'objectif de cette etude est de decrire des patients souffrant de la maladie de type Alzheimer presentant un comportement de deambulation et vivant a domicile. Methode. 571 patients souffrant de la maladie de type Alzheimer et vivant a domicile ont ete etudies. Les capacites cognitives ont ete quantifiees par une batterie de tests neuro-cognitifs standardises. Le statut nutritionnel, le risque de chute et l'autonomie ont ete evalues de meme que le fardeau supporte par les familles. Les troubles du comportement ont ete apprecies en compagnie des aidants en utilisant le Neuro-Psychiatric Inventory. Les patients avec ou sans comportement de deambulation ont ete decrits. Resultats. La prevalence de la deambulation etait de 12,6 %. Les patients deambulants avaient une alteration cognitive plussevere, moins d'autonomie et sont plus frequemment denutris. Les troubles du comportement significativement associes au comportement de deambulation etaient les delires, l'agressivite, l'irritabilite, la depression, l'anxiete, l'euphorie, l'apathie, la desinhibition et les troubles du comportement alimentaire. Un sous-groupe de patients semble presenter un syndrome frontal. Conclusion. La deambulation est frequente chez les patients souffrant de la maladie de type Alzheimer et vivant a domicile. Une priseen charge specifique devrait etre organisee pour aider ces patients fragiles et leurs aidants.

Resume Propos. La plupart des patients atteints de la maladie d'Alzheimer sont pris en charge au domicile par un aidant informel. L'effet des differents facteurs de stress sur ces aidants represente le fardeau. Objectifs. Determiner (1) le niveau du fardeau des aidants informels de patients atteints de la maladie d'Alzheimer (2) les facteurs associes a un niveau eleve de fardeau. Methodes. Etude transversale des aidants informels de personnes âgees dementes se presentant a la consultation de services depsychogeriatrie, geriatrie ou neurologie dans 16 CHU francais. Les aidants de 531 patients ayant une demence legere a moderee ont ete interviewes avec un questionnaire structure centre sur les caracteristiques relatives aux aidants (notion de cohabitation avec le patient, fardeau ressenti evalue par l'echelle de Zarit) et les patients ont ete examines a l'inclusion pour evaluer leurs fonctions cognitives, l'existence de troubles fonctionnels et du comportement. Resultats. L'analyse logistique de regression a montre que les caracteristiques des patients (MMSE, troubles comportementaux,troubles nutritionnels), les caracteristiques des aidants (sexe feminin, nombre de tâches liees a l'aide, cohabitation) et e recours a des services medicaux etaient independamment associees a un niveau eleve de fardeau. Dans cette etude le fardeau eleve des aidants etait lie de facon independante a la severite de l'atteinte cognitive et aux troubles du comportement. Cependant, ni la duree de maladie ni les incapacites a realiser les activites de la vie quotidienne n'etaient liees au fardeau. Ces resultats peuvent orienter des interventions adaptees d'aide aux aidants informels.

Background. - Alzheimer's disease is a chronic pathology requiring regular follow-up. The predictive factors of rapid cognitive decline remain unclear. Objectives. - To analyse the baselines characteristics of patients at increased risk of rapid cognitive decline. Methods. - 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. Results. - 54 % of patients presented a rapid cognitive decline. Logistic regression analysis showed a positive association between rapid cognitive decline and a MMSE less than or equal to 20 (p

Background. Peripheral C4A treatment (cerebral and peripheral vasotherapeutics) and especially Ginkgo biloba extracts are prescribed for a number of symptoms, particularly memory impairment, in elderly patients. It is postulated that because of its pharmacological actions, this treatment could prevent the decline of cognitive function, but no studies have been published to date to test its efficacy in prevention of Alzheimer’s disease. The potential association between use of C4A treatments, in particular EGb 761 (standardized Ginkgo biloba extracts), and dementia of the Alzheimer type was investigated. Methods. A case-control study was nested in a cohort of 1462 community-dwelling elderly women aged over 75 years. Sixty-nine women with Alzheimer-type dementia were compared with 345 paired women whose cognitive function remained normal. This study involved women whose cognitive function was evaluated at baseline by use of Pfeiffer’s test and whose medication history was taken. The onset of cognitive impairment was investigated over a 7-year follow-up period. In order to study the factors associated with the onset of dementia, the data concerning women with a score of >8 on Pfeiffer’s test at inclusion, indicating normal cognitive function, were analyzed. Results. A multivariate analysis including potential confounding factors showed that fewer women who developed Alzheimer’s dementia had been prescribed C4A treatment (including EGb 761) for at least 2 years (odds ratio 5 0.31, 95% confidence interval 5 0.12–0.82, p 5 .018). Figures for EGb 761 alone were similar but did not reach statistical significance (odds ratio 5 0.38, 95% confidence interval 5 0.08–1.76, p 5 .22). Conclusion. These results suggest that C4A treatment may reduce the risk of developing Alzheimer’s dementia in elderly women. The potential preventive effect of C4A treatments, including EGb 761, requires further examination. To establish a causal relationship, these findings have to be confirmed with prospective studies.

Background: There are presently no published data on age-related changes in body composition in French individuals older than 65 or 80 years. This paper presents a cross-sectional study of 7518 community-residing French women older than 75 years. Methods: We examined age differences changes in body composition and anthropometry between age groups (76–80, 81–85, and 86–95 years of age). Whole body composition was estimated using a dual energy X-ray absorptiometry (DXA) scanner. Measurements of appendicular skeletal muscle (ASM) mass and sarcopenia were performed for a subsample of 1321 women. Results: Significant age differences exist in total fat mass and total bone mineral content in elderly women between 76 and 95 years of age. There was also a significant decreased in fat free soft tissue mass from 76 to 85. The decline in fat free mass may be reduced over 85 years of age. The prevalence of low muscle mass, or sarcopenia, increased with age from 8.9 in 76–80 to 10.9% in 86–95 age group, but the difference was not statistically significant. Conclusions: Interventional programs developed to prevent or reduce sarcopenia would have a better influence on population under 85 years, i.e. when the decline in ASM mass is the most severe. Others longitudinal studies could be performed to confirm our results.

Background Patients with Alzheimer's disease (AD) commonly develop aversive feeding behaviours. These behaviours lead to weight loss and frequently to physicians using tube feeding. Little is known about factors correlated with feeding difficulties during AD. Objective To investigate predictors of aversive feeding behaviours (AFBs) which occured during a one-year interval among AD patients living at home with a caregiver. Method One-year study initiated in January 1998 with 224 AD patients and their caregivers. Main outcome measures: all patients underwent a nutritional, psychologic and functional evaluation at baseline and one year later. Feeding difficulties were assessed using the Feeding Dependency Scale and the Aversive Feeding Behaviour Inventory. The Burden Interview was also done to assess the material and emotional burden. Results Initial feeding difficulties were significantly associated with the age of the caregiver, the severity of the disease and the initial patient's autonomy and psychological functioning (mood and behaviour disorders). AD patients, who lived with a more affected caregiver at baseline, developped feeding difficulties and AFBs during the follow-up. Logistic regression analysis showed a positive association between AFBs worsening and the initial caregiver's burden after controlling for counfounding factors. On the other hand, memory impairment was inversely associated with AFBs. Conclusions Both cognitive impairment and family stress can help in predicting which AD patients living at home will develop AFBs. Nutritional information and support to families are probably the best strategies to prevent AFBs during AD and to improve consequently the patient's and caregiver's quality of life. Copyright © 2002 John Wiley & Sons, Ltd.

The frailty syndrome has recently attracted attention of the scientific community and public health organizations as precursor and contributor of age-related conditions (particularly disability) in older persons. in parallel, dementia and cognitive disorders also represent major healthcare and social priorities. although physical frailty and cognitive impairment have shown to be related in epidemiological studies, their pathophysiological mechanisms have been usually studied separately. an international Consensus Group on “Cognitive Frailty” was organized by the international academy on nutrition and aging (i.a.n.a) and the international association of Gerontology and Geriatrics (i.a.G.G) on april 16th, 2013 in toulouse (France). the present report describes the results of the Consensus Group and provides the first definition of a “Cognitive Frailty” condition in older adults. specific aim of this approach was to facilitate the design of future personalized preventive interventions in older persons. Finally, the Group discussed the use of multidomain interventions focused on the physical, nutritional, cognitive and psychological domains for improving the well-being and quality of life in the elderly. the consensus panel proposed the identification of the so-called “cognitive frailty” as an heterogeneous clinical manifestation characterized by the simultaneous presence of both physical frailty and cognitive impairment. in particular, the key factors defining such a condition include: 1) presence of physical frailty and cognitive impairment (Cdr=0.5); and 2) exclusion of concurrent ad dementia or other dementias. under different circumstances, cognitive frailty may represent a precursor of neurodegenerative processes. a potential for reversibility may also characterize this entity. a psychological component of the condition is evident and concurs at increasing the vulnerability of the individual to stressors.

Background. A number of clinical conditions have been shown to be associated with frailty in elderly people. We hypothesized that incapacities on the Instrumental Activities of Daily Living (IADLs) scale could make it possible to identify this population. We investigated the associations between IADL incapacities and the various known correlates of frailty in a cohort of community-dwelling elderly women. Methods. Cross-sectional analysis was carried out on the data from 7364 women aged over 75 years (EPIDOS Study). The IADL was the dependent variable. Sociodemographic, medical, and psychological performance measures were obtained during an assessment visit. Falls in the previous 6 months and fear of falling were also ascertained. Body composition was measured by dual-energy x-ray absorptiometry. The factors associated with disability in at least one IADL were included in a logistic regression model. Results. Thirty-two percent of the population studied had disability in at least one IADL item. This group was significantly older (81.7 � 4.1 yr vs 79.8 � 3.4 yr), had more frequent histories of heart disease, stroke, depression or diabetes, and was socially less active ( p � .001). These associations persisted after multivariate analysis. Cognitive impairment as assessed by the Pfeiffer test (Pfeiffer score � 8) was closely associated with disabilities on the IADL (OR 3.101, 95% confidence interval [CI] 2.19‐4.38). Falls and fear of falling were also more frequent in the group of women with an abnormal IADL ( p � .001) but only fear of falling remained significantly associated with incapacities on at least one IADL item after logistic regression (OR 1.47, 95% CI 1.28‐1.69). Women with disability on at least one IADL item also had lower bone mineral density, this was independent of the other factors. Conclusion. Our results confirmed that women with disability on at least one IADL item are frailer because they had more associated disorders, poorer cognitive function and more frequent falls. Disabilities on this scale could be a good tool for identifying individuals at risk of frailty among elderly persons living at home and in apparent good health. This finding requires confirmation by longitudinal studies.

Approximately 6-8% of all persons aged >65 y have Alzheimer disease and the prevalence of the disease is increasing. Any intervention strategy aimed at decreasing risks or delaying the onset of the disease will therefore have a substantial effect on health care costs. Nutrition seems to be one of the factors that may play a protective role in Alzheimer disease. Many studies suggest that oxidative stress and the accumulation of free radicals are involved in the pathophysiology of the disease. Several studies have shown the existence of a correlation between cognitive skills and the serum concentrations of folate, vitamin B-12, vitamin B-6, and, more recently, homocysteine. However, nutritional factors have to be studied not alone but with the other factors related to Alzheimer disease: genetics, estrogen, antiinflammatory drug use, and socioeconomic variables. The objective of this article was to review recent studies in this field.

Background: -Epidemiologic studies have shown that weight loss is commonly associated with Alzheimer disease (AD) and is a manifestation of the disease itself. The etiology of weight loss in AD appears multifactorial. Hypotheses to explain the weight loss have been suggested (eg, atrophy of the mesial temporal cortex, biological disturbances, and higher energy expenditure); however, none have been proven. Objective: In the first part of this article, we describe weight loss in AD (epidemiologic data and hypotheses to explain weight loss and anorexia in AD). In the second part we report the results of a longitudinal study of the changes in nutritional variables in a cohort of patients with a probable diagnosis of AD. Design: We followed subjects with AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association) who were recruited from the Alzheimer's Disease Center in Toulouse. All subject underwent a nutritional, neuropsychologic, and functional evaluation. The Zarit scales were used to assess caregiver burden and caregiver reactions to the patients' behavioral and autonomic disorders. Results: We showed that only results of the Burden Interview and the Memory and Behavior Problems Checklist, which explored caregiver burden, predicted weight loss in AD. It is possible that caregivers who consider themselves overburdened by the disease process are not willing to invest adequate resources to allow AD patients to properly nourish themselves. Conclusion: Nutritional education programs for the caregivers of AD patients seem to be the best way to prevent weight loss and improve the nutritional status of these patients.

Objectives: To assess whether angiotensin-converting enzyme inhibitor (ACE-I) treatment is associated with less cognitive decline in older adults with Alzheimer's disease (AD) than in those using other hypertensive or no drugs. Design: Four-year prospective multicenter cohort study with a biannual assessment. Setting: Memory clinics from 16 university hospitals in France. Participants: Community-dwelling older adults with mild to moderate AD (N = 616). Measurements: Participants were stratified into four groups according to type and duration of antihypertensive drug treatment. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE). Linear mixed-effects models were used to assess differences in decline in MMSE score between the four groups. Hypertension at each visit was included in the model. Results: Sixty-one participants had used ACE-Is continuously, 57 had used them intermittently, 189 had used other antihypertensive drugs, and 309 never used any antihypertensive drugs. Continuous ACE-Is users had a 4-year decline in MMSE of 6.4 ± 1.6 points (P < .001), intermittent ACE-Is users of 7.9 ± 1.1 points (P < .001), continuous or intermittent users of other antihypertensive drugs of 8.8 ± 0.7 points (P < .001), and never-users of 10.2 ± 0.6 points (P < .001). MMSE decline between the four groups was significantly different (adjusted P = .02). In subgroup analysis, the 118 (19.2%) participants who had continuously or intermittently used ACE-Is had a significant difference in 4-year MMSE decline from the 498 (80.8%) who had never used ACE-Is (7.5 ± 0.9 vs 9.7 ± 0.4; P = .03). Conclusion: The use of ACE-Is in older adults with AD is associated with a slower rate of cognitive decline independent of hypertension. Future research is needed to explore the role of ACE-Is in long-term AD progression.

According to international recommendations [from the American College of Cardiology/American Heart Association/European Society of Cardiology] and those of the Haute Autorite de Sante (HAS) in France, treatment with a vitamin K antagonist is recommended in patients with atrial fibrillation (AF) in the presence of a high thromboembolic risk factor [history of stroke, transient ischemic attack, systemic embolism, or valvular heart disease, or presence of a mechanical heart valve prosthesis] or at least two moderate risk factors (age ≥75 years, hypertension, congestive heart failure, or diabetes). In patients with a major contraindication, the vitamin K antagonist can be replaced by an antiplatelet agent (APA). These recommendations are not systematically observed in patients with Alzheimer disease (AD). The aim of our study was to determine the factors associated with undertreatment of AF in geriatric outpatients with AD. Use of oral anticoagulants or APAs was studied in 66 patients with AF who were included in the French Network on Alzheimer Disease (REAL.FR) cohort, consisting of 686 outpatients living at home, supported by an informal caregiver, and suffering from Alzheimer-type dementia, with a Mini Mental Status Examination (MMSE) score between 10 and 26. First, demographic characteristics (age, sex, body mass index [BMI], living arrangements, educational level), medical conditions (comorbidity, number of medications), disability (activities of daily living [ADL], instrumental activities of daily living [IADL]), risk of falls (one-leg balance test), cognitive status (according to MMSE, Alzheimer’s Disease Assessment Scale—Cognitive Subscale [ADAS-Cog], and Clinical Dementia Rating [CDR] scores), risk factors for stroke (hypertension, history of stroke, congestive heart failure, diabetes, or age ≥75 years) and potential contraindications to oral anticoagulants (OACs) or APAs (polypharmacy, risk of falls, renal failure, gastrointestinal diseases) of patients receiving OACs were compared with those of patients receiving APAs and those of patients receiving no treatment for AF. Then the same characteristics were compared between patients receiving no treatment for AF and those receiving OACs or APAs. Only 56 % (n = 37) of patients with AF were receiving OACs or APAs at the baseline visit, of whom 18 (49 %) were receiving OACs and 19 (51 %) were receiving APAs. Bivariate analysis showed that patients receiving OACs or APAs were significantly more likely to have a history of cardiovascular disease (p = 0.005)—in particular, hypertension (p = 0.037)—less likely to be living alone and unaided (p = 0.038), and less likely to be taking nonsteroidal anti-inflammatory drugs [NSAIDs] (p = 0.001). Despite the national and international recommendations, nearly half of AD patients with AF do not receive OACs or APAs. A history of cardiovascular disease—in particular, hypertension—improves access to treatment, but use of NSAIDs and living alone without home care seem to be the main factors associated with non-prescription of OACs or APAs.

The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom, the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWIG) in Germany and the Haute Autorité de Santé (HAS) in France have recently set out guidelines on prescription of anti-dementia medication. The HAS proposes in particular that continuation of these drugs for longer than one year should be decided in multidisciplinary team meetings (MDTM).To assess the feasibility of MDTM and the satisfaction of coordinating physicians from institutions for the dependent elderly (nursing home, NH) and expert physicians from memory clinics who have participated in the meetings.Survey carried out among physicians who had participated in the MDTM held as part of the IDEM study (Interest of systematic tracking of dementia cases in NH: analysing the contribution of MDTM in Alzheimer's disease and related diseases; PHRC National 2009, Code 0910701). The survey evaluated the organization of MDTM and the physicians' opinion of these meetings.The cases of 574 patients were discussed in MDTM involving 133 healthcare professionals (32 coordinating physicians, 48 expert physicians, 4 general practitioners and 49 other health professionals). The mean number of participants was 4.2±1.6. About 16 minutes were spent discussing the case of each resident. About 90% of physicians considered that the meetings were useful. Overall assessment of their efficacy was 11.5/20 for the coordinating physicians and 14.1/20 for the expert physicians. The benefits of MDTM in relation to the work entailed were considered important by 60% of expert physicians and 33% of coordinating physicians.Our survey confirmed the feasibility of MDTM in the field of Alzheimer's disease. The overall benefit/workload ratio of the meetings was considered to be favorable for the expert physicians. The benefits of MDTM were turned out to be less appreciated by the coordinating physicians according to high workload involved.

Background Emergency room (ER) re-hospitalizations are prevalent in severe Alzheimer's disease affected older patients. Design Quasi-experimental before and after study. Setting Discharge of severely demented patients from a Special Alzheimer Acute Care Unit. Participants A total of 390 patients hospitalized in the unit from 2007 through 2009, with at least one of the following characteristics: severe disruptive behavioral and psychological symptoms of dementia (BPSD) (agitation, aggressiveness, and psychotic symptoms), change of living arrangement related to BPSD, exhaustion of the principal caregiver, and discharge of a subject with anosognosia living alone in the community. Intervention The intervention consisted of an individualized care plan, targeting the problems observed during the hospital stay, implemented by the means of regular telephone contacts (in the first week after discharge, before the end of the first month, and then at 3 and 6 months) between a geriatric team and the patient's caregiver. Information was gathered on functional decline, BPSD, change of living arrangement and treatment. The calls were followed by a telephone intervention providing advice, support, and information to the caregiver. When required, these calls were followed by a consultation with a physician or psychologist, or by a consultation in the patient's home. Measurements The primary outcome measure was the ER re-hospitalization rate, defined as occurring within 31 days of discharge. Results The early ER re-hospitalization rate was 8.39% in 2007 versus 8.02% in 2008 (p = 0.818) and 7.47% in 2009 (p = 0.563). Vocal disruptive behavior are more prevalent in re-hospitalized patients (9.64% versus 3.97%, p = 0.05) than in non re-hospitalized patients. Conclusion We found a nonsignificant decrease of early ER re-hospitalization rate at 1 month after discharge. Interventions addressing severe dementia affected patients with BPSD are needed, as this is a major issue in the organization of health care systems. Copyright © 2013 John Wiley & Sons, Ltd.

OBJECTIVES: To explore the extent to which client characteristics, decision-maker attributes, and country influence judgments of institutional long-term care (ILTC) appropriateness for people with dementia.DESIGN, SETTING, AND PARTICIPANTS: A total of 161 experts in dementia care from 8 European countries reviewed a series of 14 vignettes representing people with dementia on the cusp of ILTC admission and indicated the most appropriate setting in which to support each case in a simple discrete choice exercise: own home, very sheltered housing, residential home, or nursing home. At least 16 experts participated in each country (Estonia, Finland, France, Germany, the Netherlands, Spain, Sweden, and the United Kingdom).MEASUREMENTS: Descriptive statistics were used to characterize the experts and their placement preferences. Logistic regression modeling was used to explore the extent to which the sociodemographic and clinical characteristics of people with dementia, and the profession, workplace, and country of decision-makers were associated with ILTC recommendation.RESULTS: Client characteristics, decision-maker attributes, and country all seemed to play a part in influencing professionals' perceptions of the appropriateness of ILTC for people with dementia. Expert decision-makers were more likely to recommend ILTC for individuals who required help with mobility or had multiple care needs, and appeared to give more weight to carers' than clients' wishes. Community-based social workers were less likely than other professional groups to favor ILTC placement. Experts in Finland, Germany, and the United Kingdom were less likely to recommend ILTC than experts in France, the Netherlands, and Estonia; experts in Sweden and Spain took an intermediate position.CONCLUSION: This study provides new understanding of the factors that shape professionals' perceptions of ILTC appropriateness and highlights the need to construct multifaceted models of institutionalization when planning services for people with dementia. It also has several important clinical implications (including flagging interventions that could decrease the need for ILTC), and provides a basis for enhancing professionals' decision-making capabilities (including the greater involvement of clients themselves).

International audience; ABSTRACT: Cost-of-illness studies (COI) can identify and measure all the costs of a particular disease, including the direct, indirect and intangible dimensions. They are intended to provide estimates about the economic impact of costly disease. Alzheimer disease (AD) is a relevant example to review cost of illness studies because of its costliness.The aim of this study was to review relevant published cost studies of AD to analyze the method used and to identify which dimension had to be improved from a methodological perspective. First, we described the key points of cost study methodology. Secondly, cost studies relating to AD were systematically reviewed, focussing on an analysis of the different methods used. The methodological choices of the studies were analysed using an analytical grid which contains the main methodological items of COI studies. Seventeen articles were retained. Depending on the studies, annual total costs per patient vary from $2,935 to $52, 954. The methods, data sources, and estimated cost categories in each study varied widely. The review showed that cost studies adopted different approaches to estimate costs of AD, reflecting a lack of consensus on the methodology of cost studies. To increase its credibility, closer agreement among researchers on the methodological principles of cost studies would be desirable.

Emergency room (ER) re-hospitalizations are prevalent in severe Alzheimer's disease affected older patients.Quasi-experimental before and after study.Discharge of severely demented patients from a Special Alzheimer Acute Care Unit.A total of 390 patients hospitalized in the unit from 2007 through 2009, with at least one of the following characteristics: severe disruptive behavioral and psychological symptoms of dementia (BPSD) (agitation, aggressiveness, and psychotic symptoms), change of living arrangement related to BPSD, exhaustion of the principal caregiver, and discharge of a subject with anosognosia living alone in the community.The intervention consisted of an individualized care plan, targeting the problems observed during the hospital stay, implemented by the means of regular telephone contacts (in the first week after discharge, before the end of the first month, and then at 3 and 6 months) between a geriatric team and the patient's caregiver. Information was gathered on functional decline, BPSD, change of living arrangement and treatment. The calls were followed by a telephone intervention providing advice, support, and information to the caregiver. When required, these calls were followed by a consultation with a physician or psychologist, or by a consultation in the patient's home.The primary outcome measure was the ER re-hospitalization rate, defined as occurring within 31 days of discharge.The early ER re-hospitalization rate was 8.39% in 2007 versus 8.02% in 2008 (p = 0.818) and 7.47% in 2009 (p = 0.563). Vocal disruptive behavior are more prevalent in re-hospitalized patients (9.64% versus 3.97%, p = 0.05) than in non re-hospitalized patients.We found a nonsignificant decrease of early ER re-hospitalization rate at 1 month after discharge. Interventions addressing severe dementia affected patients with BPSD are needed, as this is a major issue in the organization of health care systems.

The formation of the first Gerontopole in Toulouse was a response to a mission letter sent by French Ministers of Health on February 2007. The mission of the Toulouse Gerontopole is based around three major axes: 1) To facilitate the access of frail elderly people to innovative therapy and clinical research: the Gerontopole set up the national network for clinical investigation into Alzheimer's disease (AD) funded through the CeNGEPS (National Centre For Management of Trials on Health Products) calls for proposals since July 2008. In addition, the Gerontopole coordinates several national clinical trials with promising drugs with potential effect on the mechanisms and evolution of AD and actively participates in studies on biomarkers; 2) To develop health promotion actions and prevention trials for healthy elderly people, through the Institute of Aging: the Gerontopole has implemented the GuidAge (Phase III trial concerning the efficiency of Ginkgo Biloba on the impact and delay of appearance of an Alzheimer type dementia) and MAPT (Multi-domain Alzheimer Preventive Trial) studies on prevention of AD and cognitive decline. It is curently working on the new generation of preventive trials based on biomarkers; 3) To develop clinical research for dependant elderly people, through the implementation of the REHPA research network including 240 nursing homes in France. In December 2009, additional grants were delivered by the French government to extend the three research axes for two more years, and establish a charter of quality for geriatric care in relation with the administration and relevant agencies.

International audience; 1680 participants were randomized over the recruitment period in MAPT study. A total of 1290 participants were recruited in the 7 University Hospital centers, and 390 participants in the 6 memory clinics around Toulouse Gerontopole / Alzheimer Disease research clinical center. The first randomization was on May 30, 2008, and the targeted number of randomized participants was reached on February 24, 2011; 2595 subjects were finally screened, of which 1680 fulfilled the eligibility criteria which represents 64.8%. Approximately, one quarter of screened people refused to participate after the detailed presentation of the study and 4.3% were still interested in participating but missed for unknown reasons the baseline visit even after repeated contacts. Of the 1810 subjects who signed the consent for participating to the study at the baseline visit, 130 (7.1%) were excluded because one of the eligibility criteria was not satisfied. Interestingly, the higher percentage of randomizations compared to screened participants is the personal contact source; almost 85 % of screened participants entered in the study. In an equivalent way, Medias and conferences are efficient recruiting sources to enrol volunteers in the study. Unexpectedly, only about 60% of screened participants from the hospital and GP sources were randomized and 33.2% from health care services. Almost a quarter of the randomized participants come from the hospital outpatients clinics and approximately 20% from public conferences. A total of 1128 contacts yielded to 556 screened volunteers and 345 randomized participants in the coordinating center of Toulouse. Thus, 30 % of contacts were recruited.