Cognitive and functional patterns of nondemented subjects with equivocal visual amyloid PET findings.

PURPOSE: 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. METHODS: 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 (18)F-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. 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. CONCLUSION: 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.

MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.

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.

Cognitive frailty: rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group.

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.

Looking for frailty in community-dwelling older persons: the Gérontopôle Frailty Screening Tool (GFST).

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.

Multidisciplinary team meetings (MDTM) in detection of Alzheimer's disease: data from the IDEM study.

INTRODUCTION: 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). OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The integration of frailty into clinical practice: preliminary results from the Gérontopôle.

BACKGROUND: 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). INTERVENTION: 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. RESULTS: 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). CONCLUSION: 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.

Recruitment strategies for preventive trials. The MAPT study (MultiDomain Alzheimer Preventive Trial).

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.

IAGG workshop: health promotion program on prevention of late onset dementia.

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.

How should we deal with missing data in clinical trials involving Alzheimer's disease patients?

Missing data are frequent in Alzheimer's disease (AD) trials due to the age of participants and the nature of the disease. This can lead to bias and decreased statistical power. We assessed the level and causes of missing data in a 2-year randomised trial of an AD patient management program (PLASA study), and conducted sensitivity analyses on the primary endpoint (functional decline), using various methods for handling missing data: complete case, LOCF, Z-score LOCF, longitudinal mixed effects model, multiple imputation. By 2 years, 32% of the 1131 subjects had dropped out, with the commonest reasons being death (28% of dropouts) and refusal (22%). Baseline cognitive and functional status were predictive of dropout. All sensitivity analyses led to the same conclusion: no effect of the intervention on the rate of functional decline. All analyses demonstrated significant functional decline over time in both groups, but the magnitude of decline and between-group (intervention versus usual care) differences varied across methods. In particular, the LOCF analysis substantially underestimated 2-year decline in both groups compared to other methods. Our results suggest that data were not "missing completely at random", meaning that the complete case method was unsuitable. The LOCF method was also unsuitable since it assumes no decline after dropout. Methods based on the more plausible "missing at random" hypothesis (multiple imputation, longitudinal mixed effects models, z-score LOCF) appeared more appropriate. This work highlights the importance of considering the validity of the underlying hypotheses of methods used for handling missing data in AD trials.

Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) Task Force.

INTRODUCTION: The use of a simple, safe, and easy to perform assessment tool, like gait speed, to evaluate vulnerability to adverse outcomes in community-dwelling older people is appealing, but its predictive capacity is still questioned. The present manuscript summarises the conclusions of an expert panel in the domain of physical performance measures and frailty in older people, who reviewed and discussed the existing literature in a 2-day meeting held in Toulouse, France on March 12-13, 2009. The aim of the IANA Task Force was to state if, in the light of actual scientific evidence, gait speed assessed at usual pace had the capacity to identify community-dwelling older people at risk of adverse outcomes, and if gait speed could be used as a single-item tool instead of more comprehensive but more time-consuming assessment instruments. METHODS: A systematic review of literature was performed prior to the meeting (Medline search and additional pearling of reference lists and key-articles supplied by Task Force members). Manuscripts were retained for the present revision only when a high level of evidence was present following 4 pre-selected criteria: a) gait speed, at usual pace, had to be specifically assessed as a single-item tool, b) gait speed should be measured over a short distance, c) at baseline, participants had to be autonomous, community-dwelling older people, and d) the evaluation of onset of adverse outcomes (i.e. disability, cognitive impairment, institutionalisation, falls, and/or mortality) had to be assessed longitudinally over time. Based on the prior criteria, a final selection of 27 articles was used for the present manuscript. RESULTS: Gait speed at usual pace was found to be a consistent risk factor for disability, cognitive impairment, institutionalisation, falls, and/or mortality. In predicting these adverse outcomes over time, gait speed was at least as sensible as composite tools. CONCLUSIONS: Although more specific surveys needs to be performed, there is sufficient evidence to state that gait speed identifies autonomous community-dwelling older people at risk of adverse outcomes and can be used as a single-item assessment tool. The assessment at usual pace over 4 meters was the most often used method in literature and might represent a quick, safe, inexpensive and highly reliable instrument to be implemented.

PUFA for prevention and treatment of dementia?

Polyunsaturated fatty acids (PUFA) play a crucial role in cerebral structure and function. Omega-3 PUFA is an exciting area of research, with docosahexaenoic acid (DHA) emerging as a new potential agent for prevention of cognitive decline and treatment of Alzheimer's disease. Preclinical studies suggest that DHA maintains membrane fluidity, improves synaptic and neurotransmitter functioning, enhances learning and memory performances and displays neuroprotective properties. Several epidemiological studies supported the association between Omega-3 PUFA consumption and a lower prevalence of dementia. Although data are divergent, a growing body of evidence supports the view that regular consumption of dietary fish and seafood (which are rich in omega-3 PUFA) prevents cognitive decline. Finally, at present, few data are available from randomized clinical trials (RCTs). on the association between cognition and Omega-3. Ongoing RCTs that assess the effect of Omega-3 might provide new evidence on prevention and treatment of dementia. In this review, we summarize preclinical and clinical research suggesting that DHA exerts beneficial effects on cognitive function with ageing.

Rapid cognitive decline in Alzheimer's disease. Consensus paper.

The rate of cognitive decline in Alzheimer's disease (AD) varies considerably between individuals, with some subjects showing substantial deterioration and others showing little or no change over the course of the disease. These wide variations support the relatively new concept of Rapid Cognitive Decline (RCD). Patients with an accelerated rate of cognitive decline have showed to present a worse evolution in terms of mortality, loss of autonomy and institutionalisation. The conclusions from RCD studies conducted in the past years remain very heterogeneous and sometimes contradictory. This is possibly due to methodological differences, mainly the different "a priori" definitions of RCD used to identify rapid decliners. Consequently of this, there is considerable variation in reported frequency of patients with RCD which may vary from 9.5% to 54%. The lack of both consensus definition and consensual clinical assessment tools is one of the major barriers for establishing an appropriated management of rapid decliners in clinical practice. Presently, management of rapid decliners in AD remains to be a challenge waiting to better know predictive factors of a RCD. To date no specific guidelines exist to follow-up or to treat patients with this condition. This consensus paper proposes the loss of 3 points or greater in Mini-Mental State Examination (MMSE) during six months as an empirical definition of rapid cognitive decline to be used in routine medical practice and to be relevant for clinical-decision making in patients with mild to moderately-severe AD.

Prevention of progression to dementia in the elderly: rationale and proposal for a health-promoting memory consultation (an IANA Task Force).

Alzheimer's disease (AD) is the most frequent form of dementia and according to the most recent estimation it affects nearly 27 million people in the world. The onset of the disease is generally insidious. It is becoming increasingly evident that the underlying pathophysiological mechanisms are active long before the appearance of the clinical symptoms of the disease. In the current context, it is important to develop strategies to delay the onset of cognitive decline. Delaying the onset by 5 years would reduce the prevalence by half at term, and a delay of 10 years would reduce it by three-quarters. The effectiveness of currently suggested preventive approaches remains to be confirmed, but certain strategies could be applied straight away to at-risk subjects. We propose that a health-promoting memory consultation should be set up for elderly persons who have attended a specialized memory consultation and in whom the diagnosis of dementia and of AD in particular, has not been established by standardized tools. Through this consultation, they would be offered full multidimensional investigation of all aspects of their health status, follow-up could be organized, general practitioners in private practice could be made more conscious of this population and the elderly could be made more aware of the risk factors to which they are exposed. The development of an information policy for the elderly would meet a present need. In our reflection, we must take into account the question of how to give this preventive consultation its due place in the healthcare pathway of the elderly person in order to ensure coordinated follow-up with all the other health professionals involved. The principle of the health-promoting memory consultation is undergoing validation in a large French multicentre preventive trial in 1200 frail elderly persons aged 70 years followed for three years, the Multidomain Alzheimer Preventive Trial (MAPT).

A randomized trial of the impact of a specific care plan in 1120 Alzheimer's patients (PLASA Study) over a two-year period: design and baseline data.

OBJECTIVE: To describe the design anf 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 biannually 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.

Apathy and depression in Alzheimer's disease are associated with functional deficit and psychotropic prescription.

BACKGROUND: Apathy and depression are the most common neuropsychiatric features in Alzheimer's disease (AD). The clinical and functional specific correlates of these syndromes are not well known independently from cognitive deficits and other behavioral disturbances. MATERIAL AND METHODS: Six hundred and eighty-six patients diagnosed with possible or probable AD were included in a prospective multicenter study (REAL-FR). They had an assessment of their cognitive and functional status. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory (NPI) and caregiver's burden was measured with Zarit's Burden Scale. RESULTS: A majority of patients at any stage of the disease presented with one or several behavioral and psychological disturbances. Apathy concerned 43% of patients and, with or without depression, was associated with more pronounced deficits in global cognition, everyday life and instrumental abilities, nutritional status and with a higher burden level. A high level of psychotropic prescription, especially with antidepressant, was observed in patients with apathy. In a multivariate analysis taking into account the cognitive and functional variables of AD, apathy and depression were the only significant predictors of psychotropic prescription. CONCLUSION: Some negative neuropsychiatric symptoms such as apathy and depression have a specific relation with functional and therapeutic outcomes of AD, independently from cognitive status. Further studies are needed to establish if apathy represents a particularly severe phenotype of AD.

The potential influence of silica present in drinking water on Alzheimer's disease and associated disorders.

Silica present in drinking water may be protective with respect to the decrease of cognitive function as it was suggested by several epidemiologic studies. Data from French cohort have demonstrated that aluminium in drinking water seems to have a deleterious effect and increased the risk of cognitive impairment when the silica concentrations were low. Moreover, it has been shown that the performances to a cognitive test were positively correlated to the consumption of silica and that the risk of Alzheimer's disease (AD) was reduced in subjects who had the higher daily silica intake compared to the others. The silica is probably the natural antidote of the aluminium and could play a benefit role by decreasing the biodisponibility of aluminium, whose neurotoxicity is now clearly established. Data have suggested the possible use of silicates as a therapeutic agent for AD since both model tangles and precipitated beta-pleated sheets of betaA4 can be reversed to soluble forms by silicates. The role of silica in drinking water on cognitive function has been however little studied and clear results have not yet emerge. The potential benefit of silica needs to be confirmed in additional investigations to exclude causes of error related to certain methodological biases. If such association do indeed exist, interventional strategies could be set up to reduce the incidence of AD. The aim of this paper is to review articles published on silica present in drinking water in relation with AD and associated disorders.

IANA task force on nutrition and cognitive decline with aging.

Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta analyses should be developed, and on the basis of their results the most appropriate interventional studies can be planned. These studies must control for the greatest number of known confounding factors and take into account the impact of the standard social determinants of food habits, such as the regional cultures, social status, and educational level.

IANA (International Academy on Nutrition and Aging) Expert Group: weight loss and Alzheimer's disease.

Weight loss, together with psychological and behavioural symptoms and problems of mobility, is one of the principal manifestations of Alzheimer's disease (AD). Weight loss may be associated with protein and energy malnutrition leading to severe complications (alteration of the immune system, muscular atrophy, loss of independence). Various explanations have been proposed such as atrophy of the mesial temporal cortex, biological disturbances, or feeding behaviours; however, none has been proven. Prevention of weight loss in AD is a major issue. It requires regular follow-up and must be an integral part of the care plan. The aim of this article is to review the present state of scientific knowledge on weight loss associated with AD. We will consider four points: the natural history of weight loss, its known etiological factors, its consequences and the various management options.

Rapid cognitive decline: searching for a definition and predictive factors among elderly with Alzheimer's disease.

The pattern and rate of cognitive decline in AD patients is far from uniform. In clinical practice, certain patients present episodes of rapid cognitive loss, whereas others deteriorate more progressively. At present time, there is little known about rapid decline in cognitive function in patients with AD, and moreover among older population. The main objective of this review was to elaborate a proposal of definition of rapid cognitive decline in order to facilitate its applicability into ordinary medical practice and to be relevant for clinical-decision making in old patients with AD. After the literature review, our results from longitudinal prospective studies and our clinical practice experience, we propose the following definition of rapid cognitive decline: a four-point or greater loss on the MMSE within six months and the loss of at least one point on the MMSE during the following six months. After ELSA cohort's results, 11% of an AD population of 312 patients were rapid cognitive decliners, complying with our proposed definition. They represent a non-negligible proportion of the population afflicted by AD.