Alzheimer Disease: Andrieu S

Vellas B, Gauthier S, Allain H, Andrieu S, Aquino JP, Berrut G, Berthel M, Blanchard F, Camus V, Dartigues JF, Dubois B, Forette F, Franco A, Gonthier R, Grand A, Hervy MP, Jeandel C, Joel ME, Jouanny P, Lebert F, Michot P, Montastruc JL, Nourhashemi F, Ousset PJ, Pariente J, Rigaud AS, Robert P, Ruault G, Strubel D, Touchon J, Verny M, Vetel JM, Anonymous00344. · CHU Casselardit, Toulouse. · Rev Neurol (Paris). · Pubmed #16244574 No free full text.

Abstract: Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary team including geriatritians, neurologists, epidemiologists, psychiatrists, pharmacologists and public health specialists developed a consensus on care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians and specialists based on knowledge available in 2005. At all stages of the disease, the objective of care is to improve as much as possible quality-of-life for the patient and his/her family, including a life project until the end of life. It is always possible to do something for these patients and their family: nutritional status, behavior disorders, and incapacities to deal with basic activities of daily life have to be taken in consideration. Resource allocation and proximity care have to be targeted. Research areas necessary to improve the care of patients with severe dementia has been selected.

Andrieu S, Reynish W, Vellas B. · No affiliation provided · J Nutr Health Aging. · Pubmed #11135799 No free full text.

This publication has no abstract.

Vellas B, Coley N, Andrieu S. · Gerontopole, CHU Toulouse, Department of Geriatric Medicine, Toulouse, France. · J Alzheimers Dis. · Pubmed #18953115 No free full text.

Abstract: Disease modifying trials are becoming increasingly common in the field of Alzheimer's disease (AD) as the search for a treatment able to slow the progression of this disease continues. In this paper, we briefly discuss the methodological considerations for disease modifying trials that were addressed during three recent international task force meetings involving specialists in the field of AD trials. Topics covered included study design, the identification of appropriate outcomes, the use of biomarkers, and the identification of suitable study populations. We also provide an update on recent disease modifying trials which have enabled us to gain experience in the use of biomarkers and have helped to define suitable outcomes, and consider how they can help us to shape future perspectives for disease modifying trials.

Coley N, Andrieu S, Gardette V, Gillette-Guyonnet S, Sanz C, Vellas B, Grand A. · INSERM Unit 558, Toulouse, France. · Epidemiol Rev. · Pubmed #18779228 No free full text.

Abstract: The prevention of neurodegenerative dementias, such as Alzheimer disease, is a growing public health concern, because of a lack of effective curative treatment options and a rising global prevalence. Various potential risk or preventive factors have been suggested by epidemiologic research, including modifiable lifestyle factors, such as social contacts, leisure activities, physical exercise, and diet, as well as some preventive pharmacologic strategies, such as hormone replacement therapy, nonsteroidal antiinflammatory drugs, and Ginkgo biloba. Some factors have been targeted by interventions tested in randomized controlled trials, but many of the results are in conflict with observational evidence. The aim of this paper is to review the epidemiologic data linking potential protective factors to dementia or cognitive decline and to discuss the methodological limitations that could explain conflicting results. A thorough review of the literature suggests that, even if there are consistent findings from large observational studies regarding preventive or risk factors for dementia, few randomized controlled trials have been designed specifically to prove the protective effects of interventions based on such factors on dementia incidence. Because of the multifactorial origin of dementia, it appears that multidomain interventions could be a suitable candidate for preventive interventions, but designing such trials remains very challenging for researchers.

Vellas B, Andrieu S, Sampaio C, Coley N, Wilcock G, Anonymous00158. · Inserm U558, Toulouse, France. · Lancet Neurol. · Pubmed #18420157 No free full text.

Abstract: Harmful consequences in health status caused by disease are referred to as outcomes, and in clinical studies the measures of these outcomes are called endpoints. A major challenge when deciding on endpoints is to represent the outcomes of interest accurately, and the accuracy of such representation is assessed through validation. Complex diseases like Alzheimer's disease have many different and interdependent outcomes. We present a consensus for endpoints to be used in clinical trials in Alzheimer's disease, agreed by a European task force under the auspices of the European Alzheimer Disease Consortium. We suggest suitable endpoints for primary and secondary prevention trials, for symptomatic and disease-modifying trials in very early, mild, and moderate Alzheimer's disease, and for trials in severe Alzheimer's disease. A clear and consensual definition of endpoints is crucial for the success of further clinical trials in the field and will allow comparison of data across studies.

Berr C, Akbaraly TN, Nourashemi F, Andrieu S. · Inserm, U888, Université Montpellier 1, Montpellier (34). · Presse Med. · Pubmed #17560760 No free full text.

Abstract: Dementia is a major public health problem and its burden will increase in the 30 years to come. Prevalence increases with age and incidence is slightly higher in women than men, especially after the age of 80 years. Survival after the onset of dementia is approximately 5 years. Lifestyle and health habits are a keystone for dementia: risk factors include physical, intellectual and social activity and nutritional habits. Data from well-conducted intervention studies are necessary to show whether better care for hypertension, diabetes, and dyslipidemia might decrease the incidence of dementia.

Gillette Guyonnet S, Abellan Van Kan G, Andrieu S, Barberger Gateau P, Berr C, Bonnefoy M, Dartigues JF, de Groot L, Ferry M, Galan P, Hercberg S, Jeandel C, Morris MC, Nourhashemi F, Payette H, Poulain JP, Portet F, Roussel AM, Ritz P, Rolland Y, Vellas B. · Service de Medecine Interne et de Gerontologie Clinique, Pavillon J.P. Junod, Centre Hospitalier Universitaire La Grave-Casselardit, Toulouse cedex 9, France. · J Nutr Health Aging. · Pubmed #17435956 No free full text.

Abstract: 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.

Gillette Guyonnet S, Andrieu S, Vellas B. · Service de Medecine Interne et de Gerontologie Clinique, Pavillon J.P. Junod, Centre Hospitalier Universitaire La Grave-Casselardit, Toulouse cedex 9, France. · J Nutr Health Aging. · Pubmed #17435954 No free full text.

Abstract: 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.

Gillette Guyonnet S, Abellan Van Kan G, Alix E, Andrieu S, Belmin J, Berrut G, Bonnefoy M, Brocker P, Constans T, Ferry M, Ghisolfi-Marque A, Girard L, Gonthier R, Guerin O, Hervy MP, Jouanny P, Laurain MC, Lechowski L, Nourhashemi F, Raynaud-Simon A, Ritz P, Roche J, Rolland Y, Salva T, Vellas B, Anonymous00256. · No affiliation provided · J Nutr Health Aging. · Pubmed #17315079 No free full text.

Abstract: 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.

Vellas B, Andrieu S, Sampaio C, Wilcock G, Anonymous00068. · Alzheimer Disease Research and Clinical Center, University of Toulouse, Toulouse, France. · Lancet Neurol. · Pubmed #17166802 No free full text.

Abstract: After symptomatic treatments, the new target for therapeutic approaches in Alzheimer's disease is the development of disease-modifying drugs. The concept of disease modification in Alzheimer's disease is controversial and the design of these trials raises many questions. Which populations should be studied? For how long? With which principal and secondary endpoints? Are surrogate markers available? Here, we present a European consensus on disease-modifying trials in Alzheimer's disease, agreed under the auspices of the European Alzheimer's Disease Consortium and based on the European perspective of the concept of disease modification, study designs, the role for biomarkers, risk benefit, and pharmacoeconomic issues.

Vellas B, Andrieu S, Ousset PJ, Ouzid M, Mathiex-Fortunet H, Anonymous00380. · INSERM (French National Institute of Health and Medical Research), U558, F-31073 Toulouse, France. · Neurology. · Pubmed #17101932 No free full text.

Abstract: BACKGROUND: Preventive approaches in the field of Alzheimer disease (AD) is important but these trials raise many questions. Which protective factor should be studied? What population should be studied? With which principal and secondary criteria? We present here the design of the ongoing GuidAge Study. In the past, several studies suggest that Ginkgo biloba could have a potential benefit effect on cognitive function. The aim of the GuidAge Study is to evaluate the efficacy of 240 mg/d of EGb 761 in the prevention of AD. METHODS: GuidAge is a 5-year double-blind randomized trial conducted in France by a private practice/hospital network of general practitioners and hospital practitioners specializing in memory disorders. This study enrolled elderly subjects with spontaneous memory complaint and the primary outcome is the incidence of AD during a 5 years follow-up period. A total of 2854 subjects were enrolled between March 2002 and September 2004. The age of the study population was 76.8 +/- 4.4 with mean MMSE at entry 27.8 +/- 1.7. CONCLUSION: The GuidAge study is the largest study carried out in Europe on the prevention of AD. Final results should be available in 2010.

Nourhashémi F, Gillette S, Andrieu S. · Hôpitaux de Toulouse (P. B. Vellas), 31300 Toulouse. · Rev Prat. · Pubmed #16396231 No free full text.

Abstract: Alzheimer's disease (AD) is the main cause of progressive decline during which there is progressive dependence on family members and the health care system. The first step in the treatment is to make a diagnosis and communicate it to patients and families. The many things that should be done for optimal management must be started early. In the majority of patients enhancement of cholinergic function can produce a plateau for a period of time or at least can reduce the speed of decline. Comprehensive and appropriate treatment plans that meet all patients' needs can only be developed as a result of thorough assessment of the patient, the family, and the home environment. The assessment should address the patient's medical condition, including functional status, cognitive status, other medical conditions and non cognitive symptoms of AD. The assessment should also address the caregiver's needs and risks. Physicians should solicit and consider their input in post-diagnostic treatment planning. Comprehensive reassessment should occur every 6 months or more frequently with any sudden decline or be havioral change. The primary care practitioner should provide information and education about current level of disease and should talk with the patient and family to establish treatment goals.

Vellas B, Gauthier S, Allain H, Andrieu S, Aquino JP, Berrut G, Berthel M, Blanchard F, Camus V, Dartigues JF, Dubois B, Forette F, Franco A, Gonthier R, Grand A, Hervy MP, Jeandel C, Joel ME, Jouanny P, Lebert F, Michot P, Montastruc JL, Nourhashemi F, Ousset PJ, Pariente J, Rigaud AS, Robert P, Ruault G, Strubel D, Touchon J, Verny M, Vetel JM. · No affiliation provided · J Nutr Health Aging. · Pubmed #16222399 No free full text.

This publication has no abstract.

Reynish W, Andrieu S, Nourhashemi F, Vellas B. · Department of Clinical Gerontology and Internal Medicine, University Hospital of Toulouse, France. · J Gerontol A Biol Sci Med Sci. · Pubmed #11682574 No free full text.

Abstract: Nutritional factors are integrally linked with Alzheimer's disease (AD). Although AD patients have no changes in energy metabolism, fluctuations in weight are fairly common. The potential role of vitamin B(12) and folate, with the production of hyperhomocysteinemia, in the pathophysiology of AD is explored. The role of free-radical damage in AD is discussed. It is stressed that alterations in dietary lipids may play an important role in cognitive defects in AD secondary to their effects on neuronal membrane lipids. More research is needed on the role of nutrition in the ongoing development of cognitive changes in AD.

Nourhashemi F, Gillette-Guyonnet S, Andrieu S, Ghisolfi A, Ousset PJ, Grandjean H, Grand A, Pous J, Vellas B, Albarede JL. · Department of Internal Medicine and Clinical Gerontology, University Hospital, Toulouse, France. · Am J Clin Nutr. · Pubmed #10681273 links to  free full text

Abstract: 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.

Gillette-Guyonnet S, Nourhashemi F, Andrieu S, de Glisezinski I, Ousset PJ, Riviere D, Albarede JL, Vellas B. · Departments of Gerontology and Internal Medicine and Exploration of Respiratory Function and Sports Medicine, Purpan University Hospital, Toulouse, France. · Am J Clin Nutr. · Pubmed #10681272 links to  free full text

Abstract: 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.

Andrieu S, Ousset PJ, Coley N, Ouzid M, Mathiex-Fortunet H, Vellas B, Anonymous00313. · Inserm, U558, F-31073, Toulouse, France. · Curr Alzheimer Res. · Pubmed #18690838 No free full text.

Abstract: Primary and secondary prevention strategies for Alzheimer's disease (AD) are urgently needed. We have initiated a five-year prospective prevention study involving patients spontaneously reporting memory complaints. The primary objective is to determine the effect of treatment with EGb 76 on the rate of conversion from memory complaints to AD using survival analysis. Ambulatory patients aged at least 70 years who spontaneously reported a memory complaint during a GP or memory centre consultation were eligible for inclusion. Patients with major objective memory impairment or clinically relevant symptoms of anxiety and depression were excluded. Subjects were randomised to receive either EGb 761 120mg bid or matching placebo. Participants undergo an annual visit at a memory centre, where a series of neuropsychological tests are administered to assess cognitive function (Grober and Buschke, Trail-Making and controlled oral word association tests) and cognitive status (MMS and CDR). Functional status is evaluated with the Instrumental Activities of Daily Living questionnaire. The primary outcome is the transition to a diagnosis of AD (DSM-IV and NINCDS-ADRDA criteria), determined at the annual memory centre visit. A total of 4066 patients were screened for participation, of whom 2854 fulfilled the eligibility criteria and were entered into the study. Their mean age was 76.8+/-4.4 years and 66.7% were female. The mean MMSE score was 27.8+/-1.7 and 55.5% presented a CDR score of 0.5. This study will enable us to evaluate the efficacy of EGb761 in the prevention of AD, and to assess the usefulness of various baseline characteristics as predictors of conversion to AD in this population.

Lauque S, Arnaud-Battandier F, Gillette S, Plaze JM, Andrieu S, Cantet C, Vellas B. · Alzheimer Research and Clinical Center, Toulouse University Hospital, Toulouse, France. · J Am Geriatr Soc. · Pubmed #15450048 No free full text.

Abstract: 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.

Rivière S, Gillette-Guyonnet S, Voisin T, Reynish E, Andrieu S, Lauque S, Salva A, Frisoni G, Nourhashemi F, Micas M, Vellas B. · Department of Internal medicine and Clinical Gerontology, Hôpital la Grave-Casselardit, Toulouse, France. · J Nutr Health Aging. · Pubmed #11753499 No free full text.

Abstract: BACKGROUND: Weight loss is a common problem in patients with Alzheimer's Disease (AD). It is a predictive factor of mortality and it decreases patients' and caregivers' quality of life. OBJECTIVE: To determine if a nutritional education program can prevent weight loss in AD patients. SUBJECTS: 151 AD patients and their caregivers were enrolled to follow the intervention and 74 AD patients and their caregivers constituted a control group. METHOD: Caregivers in the intervention group followed 9 nutritional sessions of one hour each, over one year. Caregivers in the control group didn't follow any sessions but were offered advice provided in a normal follow-up. Patients weight, nutritional state, cognitive function, autonomy, mood, behaviour disorders at baseline and at 6- and 12-month follow-up. Caregivers burden, nutritional and AD knowledge at the baseline and at the 12-month follow-up. RESULTS: During the year follow-up, the mean weight increased in the intervention group (0.7+/-3.6 kg) whereas it decreased in the control group (-0.7+/-5.4 kg) (p<0.05). The nutritional status (MNA) was maintained in the intervention group (0.3+/-2.6) whereas it decreased significantly in the control group (-1.0+/-3.4) (p<0.005). After adjustment for baseline differences between the two groups (caregiver age, nutritional state, eating behaviour disorders, depression), the weight change between the two groups was not significant (0.6+/-0.4 kg vs. -0.6+/-0. 6 kg respectively in intervention group and control group). However, the percentage of patients with significant weight loss is decreased. The MMSE change became significant between the two groups: -2.3+/-0.3 vs. -3.4+/-0.4 respectively in intervention group and control group (p<0.05). CONCLUSIONS: These results suggest that a nutritional educational program intended for caregivers of AD patients could have a positive effect on patients weight and cognitive function.

Gillette-Guyonnet S, Andrieu S, Dantoine T, Dartigues JF, Touchon J, Vellas B, Anonymous00037. · Gérontopôle de Toulouse, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France. · Alzheimers Dement. · Pubmed #19328438 No free full text.

Abstract: BACKGROUND: Because no effective curative approaches are available, preventive approaches in the field of Alzheimer's disease (AD) are needed. We present the design of the ongoing Multidomain Alzheimer Preventive Trial (MAPT) Study. Several previous studies suggested that many factors may be involved in the occurrence of AD at late ages. Because of the probable multifactorial nature of AD, it seems logical to initiate multidomain interventions to examine their potential synergistic effects. The MAPT Study aims to evaluate the efficacy of a multidomain intervention (nutritional, physical, and cognitive training) and omega 3 treatment in the prevention of cognitive decline in frail elderly persons aged 70 years or over. The study also collects imaging and biological data that could be used in future AD prevention and treatment trials. METHODS: The MAPT Study is a 3-year, randomized, controlled trial conducted by university hospital practitioners specializing in memory disorders in four French cities (Bordeaux, Limoges, Montpellier, and Toulouse). The study plans to enroll 1200 frail elderly subjects on the basis of at least one of the following criteria: subjective memory complaint spontaneously expressed to a general practitioner, limitation in one instrumental activity of daily living (IADL), and slow walking speed. To demonstrate the protective effect of interventions, subjects are randomized into one of the following four groups: omega 3 alone, multidomain intervention alone, omega 3 plus multidomain intervention, or placebo (n = 300 each). The principal outcome measure is a change in cognitive function at 3 years, as determined by the Grober and Buschke Test. CONCLUSIONS: The MAPT Study is the first preventive trial involving multidomain interventions. Final results should be available in 2013.

Rolland Y, Abellan van Kan G, Nourhashemi F, Andrieu S, Cantet C, Guyonnet-Gillette S, Vellas B. · Inserm, U558, Toulouse, France. · J Alzheimers Dis. · Pubmed #19276547 No free full text.

Abstract: Among elderly without cognitive impairment, poor physical performances have been reported to predict cognitive decline and dementia. Our aim was to explore the predictive value of balance impairment for cognitive decline in 686 community-dwelling Alzheimer's disease (AD) patients (REAL.FR study). Being unable to stand on one leg for five seconds or more defined balance impairment. Cognitive decline was assessed using the Mini-Mental Status Examination (MMSE) score. Co-morbidities, behavioral and psychological symptoms of dementia (BPSD) using the Neuropsychiatric Inventory score, medication, and level of education were assessed at the hospital. MMSE and balance were reported every six months during two years. Linear mixed model analyses were performed. At baseline, participants with balance impairment (15.2% of the sample) were significantly older, had a lower MMSE score and more BPSD, co-morbidities, and medication. After adjustment for the potential covariates, the presence of balance impairment at each assessment was associated with a mean MMSE decline of 9.2 (1.4) points at two years; having no balance impairment at each assessment was associated with a mean MMSE decline of 3.8 (0.3) points at two years (p < 0.001). An abnormal one-leg balance test is a marker of more advanced dementia and predicts a higher rate of cognitive decline.

Abellan van Kan G, Rolland Y, Nourhashémi F, Coley N, Andrieu S, Vellas B. · Inserm U558, Department of Geriatric Medicine, CHU Toulouse, Toulouse, France. · Dement Geriatr Cogn Disord. · Pubmed #19246908 No free full text.

Abstract: BACKGROUND/AIMS: To assess if cardiovascular disease risk factors (CVDRF) are predictive factors for poorer evolution of Alzheimer's disease (AD) patients in terms of cognitive decline. METHODS: The Réseau de la maladie d'Alzheimer - France (REAL.FR) study is a prospective multicentre cohort which has recruited 686 community-dwelling patients presenting mild to moderate AD. The presence of CVDRF and associated treatments was recorded at baseline. The rate of cognitive decline of AD patients was assessed using the Mini Mental State Examination (MMSE) and the Alzheimer Disease Assessment Scale cognitive subscale (ADAS-Cog), after 2 years of follow-up. RESULTS: Of the 629 patients at baseline, 268 (42.6%) had no CVDRF, 256 (40.7%) reported 1 CVDRF and 105 (16.7%) reported 2-3. At inclusion, hypertension was present in 44.1% of patients, hypercholesterolaemia in 22.6% and diabetes in 9.4%. No statistically significant differences (p values of 0.9 for MMSE and 0.8 for ADAS-Cog) in mean cognitive decline after 2 years of follow-up were found comparing different subgroups of patients with CVDRF to the non-CVDRF group. CONCLUSIONS: Although there is evidence that CVDRF contribute to the onset of AD, these results suggest that CVDRF may not be part of the underlying processes that affect progression of AD.

Gillette Guyonnet S, Abellan Van Kan G, Andrieu S, Aquino JP, Arbus C, Becq JP, Berr C, Bismuth S, Chamontin B, Dantoine T, Dartigues JF, Dubois B, Fraysse B, Hergueta T, Hanaire H, Jeandel C, Lagleyre S, Lala F, Nourhashemi F, Ousset PJ, Portet F, Ritz P, Robert P, Rolland Y, Sanz C, Soto M, Touchon J, Vellas B. · Gerontopole, Pole Geriatrie Gerontologie, Hopital La Grave-Casselardit, Toulouse. · J Nutr Health Aging. · Pubmed #18810298 No free full text.

Abstract: 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).

Vellas B, Gillette-Guyonnet S, Andrieu S. · Department of Internal Medicine and Clinical Gerontology, Gerontopole, Toulouse Université Hospital, CHU La Grave-Casselardit, Toulouse, France; Inserm U 558, Toulouse, France. · Alzheimers Dement. · Pubmed #18631991 No free full text.

Abstract: A few years ago at the European Alzheimer's Disease Consortium-Alzheimer's Disease Cooperative Study meeting in Geneva we discussed with Leon Thal the possibility of building large multi-domain primary preventive international trials for Alzheimer's disease (AD) both in North America and in the European Union. AD is a multifactorial phenomenon, and we will be more likely to succeed in preventive trials if we build a strategy using all potential protective factors to have the most potential effect instead of a simple and unique intervention. Leon Thal suggested that this could have a much bigger impact than all the drugs we might ever hope to develop. The main objective of this article is to present the rationale for multi-domain preventive approaches.

Cortes F, Nourhashémi F, Guérin O, Cantet C, Gillette-Guyonnet S, Andrieu S, Ousset PJ, Vellas B, Anonymous00214. · Department of Internal Medicine and Clinical Gerontology, Centre Hospitalier Universitaire Purpan-Casselardit, Toulouse, France. · Alzheimers Dement. · Pubmed #18631947 No free full text.

Abstract: BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.