Alzheimer Disease: Ousset PJ

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.

Villars H, Gillioz AS, Hein C, Voisin T, Nourhashemi F, Soto ME, Arbus C, Ousset PJ, Vellas B. · Service de médecine interne gériatrique et gérontologie clinique, Gérontopôle, CHU Toulouse, Hôpital Purpan Casselardit, Toulouse. · Rev Neurol (Paris). · Pubmed #18680826 No free full text.

This publication has no abstract.

Aalten P, Verhey FR, Boziki M, Brugnolo A, Bullock R, Byrne EJ, Camus V, Caputo M, Collins D, De Deyn PP, Elina K, Frisoni G, Holmes C, Hurt C, Marriott A, Mecocci P, Nobili F, Ousset PJ, Reynish E, Salmon E, Tsolaki M, Vellas B, Robert PH. · Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, Maastricht University Hospital, Maastricht, The Netherlands. · Dement Geriatr Cogn Disord. · Pubmed #18025783 links to  free full text

Abstract: BACKGROUND/AIMS: The aim of this study was to determine the consistency of neuropsychiatric subsyndromes of the Neuropsychiatric Inventory across several clinical and demographic subgroups (e.g. dementia subtypes, dementia severity, medication use, age and gender) in a large sample of outpatients with dementia. METHODS: Cross-sectional data of 2,808 patients with dementia from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis. Subanalyses were performed for dementia subtypes, dementia severity, medication use, age and gender. RESULTS: The results showed the relatively consistent presence of the 4 neuropsychiatric subsyndromes 'hyperactivity', 'psychosis', 'affective symptoms' and 'apathy' across the subanalyses. The factor structure was not dependent on dementia subtypes, age and gender but was dependent on dementia severity and cholinesterase use. The factors hyperactivity and affective symptoms were present in all subanalyses, but the presence of the factors apathy and psychosis was dependent on use of cholinesterase inhibitors and dementia severity, respectively. CONCLUSION: The present study provided evidence of the relative consistency of neuropsychiatric subsyndromes across dementia subtypes, age and gender, thereby stressing the importance of thinking about neuropsychiatric subsyndromes instead of separate symptoms. However, the subsyndromes apathy and psychosis were dependent on use of cholinesterase inhibitors and dementia severity.

Aalten P, Verhey FR, Boziki M, Bullock R, Byrne EJ, Camus V, Caputo M, Collins D, De Deyn PP, Elina K, Frisoni G, Girtler N, Holmes C, Hurt C, Marriott A, Mecocci P, Nobili F, Ousset PJ, Reynish E, Salmon E, Tsolaki M, Vellas B, Robert PH. · Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, Maastricht University Hospital, Maastricht, The Netherlands. · Dement Geriatr Cogn Disord. · Pubmed #17986816 links to  free full text

Abstract: BACKGROUND/AIMS: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer's disease (AD). METHODS: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis. RESULTS: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients. CONCLUSION: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD.

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.

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.

Balardy L, Ousset PJ, Vellas B. · Service de Médecine Interne, Gérontologie Clinique, Chu Toulouse-Purpan. · Soins. · Pubmed #15208953 No free full text.

This publication has no abstract.

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.

Guyonnet S, Nourhashemi F, Ousset PJ, de Glisezinski I, Rivière D, Albarede JL, Vellas B. · Service de Gérontologie Clinique et Médecine Interne, CHU Purpan-Casselardit, Toulouse. · Rev Neurol (Paris). · Pubmed #10427597 No free full text.

Abstract: Weight loss is a nutritional problem commonly associated with Alzheimer disease. Two types of weight loss have been described. A severe weight loss correlated with a decrease in daily caloric intake and with increased difficulties in performing the activities of daily living. A slowly progressive but clinically significant loss, not associated with either a decrease in caloric intake or an inflammatory syndrome. It is difficult to explain this type of weight loss as subjects have adequate caloric intakes. Several hypothesis are however considered as increased energy requirements (which can result from increased energy expenditure, from increased metabolic disorder, or from increased growth hormone secretion), or mesial temporal cortex atrophy. But, at the present time, no study can give a proper explanation. Vitamin deficiencies, specially vitamin B6, B12 and folates, high homocysteine level, antioxidants deficiencies (especially, vitamin E deficiency), iron, counter, and phenol derived could also influence the memory capacities and have an effect upon cognitive impairment, as reported in epidemiological studies. The prevention of nutritional deficiencies in patients with Alzheimer's disease, could be one of the strategies to improve the caregiver and the patients quality of life.

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.

Galluzzi S, Talassi E, Belussi M, Scheltens P, van de Pol L, Nobili F, Rodriguez G, Froelich L, Damian M, Martinez-Lage P, Gomez-Isla T, Reynish E, Ousset PJ, Vellas B, Frisoni GB. · LENITEM Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Centro S. Giovanni di Dio Fatebenefratelli, Brescia, Italy. · Dement Geriatr Cogn Disord. · Pubmed #18841016 No free full text.

Abstract: OBJECTIVE: To study multi-center variability of medial temporal lobe atrophy (MTA) in patients with Alzheimer's disease (AD) recruited in a European observational study of AD. METHODS: 117 mild to moderate AD patients from 5 European centers (Amsterdam, The Netherlands; Brescia and Genova, Italy; Mannheim, Germany; Pamplona, Spain) had magnetic resonance imaging scans performed as part of the routine diagnostic examination. MTA was assessed with the visual Scheltens scale. RESULTS: AD patients from Brescia, Genova, Pamplona, and Mannheim had a mean 32% prevalence of no or borderline MTA vs. 62% of patients from Amsterdam (p = 0.002 for the difference between Amsterdam and all the other centers). The peculiar distribution of MTA in the Amsterdam patients may be attributable to younger age (70.7 +/- 8.4 vs. 75.3 +/- 6.8 years, p = 0.002), milder dementia severity (score 0.5 on the clinical dementia rating scale: 52 vs. 23%, p = 0.003), and less frequent depression (14 vs. 49%, p < 0.0005 in Amsterdam vs. all the other centers, respectively). CONCLUSION: Patients with probable AD recruited in different centers of Europe generally have similar MTA distribution, even if peculiar demographic and clinical findings might explain occasional differences. These results have implications for clinical trials in AD with biological markers as outcome measures.

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).

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.

Soto ME, Andrieu S, Cantet C, Reynish E, Ousset PJ, Arbus C, Gillette-Guyonnet S, Nourhashémi F, Vellas B, Anonymous00036. · Department of Geriatric Medicine, Toulouse University Hospital, Toulouse, France. · Dement Geriatr Cogn Disord. · Pubmed #18617740 No free full text.

Abstract: 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: >or=3 points and >or=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 >or=3 points during the first 6 months of follow-up in the MMSE score and 77 patients (13.6%) lost >or=4 points. Patients with moderate disease and a loss of >or=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 >or=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.

Visser PJ, Verhey FR, Boada M, Bullock R, De Deyn PP, Frisoni GB, Frolich L, Hampel H, Jolles J, Jones R, Minthon L, Nobili F, Olde Rikkert M, Ousset PJ, Rigaud AS, Scheltens P, Soininen H, Spiru L, Touchon J, Tsolaki M, Vellas B, Wahlund LO, Wilcock G, Winblad B. · Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, The Netherlands. · Neuroepidemiology. · Pubmed #18515975 No free full text.

Abstract: BACKGROUND: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer's Disease Consortium. METHODS: Clinical criteria will be based on a prospective cohort study of non-demented subjects older than 55 years and referred to a memory clinic. At baseline, a number of markers and risk factors for AD were collected, including demographic variables, measures of performance in activities of daily living, cognitive, neuroimaging and genetic markers, and serum and cerebrospinal fluid markers. Subjects will be reassessed annually for 2-3 years, and we will evaluate which combination of variables best predicts AD-type dementia at follow-up. RESULTS: Between 2003 and 2005, 881 subjects were included from 20 memory clinics. Subjects were on average 70.3 years old, and had 10.4 years of education. The average score on the Mini-Mental State Examination was 27.4.

Nourhashemi F, Gillette-Guyonnet S, Andrieu S, Rolland Y, Ousset PJ, Vellas B, Anonymous00065. · Hôpital Casselardit, Service de Médecine Interne et de Gérontologie Clinique, 31059 Toulouse, France. · J Nutr Health Aging. · Pubmed #18373036 No free full text.

Abstract: 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.

Ousset PJ, Nourhashemi F, Reynish E, Vellas B. · Department of Internal Medicine and Gerontology, Alzheimer Disease Center, CHU Purpan-Casselardit, Toulouse, France. · Alzheimer Dis Assoc Disord. · Pubmed #18317249 No free full text.

Abstract: The objective of this study is to identify, in a sample of very mild Alzheimer disease (AD) patients, factors associated with disease progression. The authors followed 160 AD patients from a multicenter cohort with a Clinical Dementia Rating (CDR) of 0.5, corresponding to very mild AD but with impairment insufficient to be classified as dementia. Patients with disease progression were defined as those with CDR> or =1 at 1 year; those with no progression (stable) remained at CDR 0.5. The baseline characteristics of these 2 groups of patients were compared in search of predictors of progression. After a 1-year follow-up, 84 (52.5%) of the patients remained stable, CDR 0.5; 76 (47.5%) progressed to a CDR score > or =1. A baseline lower nutritional status assessed by the Mini Nutritional Assessment [odds ratio 0.80, 95% confidence interval (0.68-0.94), P=0.007] and a lower cognitive performance on the Alzheimer Disease Assessment Scale [odds ratio 1.22, 95% confidence interval (1.07-1.39), P=0.003] were found as predictors of progression. The results suggest that clinical assessment of nutritional status, along with cognitive data, may help detect patients at risk of progression in very early AD. Nutritional assessment should therefore form part of clinical evaluation of patients with AD at an early stage of the disease.

Coley N, Ousset PJ, Andrieu S, Matheix Fortunet H, Vellas B. · Inserm, U558, F-31073, Toulouse, France. · J Nutr Health Aging. · Pubmed #18165849 No free full text.

Abstract: Memory complaints are relatively common in elderly people, although they are not always reported to the general practitioner (GP). These subjective complaints do not necessarily correlate with objective measures of memory impairment or cognitive performance, but they may be an early indication of impairment at a state that is undetectable by standard testing instruments. Memory complaints may also predict future cognitive decline. The GuidAge study is a secondary prevention trial for Alzheimer's disease involving non-demented individuals aged 70 years or older having spontaneously complained of memory problems to their GP. More than half of participants had a Clinical Dementia Rating score of 0.5 at baseline. The percentage of participants reporting problems on the McNair and Kahn scale varied from 6.2% to 78.6% per item. Certain specific memory complaints may be more related than others to the beginning of the neurodegenerative process, and could predict future cognitive decline. The importance of memory complaints should not be underestimated in clinical practice.

Reynish E, Cortes F, Andrieu S, Cantet C, Olde Rikkert M, Melis R, Froelich L, Frisoni GB, Jönsson L, Visser PJ, Ousset PJ, Vellas B, Anonymous00177. · Inserm, U558, Toulouse, France. · Neuroepidemiology. · Pubmed #17898521 No free full text.

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

Nourhashémi F, Ousset PJ, Gillette-Guyonnet S, Cantet C, Andrieu S, Vellas B, Anonymous00059. · CHU Toulouse, Hôpital Casselardit, Service de médecine interne et gérontologie clinique, Toulouse, France. · Int J Geriatr Psychiatry. · Pubmed #17894422 No free full text.

Abstract: 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 >or= 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 >or= 1 groups. The ADL decline was more significant in patients with CDR >or= 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.

Gillette-Guyonnet S, Andrieu S, Cortes F, Nourhashemi F, Cantet C, Ousset PJ, Reynish E, Grandjean H, Vellas B. · Department of Internal Medicine and Clinical Gerontology, Centre Hospitalier Universitaire La Grave-Casselardit, 170 avenue de Casselardit, TSA40031, 31059 Toulouse cedex 9, France. · J Gerontol A Biol Sci Med Sci. · Pubmed #16720751 No free full text.

Abstract: BACKGROUND: Alzheimer's disease is fast becoming a major public health concern with serious economic consequences. The cholinesterase inhibitors (CEIs) offer some benefit in the symptomatic treatment of the disease. This study aims to investigate the effect of CEIs on three clinically relevant domains (rapid cognitive decline, institutionalization, and weight loss) in patients with Alzheimer's disease. METHODS: A prospective observational study was performed in which a population of 455 Alzheimer's disease patients were recruited and followed up for at least 1 year between 1994 and 2002. Patients were reevaluated at 6 monthly intervals using standardized neurocognitive and geriatric evaluations in addition to complete clinical examination, standard paraclinical investigations, and recording of treatment received. RESULTS: The risk of rapid cognitive deterioration was significantly decreased in patients taking CEIs for at least 1 year compared to untreated patients (odds ratio [OR]=0.56, 95% confidence interval [CI], 0.34-0.93; p=.025). The potential benefit of CEI use was also found on institutionalization (OR=0.2, 95% CI, 0.08-0.48; p<.001) and weight loss (OR=0.56, 95% CI, 0.32-0.97; p=.039) after 1 year of follow-up. CONCLUSION: The special interest of this study is that all patients were recruited and followed in the same center with the same management care plan and the same medical team. This follow-up offers us a unique opportunity to compare the 1-year evolution of the disease in clinical practice before and after the marketing of CEIs and allows us to demonstrate a clinically significant improvement in patient outcome over time.

Gillette-Guyonnet S, Lauque S, Ousset PJ. · Centre mémoire de ressource et de recherche, Toulouse, France. · Psychol Neuropsychiatr Vieil. · Pubmed #15899603 No free full text.

Abstract: Weight loss is frequent in Alzheimer's disease. Its severity increases with the progression of the disease and may be a predictor of patients' mortality. Weight loss often precedes the diagnosis and may be considered as a feature of the disease itself. With the progression of the disease, disorders of eating behavior occur and result in weight loss and decreasing energy intake. Descriptive tools such as the Blandford Scale are helpful to assess eating disorders. Some hypotheses exist to explain the weight loss associated with Alzheimer's disease: atrophy of internal temporal cortex, increase of energy expenditure, biologic factors or modifications of body composition. Tools such as the Mini Nutritional Assessment allow assessment of nutritional status, diagnosis of malnutrition, cause identification and proposals for its correction. Patients' caregivers play a central role in prevention and management of nutritional disorders. Information programs for caregivers may reduce caregiver burden and improve patients' health status.

Vellas B, Lauque S, Gillette-Guyonnet S, Andrieu S, Cortes F, Nourhashémi F, Cantet C, Ousset PJ, Grandjean H, Anonymous00357. · Department of Internal Medicine and Clinical Gerongology, Centre Hospitalier Universitaire Purpan-Casselardit, F-31300 Toulouse, France. · J Nutr Health Aging. · Pubmed #15791349 No free full text.

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

Dumont C, Gillette-Guyonnet S, Andrieu S, Cantet C, Ousset PJ, Vellas B. · Département de médecine interne et gériatrie, cliniques universitaires Saint-Luc, UCL, 1200 Bruxelles, Belgique. · Rev Med Interne. · Pubmed #14710455 No free full text.

Abstract: 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 < or = 20 (p < 0.003) or a greater BMI (p < 0.02) and a tendency towards a negative correlation with anxiety (p = 0.06) and negative correlation with the burden severity (p < 0.05). CONCLUSIONS: Patients with a worse cognitive status, a greater BMI and less anxiety or burden were at increased risk of rapid cognitive decline. Future studies should focus on determining etiologies for patients with rapid cognitive loss and help clinicians target these patients for interventions aiming to delay or stabilise the course of this disease.