Alzheimer Disease: Dartigues JF

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.

Dartigues JF, Poncet M. · CMRR, service de neurologie, CHU Pellegrin, Bordeaux. · Rev Neurol (Paris). · Pubmed #18680827 No free full text.

This publication has no abstract.

Dartigues JF, Helmer C, Peres K, Cowppli Bony P, Auriacombe S, Orgogozo JM. · Unité INSERM 593, Université de Bordeaux II. · J Nutr Health Aging. · Pubmed #18165852 No free full text.

Abstract: Alzheimer's Disease and related disorders have recently become a priority in France and two consecutive governmental plans have been undertaken in 2001-2004 and 2004-2007. The number of prevalent cases was estimated to be 850,000 in France with an incidence of 220,000 cases. Only 50% of these cases were actually diagnosed and about 32% were treated by antidementia drugs. If the incidence and the duration of the disease do not change, the number of cases will increase to 1,200,000 in 2020 and 2,100,000 cases in 2040. In absence of curative treatment, the prevention way is necessary if one wishes to control this phenomena. The development of Memory Clinics and "Centres de Mémoires de Ressources et de Recherche" in all regions in France is one of the important measures to develop primary and secondary prevention in subjects with cognitive complaints or MCI. Several factors could be the basis of this prevention 1) Vascular risk factors (High Blood Pressure, Diabetes, Obesity, Hypercholesterolemiae, Tobacco consumption) ; 2) physical exercise ; 3) Stimulating cognitive activities ; 4) Nutrition ; 5) depressive disorders and loneliness.

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.

Cowppli-Bony P, Dartigues JF, Orgogozo JM. · Inserm U593, université de Bordeaux II. · Psychol Neuropsychiatr Vieil. · Pubmed #16556518 No free full text.

Abstract: Etiology of Alzheimer's disease (AD) is still undefined in its most frequent sporadic type, but a role of vascular risk factor is more and more evocated in its pathophysiology. This role enables to hope that preventive or curative care of vascular risk factors could decrease AD incidence. Among these factors, high blood pressure, diabetes, hypercholesterolemia and tobacco consumption were the most studied. We review the risk for AD, which had been associated with each of these factors in epidemiological studies. High blood pressure is associated with an increased risk of AD in most studies while the results are more controversial for the others factors. All these four vascular risk factors have variable interaction with the presence of cerebrovascular diseases and of the epsilon 4 allele of the apolipoprotein E gene which is a predisposition factor for sporadic AD.

Helmer C, Pasquier F, Dartigues JF. · Inserm U.593, Université de Bordeaux II, 146, rue Léo Saignat, 33076 Bordeaux Cedex, France. · Med Sci (Paris). · Pubmed #16527211 No free full text.

Abstract: Alzheimer's disease and related disorders (dementia) are a major public health problem due to the number of cases in the general population, the projections for the future, and the consequences of these diseases. We can estimate that about 850 000 cases of dementia were present in France in 2005 and this number will increase to 1,200,000 in 2020 and 2,100,000 in 2040 if the incidence and the duration of the disease did not change. The development of prevention is therefore necessary. Four ways of prevention are credible. The most important is the treatment of vascular risk factors and particularly hypertension. Other ways are nutritional factors, stimulating leisure activities and depression.

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.

Alpérovitch A, Amouyel P, Dartigues JF, Ducimetière P, Mazoyer B, Ritchie K, Tzourio C. · Inserm, unité 360, hôpital de la Salpêtrière, 75651 Paris, France. · C R Biol. · Pubmed #12360853 No free full text.

Abstract: Follow-up of cohorts recruited in general population with active screening and diagnosis of incident cases, is the most appropriate epidemiological design for studying incidence and risk factors of Alzheimer disease and other types of dementia. In France, people considered in the PAQUID study, then in the EVA study, have been the first cohorts on dementia. They have prepared the way for the Three-City (3C) study, conducted in Bordeaux, Dijon and Montpellier. About 9500 persons aged 65 years and over have been recruited in these three cities and will be followed-up during four years. The main objective of the 3C study is to investigate the relation between vascular risk and neurodegenerative diseases. The 3C study will provide essential data for defining strategies for dementia prevention. To measure the impact of the strategies on the incidence of dementia and the social burden of this disease will be an important public health objective in the near future.

Dartigues JF, Helmer C, Dubois B, Duyckaerts C, Laurent B, Pasquier F, Touchon J. · Unité INSERM 330, Université de Bordeaux II, Bordeaux. · Rev Neurol (Paris). · Pubmed #11976590 No free full text.

Abstract: Alzheimer's Disease is a major Public Health problem for many reasons. First, it is a frequent disease since, in France, the prevalence was estimated at about 400.000 cases, and the annual incidence at 100.000 cases. The frequency of the disease increases, in particular due to the ageing of the population. This disease has major consequences on the life of the patient and his/her caretaker. The cost of the disease is important, estimated at about 50 milliards of French francs. Pharmaceutical treatment and other interventions are possible in particular to delay the nursing home placement. On the other hand, this disease is often ignored, under-diagnosed, underestimated and exposed to inequality in resorting to care. In summary, Alzheimer's Disease (AD) has all the criteria required for a major public health problem. In spite of this observation, AD is not yet considered as a priority for health authorities, although attitudes are changing.

Dartigues JF, Letenneur L. · INSERM U330, Université de Bordeaux, France. · Curr Opin Neurol. · Pubmed #10970054 No free full text.

Abstract: The genetics of Alzheimer's disease is one of the most complex topics to study from an epidemiological point of view, particularly in population-based studies on polymorphisms of genes. The present review focuses primarily on some conflicting results on genetic epidemiology of Alzheimer's disease, and the major difficulties met in such studies.

Raoux N, Amieva H, Le Goff M, Auriacombe S, Carcaillon L, Letenneur L, Dartigues JF. · INSERM, U897, Bordeaux cedex, France; University Victor Segalen Bordeaux 2, Bordeaux Cedex, France. · Cortex. · Pubmed #18761132 No free full text.

Abstract: Reduced semantic fluency performances have been reported in the preclinical phase of Alzheimer's disease (AD). To investigate the cognitive processes underlying this early deficit, this study analyzed the verbal production of predemented subjects for the animals category with the qualitative parameters related to clustering (i.e. the ability to generate words belonging to semantic subcategories of animals) and switching (i.e. the ability to shift from one subcategory to another) proposed by Troyer. This qualitative analysis was applied to the PAQUID (Personnes Agées QUID) cohort, a 17-year longitudinal population-based study. The performances on the animal verbal fluency task of 51 incident cases of possible and probable AD were analyzed at the onset of dementia, 2 years and 5 years before dementia onset. Each case was matched for age, sex and education to two control subjects leading to a sample of 153 subjects. The mean cluster size and the raw number of switches were compared in the two samples. The results revealed a significantly lower switching index in the future AD subjects than in the elderly controls including 5 years before dementia incidence. A significant decline in this parameter was evidenced all along the prodromal phase until the clinical diagnosis of dementia. In contrast, the mean cluster size could not discriminate the two groups. Therefore the results support the hypothesis that impaired shifting abilities - rather than semantic memory storage degradation - could explain the early decline in semantic fluency performance occurring in the predementia phase of AD.

Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, Michel BF, Boada M, Frank A, Hock C. · Federation of Neurology, CHU Pellegrin, Bordeaux, France. · Neurology. · Pubmed #12847155 No free full text.

Abstract: BACKGROUND: AD is characterized by cerebral deposition of beta-amyloid plaques with amyloid beta-peptide (Abeta) 42 as the major peptide constituent, along with neurofibrillary tangles and neuronal loss. In transgenic mice, active immunization against Abeta42 removes these plaques and improves cognitive function. A Phase I study in AD patients demonstrated good safety and tolerability of multiple injections of aggregated Abeta42 (AN1792) with QS-21 as adjuvant. METHODS: Three hundred seventy-two patients with mild to moderate AD were randomized to receive IM injections of AN1792 or placebo (4:1) at baseline and at months 1, 3, 6, 9, and 12 in a multicenter Phase II safety, tolerability, and pilot efficacy study. Dosing was terminated after four early reports of meningoencephalitis, but follow-up continued. The study remains blinded, and further results will be reported after its termination. RESULTS: Symptoms and laboratory findings consistent with meningoencephalitis occurred in 18 of 298 (6%) patients treated with AN1792 compared with 0 of 74 on placebo (p = 0.020). Sixteen of the 18 had received two doses, one had received one dose, and one had received three doses of the study drug before symptoms occurred. The median latency from the first and last injections to symptoms was 75 and 40 days. No case occurred later than 6 months after the first immunization. Anti-Abeta42 antibody titers were not correlated with the occurrence or severity of symptoms or relapses. Twelve patients recovered to or close to baseline within weeks, whereas six remain with disabling cognitive or neurologic sequelae. All 18 patients remain alive to date (December 31, 2002), 6 months to >1 year after symptom onset. CONCLUSIONS: Postvaccination meningoencephalitis occurred without clear relation to serum anti-Abeta42 antibody titers. Potential mechanisms such as T-cell and microglial activation may be responsible and are under consideration to develop a safer anti-Abeta immunotherapy for AD.

Dartigues JF, Goulley F, Bourdeix I, Péré JJ, Barberger-Gateau P. · INSERM U 330. Université de Bordeaux II. France. · Rev Neurol (Paris). · Pubmed #12386525 No free full text.

Abstract: Six hundred and sixty nine out patients with mild to moderate Alzheimer's disease were enrolled by 193 French neurologists, psychiatrists and gerontologists. The patients, 38p.cent males and 62p.cent females with a mean age of 75 years were progressively titrated from 3 to 12mg by day of rivastigmine, Exelon((R)), a day, and treated for 6 months. Mean Mini-Mental State (MMS) at baseline was 18.6. Concomitant pathologies and treatments were present in 89p.cent of the patients. Safety was good though 86p.cent reported an adverse event which was mild in most of the cases. The premature drop out rate was 29p.cent. Seventy-five patients showed no change or an improvement in their 4 Instrumental Activities of Daily Living (IADL) score with no change in the MMS at the end of treatment (18.8). Four items of the Neuro-Psychiatric Inventory (NPI): delusions, anxiety, apathy, and irritability were significantly improved at week 12 and the improvement in anxiety was still significant at the end of treatment. The total score frequency X severity showed a tendency to improvement. The correlations between the sum of the 4 IADL, MMS and NPI scores were strongly significant.

Shikiar R, Shakespeare A, Sagnier PP, Wilkinson D, McKeith I, Dartigues JF, Dubois B. · MEDTAP International, Seattle, Washington, USA. · J Am Geriatr Soc. · Pubmed #10733052 No free full text.

Abstract: OBJECTIVE: To assess the impact on burden reported by caregivers of patients with mild to moderate Alzheimer's disease (AD) who were treated with metrifonate during a randomized double blind clinical trial. DESIGN: Randomized clinical trial, with a 2-week screening period and a 26-week double blind, placebo controlled, treatment phase. Caregivers were assessed at baseline, at 12 weeks, and at end of trial. SETTING: Caregivers were interviewed at clinics as part of the assessment of the patients. PARTICIPANTS: Six hundred and three caregivers of AD patients who were enrolled in the MALT trial; 591 (98%) provided data suitable for analysis at baseline, and 546 (91%) provided data allowing for inclusion in the analysis of change scores. MEASUREMENTS: The Caregiver Burden Assessment consisted of the Screen for Caregiver Burden, including both subjective (SCB-subj) and objective (SCB-obj) scores; the cognitive subscale of Poulshock and Deimling (PD); an abridged version of the Relatives Stress Scale (aRSS); assessments of time spent in providing care, including the Caregiver Activity Time Scale (CATS); and demographic and background variables on both the patient and caregiver. RESULTS: Treatment of mild to moderate AD patients with metrifonate for a duration of 26 weeks significantly reduced the psychological burden of care to the caregivers, as measured by the SCB-subj, the PD, and the aRSS. There were no statistically significant differences on the measures assessing the time spent in caregiving, except for the caregiver's subjective impression of the change in time spent providing care during the trial. When comparing individual dose groups, most of the measures of burden showed the largest benefits in burden for the 60/80 mg group, followed by the 40/50 mg group, and then the placebo group. However, there was no statistically significant dose effect. CONCLUSIONS: This study provides the first evidence from a randomized clinical trial of any acetylcholinesterase inhibitor used in the treatment of AD demonstrating a positive impact on the patient's caregiver as well as benefits to the patient. These results were shown consistently across several measurement scales and were observed after six months of treatment. These findings reinforce the clinical significance of research that has shown that metrifonate has beneficial impacts on the cognitive, behavioral, and functional abilities of AD patients. Because caregiver burden is a leading factor in the decision for institutional care placement, the ability to favorably impact that burden through pharmacological treatment of the patient is important.

Salamon R, Dartigues JF. · Unité INSERM 330, Université de Bordeaux Victor Segalen, Bordeaux II, France. · Bull Acad Natl Med. · Pubmed #10371772 No free full text.

Abstract: The Paquid research program was specifically designed to study the epidemiology of Alzheimer's disease (AD). Paquid is a prospective study of a representative random sample of 4,134 elderly people living in Gironde and Dordogne, two administrative areas around Bordeaux in South-Western France. This program allowed to obtain prevalence, incidence, survival of AD and to analyze risk factors, consequences and premonitory signs of this disease.

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.

Le Goff M, Helmer C, Foubert-Samier A, Cowppli-Bony P, Berr C, Dartigues JF. · Inserm U897 et Université Victor-Segalen Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux cedex, France. · C R Biol. · Pubmed #19304268 No free full text.

Abstract: It is necessary to develop the prevention of Alzheimer's disease, because of the increase in the number of cases and unavailability of a curative treatment. From the data of the cohort PAQUID, we studied the risk of dementia according to leisure activities and the age of cessation of professional activity. The practice of a sport and reading decreases by 25% the risk of dementia during 15 years. The age of cessation of professional activity is not associated with the risk of dementia. An active life seems to be a possible way to prevent dementia.

Amieva H, Le Goff M, Millet X, Orgogozo JM, Pérès K, Barberger-Gateau P, Jacqmin-Gadda H, Dartigues JF. · Institut National de la Sante et de la Recherche Médicale, U897, France. · Ann Neurol. · Pubmed #19067364 No free full text.

Abstract: OBJECTIVE: Whereas cognitive deficits are known to be detectable long before the typical symptoms of Alzheimer's disease (AD) are evident, previous studies have failed to determine when cognitive functioning actually begins to decline before dementia. Utilizing the long follow-up of the PAQUID study, we examined the emergence of the first clinical symptoms over a 14-year period of follow-up before the dementia phase of AD. METHODS: This study relies on a case-control sample selected from the PAQUID cohort. Of the 3,777 initial subjects of the cohort, 350 subjects experienced development of AD during the 14 years of follow-up. The cases were matched to 350 elderly control subjects. The evolution of scores on cognitive, functional, and depression scales was described throughout the 14-year follow-up using a semiparametric extension of the mixed-effects linear model. RESULTS: The first decline in cognitive performances appeared as early as 12 years before dementia in measures of semantic memory and conceptual formation. Then, more global deficits appeared that were concomitant with an increase in memory complaints and depressive symptoms. About 2 years later, as a consequence of cognitive dysfunction, the subjects started to become slightly dependent in their activities of daily living. In the last 3 years, the impairment significantly worsened until the subjects reached the dementia phase. INTERPRETATION: This approach, describing the 14 years preceding dementia, provides a clear illustration of the particularly long and progressive prodromal phase of AD, and shows the successive emergence of cognitive deficits, depressive symptoms, and functional impairment during this phase.

Rondeau V, Jacqmin-Gadda H, Commenges D, Helmer C, Dartigues JF. · Division of Biostatistics, Unité 897, Institut National de la Santé et de la Recherche Médicale, Bordeaux F-33076, France. · Am J Epidemiol. · Pubmed #19064650 No free full text.

Abstract: The authors examined associations between exposure to aluminum or silica from drinking water and risk of cognitive decline, dementia, and Alzheimer's disease among elderly subjects followed for 15 years (1988-2003). They actively searched for incident cases of dementia among persons aged 65 years or over living in 91 civil drinking-water areas in southern France. Two measures of exposure to aluminum were assessed: geographic exposure and individual exposure, taking into account daily consumption of tap water and bottled water. A total of 1,925 subjects who were free of dementia at baseline and had reliable water assessment data were analyzed. Using random-effects models, the authors found that cognitive decline with time was greater in subjects with a higher daily intake of aluminum from drinking water (>or=0.1 mg/day, P=0.005) or higher geographic exposure to aluminum. Using a Cox model, a high daily intake of aluminum was significantly associated with increased risk of dementia. Conversely, an increase of 10 mg/day in silica intake was associated with a reduced risk of dementia (adjusted relative risk =0.89, P=0.036). However, geographic exposure to aluminum or silica from tap water was not associated with dementia. High consumption of aluminum from drinking water may be a risk factor for Alzheimer's disease.

Letenneur L, Pérès K, Fleury H, Garrigue I, Barberger-Gateau P, Helmer C, Orgogozo JM, Gauthier S, Dartigues JF. · INSERM, U897, Bordeaux, France. · PLoS One. · Pubmed #18982063 links to  free full text

Abstract: BACKGROUND: Herpes Simplex Virus (HSV) infection has been proposed as a possible risk factor of Alzheimer's Disease (AD) notably because it is neurotropic, ubiquitous in the general population and able to establish lifelong latency in the host. The fact that HSV was present in elderly subjects with AD suggests that the virus could be a co-factor of the disease. We investigated the risk of developing AD in anti-HSV immunoglobulin G (IgG) positive subjects (indicator of a lifelong infection to HSV) and IgM-positive subjects (indicator of primary infection or reactivation of the virus) in a longitudinal population-based cohort of elderly subjects living in the community. METHODS: Cox proportional hazard models were used to study the risk of developing AD according to the presence or not of anti-HSV IgG and IgM antibodies, assessed in the sera of 512 elderly initially free of dementia followed for 14 years. RESULTS: During the follow-up, 77 incident AD cases were diagnosed. Controlled for age, gender, educational level and Apolipoprotein E4 (APOE4) status, IgM-positive subjects showed a significant higher risk of developing AD (HR = 2.55; 95% CI [1.38-4.72]), although no significant increased risk was observed in IgG-positive subjects (HR = 1.67; 95%CI [0.75-3.73]). No modification effect with APOE4 status was found. CONCLUSION: Reactivation of HSV seropositivity is highly correlated with incident AD. HSV chronic infection may therefore be contributive to the progressive brain damage characteristic of AD.

Vidal JS, Lacombe JM, Dartigues JF, Pasquier F, Robert P, Tzourio C, Alpérovitch A. · Institut National de la Santé et de la Recherche Médicale (INSERM-U708), Bordeaux, France. · Neuroepidemiology. · Pubmed #18815451 No free full text.

Abstract: BACKGROUND: Clinical studies reported that treatments for Alzheimer's disease may have an impact on behavioral and psychiatric disorders. We tested the hypothesis that memantine treatment initiation modifies psychotropic medication in real-life practice patients. METHODS: A 2-year follow-up cohort study was performed. A sample of patients treated in the general population, extracted from the database of the French national healthcare system (CNAM-TS), was examined. The sample included 4,600 memantine-treated patients (mean age 79.8 years, 69% women) randomly selected from the database of the CNAM-TS covering 69% of the French population aged 65 years and over. The follow-up rate was 95.0%. This database includes exhaustive data on drug consumption. We used interrupted time series analysis of the proportion of psychotropics users (all psychotropic drugs and specific categories) before and after onset of memantine. RESULTS: There was a 39-50% regular increase in patients treated with psychotropic drugs before memantine initiation This increasing trend stopped after memantine initiation, the proportion of psychotropic users remaining stable around 53% up to the end. The trends before and after memantine onset were significantly different (p < 0.001). CONCLUSIONS: Our results suggest a temporal relationship between the onset of memantine and the stabilization of psychotropic drugs use in this large sample of elderly patients.

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).

Samieri C, Féart C, Letenneur L, Dartigues JF, Pérès K, Auriacombe S, Peuchant E, Delcourt C, Barberger-Gateau P. · Inserm, U897, Equipe Epidémiologie de Nutrition et des Comportements Alimentaires, Bordeaux, France. · Am J Clin Nutr. · Pubmed #18779288 No free full text.

Abstract: BACKGROUND: The potential preventive role of polyunsaturated fatty acids (PUFAs) in Alzheimer disease has aroused increasing interest. Plasma n-3 PUFAs have been shown to be inversely related to the risk of dementia and to depression, which is frequently associated with dementia. OBJECTIVE: The objective was to ascertain whether plasma PUFAs predict the risk of incident dementia in a cohort of older persons, independently of their depressive status. DESIGN: Of 1214 nondemented participants in the Three-City Study from Bordeaux (France) who were followed up for 4 y, 65 developed dementia. The association between the proportion of plasma fatty acids at baseline and the risk of incident dementia was assessed by multivariate proportional hazard models, taking into account depressive status assessed on the basis of the Center for Epidemiologic Studies Depression scale. RESULTS: A higher plasma eicosapentaenoic acid (EPA) concentration was associated with a lower incidence of dementia [hazard ratio (HR) for 1 SD = 0.69; 95% CI: 0.48, 0.98], independently of depressive status and after adjustment for age, education, apolipoprotein E epsilon4 allele, diabetes, and baseline plasma vitamin E and triacylglycerol. The relations between docosahexaenoic acid (DHA), total n-3 PUFAs, and incident dementia did not remain significant in multivariate models. Higher ratios of arachidonic acid (AA) to DHA and of n-6 to n-3 fatty acids were related to an increased risk of dementia, particularly in depressive subjects (n = 90): ratio of AA to DHA (HR: 2.65; 95% CI: 1.07, 6.56) and ratio of n-6 to n-3 (HR: 1.61; 95% CI: 1.04, 2.47). CONCLUSIONS: A high plasma EPA concentration may decrease the risk of dementia, whereas high ratios of n-6 to n-3 fatty acids and of AA to DHA may increase the risk of dementia, especially in depressed older persons. The role of EPA in dementia warrants further research.

Vidal JS, Lacombe JM, Dartigues JF, Pasquier F, Robert P, Tzourio C, Alpérovitch A. · Institut National de la Santé et de la Recherche Médicale (INSERM-U708), Paris, France. · Alzheimer Dis Assoc Disord. · Pubmed #18525283 No free full text.

Abstract: Clinical trials have shown modest effects of memantine, an N-methyl-D aspartate receptor antagonist, in Alzheimer disease patients and memantine effectiveness in routine clinical practice needs to be established further. In 2003, memantine was recommended in France for Alzheimer disease patients with disease severity ranging from 15 to 3 on the mini-mental state examination at the first prescription. Our study aimed at describing memantine use in real-world practice in a cohort of 5283 memantine-treated patients (mean age: 80.1 y; women: 69.4%) randomly selected from the database of the national healthcare insurance, which covers 70% of the French elderly population. Mean follow-up after starting memantine prescription was 10.4 months (range: 1 to 20 mo). Patients were older and had a less severe cognitive impairment than patients included in the first controlled clinical trials. Memantine was prescribed with a cholinesterase inhibitor in 53.3% of cases. At 6 months, 26% of the patients had stopped memantine therapy (36% at 12 mo); conversely, patients who continued treatment were highly compliant. The 1-year mortality rate (12.5%) was similar for a comparative cohort of untreated demented patients and the memantine-treated ones. Approximately one-third of the memantine-treated patients did not strictly fit with the French summary of product characteristic recommendations for the first memantine prescription.

Feldman HH, Pirttila T, Dartigues JF, Everitt B, Van Baelen B, Brashear HR, Berlin JA, Battisti WP, Kavanagh S. · University British Columbia Hospital, Vancouver, Canada. · Acta Neurol Scand. · Pubmed #18518863 No free full text.

Abstract: OBJECTIVE : To analyze mortality data from patients with Alzheimer's disease (AD), Alzheimer's plus cerebrovascular disease (AD + CVD) or vascular dementia (VaD). METHODS: (1) Meta-analysis of mortality data from double-blind, placebo-controlled, randomized trials; and (2) recontact study to collect additional longer term mortality data from previous galantamine trial participants. RESULTS (META-ANALYSIS): Across 12 trials (< or =6 months duration), there was no increased risk of mortality associated with the use of galantamine (n = 4116) compared with that of placebo (n = 2386) (OR galantamine/placebo: 0.67, 95% CI 0.41-1.10). RESULTS (RECONTACT STUDY): Median survival was 79 months for patients with AD (n = 478) and 59 months for patients with AD + CVD (n = 180) or VaD (n = 145). Prolonged galantamine treatment (> vs < or =6 months) was not associated with decreased survival time (75 vs 61 months respectively; P = 0.02). Cox regression analyses were consistent with the Kaplan-Meier analyses. CONCLUSIONS: We found no short-term or longer term evidence of increased risk of mortality associated with the use of galantamine in patients with AD, AD + CVD or VaD.