Alzheimer Disease: Helmer C

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.

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.

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.

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.

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.

Carcaillon L, Pérès K, Péré JJ, Helmer C, Orgogozo JM, Dartigues JF. · Inserm, Unit 593, Bordeaux, France. · Dement Geriatr Cogn Disord. · Pubmed #17476100 No free full text.

Abstract: BACKGROUND/AIMS: Current findings suggest the existence of a category of fast cognitive decliners with a poorer prognosis but better treatment response. Our study aimed at confirming the concept of fast decliners at the time of Alzheimer's disease (AD) diagnosis which best predicts mortality, in an unselected sample. METHODS: 245 incident cases of AD were selected from the French longitudinal cohort PAQUID. We investigated a different threshold of cognitive decline [measured by the annual loss of points in the Mini Mental State Examination (MMSE) score] to define when a subject could be considered as a fast decliner. We used Cox proportional hazards models to study the relation between cognitive decline and mortality. RESULTS:The significant threshold of decline associated with a higher mortality rate was a loss of 3 points per year in the MMSE score. Among the 245 AD cases, 83 (33.9%) subjects were considered as fast decliners. Of them, 78.3% died during the follow-up compared with 63.0% of the slow decliners (RR = 1.7, 95% CI 1.2-2.5). CONCLUSION:These results constitute an empirical validation of the concept of fast decliners in community-based AD patients and justify the cutoff of 3 points for the definition of this condition.

Dartigues JF, Carcaillon L, Helmer C, Lechevallier N, Lafuma A, Khoshnood B. · Inserm U. 593, Université de Bordeaux 2, Bordeaux, France. · J Am Geriatr Soc. · Pubmed #17341242 No free full text.

Abstract: OBJECTIVES: To assess the effects of treatment for memory impairment and the Ginkgo biloba extract (EGb 761) on dementia, mortality, and survival without dementia. DESIGN: Prospective community-based cohort study. SETTING: France. PARTICIPANTS: Three thousand five hundred thirty-four subjects aged 65 and older. MEASUREMENTS: Information on drug consumption was obtained by interview and visual assessment of patients' medicine chests. Active screening of dementia was performed every 2 years over a 13-year period. The independent effects of treatment for memory impairment and the Ginkgo biloba extract on the risks of dementia and death were estimated using Cox proportional hazards models, adjusted for potentially confounding factors (including comorbidities). RESULTS: The initial consumption of Ginkgo biloba did not modify the risk of dementia (relative risk (RR)=1.16, 95% confidence interval (CI)=0.84-1.60), whereas the consumption of other treatments for memory impairment was associated with a higher risk of dementia (RR=1.35, 95% CI=1.11-1.63). Subjects who took Ginkgo biloba had a significantly lower risk of mortality in the long term (RR=0.76, 95% CI=0.62-0.93), even after adjustment for potentially confounding factors. The initial consumption of treatment for memory impairment other than Ginkgo biloba did not modify the risk of mortality. CONCLUSION: These results suggest that treatment with EGb 761 may increase the probability of survival in the elderly population. These findings need to be corroborated and further assessed using randomized, controlled trials.

Helmer C, Andrieu S, Pérès K, Orgogozo JM, Vellas B, Dartigues JF, Anonymous00250. · INSERM U593, Université de Bordeaux-2, Bordeaux, France. · Dement Geriatr Cogn Disord. · Pubmed #17215578 No free full text.

Abstract: BACKGROUND/AIMS: To determine the predictive value of the 6-month evolution of the ADAS-cog score in initially mild to moderate Alzheimer's disease (AD) patients on the risk of death or severe dementia (MMSE <10) within 2 years. METHODS: Cognition was assessed every 6 months using the ADAS-cog scale in the Real.fr study, a cohort of AD patients. Six classes of ADAS-cog evolution were distinguished, from the severest deterioration (decline >or=7 points) to the greatest cognitive improvement (gain >or=4 points). RESULTS: Among 536 AD patients, 53 (9.9%) had a 6-month decline of 7 points or more. This group with the severest deterioration was significantly associated with the risk of severe dementia or death at 2 years (relative risk, RR = 3.8, 95% confidence interval, CI = 2.1-6.8), even after adjustment for baseline MMSE, disability and ADAS-cog score (RR = 2.6, 95% CI = 1.4-5.0). In addition, subjects with a decline by at least 4 points were also at greater risk of severe dementia. CONCLUSION: These results confirm the value of the ADAS-cog scale as a judgement criterion in clinical trials since it is a good surrogate marker of long-term prognosis. The proportion of fast decliners on the ADAS-cog could be a helpful judgement criterion for future trials in AD.

Amieva H, Jacqmin-Gadda H, Orgogozo JM, Le Carret N, Helmer C, Letenneur L, Barberger-Gateau P, Fabrigoule C, Dartigues JF. · INSERM (Institut National de la Santé et de la Recherche Médicale) Unit 593, Bordeaux, France. · Brain. · Pubmed #15774508 links to  free full text

Abstract: Better knowledge of the preclinical phase of Alzheimer's disease would be an important advance to allow earlier treatment of this ominous disease. This prodromal period was investigated in the Paquid cohort by analysing change in cognitive performances at five time points over a 9 year period. Neuropsychological measures including global cognitive functioning (Mini-Mental State Examination), visuo-spatial memory (Benton Visual Retention Test), verbal fluency (Isaacs Set Test) and abstract thinking (Wechsler Similarities Test) were assessed in 215 future Alzheimer's disease subjects and 1050 individuals without dementia. The results showed that cognitive performances of the pre-morbid subjects at baseline were already lower than those of individuals without dementia (1.4 points less on the Mini-Mental State Examination; 1.8 points less on the Benton Visual Retention Test; 4 points less on the Isaacs Set Test and 0.8 points less on the Wechsler Similarities Test). For some neuropsychological tests, an acceleration of the decline occurred approximately 3 years before the diagnosis and, for each test, the course of decline was modulated by education level. These findings show that abnormally low performances can be evidenced 9 years before the clinical diagnosis of Alzheimer's disease in several domains of cognition beyond memory and that cognitive change over time can be influenced by education.

Ramaroson H, Helmer C, Barberger-Gateau P, Letenneur L, Dartigues JF, Anonymous00037. · Unité INSERM 330, Université Victor Segalen Bordeaux II. · Rev Neurol (Paris). · Pubmed #12773869 No free full text.

Abstract: The progression of the prevalence of dementia in developed countries will increase the difficulties of medical and psycho-social management of demented patients and their family. The aim of this study was to estimate the prevalence of dementia among subjects aged 75 years and over. These subjects have been followed-up ten years after the baseline examination of the PAQUID study, a prospective population-based cohort study on normal and pathological aging after 65 years. A total of 1,461 subjects, aged 75 years and over, have been visited. The prevalence of dementia was estimated to be at 17.8 p.cent. About 38.5 p.cent of these demented subjects ware living in an institution, which leads to the fact that more than the two thirds of the subjects living in an institution were demented persons. Alzheimer's disease was the main etiology of dementia (79.6 p.cent). Based on the French population census, currently there would be about 769,000 demented people aged 75 years or over in France. Dementia accounts for 72 p.cent of the potential need for the French subvention for dependent persons, called Allocation Personnalisee d'Autonomie P. These results point out the importance of regarding dementia as a Public Health priority and of developing necessary measures for caring for these subjects, whether residing in their home or an institution.

Helmer C, Letenneur L, Rouch I, Richard-Harston S, Barberger-Gateau P, Fabrigoule C, Orgogozo JM, Dartigues JF. · INSERM U 330, Université de Bordeaux II, 146 Rue Léo Saignat, 33076 Bordeaux cedex, France. · J Neurol Neurosurg Psychiatry. · Pubmed #11511701 links to  free full text

Abstract: OBJECTIVE: To determine whether principal occupation during life is a risk factor for incident Alzheimer's disease, vascular dementia, or dementia with parkinsonism. METHODS: This study was carried out from the PAQUID (Personnes Agées QUID) cohort, an epidemiological study on normal and pathological aging after 65 years in the south west of France. At baseline, 2950 non-demented people living at home were identified and re-examined 1, 3, 5, 8, and 10 years later with identical standardised neurological and neuropsychological measures. Cox proportional hazards models with delayed entry were used, taking age as the time scale and adjusting for sex, education, tobacco, and wine consumption to estimate the risk ratio (RR) of incident dementia, Alzheimer's disease, vascular dementia, and dementia with parkinsonism associated with occupational category. RESULTS: Of the 2950 subjects, 393 became demented, of whom 251 had Alzheimer's disease, 112 had vascular dementia, and 27 had dementia with parkinsonism. The risk of Alzheimer's disease was not related to a given occupation. However the risk of dementia with parkinsonism seemed to be increased in farmers in comparison with professionals and managerials, particularly among women (RR 7.47; 95%CI, 1.80-31.07). CONCLUSION: The data suggest that occupation does not change the risk of Alzheimer's disease, which seems to be more influenced by cognitive abilities in childhood and adolescence than by occupation in adult life. However, being a farmer may increase the risk of dementia with parkinsonism among women; occupation could act by the way of differences in health behaviour or in exposure to environmental factors.

Jagger C, Andersen K, Breteler MM, Copeland JR, Helmer C, Baldereschi M, Fratiglioni L, Lobo A, Soininen H, Hofman A, Launer LJ. · Department of Epidemiology and Public Health, University of Leicester, UK. · Neurology. · Pubmed #10854356 No free full text.

Abstract: The effect of dementia on time to death and institutionalization in elderly populations is of importance to resource planning, as well as to patients and their carers. The authors report a collaborative reanalysis of nine population-based studies conducted in Europe to compare dementia cases and noncases in risk of and time to death and to institutionalization. Prevalent and incident cases were more likely than noncases to reside in an institution at baseline and were more likely to enter institutional care. Prevalent cases also had over twice the risk of death compared to noncases and survival for men with dementia was consistently lower than that for women with dementia of the same age group.

Helmer C, Damon D, Letenneur L, Fabrigoule C, Barberger-Gateau P, Lafont S, Fuhrer R, Antonucci T, Commenges D, Orgogozo JM, Dartigues JF. · INSERM U 330, Université de Bordeaux II, France. · Neurology. · Pubmed #10599764 No free full text.

Abstract: OBJECTIVE: To analyze the relationship between marital status and risk of AD or dementia. METHODS: This study was carried out from the Personnes Agées QUID (PAQUID) cohort, an epidemiologic study on normal and pathologic aging after age 65 years. The PAQUID cohort began in 1988. Individuals were followed up at 1, 3, and 5 years, with an active detection of dementia. Marital status was divided into four categories: widowed, never married, divorced or separated, and the reference category, married or cohabitant. The longitudinal relationship between marital status and risk of incident AD or dementia was analyzed by a Cox model with delayed entry. RESULTS: Among the 3,675 individuals initially not demented, 2,106 were married or cohabitants, 1,287 were widowers, 179 were never married, and 103 were divorced or separated. Among the 2,881 individuals reevaluated at least once for the risk of dementia during the 5-year follow-up, 190 incident cases of dementia were identified, including 140 with AD. The relative risks (RRs) of dementia (RR = 1.91, p = 0.018) and of AD (RR = 2.68, p<0.001) were increased for the never-married individuals compared with those who were married or cohabitants. This excess of risk was specifically associated with AD. Adjustment for other risk factors of dementia (education, wine consumption), or for factors reflecting social environment, leisure activities, and depression, did not modify the risk of AD for never-married individuals (RR = 2.31, p = 0.02). CONCLUSIONS: We confirmed an association between marital status and AD, with an excess risk observed among never-married individuals. This association may provide clues about the pathogenesis of AD.

Letenneur L, Gilleron V, Commenges D, Helmer C, Orgogozo JM, Dartigues JF. · Unité INSERM 330, Université Victor Segalen, Bordeaux, France. · J Neurol Neurosurg Psychiatry. · Pubmed #10071096 links to  free full text

Abstract: OBJECTIVES: To examine the age specific risk of Alzheimer's disease according to sex, and to explore the role of education in a cohort of elderly community residents aged 65 years and older. METHODS: A community based cohort of elderly people was studied longitudinally for 5 years for the development of dementia. Dementia diagnoses were made according to the DSM III R criteria and Alzheimer's disease was assessed using the NINCDS-ADRDA criteria. Among the 3675 non-demented subjects initially included in the cohort, 2881 participated in the follow up. Hazard ratios of dementia were estimated using a Cox model with delayed entry in which the time scale is the age of the subjects. RESULTS: During the 5 year follow up, 190 incident cases of dementia, including 140 cases of Alzheimer's disease were identified. The incidence rates of Alzheimer's disease were 0.8/100 person-years in men and 1.4/100 person-years in women. However, the incidence was higher in men than in women before the age of 80 and higher in women than in men after this age. A significant interaction between sex and age was found. The hazard ratio of Alzheimer's disease in women compared with men was estimated to be 0.8 at 75 years and 1.7 at 85 years. The risks of dementia and Alzheimer's disease were associated with a lower educational attainment (hazard ratio=1.8, p<0.001). The increased risk of Alzheimer's disease in women was not changed after adjustment for education. CONCLUSION: Women have a higher risk of developing dementia after the age of 80 than men. Low educational attainment is associated with a higher risk of Alzheimer's disease. However, the increased risk in women is not explained by a lower educational level.