Association of Retinal Nerve Fiber Layer Thickness With Brain Alterations in the Visual and Limbic Networks in Elderly Adults Without Dementia.

Importance: The eye is a sensory organ that is easily accessible for imaging techniques, allowing the measurement of the retinal nerve fiber layer (RNFL) thickness. The eye is part of the central nervous system, and its neurons may be susceptible to degeneration; therefore, changes in the RNFL thickness may reflect microstructural and volume alterations in the brain. Objective: To explore the association between the peripapillary RNFL thickness and brain alterations in the visual and limbic networks in elderly people without dementia. Design, Setting, and Participants: Cross-sectional analysis of the Three-City/Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (Alienor) Study cohort (April 2009 to December 2010). The dates of analysis were July 2017 to August 2018. The setting was a population-based study in France. The brain volume analysis included 104 participants, and the diffusion tensor imaging analysis included 79 participants. Main Outcomes and Measures: Global RNFL was assessed by spectral-domain optical coherence tomography. Brain volumes were assessed via T1-weighted magnetic resonance imaging by measurement of the global white and gray matter fractions and the hippocampal fraction. Brain microstructural alterations were assessed with diffusion tensor imaging at the level of the posterior thalamic radiations, the limbic system tracts (the fornix and cingulum bundles), and the posterior limb of the internal capsule (control region). Linear regression models adjusted for several confounders were performed. Results: Among a total of 104 participants, the mean (SD) age was 80.8 (3.9) years, and the cohort was 56.7% women (n = 59). The mean (SD) global RNFL thickness was 89.3 (12.9) µm. A thicker RNFL was associated with a greater hippocampal fraction (quantity of increase ß = 0.013; 95% CI, 0.001-0.025 per 10-µm increase in the RNFL thickness) and better diffusion tensor imaging variables in the global cingulum (mean diffusivity ß = -0.007; 95% CI, -0.015 to -0.000) and the hippocampal part of the cingulum (mean diffusivity ß = -0.009; 95% CI, -0.016 to -0.002 and radial diffusivity ß = -0.010; 95% CI, -0.018 to -0.002) and the posterior thalamic radiations (fractional anisotropy ß = 0.008; 95% CI, 0.000-0.017). No significant associations were found with other magnetic resonance imaging volumes or with other diffusion tensor imaging variables. In particular, there was no significant association with the control region of interest. Conclusions and Relevance: Results of this study suggest that in elderly individuals without dementia, a thicker RNFL was associated with better magnetic resonance imaging variables both in a region that included the visual pathways and in regions particularly involved in the neurodegenerative processes of Alzheimer disease.

Fish Intake, Genetic Predisposition to Alzheimer Disease, and Decline in Global Cognition and Memory in 5 Cohorts of Older Persons.

Fish are a primary source of long-chain omega-3 fatty acids, which may help delay cognitive aging. We pooled participants from the French Three-City study and 4 US cohorts (Nurses' Health Study, Women's Health Study, Chicago Health and Aging Project, and Rush Memory and Aging Project) for whom diet and cognitive data were available (n = 23,688 white persons, aged ≥65 years, 88% female, baseline year range of 1992-1999, and median follow-up range of 3.9-9.1 years) to investigate the relationship of fish intake to cognitive decline and examine interactions with genes related to Alzheimer disease. We estimated cohort-specific associations between fish and change in composite scores of global cognition and episodic memory using linear mixed models, and we pooled results using inverse-variance weighted meta-analysis. In multivariate analyses, higher fish intake was associated with slower decline in both global cognition and memory (P for trend ≤ 0.031). Consuming ≥4 servings/week versus <1 serving/week of fish was associated with a lower rate of memory decline: 0.018 (95% confidence interval: 0.004, 0.032) standard units, an effect estimate equivalent to that found for 4 years of age. For global cognition, no comparisons of higher versus low fish intake reached statistical significance. In this meta-analysis, higher fish intake was associated with a lower rate of memory decline. We found no evidence of effect modification by genes associated with Alzheimer disease.

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.

BACKGROUND: No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. METHODS: The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). FINDINGS: 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. INTERPRETATION: The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. FUNDING: French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.

Vitamin D Deficiency in Community-Dwelling Elderly Is Not Associated with Age-Related Macular Degeneration.

BACKGROUND: Elderly persons are at elevated risk of vitamin D deficiency, which is involved in various health problems. However, its relation with age-related macular degeneration (AMD) is debated. OBJECTIVES: We investigated factors associated with plasma 25-hydroxyvitamin D [25(OH)D] deficiency and the associations between plasma 25(OH)D concentrations and AMD in elderly subjects. METHODS: Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes (ALIENOR) is a population-based study on eye diseases performed in elderly residents of Bordeaux, France. Plasma 25(OH)D concentrations were assessed from blood samples and categorized as <25 nmol/L (deficiency), 25-49 nmol/L (insufficiency), or ≥50 nmol/L (sufficiency). AMD was classified as: no AMD, early AMD, and late AMD. Associations between baseline characteristics and plasma 25(OH)D status were examined with multinomial logistic regression analysis. Associations between AMD and plasma 25(OH)D status were estimated using generalized estimating equation logistic regressions. RESULTS: Six hundred ninety-seven subjects with complete data were included. The prevalence of plasma 25(OH)D deficiency and insufficiency were 27.3% and 55.9%, respectively. In multivariate analysis, 25(OH)D deficiency was significantly associated with older age (P = 0.0007), females (P = 0.0007), absence of physical activity (P = 0.01), absence of vitamin D supplementation (P < 0.0001), higher plasma total cholesterol (P = 0.007), use of fibrates (P < 0.0001), lower alcohol consumption (P = 0.02), and season of blood sampling (P < 0.0001). After adjustment for these covariates and dietary omega-3 polyunsaturated fatty acid intake, smoking, and body mass index, no significant associations were found between early AMD and 25(OH)D insufficiency or deficiency (OR: 0.71, P = 0.12; OR: 0.73, P = 0.23, respectively) or with late AMD (OR: 1.04, P = 0.93; OR: 0.74, P = 0.59, respectively). CONCLUSION: These findings underline the very high prevalence of plasma 25(OH)D deficiency in this elderly population but do not support a specific role for vitamin D in AMD.

High concentrations of plasma n3 fatty acids are associated with decreased risk for late age-related macular degeneration.

High dietary intakes of n3 (ω3) polyunsaturated fatty acids (PUFA) and fish have been consistently associated with a decreased risk for age-related macular degeneration (AMD). We assessed the associations of late AMD with plasma n3 PUFA, a nutritional biomarker of n3 PUFA status. The Antioxydants Lipides Essentiels Nutrition et Maladies Occulaires (Alienor) Study is a prospective, population-based study on nutrition and age-related eye diseases performed in 963 residents of Bordeaux (France) aged ≥73 y. Participants had a first eye examination in 2006-2008 and were followed for 31 mo on average. Plasma fatty acids were measured by GC from fasting blood samples collected in 1999-2001. AMD was graded from non-mydriatic color retinal photographs at all examinations and spectral domain optical coherence tomography at follow-up. After adjustment for age, gender, smoking, education, physical activity, plasma HDL-cholesterol, plasma triglycerides, CFH Y402H, apoE4, and ARMS2 A69S polymorphisms, and follow-up time, high plasma total n3 PUFA was associated with a reduced risk for late AMD [OR = 0.62 for 1-SD increase (95% CI: 0.44-0.88); P = 0.008]. Associations were similar for plasma 18:3n3 [OR = 0.62 (95% CI: 0.43-0.88); P = 0.008] and n3 long-chain PUFA [OR = 0.65 (95% CI: 0.46-0.92); P = 0.01]. This study gives further support to the potential role of n3 PUFAs in the prevention of late AMD and highlights the necessity of randomized clinical trials to determine more accurately the value of n3 PUFAs as a means of reducing AMD incidence.

Ginkgo biloba extract and long-term cognitive decline: a 20-year follow-up population-based study.

BACKGROUND: Numerous studies have looked at the potential benefits of various nootropic drugs such as Ginkgo biloba extract (EGb761®; Tanakan®) and piracetam (Nootropyl®) on age-related cognitive decline often leading to inconclusive results due to small sample sizes or insufficient follow-up duration. The present study assesses the association between intake of EGb761® and cognitive function of elderly adults over a 20-year period. METHODS AND FINDINGS: The data were gathered from the prospective community-based cohort study 'Paquid'. Within the study sample of 3612 non-demented participants aged 65 and over at baseline, three groups were compared: 589 subjects reporting use of EGb761® at at least one of the ten assessment visits, 149 subjects reporting use of piracetam at one of the assessment visits and 2874 subjects not reporting use of either EGb761® or piracetam. Decline on MMSE, verbal fluency and visual memory over the 20-year follow-up was analysed with a multivariate mixed linear effects model. A significant difference in MMSE decline over the 20-year follow-up was observed in the EGb761® and piracetam treatment groups compared to the 'neither treatment' group. These effects were in opposite directions: the EGb761® group declined less rapidly than the 'neither treatment' group, whereas the piracetam group declined more rapidly (ß = -0.6). Regarding verbal fluency and visual memory, no difference was observed between the EGb761® group and the 'neither treatment' group (respectively, ß = 0.21 and ß = -0.03), whereas the piracetam group declined more rapidly (respectively, ß = -1.40 and ß = -0.44). When comparing the EGb761® and piracetam groups directly, a different decline was observed for the three tests (respectively ß = -1.07, ß = -1.61 and ß = -0.41). CONCLUSION: Cognitive decline in a non-demented elderly population was lower in subjects who reported using EGb761® than in those who did not. This effect may be a specific medication effect of EGb761®, since it was not observed for another nootropic medication, piracetam.

From genetics to dietetics: the contribution of epidemiology to understanding Alzheimer's disease.

Late-life dementia results from non-modifiable risk factors such as age and genetics, modulated by deleterious and protective environmental factors among which nutrition may play a major role. This paper highlights five major recent contributions of the French Three-City (3C) and PAQUID epidemiological studies to Alzheimer's disease (AD) knowledge, targeting genetic and dietary risk factors, and the impact of cognitive decline in daily living. The 3C study contributed to a large genome-wide association study to identify new genetic risk factors for AD. In addition to apolipoprotein E (APOE), two loci gave replicated evidence of association: one within CLU, encoding clusterin or apolipoprotein J, and the other within CR1, encoding the complement component receptor 1. Although the attributable fraction of risk for these polymorphisms is moderate, genetic studies provide significant insights into the molecular bases of AD. Regarding dietary data, findings from 3C suggest that healthy diets associating sources of both omega 3 fatty acids (fish) and antioxidants (fruits and vegetables) such as the Mediterranean diet, and caffeine could be associated with decreased risk for AD. However, the protective effect of omega3 fatty acids might be limited to APOE4 non-carriers. Future research should focus on gene-nutrient interactions. Regarding the functional impact of prodromal AD, the PAQUID study showed that taking into account mild functional limitations considerably increases the predictive value of neuropsychological tests for conversion to dementia. Research should focus on sensitive instruments to capture early functional decline to improve the identification of elderly patients at high risk of conversion to dementia.

Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised placebo-controlled trial.

BACKGROUND: Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. METHODS: In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510. FINDINGS: Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio [HR] 0·84, 95% CI 0·60-1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69-1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77-1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups. INTERPRETATION: Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. FUNDING: Ipsen.

Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe.

OBJECTIVE: The long-chain ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are potential candidates for interventions to delay Alzheimer disease (AD), but evidence from clinical studies is mixed. We aimed at determining whether plasma levels of EPA or DHA predict atrophy of medial temporal lobe (MTL) gray matter regions in older subjects. METHODS: A total of 281 community dwellers from the Three-City Study, aged 65 years or older, had plasma fatty acid measurements at baseline and underwent MRI examinations at baseline and at 4 years. We studied the association between plasma EPA and DHA and MTL gray matter volume change at 4 years. RESULTS: Higher plasma EPA, but not DHA, was associated with lower gray matter atrophy of the right hippocampal/parahippocampal area and of the right amygdala (p < 0.05, familywise error corrected). Based on a mean right amygdala volume loss of 6.0 mm(3)/y (0.6%), a 1 SD higher plasma EPA (+0.64% of total plasma fatty acids) at baseline was related to a 1.3 mm(3) smaller gray matter loss per year in the right amygdala. Higher atrophy of the right amygdala was associated with greater 4-year decline in semantic memory performances and more depressive symptoms. CONCLUSION: The amygdala, which develops neuropathology in the early stage of AD and is involved in the pathogenesis of depression, may be an important brain structure involved in the association between EPA and cognitive decline and depressive symptoms.

Dietary omega-3 fatty acids and the risk for age-related maculopathy: the Alienor Study.

PURPOSE: Previous studies have suggested a lower risk for age-related maculopathy (ARM) in subjects with high dietary intake of long-chain omega-3 polyunsaturated fatty acids (PUFA). The authors report the associations of ARM with past dietary intakes in French elderly subjects. METHODS: The Alienor Study is a population-based epidemiologic study on nutrition and age-related eye diseases performed in residents of Bordeaux 73 years of age and older. Six hundred sixty-six subjects (1289 eyes) with complete data were included in the analyses. ARM was classified from retinal photographs taken in 2006 to 2008 in five exclusive stages: late neovascular ARM (n = 21 subjects, 29 eyes); late atrophic ARM (n = 19 subjects, 33 eyes); large soft indistinct drusen and/or reticular drusen and/or large distinct drusen with pigment abnormalities (early ARM2, n = 67 subjects, 100 eyes); large soft distinct drusen alone or pigment abnormalities alone (early ARM1, n = 119 subjects, 163 eyes); and no ARM (n = 440 subjects, 964 eyes). Dietary intakes were estimated from a 24-hour dietary recall performed by dieticians (2001-2002). Associations were estimated using logistic Generalized Estimating Equation. RESULTS: After multivariate adjustment, subjects with high intake of long-chain omega-3 PUFA showed a decreased risk for early ARM1 (odds ratio [OR], 0.83; 95% confidence interval [95% CI], 0.71-0.98; P = 0.03) and late neovascular ARM (OR, 0.26; 95% CI, 0.08-0.83; P = 0.02). Associations with late atrophic ARM were in the same direction but did not reach statistical significance (OR, 0.74; 95% CI, 0.52-1.06; P = 0.10). Overall, high intakes of long-chain omega-3 PUFA were associated with reduced risk for late ARM (OR, 0.59; 95% CI, 0.39-0.88; P = 0.01). CONCLUSIONS: These results confirm a decreased risk for ARM in subjects with high intake of long-chain omega-3 PUFA.

Commentary on "A roadmap for the prevention of dementia II. Leon Thal Symposium 2008." The Multidomain Alzheimer Preventive Trial (MAPT): a new approach to the prevention of Alzheimer's disease.

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.

Aluminum and silica in drinking water and the risk of Alzheimer's disease or cognitive decline: findings from 15-year follow-up of the PAQUID cohort.

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.

Tea consumption is inversely associated with carotid plaques in women.

OBJECTIVE: The aim of this study was to assess the relationship of tea consumption with common carotid artery intima-media thickness (CCA-IMT) and carotid plaques. METHODS AND RESULTS: The study was performed on 6597 subjects aged > or = 65 years, recruited in the French population for the Three-City Study. Atherosclerotic plaques in the extracranial carotid arteries and CCA-IMT were measured using a standardized protocol. Results were tested for replication in another, younger, French population sample (EVA-Study, 1123 subjects). In the Three-City Study, increasing daily tea consumption was associated with a lower prevalence of carotid plaques in women: 44.0%, 42.5%, and 33.7% in women drinking no tea, 1 to 2 cups/d, and > or = 3 cups/d (P=0.0001). This association was independent of age, center, major vascular risk factors, educational level, and dietary habits (adjOR=0.68[95%CI:0.54 to 0.86] for women drinking > or = 3 cups/d compared with none). There was no association of tea consumption with carotid plaques in men, or CCA-IMT in both genders. In the EVA-Study, carotid plaque frequency was 18.8%, 18.5%, and 8.9% in women drinking no tea, 1 to 2 cups/d, and > or = 3 cups/d (P=0.08). CONCLUSIONS: In a large sample of elderly community subjects we showed for the first time that carotid plaques were less frequent with increasing tea consumption in women.

Vasodilators and nootropics as predictors of dementia and mortality in the PAQUID cohort.

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.

Economic impact of migraine and other episodic headaches in France: data from the GRIM2000 study.

BACKGROUND: Migraine is a prevalent and incapacitating condition that affects individuals in the prime of their productive life, thus generating an economic burden for both society and healthcare systems. The direct annual healthcare costs of migraine in France were assessed over 10 years ago, and the current study updates these figures. OBJECTIVE: The objective of this study was to determine the economic cost (primarily direct costs) of migraine and other episodic headache in France based on a general population survey of headache, the GRIM2000 (Groupe de Researche Interdisciplinaire sur la Migraine). DESIGN: From a representative general population sample of 10,585 individuals aged > or = 15 years in France in 1999, 1486 individuals experiencing headaches were identified and interviewed regarding healthcare resource consumption in the previous 6 months. By applying unit costs to the resource data, costings (in 1999 values) were determined for physician consultations, hospitalisation, medication use and diagnostic/laboratory tests, and evaluated from a healthcare system perspective. Information on absenteeism and lost productivity was derived from the Migraine Disability Assessment Score (MIDAS) questionnaire. RESULTS: The prevalence of migraine (including migrainous disorder) was determined to be 17%. Total annual direct healthcare costs were estimated to be Euros 128 per individual with migraine in 1999, corresponding to Euros 1044 million when extrapolated to all individuals experiencing migraine and aged > or = 15 years. Around two-thirds of this cost accrued to the social security system (Euros 698 million; Euros 85 per individual). The total annual direct cost of other forms of episodic headache was much lower at Euros 28 per individual (social security cost Euros 18); with a prevalence of 9.2%, the annual national direct cost for other forms of episodic headache totalled Euros 124 million. The principal cost element was physician consultations. However, it was found that many individuals had never consulted a physician for their headaches, and self-medication contributed substantially to the medication costs (the second greatest cost factor for migraine). The cost per individual rose steeply with increasing severity of headache. CONCLUSIONS: The direct healthcare costs of migraine do not seem to have risen significantly over the past decade. A small minority of individuals with more severe headaches consume most of the healthcare resources devoted to migraine, while most individuals generate relatively low direct costs. The total annual direct costs in France for migraine are almost 10-fold higher than those of other episodic headache.