Alzheimer Disease: Tzourio C

Viswanathan A, Rocca WA, Tzourio C. · Department of Neurology and Clinical Trials Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Neurology. · Pubmed #19171835 No free full text.

Abstract: In recent years, accumulating evidence has suggested that vascular risk factors contribute to Alzheimer disease (AD). Vascular dementia had been traditionally considered secondary to stroke and vascular disease. It has been traditionally distinguished from AD, considered to be a purely neurodegenerative form of dementia. However, in light of this more recent literature, it appears that there is a spectrum: ranging from patients with pure vascular dementia to patients with pure AD and including a large majority of patients with contributions from both Alzheimer and vascular pathologies. In this article, we discuss the impact of vascular risk factors on AD and its consequences at the individual level and at the population level by highlighting the concept of attributable risk. We then discuss the key questions and next steps involved in designing a therapeutic trial to control vascular risk factors for the prevention of dementia.

Tzourio C. · INSERM U708 Neuroepidemiology, Paris, France. · Dialogues Clin Neurosci. · Pubmed #17506226 No free full text.

Abstract: Hypertension is a known risk factor for stroke, and thus for vascular dementia. However, recent large observational studies have suggested that high blood pressure may also play a role in Alzheimer's disease. The mechanisms linking hypertension to Alzheimer's disease remain to be elucidated, but white matter lesions seen on cerebral magnetic resonance imaging appear to be a good marker of this association. It is not yet clearly established whether lowering blood pressure reduces the risk of white matter lesions and dementia, so large trials dealing with this question are eagerly awaited. These future trials could confirm the hope that, by lowering blood pressure, we may have a preventive treatment for dementia. This issue is of major importance, as the number of cases of dementia is expected to rise

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.

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.

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.

Bruandet A, Richard F, Tzourio C, Berr C, Dartigues JF, Alpérovitch A, Amouyel P, Helbecque N. · INSERM, U744, Lille, France. · J Alzheimers Dis. · Pubmed #18431000 No free full text.

Abstract: The purpose of this study was to examine the impact of two polymorphisms (rs4291A>T and rs4343G>A) in the ACE gene on the risk of Alzheimer's disease (AD), using a population-based cohort of 9294 subjects selected from the electoral rolls of three French cities (the Three-City Study). Two follow-up examinations took place 2 and 4 years after inclusion. Diagnosis of dementia was assessed at baseline and at each follow-up examination by neurologists independent of the 3C Study group. For the present analysis, subjects whose mother tongue was not French, those from abroad and those lost at follow-up were excluded, leaving a sample of 6791 subjects. 108 subjects were demented at baseline and 216 subjects, among which 141 had AD, developed a dementia during follow-up. The genotype distributions of the ACE SNPs rs4291 and rs4343 did not differ according to cognitive status. After adjustment for confounding variables, the risk of developing AD was similar whatever the genotype (rs4291 AT vs TT: OR=0.90, p=0.65; AA vs TT: OR=1.05, p= 0.84; rs4343 GA vs GG: OR=1.15, p= 0.48; AA vs GG: OR=1.25, p= 0.37). No global haplotype effect could be observed on the risk of AD.

Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alpérovitch A. · INSERM, U593, University Victor Segalen Bordeaux 2, case 11, 146 rue Léo-Saignat, F-33076 Bordeaux cedex, France. · Neurology. · Pubmed #17998483 No free full text.

Abstract: BACKGROUND: Dietary fatty acids and antioxidants may contribute to decrease dementia risk, but epidemiologic data remain controversial. The aim of our study was to analyze the relationship between dietary patterns and risk of dementia or Alzheimer disease (AD), adjusting for sociodemographic and vascular risk factors, and taking into account the ApoE genotype. METHODS: A total of 8,085 nondemented participants aged 65 and over were included in the Three-City cohort study in Bordeaux, Dijon, and Montpellier (France) in 1999-2000 and had at least one re-examination over 4 years (rate of follow-up 89.1%). An independent committee of neurologists validated 281 incident cases of dementia (including 183 AD). RESULTS: Daily consumption of fruits and vegetables was associated with a decreased risk of all cause dementia (hazard ratio [HR] 0.72, 95% CI 0.53 to 0.97) in fully adjusted models. Weekly consumption of fish was associated with a reduced risk of AD (HR 0.65, 95% CI 0.43 to 0.994) and all cause dementia but only among ApoE epsilon 4 noncarriers (HR 0.60, 95% CI 0.40 to 0.90). Regular use of omega-3 rich oils was associated with a decreased risk of borderline significance for all cause dementia (HR 0.46, 95% CI 0.19 to 1.11). Regular consumption of omega-6 rich oils not compensated by consumption of omega-3 rich oils or fish was associated with an increased risk of dementia (HR 2.12, 95% CI 1.30 to 3.46) among ApoE epsilon 4 noncarriers. CONCLUSION: Frequent consumption of fruits and vegetables, fish, and omega-3 rich oils may decrease the risk of dementia and Alzheimer disease, especially among ApoE epsilon 4 noncarriers.

Dufouil C, Richard F, Fiévet N, Dartigues JF, Ritchie K, Tzourio C, Amouyel P, Alpérovitch A. · Institut National de la Santé et de la Recherche Médicale U360, Hopital La Salpêtrière, Paris, France. · Neurology. · Pubmed #15883313 No free full text.

Abstract: OBJECTIVE: To examine the association of plasma cholesterol levels, lipid-lowering agent (LLA) intake, and APOE genotype with dementia prevalence. METHODS: The Three-City Study is a population-based cohort of 9,294 subjects selected from the electoral rolls of three French cities (Bordeaux, Dijon, Montpellier). Baseline examination included extensive assessment of exposure to vascular risk factors (including cholesterol levels and LLA use [statin or fibrate]) and clinical diagnosis of dementia. RESULTS: Two percent of participants were demented at baseline. Overall 32.4% of participants had hyperlipidemia, and 15.6% were prescribed statins and 13.7% fibrates. After adjusting for age, gender, education level, and study center, the odds ratio (OR) for dementia was observed to be lower among LLA users (OR = 0.61, 95% CI = 0.41 to 0.91) compared with subjects taking no LLAs. There was no differential effect between statin and fibrate users. The odds for dementia were increased in subjects with hyperlipidemia (OR = 1.43, 95% CI = 1.03 to 1.99). Further adjustment for potential confounders did not modify these associations. In addition, the association between LLA intake and dementia was not modified by APOE genotype, whereas hyperlipidemia was significantly associated with increased dementia prevalence only in non-epsilon4 carriers and non-Alzheimer disease cases. Finally, in participants taking LLAs, the odds for dementia were decreased only in those having normal lipid levels. CONCLUSIONS: This observational study provides further evidence that lipid-lowering agents are associated with decreased risk of dementia, whereas hyperlipidemia is associated with increased odds for non-Alzheimer-disease-type dementia. These effects appear to be independent of all major potential confounders.

Tzourio C, Dufouil C, Ducimetière P, Alpérovitch A. · INSERM U 360, Hôpital de la Salpêtrière, Paris, France. · Neurology. · Pubmed #10599763 No free full text.

Abstract: OBJECTIVE: To examine whether baseline high blood pressure and antihypertensive treatment predicts cognitive decline in elderly individuals. METHODS: A longitudinal population-based study of elderly individuals (n = 1,373) in Nantes (western France) was undertaken. Individuals 59 to 71 years of age were selected from electoral rolls. High blood pressure at baseline was defined as systolic blood pressure > or =160 mm Hg or diastolic blood pressure > or =95 mm Hg. Cognitive decline was defined as a drop of 4 points or more on the Mini-Mental State Examination between baseline and the 4-year assessment. RESULTS: There is an association between high blood pressure at baseline and cognitive decline at the 4-year assessment (odds ratio, 2.8; 95% CI, 1.6 to 5.0). In participants with high blood pressure, the risk of cognitive decline was 4.3 (95% CI, 2.1 to 8.8) in those without antihypertensive therapy and 1.9 (95% CI, 0.8 to 4.4) in those being treated. In participants with high blood pressure both at baseline and at the 2-year assessment, the risk for untreated participants was 6.0 (95% CI, 2.4 to 15.0) compared with 1.3 (95% CI, 0.3 to 4.9) in treated participants. CONCLUSIONS: High blood pressure was associated with cognitive decline. In individuals with high blood pressure, cognitive decline occurred in a relatively short time period and the risk was highest in untreated hypertensive patients.