Catherine Helmer

Are sex and educational level independent predictors of dementia and Alzheimer’s disease? Incidence data from the PAQUID project

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.

Metabolic syndrome and risk for incident Alzheimer's disease or vascular dementia: the Three-City Study.

OBJECTIVE—Associations between metabolic syndrome and its individual components with risk of incident dementia and its different subtypes are inconsistent. RESEARCH DESIGN AND METHODS—The 7,087 community-dwelling subjects aged ≥65 years were recruited from the French Three-City (3C) cohort. Hazard ratios (over 4 years) of incident dementia and its subtypes (vascular dementia and Alzheimers disease) and association with metabolic syndrome (defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria) and its individual components (hypertension, large waist circumference, high triglycerides, low HDL cholesterol, and elevated fasting glycemia) were estimated in separate Cox proportional hazard models. RESULTS—Metabolic syndrome was present in 15.8% of the study participants. The presence of metabolic syndrome increased the risk of incident vascular dementia but not Alzheimers disease over 4 years, independent of sociodemographic characteristics and the apolipoprotein (apo) Eε4 allele. High triglyceride level was the only component of metabolic syndrome that was significantly associated with the incidence of all-cause (hazard ratio 1.45 [95% CI 1.05–2.00]; P = 0.02) and vascular (2.27 [1.16–4.42]; P = 0.02) dementia, even after adjustment of the apoE genotype. Diabetes, but not impaired fasting glycemia, was significantly associated with all-cause (1.58 [1.05–2.38]; P = 0.03) and vascular (2.53 [1.15–5.66]; P = 0.03) dementia. CONCLUSIONS—The observed relation between high triglycerides, diabetes, and vascular dementia emphasizes the need for detection and treatment of vascular risk factors in older individuals in order to prevent the likelihood of clinical dementia.

Natural history of decline in instrumental activities of daily living performance over the 10 years preceding the clinical diagnosis of dementia: a prospective population-based study.

OBJECTIVES: To study the subtle changes in instrumental activities of daily living (IADLs) over the 10 years preceding the clinical diagnosis of dementia.

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 Alzheimers 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 Alzheimers disease.

Effectiveness of disease-management programs for improving diabetes care: a meta-analysis

Background We conducted a meta-analysis of randomized controlled trials to assess the effectiveness of disease-management programs for improving glycemic control in adults with diabetes mellitus and to study which components of programs are associated with their effectiveness. Methods We searched several databases for studies published up to December 2009. We included randomized controlled trials involving adults with type 1 or 2 diabetes that evaluated the effect of disease-management programs on glycated hemoglobin (hemoglobin A1C) concentrations. We performed a meta-regression analysis to determine the effective components of the programs. Results We included 41 randomized controlled trials in our review. Across these trials, disease-management programs resulted in a significant reduction in hemoglobin A1C levels (pooled standardized mean difference between intervention and control groups −0.38 [95% confidence interval −0.47 to −0.29], which corresponds to an absolute mean difference of 0.51%). The finding was robust in the sensitivity analyses based on quality assessment. Programs in which the disease manager was able to start or modify treatment with or without prior approval from the primary care physician resulted in a greater improvement in hemoglobin A1C levels (standardized mean difference −0.60 v. −0.28 in trials with no approval to do so; p < 0.001). Programs with a moderate or high frequency of contact reported a significant reduction in hemoglobin A1C levels compared with usual care; nevertheless, only programs with a high frequency of contact led to a significantly greater reduction compared with low-frequency contact programs (standardized mean difference −0.56 v. −0.30, p = 0.03). Interpretation Disease-management programs had a clinically moderate but significant impact on hemoglobin A1C levels among adults with diabetes. Effective components of programs were a high frequency of patient contact and the ability for disease managers to adjust treatment with or without prior physician approval.

Functional Impairment in Instrumental Activities of Daily Living: An Early Clinical Sign of Dementia?

OBJECTIVE: To estimate the predictive value of four IADLs on 3‐ and 5‐year incident dementia.

Marital status and risk of Alzheimer’s disease A French population-based cohort study

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.

Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population

We performed a three-stage genome-wide association study (GWAS) to identify common Parkinsons disease (PD) risk variants in the European population. The initial genome-wide scan was conducted in a French sample of 1039 cases and 1984 controls, using almost 500 000 single nucleotide polymorphisms (SNPs). Two SNPs at SNCA were found to be associated with PD at the genome-wide significance level (P < 3 × 10(-8)). An additional set of promising and new association signals was identified and submitted for immediate replication in two independent case-control studies of subjects of European descent. We first carried out an in silico replication study using GWAS data from the WTCCC2 PD study sample (1705 cases, 5200 WTCCC controls). Nominally replicated SNPs were further genotyped in a third sample of 1527 cases and 1864 controls from France and Australia. We found converging evidence of association with PD on 12q24 (rs4964469, combined P = 2.4 × 10(-7)) and confirmed the association on 4p15/BST1 (rs4698412, combined P = 1.8 × 10(-6)), previously reported in Japanese data. The 12q24 locus includes RFX4, an isoform of which, named RFX4_v3, encodes brain-specific transcription factors that regulate many genes involved in brain morphogenesis and intracellular calcium homeostasis.

Seropositivity to Herpes Simplex Virus Antibodies and Risk of Alzheimer's Disease: A Population-Based Cohort Study

Background Herpes Simplex Virus (HSV) infection has been proposed as a possible risk factor of Alzheimers 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.

Education, occupation, leisure activities, and brain reserve: a population-based study

The influence of education, occupation, and leisure activities on the passive and active components of reserve capacity remains unclear. We used the voxel-based morphometry (VBM) technique in a population-based sample of 331 nondemented people in order to investigate the relationship between these factors and the cerebral volume (a marker of brain reserve). The results showed a positive and significant association between education, occupation, and leisure activities and the cognitive performances on Isaacs set test. Among these factors, only education was significantly associated with a cerebral volume including gray and white matter (p = 0.01). In voxel-based morphometry analyses, the difference in gray matter volume was located in the temporoparietal lobes and in the orbitofrontal lobes bilaterally (a p-value corrected <0.05 by false discovery rate [FDR]). Although smaller, the education-related difference in white matter volume appeared in areas connected to the education-related difference in gray matter volume. Education, occupation attainment, and leisure activities were found to contribute differently to reserve capacity. Education could play a role in the constitution of cerebral reserve capacity.