Luc Letenneur

Rates and risk factors for dementia and Alzheimer’s disease Results from EURODEM pooled analyses

Objective: To investigate the risk of AD associated with a family history of dementia, female gender, low levels of education, smoking, and head trauma. Background: These putative factors have been identified in cross-sectional studies. However, those studies are prone to bias due to systematic differences between patients and control subjects regarding survival and how risk factors are recalled. Methods: The authors performed a pooled analysis of four European population-based prospective studies of individuals 65 years and older, with 528 incident dementia patients and 28,768 person-years of follow-up. Patients were detected by screening the total cohort with brief cognitive tests, followed by a diagnostic assessment of those who failed the screening tests. Dementia was diagnosed with the Diagnostic and Statistical Manual of Mental Disrders, 3rd ed. (revised), and AD was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria. Incident rates and relative risk (95% CI) express the association of a risk factor for dementia. Results: Incident rates for dementia and AD were similar across studies. The incidence of AD increased with age. At 90 years of age and older the incidence was 63.5 (95% CI, 49.7 to 81.0) per 1,000 person-years. Female gender, current smoking (more strongly in men), and low levels of education (more strongly in women) increased the risk of AD significantly. A history of head trauma with unconsciousness and family history of dementia did not increase risk significantly. Conclusion: Contrary to previous reports, head trauma was not a risk factor for AD, and smoking did not protect against AD. The association of family history with the risk of AD is weaker than previously estimated on the basis of cross-sectional studies. Female gender may modify the risk of AD, whether it be via biological or behavioral factors.

Incidence and outcome of mild cognitive impairment in a population-based prospective cohort

Objective: To estimate the age-specific incidence rate of mild cognitive impairment (MCI) according to sex and educational level and to explore the course of MCI, particularly its progression to AD, in a population-based cohort. Methods: A community-based cohort of nondemented elderly people (Personnes Agées QUID [PAQUID]) was followed longitudinally for 5 years. MCI was defined as memory complaints with objective memory impairment, without dementia, impairment of general cognitive functioning, or disability in activities of daily living. Incidence rates were calculated using the person–years method. A descriptive analysis at the different follow-up times was performed to study the course of MCI. Results: At baseline, there were 58 prevalent cases of MCI (2.8% of the sample). During a 5-year follow-up, 40 incident cases of MCI occurred in 1,265 subjects at risk. The global incidence rate of MCI was 9.9/1,000 person–years. MCI was a good predictor of AD with an annual conversion rate of 8.3% and a good specificity, but it was very unstable over time: Within 2 to 3 years, only 6% of the subjects continued to have MCI, whereas >40% reverted to normal. Conclusions: Conventionally defined MCI has reasonable predictive value and specificity for AD. However, MCI was very unstable across time in this study. Furthermore, the definition of MCI seems to be too restrictive and should probably be extended to other categories of individuals also at high risk of developing AD.

Dietary patterns and risk of dementia The Three-City cohort study

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 ε4 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 ε4 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 ε4 noncarriers. GLOSSARY: AD = Alzheimer disease; BMI = body mass index; CCPPRB = Consultative Committee for the Protection of Persons participating in Biomedical Research; DHA = docosahexaenoic acid; EI = energy intake; HR = hazard ratio; PUFA = polyunsaturated fatty acids.

Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies

Objective: To study the difference in risk for dementing diseases between men and women. Background: Previous studies suggest women have a higher risk for dementia than men. However, these studies include small sample sizes, particularly in the older age groups, when the incidence of dementia is highest. Methods: Pooled analysis of four population-based prospective cohort studies was performed. The sample included persons 65 years and older, 528 incident cases of dementia, and 28,768 person-years of follow-up. Incident cases were identified in a two-stage procedure in which the total cohort was screened for cognitive impairment, and screen positives underwent detailed diagnostic assessment. Dementia and main subtypes of AD and vascular dementia were diagnosed according to internationally accepted guidelines. Sex- and age-specific incidence rates, and relative and cumulative risks for total dementia, AD, and vascular dementia were calculated using log linear analysis and Poisson regression. Results: There were significant gender differences in the incidence of AD after age 85 years. At 90 years of age, the rate was 81.7 (95% CI, 63.8 to 104.7) in women and 24.0 (95% CI, 10.3 to 55.6) in men. There were no gender differences in rates or risk for vascular dementia. The cumulative risk for 65-year-old women to develop AD at the age of 95 years was 0.22 compared with 0.09 for men. The cumulative risk for developing vascular dementia at the age of 95 years was similar for men and women (0.04). Conclusion: Compared with men, women have an increased risk for AD. There are no gender differences in risk for vascular dementia.

Fish, meat, and risk of dementia: cohort study

We obtained data from the PAQUID (Personnes Agees QUID) epidemiological study of cognitive and functional ageing (www.healthandage.net/html/min/paquid/entrance.htm). During the third wave of the study (1991-2) investigators visited 1674 people aged 68 and over without dementia and living at home in 75 parishes in southwestern France and recorded their frequency of consumption of meat and fish or seafood: daily, at least once a week (but not every day), from time to time (but not every week), never. Participants were followed up two, five, and seven years afterwards: 1416 (84.6 %) had at least one follow up visit. All the participants who had lost three points or more on the mini-mental state examination since a previous visit or were suspected of having dementia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders , third edition, revised (DSM-III-R) were visited by a neurologist to confirm the diagnosis. We …

Social and leisure activities and risk of dementia: a prospective longitudinal study

OBJECTIVE: To study the relationship between social and leisure activities and risk of subsequent dementia in older community residents.

Instrumental Activities of Daily Living as a Screening Tool for Cognitive Impairment and Dementia in Elderly Community Dwellers

To identify which Instrumental Activities of Daily Living (IADL) are related to cognitive impairment, independent of age, sex, and education; to assess the performance of an IADL score using these items in screening for cognitive impairment and dementia in elderly community dwellers.

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.

Body mass index and incidence of dementia The PAQUID study

To study the relationship between body mass index (BMI) and risk of dementia, a cohort of 3,646 individuals aged ≥65 years living at home and without cognitive disorders at baseline were followed up for 8 years (the PAQUID [Personnes Agées Quid] Study). Subjects with a BMI < 21 had an increased risk of developing dementia as compared with subjects whose BMI was between 23 and 26 (odds ratio = 1.48, 95% CI = 1.08 to 2.04). However, when individuals who developed dementia early during the follow-up were excluded from the analysis, this relationship was no longer significant. A low BMI does not in itself seem to be a risk factor for dementia.

The effect of education on cognitive performances and its implication for the constitution of the cognitive reserve.

Some studies have suggested that people with a high educational level have a lower risk of developing dementia compared to people with a low educational level. This protective effect of education has been explained by the constitution of a cognitive reserve which might delay the cognitive and functional expression of neurodegenerative illnesses. The aim of this study is, on the one hand, to evaluate the impact of education on cognitive functioning, which is thought to support the cognitive reserve capacity, and on the other, to determine the extent to which cognitive functioning is affected by other explanatory variables. The analysis was conducted on 1,022 individuals without physical or neurological disorders in the Personnes Agées Quid study. These participants were aged 66 and over and had completed a neuropsychological battery. The effect of some demographic and socioeconomic variables on cognitive performance was also analyzed. Multivariate analysis showed a significant effect of education on most neuropsychological performances, independently of the other variables, and more particularly, in the high-attention-demanding tests. A principal component analysis demonstrated that education specifically increases 2 cognitive components: controlled processes and conceptualization ability. Moreover, mental stimulation occurring after the education years, such as high-complex activity occupations, seems to increase the controlled component. All these results suggest that the effect of education on cognitive reserve may be explained by an increase in controlled processes and conceptualization abilities. These 2 cognitive components might delay the clinical expression of neurodegenerative illnesses by maintaining global cognitive efficiency. Of these 2 components, controlled processes were also influenced by high attention-demanding occupations.