Epidemiology and prevalence of Alzheimer's disease and risk factors

An estimation of the evolving prevalence of dementia remains difficult for two main reasons. There is the problem of the underdiagnosis of dementia in Europe, particularly in France. It is also difficult in a cross-sectional study to document a decline in cognitive function and an impairment in the ability to be involved in daily living activities, particularly in people with a very low level of education, living alone or confined to an institution. Therefore, a longitudinal study is the most accurate type of study to estimate the prevalence of dementia. The best estimation of the prevalence of dementia is given by a meta-analysis of the European longitudinal studies on dementia published in 2000.1 In these studies, the estimation of the prevalence of dementia reaches 6.3% after the age of 65 years. The most frequent cause is Alzheimer's disease (AD) (4.3%), followed by mixed vascular dementia (1.5%).2 The risk of dementia increases with age and is higher in women. This last observation can be explained by the difference in survival rates between men and women with dementia and AD. However, the incidence value of dementia represents the real risk of the disease in the population. The risk of dementia and AD is higher in women than in men, but the risk of vascular dementia is more significant in men (Table 1).3 This difference between the sexes is not observed in the USA or Canada. It could reflect a difference in life expectancy between men and women, which is much higher in Europe than in the USA or Canada. Another more qualitative explanation is related to the difference in the strategies for coping with stress between women in the USA and in France, and also the difference in the social support networks between the USA, Canada and Europe. Indeed, the French Paquid study4 and the four-nations study, which compared the USA, Japan, Germany and France, show that the strategies for coping are completely different in these four countries. In 1999, the prevalence of AD for those over 64 years of age in France was estimated to be 434 700 cases (106 500 men and 328 200 women). Therefore, AD in France can be considered as a disease of very old women, often living alone. Demographic projections for 2010 indicate that there will be a significant increase in the number of people aged between 80 and 89 years, particularly between 80 and 84 years, with an increase of 93.7% for men and 89% for women. The prevalence of AD in the population aged over 65 years is projected to increase to 497 600 cases (127 800 men and 369 800 women). This figure is very conservative because of the progress being made in the management of dementia, thus increasing the survival rates of patients with this condition. Therefore, developing preventive strategies becomes crucial. It has been shown that delaying the onset of dementia by 1 year would decrease the prevalence of AD and dementia by 25%. A risk factor can be considered as a good candidate for the protection against dementia if it meets the following five standard epidemiological criteria: (i) there is the presence of a statistical association between exposure to the factor and a lower risk of dementia, without bias; (ii) the association between exposure to the factor and a lower risk of dementia is replicated by at least one other study; (iii) the exposure to the factor occurred clearly before the onset of the disease that caused dementia; (iv) the association between exposure to the factor and a lower risk of dementia must be plausible and coherent with what is known of the natural history and biology of the disease; and (v) there is an experimental confirmation of the association between exposure to the factor and a lower risk of dementia. The only randomized study that has shown a decrease in the risk of AD and dementia is the Syst-Eur study,5 but results need to be confirmed by at least one other trial. Potential risk factors can be classified into three categories. The A category includes potential individual risk factors for which an experimental confirmation is possible: nitrendipine, estrogens, anti-inflammatory drugs, and statines, for example. Three studies have shown an association between exposure to statins and the risk of dementia and AD.6-8 Unfortunately, results of the first randomized placebo-controlled trial of simvastatin (which protects the heart by lowering cholesterol), conducted in 20 536 high-risk individuals, did not confirm that simvastatin could protect people against dementia.9 The risk of dementia was equivalent in both treated and control groups (0.3%) and the risk of cognitive deficit also remained the same 5 years after the beginning of the trial (Table 2). The B category of risk factors includes those individual ones for which an experimental confirmation is not possible. Therefore, it is crucial to be able to explain the physiopathology of the mechanism. For example, some studies have shown that diabetes increases the risk of AD10-13 whereas others found no association.14, 15 Results of the French Paquid longitudinal study with an 8-year follow-up show no relationship between treated diabetes and the risk of dementia or AD (Table 3). Since methodological differences could produce such controversial results, we conducted a study strictly equivalent to the Rotterdam study,10, 12 with the same data for exposure on diabetes, using identical diagnosis criteria for dementia, and identical statistical analysis conducted by a single person. We compared 2721 persons from the Paquid cohort and 3913 persons from the Rotterdam study cohort. After 2.5 years of follow-up, 76 patients in the Paquid cohort and 54 patients in the Rotterdam cohort were diagnosed with AD. Statistical analysis confirmed a strong association between diabetes and AD in the Rotterdam population but no such association in the Paquid population. Both results could be valuable because of different risk factors in both regions. Indeed, AD could have a multifactorial origin and thus various solutions. These observations are a reminder that we should be careful when extrapolating results from one geographic region to another and that development of epidemiological studies to understand these differences should be encouraged. The C category of risk factors includes possible collective risk factors for which an experimental confirmation may or may not be possible, such as social activities. A comparative study of the prevalence of dementia has been conducted on the elderly population (over 75 years of age) in two Sicilian communities with different psychosocial backgrounds:16 Troina and Santa Agata Militello. Surprisingly, the prevalence of dementia is significantly higher in the population with a higher level of education, Santa Agata Militello (28.4%), compared with Troina (21.9%). However, social collective activities, especially religious manifestations, are of particular importance in Troina. If this association between dementia and social collective activities is confirmed, a preventive strategy could be developed. In the same way, the Paquid study shows that some leisure activities could be associated with a lower risk of dementia and AD (P = 0.05), particularly odd jobs (relative risk = 0.48), gardening (relative risk = 0.53) and traveling (relative risk = 0.48). The habits of a cohort of subjects older than 75 years of age in 1988 were compared to an equivalent cohort in 1998. The number of social activities increased during this period of 10 years from four to five activities, and the proportion of subjects involved in such activities as odd jobs, gardening and traveling also increased. The conclusion is that old people in France are more active now compared to people of equivalent age 10 years ago. Thus, we can be optimistic about the reduced risk of dementia because social activities have increased.

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