respect is that risk factors may change over time.17 The impact of environmental factors, such as smoking, diet, physical activity, and vascular disease, may change over time both within an individual and across birth cohorts. Risk factors such as blood pressure change with ageing. Furthermore, the disease, once it has started, may in turn influence the risk factor. For example, the diet of a demented individual may change, when the person forgets to eat his or her meals on a regular basis. Therefore, the relationship between a risk factor and disease may differ depending on the age the risk factor is measured relative to the outcome. The age related changes in risk factors make causal inferences as to the development of dementia difficult. Studies of blood pressure in relation to dementia form a good example of how the relationship between risk factors and dementia may be influenced by the moment when the risk factor is measured.12 18 There have been conflicting reports, with some studies suggesting that low blood pressure is associated with dementia, whereas others report the opposite, namely that high blood pressure is a risk factor for dementia. Important in this respect is that blood pressure has been shown to decrease as a consequence of dementia. It is therefore important that this risk factor (blood pressure) is measured before the disease process starts. However, by the age most ageing studies begin—that is, 65 years old— individuals have already experienced the initial neuropathologic changes that eventually lead to dementia. As soon as the disease process has started (this may be years, possibly decades, before the dementia becomes overt), it is too late to measure risk factors, as the disease may have started to influence the risk factor itself. Therefore, it seems as though risk factors should be measured as early as possible. By now, there are several studies with more than 20 years of follow up.19–21 These studies, measuring midlife risk factors to predict late life dementia, have shed some light on the perceived incongruence in earlier studies. In fact, the conflicting reports with respect to the effect of blood pressure on the development of dementia may be entirely explained by the moment of measuring the risk factor. Cross sectional studies suggest that low blood pressure is associated with dementia. Studies measuring blood pressure during midlife have consistently shown that midlife hypertension is associated with late life dementia. CONCLUSIONS c A review of the epidemiology of dementia indeed reveals that the public health problem of dementia has reached epidemic proportions. It affects about 6% of individuals over 65 years of age and has a strong age dependent prevalence. Although dementia is quite rare before 65, it certainly does occur, and dementia should always be in the differential diagnosis when evaluating patients with cognitive complaints, irrespective of age. AD is the most prevalent form of dementia, responsible for about 60–70% of cases. VaD is the second most important cause, accounting for 15–20%. c In the age group 65–69 years, there are more than two new cases per 1000 persons, every year. This number increases almost exponentially with increasing age, until over the age of 90 years, out of 1000 persons, 70 new cases of dementia can be expected every year. c Risk factors for dementia include age and the female sex, especially at high age. Moreover, genetic factors (APOE e4) and vascular risk factors play an important role. c Methodological problems associated with studies of dementia include (1) complex diagnostic procedure, (2) insidious onset, and (3) the relationship between the clinical syndrome and the disease as defined by the underlying neuropathology. Finally, it is argued that longitudinal studies are to be preferred over cross sectional studies. Authors’ affiliations .................. W M van der Flier, P Scheltens, Department of Neurology and Alzheimer Center, Vrije Universiteit Medical Center, Amsterdam, the Netherlands REFERENCES 1 Berr C, Wancata J, Ritchie K. Prevalence of dementia in the elderly in Europe. Eur Neuropsychopharmacol 2005;15:463–71. 2 Rothman K, Greenland S. Modern epidemiology, 2nd ed.