Alzheimer’s disease (AD) is a neurodegenerative disorder of unknown aetiology, with the exception of a small percentage of cases related to mutations of the amyloid precursor protein (APP), presenilins and other, as yet unknown, genes.^1,2 For sporadic cases of AD, many environmental and genetic risk factor modifiers have been described, but – with a few exceptions – most of them remain controversial. Most of these studies are observational in different populations,³ since case–control studies, which were very popular in the 1980s, showed bias.⁴ Unconfirmed associations of environmental risk factors or genetic traits with AD could be due to several factors, such as inclusion of a percentage of patients with erroneous diagnoses (a significant number of patients with clinical diagnoses of AD are found to have mixed pathologies or other diseases at post mortem examination), inadequate size or special characteristics of the sample or excessively permissive statistical evaluation.

Spain has several characteristics that make it adequate for such studies. Although in the past Spain has seen significant waves of immigration, in the last millennium immigration has not occurred at high enough levels to influence the genetic background of its population. Spain also has high-quality standards of universally free healthcare. Several studies have been published as meta-analyses⁵ or local population studies.^6–9 In this article we review some of these and other, more recent, studies.

Environmental Risk Modifiers
A summary of the available data is shown in Table 1, which presents results about environmental modifiers of the risk of AD in other countries as well as in Spain.^{3,5–14} We shall review briefly the most important results obtained in the studies performed in Spain. The most important studies reviewed in this work are those in Zaragoza and Pamplona,⁵ Gerona,⁶ the Basque Country,⁹ Central Spain7 and Leganes.⁸ A brief summary of these studies is presented in Table 2.

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