Yebenes_article_EU Neurology 10/03/2010 10:21 Page 125
International Health
Environmental and Genetic Risk Factors for Alzheimer’s Disease in Spain
Israel Ampuero,
1,2
Félix Bermejo-Pareja,
2,3
Guillermo García Ribas
2,4
and Justo García de Yébenes
1,2,4
1. Molecular Diagnostics Laboratory, Tissue Bank for Neurological Research, Madrid; 2. Centre for Biomedical Research in
Neurodegenerative Diseases Network (CIBERNED), Institute of Health Carlos III; 3. Department of Neurology, University Hospital ‘12 de Octubre’;
4. Department of Neurology, University Hospital ‘Ramón y Cajal’
Abstract
Alzheimer’s disease is a complex neurodegenerative disorder of unknown aetiology, and an important number of cases are sporadic. To date, only
some of the genetic and environmental risk factors for Alzheimer’s disease have been identified. It is very important to understand the role
of environmental and genetic risk factors in Alzheimer’s disease in order to develop therapeutic strategies. For sporadic cases of Alzheimer’s
disease, many environmental and genetic risk factor modifiers have been described, but – with a few exceptions – most of them remain
controversial. In this article we review some studies of these risk factors in a Spanish population to identify a few directives for future studies.
Keywords
Alzheimer’s disease, environmental risk factor, genetic risk factor, age, education, cardiovascular risk factors, Spanish population
Disclosure: The authors have no conflicts of interest to declare.
Received: 7 January 2009 Accepted: 14 April 2009
Correspondence: Justo García de Yébenes, Servicio de Neurología, Hospital Universitario ‘Ramón y Cajal’, Carretera de Colmenar, km 9,1, Madrid 28034, Spain.
E: jgyebenes@yahoo.com
Alzheimer’s disease (AD) is a neurodegenerative disorder of Zaragoza and Pamplona,
5
Gerona,
6
the Basque Country,
9
Central
unknown aetiology, with the exception of a small percentage of Spain
7
and Leganes.
8
A brief summary of these studies is presented
cases related to mutations of the amyloid precursor protein (APP), in Table 2.
presenilins and other, as yet unknown, genes.
1,2
For sporadic cases of
AD, many environmental and genetic risk factor modifiers have been Age
described, but – with a few exceptions – most of them remain As in other studies around the world, epidemiological investigations
controversial. Most of these studies are observational in different performed in Spain have confirmed the increased risk associated
populations,
3
since case–control studies, which were very popular in with age in AD. This effect is almost exponential until >90 years of
the 1980s, showed bias.
4
Unconfirmed associations of environmental age, when it appears to reduce its impact.
10,15
risk factors or genetic traits with AD could be due to several factors,
such as inclusion of a percentage of patients with erroneous Education
diagnoses (a significant number of patients with clinical diagnoses of Illiteracy and poor schooling are associated with an increased risk of
AD are found to have mixed pathologies or other diseases at post dementia and AD in most studies in which the population has a mixed
mortem examination), inadequate size or special characteristics of (assorted) educational background.
3,10,13,14
The same findings are
the sample or excessively permissive statistical evaluation. reported in Spain.
5–9
However, most of these studies did not
differentiate between education and its co-variates, such as low
Spain has several characteristics that make it adequate for such socioeconomic status, possible pre-natal and developmental nutrition,
studies. Although in the past Spain has seen significant waves of lack of social and familial intellectual stimulation and others.
16–19
immigration, in the last millennium immigration has not occurred at
high enough levels to influence the genetic background of its Gender
population. Spain also has high-quality standards of universally free The majority of population-based studies performed in Spain have
healthcare. Several studies have been published as meta-analyses
5
shown an increased risk of AD in females.
6,8,9
In the Neurological
or local population studies.
6–9
In this article we review some of these Disorders in Central Spain (NEDICES) study this relationship was not
and other, more recent, studies. found.
7
This has been proposed as the basis for a neuro-protective
role of oestrogens, even prompting the use of these compounds in
Environmental Risk Modifiers clinical trials, but a very confusing factor is the fact that senile
A summary of the available data is shown in Table 1, which females (around the turn of the millennium this was defined as >65
presents results about environmental modifiers of the risk of AD in years of age) had a much lower level of education than
other countries as well as in Spain.
3,5–14
We shall review briefly the contemporary males. Studies such as the Ashkelon study where
most important results obtained in the studies performed in Spain. gender was corrected for by education have not shown a difference
The most important studies reviewed in this work are those in in the risk at different ages. As a meta-analysis pointed out,
10
there
© TOUCH BRIEFINGS 2009 125
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