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Neurodegenerative Diseases Alzheimer’s Disease
Potentially Modifiable Risk Factors in the Development of Alzheimer’s Disease
Simon Forstmeier
1
and Andreas Maercker
2
1. Senior Researcher; 2. Professor, Psychopathology and Clinical Intervention, University of Zurich
Abstract
This article summarises empirical findings on major potentially modifiable risk factors in the development of Alzheimer’s disease (AD),
drawing on data from longitudinal epidemiological studies on the incidence of AD or any-cause dementia. Risk factors investigated to date
include cognitive ability, motivational ability, emotional health, physical activity, social activity and social network, vascular risk factors and
nutrition. The authors find most empirical support for two main clusters of risk factors that also represent potential targets for prevention.
First, an active and stimulating lifestyle including cognitive, social, and physical activities reduces the risk of AD. Second, the absence of
vascular risk factors such as diabetes, hypertension, hypercholesterol and obesity reduces the risk of AD. More prevention trials are
warranted to investigate the preventative effects of an active and stimulating lifestyle on the one hand, and vascular health on the other,
in delaying the onset of AD or slowing its progression.
Keywords
Alzheimer’s disease, risk factors, motivational reserve, cognitive reserve, social network, vascular risk factors, nutrition, prevention
Disclosure: The authors have no conflicts of interest to declare.
Received: 16 January 2009 Accepted: 26 August 2009
Correspondence: Simon Forstmeier, Department of Psychology, Division of Psychopathology and Clinical Intervention, University of Zurich, Binzmuehlestr. 14/17, 8050 Zurich,
Switzerland. E: s.forstmeier@psychologie.uzh.ch
As the number of people over 65 years of age continues to rise papers presented in Table 1 and to more general overview articles.
3–6
worldwide, preserving the cognitive health of older adults has Note that in epidemiological studies, AD is usually diagnosed on the
become a major societal challenge. The global prevalence of basis of clinical features rather than neuropathological evidence.
Alzheimer’s disease (AD) was estimated at 26.55 million in 2006 and
is expected to quadruple over the next 40 years.
1
However, research Cognitive Ability
on successful ageing challenges the popular notion that ageing Dozens of longitudinal studies suggest that lower pre-morbid
invariably involves a decline in cognitive functioning and quality of life, cognitive ability increases the risk of AD and dementia. Four different
and has identified factors that can increase individuals’ ‘health span’ measures have been used to estimate pre-morbid cognitive ability:
as they enter later life.
2
If onset or progression of AD could be delayed educational level, pre-morbid performance in cognitive tests, amount
by only one year, there would be 9.2 million fewer cases of the of cognitive activity and occupational attainment.
disease in 2050.
1
The goal of current research on AD and other
dementias is thus to identify both biological and psychological factors Educational Level
that may help people to maintain or enhance their cognitive health in Educational level is usually assessed as a two- or three-category
older age and to prevent or postpone the development of dementia. variable (e.g. <8 years, ≥8 years). We identified 15 studies, 11 of which
found a significantly increased risk of AD or any-cause dementia in
The most well-established risk factors for AD and other dementias are less educated individuals.
7,8
A recent meta-analysis calculated a
old age, genetic susceptibility, familial aggregation and female sex. relative risk of low versus high educational level of 1.8 (95%
However, modifiable risk factors are more important for the confidence interval [CI] 1.4–2.3) for AD and 1.6 (95% CI: 1.3–2.0) for all
development of prevention strategies. In this article, we summarise dementias.
9
Although there is strong evidence that education
empirical findings on the major modifiable risk factors of AD. We base to a low standard is a risk factor for AD, the mechanisms underlying
our overview and conclusions on several recent review papers as well this association are not yet clear. Most authors explain the protective
as on a systematic review of our own, which aimed to include all effect of education in terms of cognitive reserve:
10
education is
published studies providing an estimate of the incidence of AD or thought to stimulate underlying brain networks and make them more
dementia (‘relative risk’) associated with the risk factor examined (see efficient and flexible. In individuals with higher cognitive reserve, the
Table 1). We included only longitudinal studies whose results were underlying brain pathology may not become clinically manifest until
adjusted at least for age, sex, and education. Due to space later because their brain networks are more capable or because
restrictions, we cite only example studies and summarise the findings different, intact networks are used to replace or bypass the disrupted
of our review in Table 1. The interested reader is referred to the review networks. Other explanations of the association between education
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