Elsevier

The Lancet Neurology

Volume 13, Issue 8, August 2014, Pages 788-794
The Lancet Neurology

Articles
Potential for primary prevention of Alzheimer's disease: an analysis of population-based data

https://doi.org/10.1016/S1474-4422(14)70136-XGet rights and content

Summary

Background

Recent estimates suggesting that over half of Alzheimer's disease burden worldwide might be attributed to potentially modifiable risk factors do not take into account risk-factor non-independence. We aimed to provide specific estimates of preventive potential by accounting for the association between risk factors.

Methods

Using relative risks from existing meta-analyses, we estimated the population-attributable risk (PAR) of Alzheimer's disease worldwide and in the USA, Europe, and the UK for seven potentially modifiable risk factors that have consistent evidence of an association with the disease (diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment). The combined PAR associated with the risk factors was calculated using data from the Health Survey for England 2006 to estimate and adjust for the association between risk factors. The potential of risk factor reduction was assessed by examining the combined effect of relative reductions of 10% and 20% per decade for each of the seven risk factors on projections for Alzheimer's disease cases to 2050.

Findings

Worldwide, the highest estimated PAR was for low educational attainment (19·1%, 95% CI 12·3–25·6). The highest estimated PAR was for physical inactivity in the USA (21·0%, 95% CI 5·8–36·6), Europe (20·3%, 5·6–35·6), and the UK (21·8%, 6·1–37·7). Assuming independence, the combined worldwide PAR for the seven risk factors was 49·4% (95% CI 25·7–68·4), which equates to 16·8 million attributable cases (95% CI 8·7–23·2 million) of 33·9 million cases. However, after adjustment for the association between the risk factors, the estimate reduced to 28·2% (95% CI 14·2–41·5), which equates to 9·6 million attributable cases (95% CI 4·8–14·1 million) of 33·9 million cases. Combined PAR estimates were about 30% for the USA, Europe, and the UK. Assuming a causal relation and intervention at the correct age for prevention, relative reductions of 10% per decade in the prevalence of each of the seven risk factors could reduce the prevalence of Alzheimer's disease in 2050 by 8·3% worldwide.

Interpretation

After accounting for non-independence between risk factors, around a third of Alzheimer's diseases cases worldwide might be attributable to potentially modifiable risk factors. Alzheimer's disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression.

Funding

National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough.

Introduction

Dementia has emerged as a major societal issue, highlighted as a priority by the G8 nations because of the worldwide ageing population and the absence of any effective treatment.1 Assuming age-specific prevalence rates remain stable, the number of cases of dementia worldwide has been projected to more than triple by 2050, relative to 2010 levels.2, 3, 4 One set of projections resulted in an estimated worldwide prevalence of Alzheimer's disease (assumed to contribute 60% of dementia cases overall)5 of 106·2 million by 2050, up from 30 million in 2010.4 In Europe, a doubling of dementia cases is predicted, from 7·7 million in 2001 to 15·9 million in 2040.3 Any development of effective treatments for the underlying pathological mechanisms of Alzheimer's disease and other dementias should slow disease progression and is likely to also reduce disease-related mortality rates, ultimately leading to increased prevalence. The exact balance between reduced incidence of dementia at any given age and reduced mortality will determine the extent to which the prevalence of dementia might increase in the population, or its increase might be mitigated in future long-lived populations.4, 6, 7

Findings from projection models suggest that primary prevention, which aims to reduce the incidence of Alzheimer's disease, is likely to delay the onset and therefore reduce the future prevalence of Alzheimer's disease and other dementias at particular ages.2 For example, one projection model4 estimated that delaying Alzheimer's disease onset by 1 year would reduce the total worldwide number of cases of Alzheimer's disease in people over 60 years old in 2050 by 11%.4 However, findings from another model7 suggested that even with delayed onset, because of population ageing, the total number of Alzheimer's disease cases might still increase, with some attenuation, if people reach older ages. Each of these scenarios has different implications for society, and present knowledge should be used to estimate what these implications might be.

Focusing on primary prevention, Barnes and Yaffe8 reviewed evidence from meta-analytic reviews of seven potentially modifiable risk factors for Alzheimer's disease that were identified as having consistent evidence for an association in a 2010 US National Institutes of Health independent state-of-the-science report: diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment.9 The results of this review of the evidence and the prevalence of the different risk factors were used to calculate attributable risks and the potential effects of prevention for each risk factor. Barnes and Yaffe then combined these single risk factor attributable risks to provide total preventable fractions—51% for worldwide and 54% for the USA—which are widely quoted. Estimates for Europe were not provided separately and might be different because of different prevalence of the risk factors in the European population.

A strength of the single risk factor approach is that it highlights the potential for individual risk factors, but a major limitation is that the estimated combined population-attributable risk (PAR) makes the untenable assumption of independence of the risk factors. For example, three of the risk factors (diabetes, hypertension, and obesity) constitute the metabolic syndrome and this syndrome is related to physical inactivity, all of which are related to educational level. Therefore, the combined PAR is likely to be a substantial overestimate.

In this study, we built on this valuable approach to provide estimates of the PAR associated with diabetes, midlife hypertension, midlife obesity, physical inactivity, smoking, depression, and low educational attainment worldwide and in the USA, UK, and Europe, and to show the potential effect of reducing these risk factors on the future prevalence of Alzheimer's disease. We also modified the combined estimate of the PAR to account for the non-independence of the risk factors to provide more plausible estimates of the proportion of Alzheimer's disease cases attributable to the seven risk factors.

Section snippets

Data

The relative risk (RR) for Alzheimer's disease for each of the seven risk factors was taken from the most recent and comprehensive meta-analyses on the associations of the seven modifiable risk factors with Alzheimer's disease. Reports published between Jan 1, 2005, and May 30, 2014, were identified by searching PubMed. Older reports were taken from a previous systematic review.8 Using the search strategy implemented previously,8 articles written in English were identified using the terms

Results

Table 2 lists estimates of the PAR of Alzheimer's disease for each of the seven risk factors, along with the number of attributable cases in 2010. Because of its high prevalence, around one in five cases of Alzheimer's disease worldwide were estimated to be to some extent attributable to low educational attainment. The number was around one in ten for the USA, Europe, and the UK. In these regions, the largest proportion of cases was attributable to physical inactivity. Smoking and depression

Discussion

The findings of this study suggest that, adjusting for non-independence of risk factors, around a third of Alzheimer's disease cases worldwide can be related to the seven potentially modifiable risk factors assessed here; adjusted combined PAR estimates were about 30% across regions (panel 2). This PAR translates to around 9·6 million of the estimated 33·9 million cases of Alzheimer's disease worldwide in 2010. Using this approach, reducing the prevalence of each of the risk factors by 10% or

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