Review
Diabetes and other vascular risk factors for dementia: Which factor matters most? A systematic review

https://doi.org/10.1016/j.ejphar.2008.02.049Get rights and content

Abstract

Vascular risk factors, such as type 2 diabetes, hypertension, obesity and dyslipidaemia often co-occur. Each of these factors has been associated with an increased risk of dementia, but it is uncertain which factor imposes the greatest risk. Moreover, the effect of age at time of exposure may differ across factors. This paper systematically reviews the evidence for the association of each of these risk factors with dementia. Longitudinal population-based studies that assessed the incidence of dementia in relation to diabetes (n = 14), hypertension (n = 13), dyslipidaemia (n = 8) or obesity (n = 9) were included. All four risk factors were indeed associated with an increased risk of dementia, but the results of studies on diabetes and obesity were most consistent. The magnitude of the effects was comparable across the risk factors, with odds ratios for ‘any dementia’ around 1.5. For hypertension, obesity and dyslipidaemia age appeared to modulate the association: the risk of dementia was generally largest in studies that measured the risk factor in midlife (compared to late life) and had a long follow-up time. At midlife, the population attributable risk of dementia was highest for hypertension, up to 30% of cases of late life dementia. Later in life diabetes appears to convey the highest risk of dementia. This review shows that vascular risk factors should be regarded as a major target for preventive measures, but that timing of such measures appears to be critical.

Introduction

Type 2 diabetes mellitus is a well-known risk factor for cardiovascular disease. Diabetes is also associated with cognitive decline and an increased risk of dementia in the elderly (Awad et al., 2004, Biessels et al., 2006). Type 2 diabetes develops in the context of insulin resistance and is often accompanied by other vascular risk factors such as hypertension, dyslipidaemia and obesity. The co-occurrence of these risk factors is generally referred to as ‘the metabolic syndrome’ (Reaven, 1988). There is evidence that each of the individual risk factors of the metabolic syndrome is associated with cognitive decline and dementia. As these risk factors are potential targets for therapeutic intervention it is important to examine the contribution of each of these risk factors to the risk of dementia. In this context it is also important to assess whether the effects of the individual risk factors are independent from each other.

Several studies suggest that the association between dementia and vascular risk factors varies with age. High blood pressure in middle-age, for example, is a clear risk factor for dementia in old age (Whitmer et al., 2005b). In old age, however, low blood pressure may be associated with an increased risk of dementia (Verghese et al., 2003).

In this paper we systematically reviewed studies on the risk of dementia associated with type 2 diabetes mellitus, hypertension, obesity and dyslipidaemia. We aimed to quantify and compare the association with dementia for these four risk factors, and to address the potential modifying role of age at the time of exposure.

Section snippets

Identification of studies

This systematic review aimed to include all published studies that provide an estimate of the incidence of dementia associated with type 2 diabetes mellitus or impaired glucose metabolism, hypertension, dyslipidaemia or obesity and that met the following inclusion criteria: (1) the study population was recruited at the population level; (2) the study had a longitudinal design; (3) the results were adjusted for the basic confounders age, sex as well as educational level; and (4) adjusted odds

Type 2 diabetes mellitus/impaired glucose metabolism

We included 14 studies that compared the risk of one or more types of dementia in patients with type 2 diabetes mellitus to non-diabetic persons (Table 1a). Diabetes was most commonly identified by fasting or random blood glucose levels combined with an oral glucose tolerance test. Six studies based the diagnosis of diabetes on medical history or medication use only, or did not assess blood glucose concentration in all participants (Yoshitake et al., 1995, MacKnight et al., 2002, Arvanitakis et

Discussion

This paper systematically reviewed the evidence for the association of type 2 diabetes mellitus, hypertension, dyslipidaemia and obesity with dementia. All four risk factors were associated with an increased risk of dementia, but the results of studies on diabetes and obesity were most consistent. The magnitude of the effects was comparable across the risk factors, with odds ratios for ‘any dementia’ around 1.5. For hypertension, obesity and dyslipidaemia age appeared to modulate the

Acknowledgments

This study was supported by grant 2003.01.004 from the Dutch Diabetes Research Foundation and grant 907-00-140 from the Netherlands Organisation of Scientific Research (ZonMw).

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