In this prospective cohort study of a middle-aged population followed up for 10 years, participants with persistent metabolic syndrome had lower cognitive scores for reasoning, vocabulary, semantic fluency, and, to a lesser extent, memory, compared with participants who never had metabolic syndrome. These associations remained after adjustment for demographic variables, education, health behavior, and health status. No difference in cognitive function was observed between participants with nonpersistent metabolic syndrome and those who never had metabolic syndrome. Our study sheds light on the impact of SEP on these relationships: whereas education had little impact on the metabolic syndrome–cognition relationship, occupational position substantially attenuated the association.
There is increasing interest in the possible impact of vascular and metabolic disorders on dementia, and several studies have investigated this association in elderly individuals. Two cross-sectional studies showed that the presence of metabolic syndrome was associated with a higher prevalence of Alzheimer's disease (10
) and also with poorer cognitive function (4
). In four longitudinal studies, metabolic syndrome was shown to be associated with a greater cognitive decline (5
) and increased risk of all-cause and vascular dementia (8
). However, another study did not show evidence of the detrimental effect of metabolic syndrome on dementia (7
). Finally, two further studies carried out in the oldest old individuals found the opposite: metabolic syndrome was associated with better cognition (6
) and decelerated cognitive decline (9
The potential explanations for the above inconsistencies include differences in the length of follow-up, the sensitivity of cognitive tests to detect a decline, the low statistical power of several studies, and survival bias in studies involving the oldest old. Our study provides a further explanation: the measurement of the metabolic syndrome at one point in time may not capture the impact of long-term exposure to this syndrome as there is considerable within-individual variation in metabolic syndrome status over time. Our finding suggests that long-term exposure to metabolic syndrome, persistent metabolic syndrome rather than metabolic syndrome status, at a given moment is associated with poor cognitive function.
Because poor cognition in midlife has been shown to predict cognitive decline and dementia later in life, the examination of the role of risk factors before old age is important. It allows circumvention of the problems of survival bias and reverse causality that may be common in studies in the oldest age-groups. To date, very few studies have investigated the effects of metabolic syndrome on cognition in middle-age. Kalmijn et al. (14
) showed a long-term association between a cluster of seven metabolic cardiovascular risk factors measured at middle age and the risk of dementia among men in old age, but a recent cross-sectional study performed in 853 participants aged 61 years reported no association between metabolic syndrome and cognitive scores (13
). Thus, our observation of an association between persistent metabolic syndrome and cognitive function in a large middle-aged population constitutes a novel finding.
Our findings emphasize the potential importance of socioeconomic circumstances in the association between metabolic syndrome and cognitive function. By analyzing the relationship between metabolic syndrome and cognition after adjustment for a measure of early SEP, here education, or alternatively a later life measure of SEP, occupational position, our study highlights the different impact of these two measures. Education, although extensively examined in relation to cognitive outcomes, has been shown in several studies, including Whitehall II, not to be associated with metabolic syndrome (5
). The modest impact of education on the metabolic syndrome–cognition relationship observed in the present study is consistent with findings from other studies. On the other hand, occupational position was strongly related to sociodemographic factors, health behavior, and several health measures, and the relationship between metabolic syndrome and cognition was substantially attenuated after adjustment for occupational position. To our knowledge, no other study has taken into account the effects of later life measures of SEP, such as occupational position, making comparison with other studies difficult.
The discrepant effect of adjustment for education or occupational position should be interpreted in light of the fact that these measures cover different dimensions of SEP. Compared with education, reached by the individual usually in early adult life, midlife occupational position more accurately reflects SEP conditions over the adult life span. SEP is an important determinant of mortality and morbidity in many countries (23
), and its influence on health is believed to work in several ways. Poor SEP is seen to increase the biological vulnerability to diseases by acting directly on physiological processes but also through unhealthy behaviors (24
). Our report emphasizes the importance of taking into account SEP in the metabolic syndrome–cognition relationship to understand the potential impact of metabolic syndrome on cognitive aging. Adjustment for occupational position attenuated the association between persistent metabolic syndrome and cognition by between 41 and 86%. There are three possible implications of our findings. One, studies on cognitive aging that adjust for education to control the influence of socioeconomic factors are clearly not taking the socioeconomic environment of older adults fully into account. Two, given the size of the attenuation of the association, it is possible that the observed association between metabolic syndrome and cognition is simply the result of confounding by socioeconomic factors. This would imply that the observed association is the result of the impact of adult SEP on both metabolic syndrome and cognitive function, and there is no true causal effect of metabolic syndrome on cognition. Three, given the association between the components of the metabolic syndrome and cognition evident in the literature, it is possible that “persistent” metabolic syndrome is a risk factor for cognitive function. The attenuation observed in our analysis could therefore simply be due to occupational position being a good proxy for factors mediating the association between metabolic syndrome and cognition. Further research is needed to delineate the precise mechanisms underlying the link between metabolic syndrome and cognition.
Our report has several limitations. First, the participants of the Whitehall II study are mainly office-based civil servants, not fully representative of the British population, and analysis was restricted to “white” participants, which may limit the generalizability of our findings. Second, we showed that participants with lower cognitive performances or with metabolic syndrome were less likely to be included in our analyses. This potential selection bias would probably lead to underestimation of the relationship between metabolic syndrome and cognition. Finally, the use of a single assessment of cognitive function is a limitation as it does not allow conclusions to be drawn on the direction of causality between metabolic syndrome and cognitive decline.
In summary, this seems to be the first study to explore the association between cumulative exposure to the metabolic syndrome over a 10-year follow-up and cognitive functioning in late midlife. Our results suggest that rather than metabolic syndrome status at a given moment per se, the persistence of the syndrome is the factor that has adverse effects on later cognitive performances during adult life. Furthermore, our report showed the different effects of SEP measures on the relationship, depending on whether education or occupational position was considered; education had little impact, but occupational position had a greater impact. These results highlight the importance of the type of socioeconomic variable in identifying and targeting risk factors for cognitive aging.