In this prospective study, we found that in older women, the metabolic syndrome is associated with an increased risk of developing cognitive impairment during a 4-year period. In addition to the overall association, for every unit increase in the number of syndrome components, there was a 23% age-adjusted increase in the risk of developing cognitive impairment. These findings support the hypothesis that the metabolic syndrome is linked to an increased risk of developing cognitive impairment and dementia in older women. Finally, of the 5 components, hyperglycemia was the only component with a higher age-adjusted risk than the metabolic syndrome. These findings suggest that contrary to previous findings,28
it is important, from a clinical perspective to diagnose the syndrome, rather than just its individual components.
Our findings add to a growing body of literature that suggests the metabolic syndrome is associated with accelerated cognitive aging and risk of cognitive impairment among ethnically diverse groups of elderly people. In the Health, Aging, and Body Composition Study, the metabolic syndrome was associated with greater 5-year cognitive decline among elderly blacks and whites.19
Elderly Latinos enrolled in the Sacramento Area Latino Study of Aging who had the metabolic syndrome also had greater cognitive decline compared with those without the metabolic syndrome.18
As part of the Honolulu-Asia Aging Study, a composite score of 7 cardiovascular risk factors was associated with increased risk of vascular dementia in older Japanese-American men.29
The metabolic syndrome was also found to increase the risk of developing AD in a case-control and a population based sample.15, 17
Not all studies, however, have reported a significant association between the metabolic syndrome and cognitive decline.16, 17
This discrepancy may be explained by study population differences. For example, Vanhanen and colleagues found no significant association between the metabolic syndrome and risk of AD among men but found an association among women.17
Another study that focused on the oldest of the elderly (≥85 years) failed to find a link between the syndrome and cognitive decline, but this result may have been related to a survival bias.16
The mechanisms underlying an association between the metabolic syndrome and cognitive impairment are not completely understood, but there are several plausible pathways. One mechanism is increased cerebrovascular disease, on a microlevel and macrolevel, which in turn could be a risk for development of both AD and vascular mediated dementia.4, 30
Another possible mechanism is a direct effect on the pathogenesis of AD. For example, neurofibrillary tangles develop more often in hypertensive individuals without dementia,31
and in the setting of insulin resistance, β-amyloid aggregation is accelerated.15, 32
The metabolic syndrome, a condition closely linked to insulin resistance, could increase cognitive aging by alterations in β-amyloid deposition or clearance. Furthermore, increased neuronal degradation and brain atrophy have been linked to obesity, indicating connections between obesity and the pathologic manifestations of cognitive decline.8, 33
Another probable mechanism is the effect of the elevated inflammation often seen in the setting of the metabolic syndrome. Markers of inflammation have been associated with an increased risk of developing dementia and cognitive decline.19
Although we did not have the ability to measure inflammation in the MORE study, we previously have demonstrated that elderly people with both the metabolic syndrome and elevated inflammation are at an increased risk for cognitive decline.18, 19, 34
Our study has many strengths, including the large sample size and inclusion of high-functioning, community-dwelling women who agreed to participate in the trial. We performed an extensive clinical evaluation for cognitive impairment. Finally, we were able to adjust for possible confounders, such as age, educational level, depression, and race. Our study has several limitations that may limit the interpretation of the results. The rate of mild cognitive impairment and dementia occurrence in our study was not sufficient to allow us to analyze the effect of the metabolic syndrome on the risk of developing each outcome alone or one of the subtypes of dementia. Also, the rate of the metabolic syndrome present in our study population (10.2%) was considerably lower than that found in a representative sample of 60- to 69-year-old women in the United States (40–45%). 13
This finding may be due to our participants’ ability and willingness to participate in a trial or because our participants were from 25 countries, where prevalence of the syndrome may be lower. This finding could also be partially attributable to the women in our study having osteoporosis because having a low BMI is associated with increased risk for osteoporosis but it decreases the risk for the metabolic syndrome.35
We also had to substitute BMI for waist circumference which may have an effect on the overall results. Among women, the metabolic syndrome rates of those with a BMI of 30 or higher are lower than rates of those with a waist circumference of 88 cm or greater.36
Thus, we may have underestimated the presence of abdominal adiposity. Finally, our study was composed of mostly white women with osteoporosis, and we do no know if our findings apply to men or women of other ethnic groups.
In this study, we found that women with the metabolic syndrome have a greater risk of developing cognitive impairment. As the obesity and sedentary lifestyle epidemic escalates throughout the world, identification of the role of these modifiable behaviors in increasing risk for developing deleterious outcomes such as cognitive impairment is critical. Future research should assess whether identification of cognitive impairment among patients with the metabolic syndrome or more aggressive clinical control of the factors that compose the metabolic syndrome might lessen the risk of developing cognitive impairment in elderly people.