The association of metabolic syndrome and cognitive impairment in Jidong of China: a cross-sectional study

At present, population aging has become a serious problem in many parts of the world. A large amount of data have indicated that the proportion of older people will increase to 31% in 2050, and China will have the greatest number of older people worldwide [1]. More seriously, related diseases such as cardiovascular disease and cognitive dysfunction related to aging also significantly reduce quality of life and increase the medical burden among the elderly [2].

Cognitive impairment is a well-known disease characterized by a reduction in cognitive function beyond what was expected from normal aging. Cognitive impairment involves functions in many areas of the brain, including areas associated with memory, thinking, orientation, comprehension, calculation, learning capacity, language, judgment and daily activities [3]. Epidemiological studies have indicated that the prevalence of mild cognitive impairment (MCI) varies from 2.8–17.5% in Europe and North America and 5.4–25.0% in different parts of China [4].

Some clinical and epidemiological studies have suggested that metabolic syndrome (Mets) plays an important role in the progression of cognitive impairment [5, 6]. Mets is a combination of cardiovascular risk factors (abdominal obesity, dyslipidemia, hyperglycemia, and hypertension) [7]. Mets is prevalent among adults worldwide. For example, the prevalence of Mets among urban adults from 33 communities in China was 27.4% [8], and the age-adjusted prevalence of Mets was 23% in the US general population and 30.52% in South Korea [9, 10].

Over the last few years, extensive research and multiple reviews have suggested that there is a link between Mets and cognitive impairment [11]. In the Sacramento Area Latino Study of Aging Study, it was reported that Mets contributes to cognitive decline, and the composite measure of Mets is associated with higher odds than individual components [12]. A recent study using a rat model of Mets found that high fructose intake resulted in disrupted insulin signaling in the brain [13]. However, previous studies reported that there was no association between Mets and cognitive impairment among older US adults [14]. In addition, a previous longitudinal study showed that metabolic syndrome was a protective factor for cognitive function decline [12, 15, 16]. The inconsistent results may be due to differences in age, education and other confounders.

Therefore, the primary aim of our study was to explore whether Mets was associated with the risk of cognitive impairment.

Table 1 summarizes the demographic data of 5854 participants. There were 2154 (36.80%) participants with Mets and 3700 (63.20%) participants without Mets. Of the 2154 participants with Mets, 1556 (72.24%) had hypertriglyceridemia, 565 (26.23%) had low HDL-C, 1686 (78.27%) had high blood pressure or were diagnosed with hypertension, and 1848 (85.79%) had high FPG or were diagnosed with hyperglycemia. The age mean ± standard deviation of the people with Mets was 43.98 ± 13.58. The current study showed that older married men with smoking and alcohol abuse habits were more likely to have Mets than those without these habits (P < 0.05). The participants who were better educated had a lower prevalence of Mets (P < 0.05).

Comparisons of MMSE scores between individuals with Mets and its four components are illustrated in Fig. 1. The MMSE scores mean ± standard deviation (28.35 ± 2.10) of participants with Mets was significantly lower than that participants without Mets (28.93 ± 1.57). People with normal WC, TGs, BP and FPG had higher MMSE scores than those with elevated WC, TGs, BP, FPG, people with normal HDL-C had lower MMSE scores than that with reduced HDL-C. All differences were statistically significant (P < 0.05). (The concepts of normal and elevated or reduced are consistent with the diagnostic criteria of Mets.

We further investigated the risk of cognitive impairment and Mets in different age groups (60 years) in Fig. 2. Participants with Mets had 2.41-fold odds of having cognitive impairment in the crude model (OR 2.41, 95% CI: 2.01–2.88, P < 0.001), and the association was consistent when controlling for gender, current smoking, and current alcohol consumption (OR 1.51, 95% CI: 1.24–1.83, P < 0.001). After the stratified analysis, the association between Mets and cognitive impairment remained significant. In the group aged < 60 years, the unadjusted and adjusted odds ratios (ORs) and 95% CIs were 1.812 (1.39, 2.36) and 1.374 (1.04, 1.82), respectively. In the other group (age ≥ 60 years), the unadjusted and adjusted ORs and 95% CIs were 1.45 (1.10, 1.91) and 1.40 (1.05, 1.86), respectively.

Figure 3 provides information on Mets, each of the 5 Mets components and the odds of cognitive impairment. Abdominal obesity, elevated triglyceride, elevated blood pressure, and elevated blood glucose were found to be significantly associated with cognitive impairment in Model 1 (all P < 0.001; Fig. 3), but this association was not seen for low high-density lipoprotein.

In Model 2, abdominal obesity had an OR of 1.48 (95% CI: 1.20–1.83, P < 0.001), elevated blood pressure had an OR of 1.46 (95% CI: 1.19–1.78, P < 0.001), and elevated blood glucose had an OR of 1.32 (95% CI: 1.06–1.66, P = 0.014). However, elevated triglyceride and reduced high-density lipoprotein were not associated with cognitive impairment (all P > 0.05, Fig. 3).

In Model 3, abdominal obesity and elevated blood pressure both had statistically significant results (OR 1.36, 95% CI: 1.09–1.70, P = 0.007; OR 1.32, 95% CI 1.07–1.63, P = 0.010). However, elevated triglyceride, reduced high-density lipoprotein and elevated blood glucose were not significantly associated with cognitive impairment (all P > 0.05, Fig. 3).

The number of Mets components was related to cognitive impairment. Compared to the reference group with 0 components, the adjusted ORs and 95% CI for subjects in the groups with 3 and 4/5 Mets components were 1.86 (1.22–2.83) and 1.76 (1.15–2.67), respectively. However, similar results were not found in the group with 1 and 2 Mets components (P > 0.05; Fig. 4).

In this community-based cross-sectional study, we found that the participants with Mets had lower MMSE scores. In addition, our results still showed a correlation between Mets and cognitive impairment after stratification by age. In this study, we observed that abdominal obesity and hypertension were independent risk factors for cognitive impairment. We also found that higher levels of education were associated with better cognitive functioning and that older age and married status were associated with worse cognitive impairment. Furthermore, we explored the relationship between Mets and cognitive impairment, and the data suggested that the strongest risk was associated with the presence of three Mets components.

According to the present study, the correlation between Mets and cognitive function is still unclear, and the conclusions are not completely consistent. Previous studies have shown that hypertension and hyperglycemia may be linked to cognitive function [23]. Age and abdominal obesity were significant risk factors for cognitive decline [16]. Studies have failed to show any association between Mets and cognitive impairment [14, 24]; however, most studies have shown that participants with metabolic syndrome are associated with increased odds of cognitive impairment [12, 15, 19, 23, 25],which is consistent with our results. Although most studies have shown that Mets and its components play roles in cognitive decline, other studies have suggested that late-life Mets has a protective effect on cognitive function [16] .

Our findings provide evidence that with the presence of abdominal obesity predicts a higher risk of cognitive impairment. The significant association was still present even after multivariable adjustments. Then, the effects of overweight on brain function may be achieved through several mechanisms. First, abdominal obesity had a stronger association with visceral adiposity than body mass index (BMI) [26] . The accumulation of visceral fat leads to metabolic disorders. Adipocytes absorb glucose, damage insulin receptor basal protein insulin signal reception, and induce insulin resistance, and insulin resistance has been defined as a potential modifiable risk factor for Alzheimer’s disease (AD) [27, 28] .Second, overweight reduces serum adiponectin (APN) concentration. A lack of APN may lead to loss of neurons and synapses in the brain, increased brain Aβ-42 levels, deposition of amyloid-β protein, and increased microglia and astroglia, leading to cognitive impairment [29‐31] .

The current findings were consistent with previous work that demonstrated a relationship between chronic hypertension and reduced cognition. The effects of hypertension on cognitive function were mainly achieved through the following aspects.

On the one hand, hypertension leads to arterial smooth muscle hyperplasia, vascular remodeling, and the formation of atherosclerosis, which may promote reactive oxygen species production and inflammation in cerebral blood vessels. Oxidative stress and the inflammatory response are important mechanisms of cognitive impairment. On the other hand, hypertension destroys the mechanism of cerebral blood flow regulation, which compromises the clearance of brain metabolites, such as amyloid-β and tau, favoring their accumulation. The accumulation of amyloid-β and tau are also important mechanisms of cognitive impairment.

Previous studies have reported that type 2 diabetes mellitus (T2DM) is a risk factor for AD, and an important mechanism may be changes in brain insulin levels [32, 33]. However, a difference between hyperglycemia and cognitive impairment was not found in our study. The percentage of participants with normal blood glucose levels was 61.02%, which may partially explain why we did not observe a significant association between blood glucose and cognitive impairment. However, as shown in Fig. 2, there was a significant increase (OR = 1.199) in the risk of cognitive impairment in people with hyperglycemia.

In this community-based cross-sectional study, Mets was associated with the risk of cognitive impairment, and the difference was still significant in age subgroups. Our study supported abdominal obesity and hypertension as independent risk factors for cognitive impairment. Mets was associated with cognitive impairment, and preventing Mets and its components may reduce the incidence of cognitive impairment. Prospective studies on more diverse populations and the causal role of Mets in the development of cognitive impairment are needed.