Background
Diseases related to cognitive impairment, especially dementia, are increasingly becoming prominent health threat and bring a huge burden in older people worldwide. In 2018, there were 50 million people with dementia around the world; this number will more than triple to 152 million by 2050 [
1]. The worldwide cost of the disease was about US$ 1 trillion in 2018, and that will rise to US$ 2 trillion by 2030 [
1]. The incidence of dementia in people aged 60 years old and over is 9.9 cases per 1000 person-years in China [
2]. Based on estimation, the prevalence of dementia among individuals aged 65 years and older in China was around 5.1% [
3], and are increasing nationwide. Due to the limited treatments available for dementia at present, primary prevention is the best strategy to reduce the risk or delay the onset of dementia in late life [
4]. Mild cognitive impairment (MCI) is a key transitional state between normal aging and dementia [
5]. Individuals with MCI have a higher risk of dementia, with a rate of 10–15% per year compared with the rate for healthy controls of 1–2% per year [
6]. Therefore, identification of risk factors for MCI might be of significance to prevent dementia among older adults.
Body mass index (BMI) is considered one of the important factors affecting cognitive function. Previous studies found that unhealthy BMI was associated with cognitive function among older adults [
7]. A cross-sectional study from Malaysia concluded positive association between BMI and cognitive function, measured by Mini-Mental State Examination (MMSE) in older adults aged 60 years and above [
8]. Another cohort study of older blacks and whites (aged 53–100) conducted in the United States indicated that late-life BMI was related to change in cognitive function, with lower BMI being related to faster rates of decline in summary measures of global cognition [
9]. Some studies have found that elevated BMI was associated with lower structural integrity in a brain region connecting frontal and temporal lobes among older people, which might affect their cognitive function [
10,
11]. A retrospective cohort study found there was difference in associations between BMI, brain metabolism and connectivity in elderly females and males [
12]. However, it is also not known whether there is a gender difference in the relationship between BMI and MCI.
A recent study indicated that higher BMI was associated with relatively poorer cognitive performance in older people aged 75 to 84, while the opposite relationship was found in older people over 84 years old [
13]. Another study found that obesity was associated with a lower risk of cognitive decline among older people age 65 or older was found, but this protective association did not exist in adults aged 45 to 65 [
14]. However, a study examined increased BMI might adversely affect cognitive function in older people aged 65 and over, but not in younger cohort [
15]. The reason for the inconsistent results in different age group between BMI and cognition might be that age plays a moderating role.
Currently, the moderating role of gender and age in the relationship between BMI and MCI among Chinese older people is unclear. The percentage of people in China aged 60 years or above is 16.7% (231 million people) in 2016, which is expected to be more than 33.3% (491 million) in 2050, being about double of the percentage in 2016 [
16]. About three-quarters of China’s elderly live in rural areas. Thus, the purpose of this study was to investigate the moderating effects of gender and age on the association between BMI and MCI among Chinese rural older adults.
Discussion
In this study, we found the prevalence of MCI among rural older people was 18.5%. The prevalence in present study was higher than older adults (60+) in Shanghai suburb (by MMSE, 7.0%) [
30], and older people (65+) from 8 longevity areas of China (by MMSE, 10.0%) [
31]. A survey of community-based cohort in Zhejiang Province showed that the prevalence of MCI (by MMSE) among older adults (60+) was 14.7% [
7]. The prevalence of MCI among older people in previous studies was lower than that in present study. This may be because that we only focused on the older adults in rural areas, and previous studies have indicated that the prevalence of MCI in rural areas was significantly higher than that in urban areas [
32].
The moderating effect of gender between BMI and MCI was found. Similar to previous studies, older women with low BMI were more likely to have MCI and those with elevated or high BMI were less likely to have MCI. However, the relationships were not significant in males. Malnutrition could be a risk factor for cognitive decline among older people [
33]. BMI is an important objective indicator assessing the nutritional status among older people. Low BMI might be related to malnutrition. One possible explanation for the observed gender difference might be that differences in estrogen levels. Estrogen is a group of steroid compounds that function as primary gender hormones in women [
34]. Estrogen interacts with different types of receptors to exerted its action, including estrogen receptors ER-α and ER-β that are highly expressed in the brain [
35]. In men, testosterone is converted to estradiol by aromatase enzyme, which is located around and throughout the male brain [
36]. Since the secretion of testosterone has never completely stopped, the serum estrogen levels are higher among older men than in postmenopausal older women. Studies have shown that sex steroids such as estrogen and testosterone could protect the brain’s function during aging [
37]. Thus, different levels of steroids in men and women may affect their cognitive function to varying degrees.
The moderating effect of age between BMI and MCI was found. Different from previous studies, low BMI was positively correlated with MCI in older elderly, and elevated or high BMI was negative correlated with MCI in younger elderly. Respecting the differences between younger and older elderly, a possible explanation was that older elderly became more frail as they got older and the frailty accelerated increases. Frailty in older people were predisposed to a homeostatic failure of complex systems [
38], which could lead to more functional deficits. In Chinese rural areas, the degree of frailty of older people remained at a high level, and more than half of elderly households were moderate and advanced frailty [
39]. Studies have found that the prevalence of cognitive impairment in the frail elderly was higher than that of non-frail elderly [
40,
41]. Another possible reason was that the overall BMI decreased with age among older people. Lower BMI might affect brain atrophy through changes in metabolic and inflammatory [
42]. Another important reason might be related to alterations in body composition. Aging was characterized by the decrease of lean body mass, and higher lean body mass might reduce the risk of cognitive impairment among older people [
43], which could contribute to a lower risk of development of MCI in younger elderly with elevated or high BMI.
Inconsistent with previous studies, we found elevated BMI was positively correlated with MCI in older male elderly. Previous studies from South Korea [
14,
44], Australia [
45], and the United States [
13] have found that higher BMI was not associated with decreased cognitive function or with better cognitive performance among older men. Amyloid-beta protein produced by amyloid precursor protein (app) cleavage could form amyloid aggregates and has long been considered the culprit for Alzheimer’s [
46]. A recent study found that dysregulation of app impairs adipose tissue mitochondrial function and promotes obesity [
47]. Therefore, the association between elevated BMI and MCI in older male elderly might be due to the common pathological mechanism: abnormal amyloid precursor protein. However, the gender and age differences need to be further studied.
Moreover, we further found this association between low BMI and MCI became stronger among older women. It had been shown previously that older adults who had low BMI or lost weight were predisposed to cognitive decline. Previous studies from China [
30,
31], South Korea [
44], and the United States [
48] differing from the results of this study have found only that underweight was associated with MCI in women or older adults in general. We should pay more attention to the relationship between low BMI and cognitive function among older women.
The findings demonstrated the importance of managing the weight of rural older adults by gender and age. Government departments should strengthen the health management of malnutrition or low BMI for the rural older people, especially in the older female elderly. We recommend strengthening the information management of BMI and cognitive function among rural older adults. We suggest combine the basic public health services for the health management among older people to improve their understanding of the healthy weight. By grouping the weight of older people, high-risk groups with impaired cognitive function can be detected early to prevent the risk of dementia and maintain the well-being of older adults.
The current study had several limitations. First, waist circumference was not included to assess elevated or high BMI among older people; we will include this indicator in the following study. We would use a portable stadiometer to measure height objectively for the future research. Second, we could not determine the causal relationship between BMI and MCI as the cross-sectional data we used, longitudinal studies are needed in the future to explore the causal relationships.
Acknowledgments
We are grateful to all participants for their effort. We thank the officials of local health agencies and staffs at the study sites for their cooperation.
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