Recently, a study conducted by the yu jintai research team of Huashan Hospital affiliated to Fudan University and the team of Feng Jianfeng and Cheng Wei, professors of the Institute of Brain Intelligence of Fudan University, revealed the relationship between obesity and the risk of emerging dementia in the whole life course. The large-scale longitudinal cohort study of more than 320,000 people found that too low birth weight, obese body size in childhood and adulthood significantly increased the risk of dementia. On May 10, the study was published in the journal Molecular Psychiatry.
Association and possible mechanisms of life-cycle weight and dementia risk Courtesy of respondents
BMI (body mass index) showed a significant U-shaped relationship with dementia risk, with obesity or thinness increasing the risk of dementia. The optimal adult BMI was 29.2 kg/m2 for males and 28.5kg/m2 for females. The team further revealed a potential mechanism in which obesity may increase the risk of developing dementia by influencing metabolism, inflammation and brain structure.
“Many previous studies have shown that obesity is associated with an increased risk of developing more than 10 cancers, and that obese people are more susceptible to metabolic diseases and cardiovascular and cerebrovascular diseases.” Yu Jintai told China Science Daily, “At the same time, obesity in middle-aged and elderly people is also considered a risk factor for dementia, but there has been no large-scale cohort study to systematically explore the relationship between obesity over the life course (including birth weight, childhood BMI, adult BMI, body fat rate, etc.) and the risk of dementia.” ”
So the team used the UK Biobank cohort to include 322336 non-dementia population aged 50 to 73 years with an average follow-up time of 8.74 years, during which 5038 participants were diagnosed with new-onset dementia. Participants reported birth weight versus childhood body size and measured obesity-related indicators at baseline (2006-2010).
The study found that the risk of dementia at very low birth weight (< 1.0 kg) increased by 1.18 times compared with normal birth weight; the risk of dementia increased by 18% in people with a fatter body type in childhood compared with the average childhood body size; the adult BMI was U-shaped with the risk of dementia, and when the BMI was lower than the recommended value, for every 1kg/m2 increase (equivalent to 3 kg of weight gain for people with an average height of 173 cm), the risk of dementia decreased by 6% (males) and 5% (females), and when the BMI was higher than the recommended value, For every 1 kg/m2 increase, the risk of dementia increased by 3% (men) and 2% (women). Using mediating analysis, the researchers found that adult obesity mediated the effects of childhood obesity on dementia risk in 17.4 percent.
The mechanism of obesity and dementia is not clear, so the research team used the participants’ biological samples and brain imaging data to conduct an in-depth study of the possible mechanisms of obesity affecting the occurrence of dementia. First, BMI was associated with plasma concentrations of 3-hydroxybutyric acid, acetone, and citric acid in u-shapes, and these three were associated with a higher risk of dementia; BMI was associated with plasma concentrations of polyunsaturated fatty acids inverted U-shape, which was associated with a lower risk of dementia, and mediated analysis also confirmed that these four metabolites mediated the relationship between BMI and dementia. Second, BMI is also associated with U-shaped plasma concentrations or counts of neutrophils, lymphocytes, monocytes, and white blood cells in plasma, which also affect the risk of dementia. Finally, the research team comprehensively explored the relationship between obesity and brain structure, and found that BMI also showed a significant U-shaped relationship with cortical thickness and gray matter volume, and many obesity indicators were closely related to dementia-related brain areas such as the middle temporal lobe, prefrontal lobe, hippocampus and amygdala in both sides.
This study systematically studies the relationship between obesity and dementia in the whole life course for the first time, and explores the potential mechanism from three aspects: metabolism, inflammation and brain structure, which provides us with more specific life practice guidance for preventing dementia.
“Therefore, weight control should be done small and maintain an appropriate weight to reduce the risk of many chronic diseases in the future, including dementia.” Yu Jintai said. (Source: China Science Daily, Zhang Shuanghu, Huang Xin)
Related paper information:https://doi.org/10.1038/s41380-022-01604-9