肥胖对大脑老化和认知能力下降的影响：来自英国生物银行的一项队列研究。

IF 2 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-01-05 DOI:10.1016/j.ibneur.2025.01.001

Panlong Li , Xirui Zhu , Chun Huang , Shan Tian , Yuna Li , Yuan Qiao , Min Liu , Jingjing Su , Dandan Tian

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引用次数: 0

摘要

目的：利用大量神经影像学和遗传学数据探讨肥胖对脑结构和认知的影响。方法：对来自UK Biobank的30283名参与者进行体重指数（BMI）、灰质体积（GMV）、白质高强度（WMH）和流体智力评分（FIS）之间的关联评估。进行纵向数据分析。采用全基因组关联研究探讨BMI、GMV、WMH和FIS之间的遗传位点关联。孟德尔随机化分析应用于进一步估计肥胖对大脑和认知变化的影响。结果：观察分析显示BMI与GMV呈负相关（r = -0.15,p × 10-24），与WMH呈正相关（r = 0.08, p × 10-16）。BMI变化与GMV变化呈负相关（r = -0.04, p × 10-5）。BMI、GMV和FIS在SBK1 （rs2726032）、SGF29 （rs17707300）、TUFM （rs3088215）、AKAP6 （rs1051695）、IL27 （rs4788084）和SPI1 （rs3740689和rs935914）位点上存在遗传重叠。MR分析表明，BMI越高，GMV越低（β=-1119.12, p = 5.77 ×10-6）， WMH越高（β=42.76, p = 6.37 ×10-4）， FIS越低（β=-0.081, p = 1.92 ×10-23）。结论：肥胖与大脑衰老和认知能力下降之间的表型和遗传关联表明，控制体重可能是减缓大脑衰老的一种有希望的策略。

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Effects of obesity on aging brain and cognitive decline: A cohort study from the UK Biobank

Objective

To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data.

Methods

Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyper-intensities (WMH), and fluid intelligence score (FIS) were estimated in 30283 participants from the UK Biobank. Longitudinal data analysis was conducted. Genome-wide association studies were applied to explore the genetic loci associations among BMI, GMV, WMH, and FIS. Mendelian Randomization analyses were applied to further estimate the effects of obesity on changes in the brain and cognition.

Results

The observational analysis revealed that BMI was negatively associated with GMV (r = -0.15, p < 1

\times

10⁻²⁴) and positively associated with WMH (r = 0.08, p < 1

\times

10⁻¹⁶). The change in BMI was negatively associated with the change in GMV (r = -0.04, p < 5

\times

10⁻⁵). Genetic overlap was observed among BMI, GMV, and FIS at SBK1 (rs2726032), SGF29 (rs17707300), TUFM (rs3088215), AKAP6 (rs1051695), IL27 (rs4788084), and SPI1 (rs3740689 and rs935914). The MR analysis provided evidence that higher BMI was associated with lower GMV (β=-1119.12, p = 5.77 ×10⁻⁶), higher WMH (β=42.76, p = 6.37 ×10⁻⁴), and lower FIS (β=-0.081, p = 1.92 ×10⁻²³).

Conclusions

The phenotypic and genetic association between obesity and aging brain and cognitive decline suggested that weight control could be a promising strategy for slowing the aging brain.

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