Satizabal Claudia L, Himali Jayandra Jung, Conner Sarah C, Beiser Alexa S, Maillard Pauline, Vasan Ramachandran S, DeCarli Charles, Seshadri Sudha
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA.
Department of Population Health Sciences, UT Health San Antonio, San Antonio, TX, USA.
J Alzheimers Dis. 2024 Nov;102(2):449-458. doi: 10.1177/13872877241289043. Epub 2024 Oct 29.
Midlife obesity is related to late-onset dementia. Studying adipose tissue-secreted adipokines in the context of brain aging may help us understand this association.
To investigate associations between adipokines and brain MRI markers in middle-aged adults from the Third-Generation cohort of the Framingham Heart Study.
Serum adiponectin, retinol-binding protein 4 (RBP4), fetuin-A, and Fatty Acid-Binding Protein 4 (FABP4) concentrations were measured by enzymatic immunoassays. MRI measures included total brain, cortical gray matter, hippocampal (total and anterior), lateral ventricular, and white matter hyperintensity volumes. We used linear regression models to separately relate adipokine concentrations to MRI measures, adjusting for potential confounders.
We included 1882 participants (mean age of 48 ± 8 years, 54% women). Higher RBP4 concentrations were related to markers of brain atrophy, including smaller total (Beta ± standard error, -0.05 ± 0.02; p = 0.014) and cortical gray brain volumes (-0.06 ± 0.02; p = 0.004), and larger lateral ventricular volumes (0.06 ± 0.02; p = 0.006). Additionally, higher RBP4 (-0.06 ± 0.03; p = 0.042), Fetuin-A (-0.06 ± 0.03; p = 0.039), and FABP4 (-0.09 ± 0.03; p = 0.008) concentrations were associated with smaller anterior hippocampal volumes. Most associations remained after additional adjustment for vascular risk factors. In exploratory analyses, higher FABP4 was related to larger total brain in non-obese participants, and to smaller anterior hippocampal volumes in obese participants. Finally, higher adiponectin concentrations were related to smaller cortical gray, only in non-obese participants.
Our results suggest that adipokines are associated with markers of brain atrophy during midlife. Further studies are needed to replicate these findings and elucidate any potential mechanisms contributing to abnormal brain aging.
中年肥胖与迟发性痴呆有关。在脑老化的背景下研究脂肪组织分泌的脂肪因子可能有助于我们理解这种关联。
在弗雷明汉心脏研究的第三代队列中，调查中年成年人脂肪因子与脑磁共振成像（MRI）标志物之间的关联。
采用酶免疫分析法测定血清脂联素、视黄醇结合蛋白4（RBP4）、胎球蛋白-A和脂肪酸结合蛋白4（FABP4）的浓度。MRI测量包括全脑、皮质灰质、海马体（整体和前部）、侧脑室和白质高信号体积。我们使用线性回归模型分别将脂肪因子浓度与MRI测量结果相关联，并对潜在的混杂因素进行调整。
我们纳入了1882名参与者（平均年龄48±8岁，54%为女性）。较高的RBP4浓度与脑萎缩标志物有关，包括较小的全脑体积（β±标准误，-0.05±0.02；p=0.014）和皮质灰质体积（-0.06±0.02；p=0.004），以及较大的侧脑室体积（0.06±0.02；p=0.006）。此外，较高的RBP4（-0.06±0.03；p=0.042）、胎球蛋白-A（-0.06±0.03；p=0.039）和FABP4（-0.09±0.03；p=0.008）浓度与较小的前海马体体积相关。在对血管危险因素进行额外调整后，大多数关联仍然存在。在探索性分析中，较高的FABP4与非肥胖参与者较大的全脑体积有关，而与肥胖参与者较小的前海马体体积有关。最后，仅在非肥胖参与者中，较高的脂联素浓度与较小的皮质灰质有关。
我们的结果表明，脂肪因子与中年时期的脑萎缩标志物有关。需要进一步的研究来重复这些发现，并阐明导致脑老化异常的任何潜在机制。
