Drake Jermon A, Jakicic John M, Rogers Renee J, Aghjayan Sarah L, Stillman Chelsea M, Donofry Shannon D, Roecklein Kathryn A, Lang Wei, Erickson Kirk I
Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United States.
Center for Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, PA, United States.
Front Hum Neurosci. 2022 Nov 25;16:1001229. doi: 10.3389/fnhum.2022.1001229. eCollection 2022.
The apolipoprotein E ε4 (APOE ε4) allele and midlife obesity are independent risk factors for Alzheimer's disease (AD). Both of these risk factors are also associated with differences in brain activation, as measured by blood oxygenation level-dependent (BOLD) responses, in the absence of detectable cognitive deficits. Although the presence of these risk factors may influence brain activity during working memory tasks, no study to date has examined whether the presence of the ε4 allele explains variation in working memory brain activity while matching for levels of overweight/obesity. The primary aim of this study was to determine whether the presence of the ε4 allele is associated with differences in task-functional magnetic resonance imaging (fMRI) brain activation in adults with overweight/obesity. We predicted that ε4 carriers would have greater brain activation in regions that support working memory.
This ancillary study included 48 ( = 24 APOE ε4 carriers; = 24 APOE ε4 non-carriers), sedentary middle-aged adults (Mean age = 44.63 ± 8.36 years) with overweight/obesity (Mean BMI = 32.43 ± 4.12 kg/m) who were matched on demographic characteristics. Participants were a subsample enrolled in 12-month randomized clinical trial examining the impact of energy-restricted diet and exercise on cardiovascular health outcomes. Participants completed a n-back working memory task with fMRI, which were completed within one month of the start of the intervention. Participants also underwent pseudo-continuous arterial spin labeling scans, a MRI measure of cerebral blood flow (CBF).
Compared to non-ε4 carriers with overweight/obesity, ε4 carriers with overweight/obesity had lower fMRI brain activity in the middle frontal gyrus, pre and post central gyrus, supramarginal gyrus, superior temporal gyrus, lateral occipital cortex, and angular gyrus ( range = 2.52-3.56) during the n-back working memory task. Differences persisted even when controlling for CBF in these brain regions.
These results indicate that presence of the APOE ε4 allele in middle-aged adults with overweight/obesity is related to altered brain activity during a working memory paradigm, which may confer risk for accelerated neurocognitive decline in late adulthood. Future research is needed to clarify the clinical implications of these findings in the context of risk for AD.
载脂蛋白Eε4（APOEε4）等位基因和中年肥胖是阿尔茨海默病（AD）的独立危险因素。在没有可检测到的认知缺陷的情况下，这两种危险因素也都与脑激活差异有关，脑激活差异通过血氧水平依赖（BOLD）反应来衡量。虽然这些危险因素的存在可能会影响工作记忆任务期间的大脑活动，但迄今为止，尚无研究考察ε4等位基因的存在是否能在匹配超重/肥胖水平的情况下解释工作记忆脑活动的差异。本研究的主要目的是确定ε4等位基因的存在是否与超重/肥胖成年人的任务功能磁共振成像（fMRI）脑激活差异有关。我们预测ε4携带者在支持工作记忆的区域会有更强的脑激活。
这项辅助研究纳入了48名久坐不动的中年超重/肥胖成年人（平均年龄=44.63±8.36岁，平均体重指数=32.43±4.12kg/m²），按人口统计学特征进行匹配（n = 24名APOEε4携带者；n = 24名APOEε4非携带者）。参与者是一项为期12个月的随机临床试验的子样本，该试验考察能量限制饮食和运动对心血管健康结局的影响。参与者在fMRI下完成了一项n-back工作记忆任务，该任务在干预开始后的一个月内完成。参与者还接受了伪连续动脉自旋标记扫描，这是一种测量脑血流量（CBF）的MRI方法。
与超重/肥胖的非ε4携带者相比，超重/肥胖的ε4携带者在n-back工作记忆任务期间，额中回、中央前回和中央后回、缘上回、颞上回、枕外侧皮质和角回的fMRI脑活动较低（范围=2.52-3.56）。即使在控制这些脑区的CBF后，差异仍然存在。
这些结果表明，超重/肥胖的中年成年人中APOEε4等位基因的存在与工作记忆范式期间的脑活动改变有关，这可能会增加成年后期神经认知加速衰退的风险。需要进一步的研究来阐明这些发现在AD风险背景下的临床意义。
