Background:There is growing interest in the pathophysiological processes of preclinical Alzheimer’s disease (AD), including the potential role of leptin. Human studies have shown that both low and high levels of leptin can be associated with worse neurocognitive outcomes, suggesting this relationship may be moderated by another risk factor. Objective:We examined the association between plasma leptin levels and both neuropsychological test performance and structural neuroimaging and assessed whether body mass index (BMI) is an effect modifier of these associations. Methods:Our study sample consisted of 2,223 adults from the Framingham Heart Study Third Generation Cohort (average age = 40 years, 53% women). Results:Among the entire sample, there was no association between leptin and any of the neuropsychological domain measures or any of the MRI brain volume measures, after adjustment for BMI, APOE4, and other clinical factors. However, we did observe that BMI category was an effect modifier for the association between leptin and verbal memory (p for interaction = 0.03), where higher levels of leptin were associated with better performance among normal weight participants (BMI 18.5–24.9) kg/m2 (beta = 0.12, p = 0.02). No association was observed between leptin level and verbal memory test performance among participants who were overweight or obese. Conclusion:These findings suggest that the association between leptin and cognitive function is moderated by BMI category. Prospective examination of individuals transitioning from middle age to older adulthood will help to clarify the contribution of leptin to AD and other neurodegenerative conditions.

中文翻译：

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“早期”中年人瘦素、认知和结构性脑测量之间的关联：弗雷明汉心脏研究第三代队列的结果。

背景：人们对临床前阿尔茨海默病 (AD) 的病理生理过程越来越感兴趣，包括瘦素的潜在作用。人类研究表明，低水平和高水平的瘦素都可能与更差的神经认知结果相关，这表明这种关系可能受到另一个风险因素的影响。目的：我们检查了血浆瘦素水平与神经心理学测试表现和结构神经影像学之间的关联，并评估了体重指数 (BMI) 是否是这些关联的效应调节剂。方法：我们的研究样本包括来自弗雷明汉心脏研究第三代队列的 2,223 名成年人（平均年龄 = 40 岁，53% 为女性）。结果：在整个样本中，在调整 BMI、APOE4 和其他临床因素后，瘦素与任何神经心理学领域测量或任何 MRI 脑容量测量之间没有关联。然而，我们确实观察到 BMI 类别是瘦素和语言记忆之间关联的效应调节剂（交互作用的 p = 0.03），其中瘦素水平越高，正常体重参与者（BMI 18.5-24.9）kg/ m2（β = 0.12，p = 0.02）。在超重或肥胖的参与者中，没有观察到瘦素水平与语言记忆测试表现之间存在关联。结论：这些发现表明瘦素与认知功能之间的关联受 BMI 类别的调节。