Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
J Alzheimers Dis. 2019;71(3):921-929. doi: 10.3233/JAD-190569.
Greater body weight has been associated impairments in neurocognition and greater dementia risk, although the mechanisms linking weight and neurocognition have yet to be adequately delineated.
To examine metabolic mechanisms underlying the association between obesity and neurocognition.
We conducted a secondary analysis of weight, neurocognition, and the potentially mediating role of metabolic and inflammatory biomarkers among 160 participants from the ENLIGHTEN trial of vascular cognitive impairment, no dementia (CIND). Neurocognition was assessed using a 45-minute assessment battery assessing Executive Function, Verbal and Visual Memory. We considered three metabolic biomarkers: insulin resistance (homeostatic model assessment [HOMA-IR]), plasma leptin, and insulin-like growth factor (IGF-1). Inflammation was assessed using C-reactive protein. Multiple regression analyses were used.
Participants included 160 sedentary older adults with CIND. Participants tended to be overweight or obese (mean BMI = 32.5 [SD = 4.8]). Women exhibited higher BMI (p = 0.043), CRP (p < 0.001), and leptin (p < 0.001) compared with men. Higher BMI levels were associated with worse performance on measures of Executive Function (β= -0.16, p = 0.024) and Verbal Memory (β= -0.16, p = 0.030), but not Visual Memory (β= 0.05, p = 0.500). Worse metabolic biomarker profiles also were associated with lower Executive Function (β= -0.12, p = 0.050). Mediation analyses suggested leptin was a plausible candidate as a mediator between BMI and Executive Function.
In overweight and obese adults with vascular CIND, the association between greater weight and poorer executive function may be mediated by higher leptin resistance.
体重增加与神经认知功能受损和痴呆风险增加有关，尽管体重与神经认知之间的联系的机制尚未得到充分阐明。
研究肥胖与神经认知之间关联的代谢机制。
我们对血管性认知障碍、非痴呆（CIND）的 ENLIGHTEN 试验中的 160 名参与者进行了体重、神经认知以及代谢和炎症生物标志物的潜在中介作用的二次分析。神经认知使用 45 分钟评估测试来评估执行功能、言语和视觉记忆。我们考虑了三种代谢生物标志物：胰岛素抵抗（稳态模型评估[HOMA-IR]）、血浆瘦素和胰岛素样生长因子（IGF-1）。炎症使用 C-反应蛋白评估。使用多元回归分析。
参与者包括 160 名患有 CIND 的久坐老年人。参与者的体重指数（BMI）往往偏高或肥胖（平均 BMI=32.5[标准差[SD]=4.8]）。与男性相比，女性的 BMI（p=0.043）、CRP（p<0.001）和瘦素（p<0.001）水平更高。较高的 BMI 水平与执行功能（β=-0.16，p=0.024）和言语记忆（β=-0.16，p=0.030）的测量值更差相关，但与视觉记忆（β=0.05，p=0.500）无关。较差的代谢生物标志物谱也与执行功能较差相关（β=-0.12，p=0.050）。中介分析表明，瘦素可能是 BMI 与执行功能之间的中介因素。
在超重和肥胖的血管性 CIND 成年人中，体重增加与执行功能下降之间的关联可能是由瘦素抵抗引起的。
