胰岛素抵抗与认知功能下降有关，但与非痴呆成年人阿尔茨海默病脑脊液生物标志物的变化无关。
Insulin resistance is related to cognitive decline but not change in CSF biomarkers of Alzheimer's disease in non-demented adults.
作者信息
Ennis Gilda E, Koscik Rebecca L, Ma Yue, Jonaitis Erin M, Van Hulle Carol A, Betthauser Tobey J, Randall Allison M, Chin Nathaniel, Engelman Corinne D, Anderson Rozalyn, Suridjan Ivonne, Kollmorgen Gwendlyn, Christian Bradley T, Carlsson Cynthia M, Asthana Sanjay, Johnson Sterling C, Zetterberg Henrik, Blennow Kaj, Bendlin Barbara B
机构信息
Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA.
Wisconsin Alzheimer's Institute University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA.
出版信息
Alzheimers Dement (Amst). 2021 Jul 28;13(1):e12220. doi: 10.1002/dad2.12220. eCollection 2021.
INTRODUCTION
We investigated whether insulin resistance (IR) was associated with longitudinal age-related change in cognition and biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration in middle-aged and older adults who were non-demented at baseline.
METHODS
IR was measured with homeostatic model assessment of insulin resistance (HOMA2-IR). Core AD-related cerebrospinal fluid (CSF) biomarkers and cognition were assessed, respectively, on n = 212 (1 to 5 visits) and n = 1299 (1 to 6 visits). Linear mixed models tested whether HOMA2-IR moderated age-related change in CSF biomarkers and cognition. Linear regressions tested whether HOMA2-IR x apolipoprotein E ε4 allele ( ε4) carrier status predicted amyloid beta [Aβ] chronicity (estimated duration of amyloid positron emission tomography [PET] positivity) (n = 253).
RESULTS
Higher HOMA2-IR was associated with greater cognitive decline but not with changes in CSF biomarkers. HOMA2-IR x was not related to Aβ chronicity but was significantly associated with CSF phosphorylated tau (P-tau)/Aβ level.
DISCUSSION
In non-demented adults IR may not be directly associated with age-related change in AD biomarkers. Additional research is needed to determine mechanisms linking IR to cognitive decline.
引言
我们调查了胰岛素抵抗（IR）是否与基线时无痴呆的中老年人认知功能的纵向年龄相关变化以及阿尔茨海默病（AD）病理和神经退行性变的生物标志物有关。
方法
采用胰岛素抵抗稳态模型评估（HOMA2-IR）来测量IR。分别对n = 212名受试者（1至5次访视）和n = 1299名受试者（1至6次访视）评估了核心AD相关脑脊液（CSF）生物标志物和认知功能。线性混合模型测试了HOMA2-IR是否调节了CSF生物标志物和认知功能的年龄相关变化。线性回归测试了HOMA2-IR×载脂蛋白Eε4等位基因（ε4）携带者状态是否预测淀粉样β蛋白[Aβ]慢性状态（淀粉样正电子发射断层扫描[PET]阳性的估计持续时间）（n = 253）。
结果
较高的HOMA2-IR与更大的认知衰退相关，但与CSF生物标志物的变化无关。HOMA2-IR×ε4与Aβ慢性状态无关，但与CSF磷酸化tau蛋白（P-tau）/Aβ水平显著相关。
讨论
在无痴呆的成年人中，IR可能与AD生物标志物的年龄相关变化无直接关联。需要进一步研究以确定将IR与认知衰退联系起来的机制。
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