Diabetes Mellitus and Cognition: Pathway Analysis in the MEMENTO Cohort.
Diabetes Mellitus and Cognition: Pathway Analysis in the MEMENTO Cohort.
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DOI：
10.1212/wnl.0000000000012440
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发表时间：
2021-08-24
期刊：
影响因子：
9.9
通讯作者：
MEMENTO Cohort Study Group
中科院分区：
文献类型：
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作者：
Frison E;Proust-Lima C;Mangin JF;Habert MO;Bombois S;Ousset PJ;Pasquier F;Hanon O;Paquet C;Gabelle A;Ceccaldi M;Annweiler C;Krolak-Salmon P;Béjot Y;Belin C;Wallon D;Sauvee M;Beaufils E;Bourdel-Marchasson I;Jalenques I;Chupin M;Chêne G;Dufouil C;MEMENTO Cohort Study Group
评估阿尔茨海默病（AD）、神经变性和小血管病（SVD）生物标志物作为糖尿病和认知之间关联的介质的作用。研究样本来自MEMEMENTO，这是一个在记忆诊所招募的法国成年人队列，并筛选了孤立的主观认知主诉或轻度认知障碍。糖尿病的定义基于血糖评估、抗糖尿病药物的使用或自我报告。我们使用结构方程模型来评估AD病理学的潜在变量是否（PET平均淀粉样蛋白摄取、Aβ42/Aβ40比值和CSF磷酸化tau），SVD（白色物质高信号体积和视觉分级）和神经变性（平均皮质厚度，脑实质分数，海马体积，和平均氟脱氧葡萄糖摄取）介导糖尿病和认知的潜在变量之间的关联（5项神经心理学测试），调整潜在的混杂因素。在2，288名参与者中，有254名（11.1%）参与者患有糖尿病（中位年龄71.6岁; 61.8%为女性）。糖尿病和认知能力低下之间的关联明显由较高的神经退行性疾病介导（标准化间接效应：-0.061，95%置信区间：-0.089，-0.032），但不受SVD和AD标志物介导。当考虑记忆或执行功能的潜在变量时，结果是相似的。在老年人的大型临床队列中，糖尿病通过神经退行性变与认知能力降低相关，与SVD和AD生物标志物无关。
To assess the role of biomarkers of Alzheimer disease (AD), neurodegeneration, and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition. The study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent, or self-report. We used structural equation modeling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aβ42/Aβ40 ratio, and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (5 neuropsychological tests), adjusting for potential confounders. There were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: −0.061, 95% confidence interval: −0.089, −0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning. In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers.