Weinstein Galit, Maillard Pauline, Himali Jayandra J, Beiser Alexa S, Au Rhoda, Wolf Philip A, Seshadri Sudha, DeCarli Charles
From the Department of Neurology (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), Boston University School of Medicine, MA; The Framingham Heart Study (G.W., J.J.H., A.S.B., R.A., P.A.W., S.S.), MA; the Department of Neurology (P.M., C.D.), The University of California at Davis, Sacramento; and the Department of Biostatistics (A.S.B.), Boston University School of Public Health, MA.
Neurology. 2015 Jun 9;84(23):2329-37. doi: 10.1212/WNL.0000000000001655. Epub 2015 May 6.
To evaluate the possible early consequences of impaired glucose metabolism on the brain by assessing the relationship of diabetes, fasting blood glucose (FBG) levels, and insulin resistance with cognitive performance and brain integrity in healthy young and middle-aged adults.
The sample included dementia-free participants (mean age 40 ± 9 years; 53% women) of the Framingham Heart Study third-generation cohort with cognitive testing of memory, abstract reasoning, visual perception, attention, and executive function (n = 2,126). In addition, brain MRI examination (n = 1,597) was used to determine white matter, gray matter, and white matter hyperintensity (WMH) volumes and fractional anisotropy measures. We used linear regression models to assess relationships between diabetes, FBG, and insulin resistance with cognition, lobar gray matter, and WMH volumes as well as voxel-based microstructural white matter integrity and gray matter density, adjusting for potential confounders. Mediating effect of brain lesions on the association of diabetes with cognitive performance was also tested.
Diabetes was associated with worse memory, visual perception, and attention performance; increased WMH; and decreased total cerebral brain and occipital lobar gray matter volumes. The link of diabetes with attention and memory was mediated through occipital and frontal atrophy, and the latter also through hippocampal atrophy. Both diabetes and increased FBG were associated with large areas of reductions in gray matter density and fractional anisotropy on voxel-based analyses.
We found that hyperglycemia is associated with subtle brain injury and impaired attention and memory even in young adults, indicating that brain injury is an early manifestation of impaired glucose metabolism.
通过评估糖尿病、空腹血糖（FBG）水平和胰岛素抵抗与健康中青年成年人认知能力及脑完整性之间的关系，来评价糖代谢受损对大脑可能产生的早期影响。
样本包括弗雷明汉心脏研究第三代队列中无痴呆的参与者（平均年龄40±9岁；53%为女性），对其进行记忆、抽象推理、视觉感知、注意力和执行功能的认知测试（n = 2126）。此外，采用脑MRI检查（n = 1597）来确定白质、灰质和白质高信号（WMH）体积以及分数各向异性测量值。我们使用线性回归模型来评估糖尿病、FBG和胰岛素抵抗与认知、脑叶灰质和WMH体积以及基于体素的微观结构白质完整性和灰质密度之间的关系，并对潜在混杂因素进行校正。还测试了脑损伤对糖尿病与认知能力关联的中介作用。
糖尿病与较差的记忆、视觉感知和注意力表现相关；WMH增加；全脑和枕叶灰质体积减少。糖尿病与注意力和记忆的关联通过枕叶和额叶萎缩介导，与后者的关联还通过海马萎缩介导。在基于体素的分析中，糖尿病和升高的FBG均与大面积的灰质密度降低和分数各向异性降低相关。
我们发现，即使在年轻人中，高血糖也与轻微脑损伤以及注意力和记忆受损有关，这表明脑损伤是糖代谢受损的早期表现。
