Crane Paul K, Walker Rod L, Sonnen Joshua, Gibbons Laura E, Melrose Rebecca, Hassenstab Jason, Keene C Dirk, Postupna Nadia, Montine Thomas J, Larson Eric B
Department of Medicine, University of Washington, Seattle, WA, USA.
Group Health Research Institute, Seattle, WA, USA.
Neurobiol Aging. 2016 Dec;48:72-82. doi: 10.1016/j.neurobiolaging.2016.07.021. Epub 2016 Aug 1.
We evaluated associations between glucose and dementia-related neuropathologic findings among people without diabetes treatment history to elucidate mechanisms of glucose's potential effect on dementia. We used glucose and hemoglobin A1c values to characterize glucose exposures over 5 years before death (primary) and age bands from 55-59 through 80-84 (secondary). Autopsy evaluations included Braak stage for neurofibrillary tangles, Consortium to Establish a Registry for Alzheimer's Disease grade for neuritic plaques, macroscopic infarcts including lacunar infarcts, Lewy bodies, cerebral microinfarcts, and hippocampal sclerosis. Of 529 who came to autopsy, we included 430 with no history of diabetes treatment. We found no associations between glucose levels and Braak stage or Consortium to Establish a Registry for Alzheimer's Disease grade. There was a suggestion of a relationship between glucose and hippocampal sclerosis, although this was inconsistent across analyses. There was higher risk of Lewy bodies in substantia nigra and locus ceruleus with higher glucose levels in age band analyses. We did not find interactions between glucose levels, neuropathologic findings, and dementia. The mechanism by which glucose may impact dementia risk is still unknown.
我们评估了无糖尿病治疗史人群中血糖与痴呆相关神经病理学发现之间的关联，以阐明血糖对痴呆潜在影响的机制。我们使用血糖和糖化血红蛋白值来表征死亡前5年（主要）以及55 - 59岁至80 - 84岁年龄段（次要）的血糖暴露情况。尸检评估包括神经原纤维缠结的Braak分期、老年斑的阿尔茨海默病注册协会分级、包括腔隙性梗死在内的宏观梗死、路易小体、脑微梗死和海马硬化。在529例接受尸检的患者中，我们纳入了430例无糖尿病治疗史的患者。我们发现血糖水平与Braak分期或阿尔茨海默病注册协会分级之间无关联。尽管在各分析中结果不一致，但有迹象表明血糖与海马硬化之间存在关联。在年龄组分析中，黑质和蓝斑中出现路易小体的风险随着血糖水平升高而增加。我们未发现血糖水平、神经病理学发现与痴呆之间存在相互作用。血糖可能影响痴呆风险的机制仍不清楚。
