Higher serum total cholesterol levels in late middle age are associated with glucose hypometabolism in brain regions affected by Alzheimer's disease and normal aging
Higher serum total cholesterol levels in late middle age are associated with glucose hypometabolism in brain regions affected by Alzheimer's disease and normal aging
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DOI：
10.1016/j.neuroimage.2009.07.025
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发表时间：
2010-01-01
期刊：
影响因子：
5.7
通讯作者：
Caselli, Richard J.
中科院分区：
文献类型：
--
作者：
Reiman, Eric M.;Chen, Kewei;Caselli, Richard J.
流行病学研究表明，较高的中年血清总胆固醇水平与阿尔茨海默病（AD）的风险增加有关。在对认知正常的中年晚期人群进行的研究中，我们使用氟脱氧葡萄糖正电子发射断层扫描（PET），证明了载脂蛋白E（APOE）β 4基因剂量（晚发性AD的主要遗传风险因素）与AD影响脑区葡萄糖脑代谢率（CMRgl）测量值降低之间的相关性，我们建议使用PET作为症状前的内在表型来评估其他假定的AD风险调节因子，然后我们使用它来支持AD风险中的总胆固醇相关遗传风险评分。在本研究中，我们使用PET研究了117名认知正常的中年晚期APOE β 4纯合子、杂合子和非携带者的血清总胆固醇水平和脑葡萄糖代谢率（CMRgl）之间的关系。较高的血清总胆固醇水平与先前发现优先受AD影响的楔前叶、顶颞叶和前额区以及先前发现优先受正常衰老影响的其他额叶区的双侧CMRgl较低相关。在某些受AD影响的大脑区域，APOE β 4携带者的相关性比非携带者更大。我们推测，较高的中年血清总胆固醇水平加速与正常衰老相关的大脑过程，并与AD易感性的其他危险因素合谋。我们建议在概念验证随机对照试验中使用PET来快速评估中年降胆固醇治疗对与正常衰老和AD相关的大脑变化的影响。(c)2009 Elsevier Inc. All rights reserved.
Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer's disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late middle-aged people, we demonstrated an association between apolipoprotein E (APOE) epsilon 4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a pre-symptomatic endophenotype to evaluate other Putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE epsilon 4 homozygotes, heterozygotes and non-carriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE epsilon 4 carriers than non-carriers in some of the AD-affected brain regions. We postulate that higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD. (c) 2009 Elsevier Inc. All rights reserved.