Chuang Y-F, An Y, Bilgel M, Wong D F, Troncoso J C, O'Brien R J, Breitner J C, Ferruci L, Resnick S M, Thambisetty M
Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA.
Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
Mol Psychiatry. 2016 Jul;21(7):910-5. doi: 10.1038/mp.2015.129. Epub 2015 Sep 1.
Understanding how midlife risk factors influence age at onset (AAO) of Alzheimer's disease (AD) may provide clues to delay disease expression. Although midlife adiposity predicts increased incidence of AD, it is unclear whether it affects AAO and severity of Alzheimer's neuropathology. Using a prospective population-based cohort, Baltimore Longitudinal Study of Aging (BLSA), this study aims to examine the relationships between midlife body mass index (BMI) and (1) AAO of AD (2) severity of Alzheimer's neuropathology and (3) fibrillar brain amyloid deposition during aging. We analyzed data on 1394 cognitively normal individuals at baseline (8643 visits; average follow-up interval 13.9 years), among whom 142 participants developed incident AD. In two subsamples of BLSA, 191 participants underwent autopsy and neuropathological assessment, and 75 non-demented individuals underwent brain amyloid imaging. Midlife adiposity was derived from BMI data at 50 years of age. We find that each unit increase in midlife BMI predicts earlier onset of AD by 6.7 months (P=0.013). Higher midlife BMI was associated with greater Braak neurofibrillary but not CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuritic plaque scores at autopsy overall. Associations between midlife BMI and brain amyloid burden approached statistical significance. Thus, higher midlife BMI was also associated with greater fibrillar amyloid measured by global mean cortical distribution volume ratio (P=0.075) and within the precuneus (left, P=0.061; right, P=0.079). In conclusion, midlife overweight predicts earlier onset of AD and greater burden of Alzheimer's neuropathology. A healthy BMI at midlife may delay the onset of AD.
了解中年风险因素如何影响阿尔茨海默病（AD）的发病年龄（AAO）可能为延缓疾病表现提供线索。尽管中年肥胖预示着AD发病率增加，但尚不清楚它是否会影响AD的发病年龄和阿尔茨海默病神经病理学的严重程度。本研究利用基于人群的前瞻性队列——巴尔的摩纵向衰老研究（BLSA），旨在探讨中年体重指数（BMI）与（1）AD的发病年龄、（2）阿尔茨海默病神经病理学的严重程度以及（3）衰老过程中脑内纤维状淀粉样蛋白沉积之间的关系。我们分析了1394名基线时认知正常个体的数据（8643次随访；平均随访间隔13.9年），其中142名参与者发生了新发AD。在BLSA的两个子样本中，191名参与者接受了尸检和神经病理学评估，75名非痴呆个体接受了脑淀粉样蛋白成像检查。中年肥胖通过50岁时的BMI数据得出。我们发现中年BMI每增加一个单位，AD的发病时间就会提前6.7个月（P=0.013）。总体而言，中年BMI较高与尸检时更高的Braak神经纤维缠结评分相关，但与阿尔茨海默病注册协会（CERAD）的神经炎性斑块评分无关。中年BMI与脑淀粉样蛋白负荷之间的关联接近统计学意义。因此，中年BMI较高还与通过全脑平均皮质分布体积比测量的更高纤维状淀粉样蛋白水平相关（P=0.075），在楔前叶内也是如此（左侧，P=0.061；右侧，P=0.079）。总之，中年超重预示着AD发病更早，阿尔茨海默病神经病理学负担更重。中年保持健康的BMI可能会延缓AD的发病。
