基于人群队列研究中的长期全身炎症与认知障碍
Long-term systemic inflammation and cognitive impairment in a population-based cohort.
作者信息
Wichmann Margarete A, Cruickshanks Karen J, Carlsson Cynthia M, Chappell Rick, Fischer Mary E, Klein Barbara E K, Klein Ronald, Tsai Michael Y, Schubert Carla R
机构信息
Department of Population Health Sciences, University of Wisconsin, Madison, Wisconsin; Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin, Madison, Wisconsin; Institute on Aging, University of Wisconsin, Madison, Wisconsin.
出版信息
J Am Geriatr Soc. 2014 Sep;62(9):1683-91. doi: 10.1111/jgs.12994. Epub 2014 Aug 14.
OBJECTIVES
Evidence suggests inflammation is associated with cognitive impairment, but previous epidemiological studies have reported conflicting results.
DESIGN
Prospective population-based cohort.
SETTING
Epidemiology of Hearing Loss Study participants.
PARTICIPANTS
Individuals without cognitive impairment in 1998-2000 (N = 2,422; 1,947 with necessary data).
MEASUREMENTS
Cognitive impairment (Mini-Mental State Examination score <24 or diagnosis of dementia) was ascertained in 1998-2000, 2003-2005, and 2009-2010. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured in 1988-1990, 1998-2000, and 2009-2010; tumor necrosis factor-alpha was measured from 1998-2000.
RESULTS
Participants with high CRP in 1988-1990 and 1998-2000 had lower risk of cognitive impairment than those with low CRP at both time points (hazard ratio (HR) = 0.46, 95% confidence interval (CI) = 0.26-0.80). Risk did not differ according to 10-year IL-6 profile or baseline inflammation category in the whole cohort. In sensitivity analyses restricted to statin nonusers, those with high IL-6 at both times had greater risk of cognitive impairment than those with low IL-6 at both times (HR = 3.35, 95% CI = 1.09-10.30). In secondary analyses, each doubling of IL-6 change over 20 years was associated with greater odds of cognitive impairment in 2009-2010 in the whole cohort (odds ratio (OR) = 1.40, 95% CI = 1.04-1.89), whereas a doubling of CRP change over 20 years was associated with cognitive impairment only in statin nonusers (OR = 1.32, 95% CI = 1.06-1.65).
CONCLUSION
With data collected over 20 years, this study demonstrated greater likelihood of cognitive impairment in individuals with repeated high or increasing IL-6. The inconsistent CRP findings may reflect effects of statin medications, survival effects, or adverse effects associated with chronically low CRP. Further studies of long-term inflammation and cognitive impairment are needed.
目的
有证据表明炎症与认知障碍有关，但以往的流行病学研究报告结果相互矛盾。
设计
基于人群的前瞻性队列研究。
研究背景
听力损失研究的流行病学参与者。
研究对象
1998 - 2000年无认知障碍的个体（N = 2422；1947例有必要数据）。
测量指标
在1998 - 2000年、2003 - 2005年和2009 - 2010年确定认知障碍（简易精神状态检查表得分<24或痴呆诊断）。在1988 - 1990年、1998 - 2000年和2009 - 2010年测量血清C反应蛋白（CRP）和白细胞介素-6（IL-6）；1998 - 2000年测量肿瘤坏死因子-α。
结果
在1988 - 1990年和1998 - 2000年CRP水平高的参与者比两个时间点CRP水平低的参与者发生认知障碍的风险更低（风险比（HR）= 0.46，95%置信区间（CI）= 0.26 - 0.80）。根据10年IL-6水平或整个队列的基线炎症类别，风险没有差异。在仅限于未使用他汀类药物者的敏感性分析中，两个时间点IL-6水平高的参与者比两个时间点IL-6水平低的参与者发生认知障碍的风险更高（HR = 3.35，95%CI = 1.09 - 10.30）。在二次分析中，20年期间IL-6每增加一倍与整个队列在2009 - 2010年发生认知障碍的几率增加有关（优势比（OR）= 1.40，95%CI = 1.04 - 1.89），而20年期间CRP每增加一倍仅与未使用他汀类药物者的认知障碍有关（OR = 1.32，95%CI = 1.06 - 1.65）。
结论
通过20多年收集的数据，本研究表明IL-6反复升高或持续升高的个体发生认知障碍的可能性更大。CRP的不一致结果可能反映了他汀类药物的作用、生存效应或与长期低CRP相关的不良反应。需要对长期炎症和认知障碍进行进一步研究。
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