THE INDEPENDENT ROLE OF INFLAMMATION IN PHYSICAL FRAILTY AMONG OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT AND MILD-TO-MODERATE ALZHEIMER'S DISEASE
THE INDEPENDENT ROLE OF INFLAMMATION IN PHYSICAL FRAILTY AMONG OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT AND MILD-TO-MODERATE ALZHEIMER'S DISEASE
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DOI：
10.1007/s12603-015-0617-6
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发表时间：
2016-03-01
影响因子：
5.8
通讯作者：
Chong, M. S.
中科院分区：
文献类型：
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作者：
Tay, L.;Lim, W. S.;Chong, M. S.
目的：在认知受损的社区居住老年人中，检查炎症和内分泌失调对（i）基线虚弱状态和（ii）1年时虚弱进展的独立和联合影响。设计：前瞻性队列研究。地点：三级记忆诊所。方法：我们招募了轻度认知障碍和轻中度阿尔茨海默病患者。在基线和1年时评估身体虚弱状态。在基线时测量全身性炎症的血液生物标志物[白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）]和合成代谢激素[胰岛素样生长因子-1（IGF-1）、硫酸脱氢表雄酮（DHEAS）]，并检查其与基线时身体虚弱状态和1年时进展的关系。每个受试者被分类为（i）既不是促炎性也不是内分泌缺陷，（ii）促炎性（IL-6或TNF-α，或两者，在最高四分位数）但不是内分泌缺陷，（iii）内分泌缺陷（IGF-1或DHEAS，或两者，在最低四分位数）但不是促炎性和（iv）促炎性和内分泌缺陷。结果：99例受试者中有20例（20.2%）在基线时身体虚弱。认知功能障碍的严重程度与基线虚弱状态之间没有相关性，但虚弱组的海马萎缩明显更大（中位MTA：2（2-3）vs 1（1-2），p=0.010）。在基线时身体虚弱的受试者中，TNF-α显著较高（中位TNF-α：1.30（0.60-1.40）vs 0.60（0.50-1.30）pg/mL，p=0.035）。在校正了年龄和性别的多元逻辑回归分析中，在没有伴随内分泌缺陷的情况下，促炎状态与基线时的身体虚弱显著相关（OR=4.99，95%C。I 1.25-19.88，p=0.023）;当模型中包括MTA评分时，这不再显著。单独的促炎状态（无内分泌缺陷）显著增加了1年时虚弱进展的几率（OR=4.06，95% CI 1.09-15.10，p=0.037）。促炎和内分泌缺陷状态的组合与基线或进行性身体虚弱无显著相关性。结论：促炎状态对身体虚弱产生不同的影响，仅在不存在伴随的内分泌缺陷状态的情况下才导致基线和进行性虚弱的风险增加，并通过神经变性进行潜在的介导。
Objectives: To examine the independent and combined effects of inflammation and endocrine dysregulation on (i) baseline frailty status and (ii) frailty progression at one year, among cognitively impaired community dwelling older adults. Design: Prospective cohort study. Setting: Tertiary Memory Clinic. Methods: We recruited patients with mild cognitive impairment and mild-moderate Alzheimer's disease. Physical frailty status was assessed at baseline and 1-year. Blood biomarkers of systemic inflammation [interleukin-6 (IL-6), tumour necrosis factor-a (TNF-alpha)] and anabolic hormones [insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEAS)] were measured at baseline and examined in relation to physical frailty status at baseline and progression at 1-year. Each subject was categorized as (i) neither pro-inflammatory nor endocrine deficient, (ii) pro-inflammatory (IL-6 or TNF-alpha, or both, being in highest quartile) but not endocrine deficient, (iii) endocrine deficient (IGF-1 or DHEAS, or both, being in lowest quartile) but not pro-inflammatory and (iv) both pro-inflammatory and endocrine deficient. Results: Twenty (20.2%) of 99 subjects were physically frail at baseline. There was no association between severity of cognitive impairment and baseline frailty status, but the frail group had significantly greater hippocampal atrophy (median MTA: 2 (2-3) vs 1 (1-2), p=0.010). TNF-alpha was significantly higher in subjects who were physically frail at baseline (median TNF-alpha: 1.30 (0.60-1.40) vs 0.60 (0.50-1.30) pg/mL, p=0.035). In multiple logistic regression adjusted for age and gender, a pro-inflammatory state in the absence of concomitant endocrine deficiency was significantly associated with physical frailty at baseline (OR=4.99, 95% C. I 1.25-19.88, p=0.023); this was no longer significant when MTA score was included in the model. Isolated pro-inflammatory state (without endocrine deficiency) significantly increased the odds of frailty progression (OR=4.06, 95% CI 1.09-15.10, p=0.037) at 1-year. The combination pro-inflammatory and endocrine deficient state was not significantly associated with either baseline or progressive physical frailty. Conclusion: A pro-inflammatory state exerts differential effects on physical frailty, contributing to the increased risk of baseline and progressive frailty only in the absence of a concomitant endocrine deficient state, with potential mediation via neurodegeneration.