Worsening cognitive impairment and neurodegenerative pathology progressively increase risk for delirium.
Worsening cognitive impairment and neurodegenerative pathology progressively increase risk for delirium.
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DOI：
10.1016/j.jagp.2014.08.005
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发表时间：
2015-04
影响因子：
7.2
通讯作者：
Cunningham, Colm
中科院分区：
文献类型：
--
作者：
Davis, Daniel H. J.;Skelly, Donal T.;Murray, Carol;Hennessy, Edel;Bowen, Jordan;Norton, Samuel;Brayne, Carol;Rahkonen, Terhi;Sulkava, Raimo;Sanderson, David J.;Rawlins, J. Nicholas;Bannerman, David M.;MacLullich, Alasdair M. J.;Cunningham, Colm
关键词：
谵妄是由急性疾病引起的一种严重的神经精神障碍。虽然痴呆是主要的危险因素，但就谵妄风险而言，这通常被认为是一个二元量（即认知受损与认知正常）。我们使用人类和小鼠来验证潜在的神经退行性改变和/或认知障碍的严重程度会逐渐改变谵妄风险的假设。在一项以人群为基础的纵向研究中，Vantaa 85+对偶发性谵妄进行了随访。在随访中报告谵妄（结果）的几率使用随机效应逻辑回归建模，其中考虑了通过迷你精神状态检查（MMSE）（暴露）测量的先前认知障碍。为了研究潜在的神经退行性病理是否增加了对急性认知变化的易感性，研究人员对处于神经退行性疾病进展三个阶段的小鼠（ME7神经退行性疾病模型：对照组、12周和16周）进行了评估，评估了细菌脂多糖（LPS, 100 μg/kg）诱导的全身炎症引起的急性认知功能障碍。利用免疫组织化学方法评估突触和轴突对急性功能障碍的易感性。在Vantaa队列中，465人（88.4±2.8岁）在基线时完成了MMSE。每失去一个MMSE点，发生谵妄的风险增加5% （p = 0.02）。LPS在16周ME7小鼠中导致严重和波动的认知缺陷，但在12周ME7小鼠和对照组中发生率较低或无缺陷。这与进行性丘脑突触丧失和轴突病理有关。一项以人群为基础的现有认知障碍严重程度分级的队列研究和一项进行性神经退行性变的小鼠模型均表明，谵妄的风险随着现有认知障碍和神经病理学的严重程度而增加。
Delirium is a profound neuropsychiatric disturbance precipitated by acute illness. Although dementia is the major risk factor this has typically been considered a binary quantity (i.e., cognitively impaired versus cognitively normal) with respect to delirium risk. We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and/or cognitive impairment progressively alters delirium risk. Humans in a population-based longitudinal study, Vantaa 85+, were followed for incident delirium. Odds for reporting delirium at follow-up (outcome) were modeled using random-effects logistic regression, where prior cognitive impairment measured by Mini-Mental State Exam (MMSE) (exposure) was considered. To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change, mice at three stages of neurodegenerative disease progression (ME7 model of neurodegeneration: controls, 12 weeks, and 16 weeks) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide (LPS; 100 μg/kg). Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry. In the Vantaa cohort, 465 persons (88.4 ± 2.8 years) completed MMSE at baseline. For every MMSE point lost, risk of incident delirium increased by 5% (p = 0.02). LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls, respectively. This was associated with progressive thalamic synaptic loss and axonal pathology. A human population-based cohort with graded severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology.
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影响因子：
8.8
作者：
Greene NH;Attix DK;Weldon BC;Smith PJ;McDonagh DL;Monk TG
通讯作者：
Monk TG
影响因子：
168.9
作者：
Inouye, Sharon K.;Westendorp, Rudi G. J.;Saczynski, Jane S.
通讯作者：
Saczynski, Jane S.
DOI：
10.1111/j.1532-5415.2005.53120.x
发表时间：
2005-02-01
影响因子：
6.3
作者：
Inouye, SK;Leo-Summers, L;Agostini, JV
通讯作者：
Agostini, JV
DOI：
10.1523/jneurosci.4673-11.2012
发表时间：
2012-05-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Field RH;Gossen A;Cunningham C
通讯作者：
Cunningham C
影响因子：
2.6
作者：
Fick, Donna M.;Steis, Melinda R.;Waller, Jennifer L.;Inouye, Sharon K.
通讯作者：
Inouye, Sharon K.