The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: The VISIONS prospective cohort magnetic resonance imaging study

Center for Quality of Aging, Vanderbilt University Medical Center, Department of Medicine, Division of Allergy, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Critical care medicine (Impact Factor: 6.31). 05/2012; 40(7):2182-9. DOI: 10.1097/CCM.0b013e318250acdc
Source: PubMed


Evidence is emerging that delirium duration is a predictor of long-term cognitive impairment in intensive care unit survivors. Relationships between 1) delirium duration and brain white matter integrity, and 2) white matter integrity and long-term cognitive impairment are poorly understood and could be explored using magnetic resonance imaging.
A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging, and cognitive testing in intensive care unit survivors.
Delirium was evaluated with the Confusion Assessment Method for the Intensive Care Unit and cognitive outcomes were tested at 3 and 12-month follow-up. Following the intensive care unit stay, fractional anisotropy, a measure of white matter integrity, was calculated quantitatively using diffusion tensor imaging with a 3-T magnetic resonance imaging scanner at hospital discharge and 3-month follow-up. We examined associations between 1) delirium duration and fractional anisotropy and 2) fractional anisotropy and cognitive outcomes using linear regression adjusted for age and sepsis.
A total of 47 patients with a median age of 50 yrs completed the diffusion tensor imaging-magnetic resonance imaging protocol. Greater duration of delirium (3 vs. 0 days) was associated with lower fractional anisotropy (i.e., reduced fractional anisotropy = white matter disruption) in the genu (-0.02; p = .04) and splenium (-0.01; p = .02) of the corpus callosum and anterior limb of the internal capsule (-0.02; p =.01) at hospital discharge. These associations persisted at 3 months for the genu (-0.02; p =.02) and splenium (-0.01; p = .004). Lower fractional anisotropy in the anterior limb of internal capsule at discharge and in genu of corpus callosum at three months was associated with worse cognitive scores at 3 and 12 months.
In this pilot investigation, delirium duration in the intensive care unit was associated with white matter disruption at both discharge and 3 months. Similarly, white matter disruption was associated with worse cognitive scores up to 12 months later. This hypothesis-generating investigation may help design future studies to explore these complex relationships in greater depth.

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    • "This finding appears to be in contrast with the recent studies that showed MRI correlates of white-matter damage and brain atrophy in subjects with delirium. However, most of these studies had methodological limitations inherent in studying the difficult problem of delirium (Alsop et al., 2006; Soiza et al., 2008), such as a retrospective study design (Hatano et al., 2013; Root et al., 2013), lack of a control group, or no baseline pre-delirium imaging (Gunther et al., 2012; Morandi et al., 2012). Recently, a large prospective study (153 subjects aged 60 years or older, of which 16 developed delirium) reported a positive association between multiple brain infarcts on presurgical MRI and delirium occurrence after cardiac surgery (Otomo et al., 2013). "
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    ABSTRACT: Postoperative delirium is a common complication in older people and is associated with increased mortality, morbidity, institutionalization, and caregiver burden. Although delirium is an acute confusional state characterized by global impairments in attention and cognition, it has been implicated in permanent cognitive impairment and dementia. The pathogenesis of delirium and the mechanisms leading to these disabling consequences remain unclear. The present study is the first to address the potential predisposing role of brain morphologic changes toward postoperative delirium in a large prospective cohort of patients undergoing elective surgery using state-of-the-art magnetic resonance imaging (MRI) techniques conducted before admission. We investigated the association of MRI-derived quantitative measures of white-matter damage, global brain, and hippocampal volume with the incidence and severity of delirium. Presurgical white-matter hyperintensities (WMHs), whole brain, and hippocampal volume were measured in 146 consecutively enrolled subjects, ≥70 years old, without dementia who were undergoing elective surgery. These 3 presurgical MRI indices were tested as predictors of incidence and severity of subsequent delirium. Out of 146 subjects, 32 (22%) developed delirium. We found no statistically significant differences in WMH, whole brain, or hippocampal volume between subjects with and without delirium. Both unadjusted and adjusted (age, gender, vascular comorbidity, and general cognitive performance) regression analyses demonstrated no statistically significant association between any of the MRI measures with respect to delirium incidence or severity. In persons without dementia, preexisting cerebral WMHs, general and hippocampal atrophy may not predispose to postoperative delirium or worsen its severity. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 02/2015; 36(6). DOI:10.1016/j.neurobiolaging.2015.02.024 · 5.01 Impact Factor
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    • "Recent studies have demonstrated a relationship between delirium in the ICU and subsequent cognitive dysfunction [31-34]. Moreover, patients with longer duration of delirium also appear to have smaller brain volume at hospital discharge and at 3-months of follow-up, which appears to correlate with worse cognitive performance at 12 months [32,33]. Neurologic damage and cognitive impairment can also occur during acute renal failure [35-37]. "
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    ABSTRACT: Introduction Hospitalization increases the risk of a subsequent diagnosis of dementia. We aimed to identify diagnoses or events during a hospitalization requiring critical care that are associated with a subsequent dementia diagnosis in the elderly. Methods A cohort study of a random 5% sample of Medicare beneficiaries who received intensive care in 2005 and survived to hospital discharge, with three years of follow-up (through 2008) was conducted using Medicare claims files. We defined dementia using the International Classification of Diseases, 9th edition, clinical modification (ICD-9-CM) codes and excluded patients with any prior diagnosis of dementia or cognitive impairment in the year prior to admission. We used an extended Cox model to examine the association between diagnoses and events associated with the critical illness and a subsequent diagnosis of dementia, adjusting for known risk factors for dementia. Results Over the three years of follow-up, dementia was newly diagnosed in 4,519 (17.8%) of 25,368 patients who received intensive care and survived to hospital discharge. After accounting for known risk factors, having an infection (adjusted hazard ratio (AHR) = 1.25; 95% CI, 1.17 to 1.35), or a diagnosis of severe sepsis (AHR = 1.40; 95% CI, 1.28 to 1.53), acute neurologic dysfunction (AHR = 2.06; 95% CI, 1.72 to 2.46), and acute dialysis (AHR = 1.70; 95% CI, 1.30 to 2.23) were all independently associated with a subsequent diagnosis of dementia. No other measured ICU factors, such as need for mechanical ventilation, were independently associated. Conclusions Among ICU events, infection or severe sepsis, neurologic dysfunction, and acute dialysis were independently associated with a subsequent diagnosis of dementia. Patient prognostication, as well as future research into post-ICU cognitive decline, should focus on these higher-risk subgroups.
    Critical care (London, England) 12/2012; 16(6):R233. DOI:10.1186/cc11901 · 4.48 Impact Factor

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