A study protocol for an observational cohort investigating COGnitive outcomes and WELLness in survivors of critical illness: the COGWELL study

M Elizabeth Wilcox, Andrew S Lim, Mary P McAndrews, Richard A Wennberg, Ruxandra L Pinto, Sandra E Black, Karolina D Walczak, Jan O Friedrich, Michael S Taglione, Gordon D Rubenfeld, M Elizabeth Wilcox, Andrew S Lim, Mary P McAndrews, Richard A Wennberg, Ruxandra L Pinto, Sandra E Black, Karolina D Walczak, Jan O Friedrich, Michael S Taglione, Gordon D Rubenfeld

Abstract

Introduction: Up to 9 out of 10 intensive care unit (ICU) survivors will suffer some degree of cognitive impairment at hospital discharge and approximately half will have decrements that persist for years. The mechanisms for this newly acquired brain injury are poorly understood. The purpose of this study is to describe the prevalence of sleep abnormalities and their association with cognitive impairment, examine a well-known genetic risk factor for dementia (Apolipoprotein E ε4) that may allow for genetic risk stratification of ICU survivors at greatest risk of cognitive impairment and determine if electroencephalography (EEG) is an independent predictor of long-term cognitive impairment and possibly a candidate intermediate end point for future clinical trials.

Methods and analysis: This is a multisite, prospective, observational cohort study. The setting for this trial will be medical and surgical ICUs of five large tertiary care referral centres. The participants will be adult patients admitted to a study ICU and invasively ventilated for ≥3 days . Participants will undergo follow-up within 7 days of ICU discharge, 6 months and 1 year. At each time point, patients will have an EEG, blood work (biomarkers; gene studies), sleep study (actigraphy), complete a number of questionnaires as well as undergo neuropsychological testing. The primary outcome of this study will be long-term cognitive function at 12 months follow-up as measured by the Repeatable Battery for the Assessment of Neuropsychological Status and Trails Making Test B.

Ethics and dissemination: The study has received the following approvals: University Health Network Research Ethics Committee (13-6425-BE), Sunnybrook Health Centre Research Ethics Committee (365-2013), Mount Sinai Research Ethics Committee (14-0194-E) and St. Michael's Hospital Research Ethics Committee (14-295). Results will be made available to critical care survivors, their caregivers, the funders, the critical care societies and other researchers.

Trial registration number: NCT02086877; Pre-results.

Keywords: Critical Illness.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Flow diagram of the COGnitive Outcome and WELLness in survivors of critical illness (COGWELL) study. APOE, Apolipoprotein E; CAM-ICU, Confusion Assessment Method in the ICU; EEG, electroencephalography; ICU, intensive care unit; IQCODE-SF, Informant Questionnaire on Cognitive Decline in the Elderly Short Form; PSQI, Pittsburgh Sleep Quality Index; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; TICS, Telephone Interview for Cognitive Status.

References

    1. Hopkins RO, Jackson JC, Wallace C. Neurocognitive impairments in ICU patients with prolonged mechanical ventilation [abstract]. J Int Neuropsychol Soc 2005;11:A60.
    1. Ambrosino N, Bruletti G, Scala V, et al. . Cognitive and perceived health status in patient with chronic obstructive pulmonary disease surviving acute on chronic respiratory failure: a controlled study. Intensive Care Med 2002;28:170–7. 10.1007/s00134-001-1165-6
    1. Iwashyna TJ, Ely EW, Smith DM, et al. . Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010;304:1787–94. 10.1001/jama.2010.1553
    1. Semmler A, Widmann CN, Okulla T, et al. . Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. J Neurol Neurosurg Psychiatry 2013;84:62–9. 10.1136/jnnp-2012-302883
    1. Torgersen J, Hole JF, Kvåle R, et al. . Cognitive impairments after critical illness. Acta Anaesthesiol Scand 2011;55:1044–51. 10.1111/j.1399-6576.2011.02500.x
    1. Wilcox ME, Brummel NE, Archer K, et al. . Cognitive dysfunction in ICU patients: risk factors, predictors, and rehabilitation interventions. Crit Care Med 2013;41:S81–98. 10.1097/CCM.0b013e3182a16946
    1. Lim AS, Yu L, Kowgier M, et al. . Sleep fragmentation modifies the impact of the APOE4 allele on the risk of incident Alzheimer Disease and cognitive decline in older persons (Platform Presentation) 65th annual meeting of the American Academy of Neurology. San Diego CA, 2013.
    1. Lim AS, Yu L, Costa MD, et al. . Increased fragmentation of rest-activity patterns is associated with a characteristic pattern of cognitive impairment in older individuals. Sleep 2012;35:633–40. 10.5665/sleep.1820
    1. Lim AS, Saper CB. Sleep, circadian rhythms, and dementia. Ann Neurol 2011;70:677–9. 10.1002/ana.22637
    1. Blackwell T, Yaffe K, Ancoli-Israel S, et al. . Association of sleep characteristics and cognition in older community-dwelling men: the MrOS sleep study. Sleep 2011;34:1347–56. 10.5665/SLEEP.1276
    1. Gozal D, Capdevila OS, Kheirandish-Gozal L, et al. . APOE epsilon 4 allele, cognitive dysfunction, and obstructive sleep apnea in children. Neurology 2007;69:243–9. 10.1212/01.wnl.0000265818.88703.83
    1. Kang JE, Lim MM, Bateman RJ, et al. . Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 2009;326:1005–7. 10.1126/science.1180962
    1. Ju YE, McLeland JS, Toedebusch CD, et al. . Sleep quality and preclinical Alzheimer disease. JAMA Neurol 2013;70:1–7. 10.1001/jamaneurol.2013.2334
    1. Bushey D, Tononi G, Cirelli C. Sleep and synaptic homeostasis: structural evidence in Drosophila. Science 2011;332:1576–81. 10.1126/science.1202839
    1. Arrigoni E, Lu J, Vetrivelan R, et al. . Long-term synaptic plasticity is impaired in rats with lesions of the ventrolateral preoptic nucleus. Eur J Neurosci 2009;30:2112–20. 10.1111/j.1460-9568.2009.07001.x
    1. Mueller AD, Mear RJ, Mistlberger RE. Inhibition of hippocampal neurogenesis by sleep deprivation is independent of circadian disruption and melatonin suppression. Neuroscience 2011;193:170–81. 10.1016/j.neuroscience.2011.07.019
    1. Guzman-Marin R, Suntsova N, Methippara M, et al. . Sleep deprivation suppresses neurogenesis in the adult hippocampus of rats. Eur J Neurosci 2005;22:2111–6. 10.1111/j.1460-9568.2005.04376.x
    1. Cirelli C, Faraguna U, Tononi G. Changes in brain gene expression after long-term sleep deprivation. J Neurochem 2006;98:1632–45. 10.1111/j.1471-4159.2006.04058.x
    1. Orwelius L, Nordlund A, Nordlund P, et al. . Prevalence of sleep disturbances and long-term reduced health-related quality of life after critical care: a prospective multicenter cohort study. Crit Care 2008;12:R97 10.1186/cc6973
    1. Lee CM, Herridge MS, Gabor JY, et al. . Chronic sleep disorders in survivors of the acute respiratory distress syndrome. Intensive Care Med 2009;35:314–20. 10.1007/s00134-008-1277-3
    1. Corder EH, Saunders AM, Strittmatter WJ, et al. . Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993;261:921–3. 10.1126/science.8346443
    1. Poirier J, Davignon J, Bouthillier D, et al. . Apolipoprotein E polymorphism and Alzheimer's disease. Lancet 1993;342:697–9. 10.1016/0140-6736(93)91705-Q
    1. Saunders AM, Strittmatter WJ, Schmechel D, et al. . Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993;43:1467–72. 10.1212/WNL.43.8.1467
    1. O'Hara R, Schröder CM, Kraemer HC, et al. . Nocturnal sleep apnea/hypopnea is associated with lower memory performance in APOE epsilon4 carriers. Neurology 2005;65:642–4. 10.1212/
    1. Cosentino FI, Bosco P, Drago V, et al. . The APOE epsilon4 allele increases the risk of impaired spatial working memory in obstructive sleep apnea. Sleep Med 2008;9:831–9. 10.1016/j.sleep.2007.10.015
    1. Jordan BD, Relkin NR, Ravdin LD, et al. . Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. JAMA 1997;278:136–40. 10.1001/jama.1997.03550020068040
    1. Hou X, Guo L, Zhan Q, et al. . Extracorporeal membrane oxygenation for critically ill patients with 2009 influenza A (H1N1)-related acute respiratory distress syndrome: preliminary experience from a single center. Artif Organs 2012;36:780–6. 10.1111/j.1525-1594.2012.01468.x
    1. Ely EW, Girard TD, Shintani AK, et al. . Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients. Crit Care Med 2007;35:112–7. 10.1097/
    1. Pomara N, Willoughby L, Wesnes K, et al. . Apolipoprotein E epsilon4 allele and lorazepam effects on memory in high-functioning older adults. Arch Gen Psychiatry 2005;62:209–16. 10.1001/archpsyc.62.2.209
    1. Pomara N, Bruno D. Lower plasma β-amyloid levels are associated with moderately greater rate of cognitive decline among older people without dementia. Evid Based Ment Health 2011;14:41 10.1136/ebmh.14.2.41
    1. Woon FL, Dunn CB, Hopkins RO. Predicting cognitive sequelae in survivors of critical illness with cognitive screening tests. Am J Respir Crit Care Med 2012;186:333–40. 10.1164/rccm.201112-2261OC
    1. Jacobson SA, Leuchter AF, Walter DO, et al. . Serial quantitative EEG among elderly subjects with delirium. Biol Psychiatry 1993;34:135–40. 10.1016/0006-3223(93)90382-N
    1. Young GB, Blume WT, Campbell VM, et al. . Alpha, theta and alpha-theta coma: a clinical outcome study utilizing serial recordings. Electroencephalogr Clin Neurophysiol 1994;91:93–9. 10.1016/0013-4694(94)90030-2
    1. Young GB, Bolton CF, Archibald YM, et al. . The electroencephalogram in sepsis-associated encephalopathy. J Clin Neurophysiol 1992;9:145–52. 10.1097/00004691-199201000-00016
    1. Watson PL, Shintani AK, Tyson R, et al. . Presence of electroencephalogram burst suppression in sedated, critically ill patients is associated with increased mortality. Crit Care Med 2008;36:3171–7. 10.1097/CCM.0b013e318186b9ce
    1. Charlson M, Szatrowski TP, Peterson J, et al. . Validation of a combined comorbidity index. J Clin Epidemiol 1994;47:1245–51. 10.1016/0895-4356(94)90129-5
    1. Elixhauser A, Steiner C, Harris DR, et al. . Comorbidity measures for use with administrative data. Med Care 1998;36:8–27. 10.1097/00005650-199801000-00004
    1. Weiss AR, Johnson NL, Berger NA, et al. . Validity of activity-based devices to estimate sleep. J Clin Sleep Med 2010;6:336–42.
    1. Lim AS, Chang AM, Shulman JM, et al. . A common polymorphism near PER1 and the timing of human behavioral rhythms. Ann Neurol 2012;72:324–34. 10.1002/ana.23636
    1. Lim AS, Yu L, Costa MD, et al. . Quantification of the fragmentation of rest-activity patterns in elderly individuals using a state transition analysis. Sleep 2011;34:1569–81. 10.5665/sleep.1400
    1. Sokolove PG, Bushell WN. The chi square periodogram: its utility for analysis of circadian rhythms. J Theor Biol 1978;72:131–60. 10.1016/0022-5193(78)90022-X
    1. Richards KC, O'Sullivan PS, Phillips RL. Measurement of sleep in critically ill patients. J Nurs Meas 2000;8:131–44.
    1. Buysse DJ, Reynolds CF, Monk TH, et al. . The Pittsburgh Sleep Quality Index (PSQI): A new instrument for psychiatric research and practice. Psychiatry Research 1989;28:193–213.
    1. Hinrikus H, Suhhova A, Bachmann M, et al. . Spectral features of EEG in depression. Biomed Tech 2010;55:155–61. 10.1515/bmt.2010.011
    1. Helkala EL, Laulumaa V, Soikkeli R, et al. . Slow-wave activity in the spectral analysis of the electroencephalogram is associated with cortical dysfunctions in patients with Alzheimer's disease. Behav Neurosci 1991;105:409–15. 10.1037/0735-7044.105.3.409
    1. Soininen H, Partanen J, Laulumaa V, et al. . Longitudinal EEG spectral analysis in early stage of Alzheimer's disease. Electroencephalogr Clin Neurophysiol 1989;72:290–7. 10.1016/0013-4694(89)90064-3
    1. Richter P, Werner J, Heerlein A, et al. . On the validity of the Beck Depression Inventory. A review. Psychopathology 1998;31:160–8. 10.1159/000066239
    1. Duggan MC, Wang L, Wilson JE, et al. . The relationship between executive dysfunction, depression, and mental health-related quality of life in survivors of critical illness: Results from the BRAIN-ICU investigation. J Crit Care 2017;37:72–9. 10.1016/j.jcrc.2016.08.023
    1. Jorm AF. The Informant Questionnaire on cognitive decline in the elderly (IQCODE): a review. Int Psychogeriatr 2004;16:275–93. 10.1017/S1041610204000390
    1. Randolph C, Tierney MC, Mohr E, et al. . The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol 1998;20:310–9. 10.1076/jcen.20.3.310.823
    1. Duff K, Hobson VL, Beglinger LJ, et al. . Diagnostic accuracy of the RBANS in mild cognitive impairment: limitations on assessing milder impairments. Arch Clin Neuropsychol 2010;25:429–41. 10.1093/arclin/acq045
    1. Duff K, Humphreys Clark JD, O'Bryant SE, et al. . Utility of the RBANS in detecting cognitive impairment associated with Alzheimer's disease: sensitivity, specificity, and positive and negative predictive powers. Arch Clin Neuropsychol 2008;23:603–12. 10.1016/j.acn.2008.06.004
    1. McKay C, Casey JE, Wertheimer J, et al. . Reliability and validity of the RBANS in a traumatic brain injured sample. Arch Clin Neuropsychol 2007;22:91–8. 10.1016/j.acn.2006.11.003
    1. Hobson VL, Hall JR, Humphreys-Clark JD, et al. . Identifying functional impairment with scores from the repeatable battery for the assessment of neuropsychological status (RBANS). Int J Geriatr Psychiatry 2010;25:525–30. 10.1002/gps.2382
    1. Reitan RM, W D. The Halstead Reitan neuropsychological test battery. Tucson, AZ: Neuropsychology Press, 1985.
    1. Knopman DS, Roberts RO, Geda YE, et al. . Validation of the telephone interview for cognitive status-modified in subjects with normal cognition, mild cognitive impairment, or dementia. Neuroepidemiology 2010;34:34–42. 10.1159/000255464
    1. Plassman BL, Langa KM, Fisher GG, et al. . Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology 2007;29(1-2):125–32. 10.1159/000109998
    1. Crimmins EM, Kim JK, Langa KM, et al. . Assessment of cognition using surveys and neuropsychological assessment: the Health and Retirement Study and the Aging, Demographics, and Memory Study. J Gerontol B Psychol Sci Soc Sci 2011;66(Suppl 1):i162–i171. 10.1093/geronb/gbr048
    1. Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol 2007;165:710–8. 10.1093/aje/kwk052
    1. Davidson TA, Rubenfeld GD, Caldwell ES, et al. . The effect of acute respiratory distress syndrome on long-term survival. Am J Respir Crit Care Med 1999;160:1838–42. 10.1164/ajrccm.160.6.9903058
    1. Herridge MS, Tansey CM, Matté A, et al. . Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 2011;364:1293–304. 10.1056/NEJMoa1011802
    1. Girard TD, Kress JP, Fuchs BD, et al. . Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008;371:126–34. 10.1016/S0140-6736(08)60105-1
    1. Alexander LD, Pettersen JA, Hopyan JJ, et al. . Long-term prediction of functional outcome after stroke using the Alberta Stroke Program Early Computed Tomography Score in the subacute stage. J Stroke Cerebrovasc Dis 2012;21:737–44. 10.1016/j.jstrokecerebrovasdis.2011.03.010
    1. Clarke PJ, Lawrence JM, Black SE. Changes in quality of life over the first year after stroke: findings from the Sunnybrook Stroke Study. J Stroke Cerebrovasc Dis 2000;9:121–7. 10.1053/jscd.2000.5868
    1. Tansey CM, Matté AL, Needham D, et al. . Review of retention strategies in longitudinal studies and application to follow-up of ICU survivors. Intensive Care Med 2007;33:2051–7. 10.1007/s00134-007-0817-6

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