title: 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*.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging, and cognitive testing in intensive care unit survivors.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. alessandro@gmail.com
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morandi
authors.forename: Baxter P
authors.initials: BP
authors.lastname: Rogers
authors.forename: Max L
authors.initials: ML
authors.lastname: Gunther
authors.forename: Kristen
authors.initials: K
authors.lastname: Merkle
authors.forename: Pratik
authors.initials: P
authors.lastname: Pandharipande
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Girard
authors.forename: James C
authors.initials: JC
authors.lastname: Jackson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Thompson
authors.forename: Ayumi K
authors.initials: AK
authors.lastname: Shintani
authors.forename: Sunil
authors.initials: S
authors.lastname: Geevarghese
authors.forename: Russell R
authors.initials: RR
authors.lastname: Miller
authors.forename: Angelo
authors.initials: A
authors.lastname: Canonico
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Cannistraci
authors.forename: John C
authors.initials: JC
authors.lastname: Gore
authors.forename: E Wesley
authors.initials: EW
authors.lastname: Ely
authors.forename: Ramona O
authors.initials: RO
authors.lastname: Hopkins
mesh_terms: D000368:Aged; D016880:Anisotropy; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology*; D003337:Corpus Callosum / Q000473:pathology*; D003693:Delirium / Q000453:epidemiology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D021621:Imaging, Three-Dimensional; D007362:Intensive Care Units; D020772:Internal Capsule / Q000473:pathology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010865:Pilot Projects; D011446:Prospective Studies; D012494:Sampling Studies; D017741:Survivors; D013997:Time Factors