Max L. Gunther

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*.

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. Design, Setting, Patients:A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging, and cognitive testing in intensive care unit survivors. Measurements: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.

The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: the VISIONS cohort magnetic resonance imaging study*.

Objective:Delirium duration is predictive of long-term cognitive impairment in intensive care unit survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and long-term cognitive impairment, we conducted this exploratory investigation of the associations between delirium duration, brain volumes, and long-term cognitive impairment. Design, Setting, and Patients:A prospective cohort of medical and surgical intensive care unit survivors with respiratory failure or shock. Measurements:Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and 3-month follow-up. Delirium was evaluated using the confusion assessment method for the intensive care unit; cognitive outcomes were tested at 3- and 12-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results:A total of 47 patients completed the magnetic resonance imaging protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio at hospital discharge (0.76, 95% confidence intervals [0.10, 1.41]; p = .03) and at 3-month follow-up (0.62 [0.02, 1.21], p = .05). Longer duration of delirium was associated with smaller superior frontal lobe (−2.11 cm3 [−3.89, −0.32]; p = .03) and hippocampal volumes at discharge (−0.58 cm3 [−0.85, −0.31], p < .001)—regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher ventricle-to-brain ratio) at 3 months was associated with worse cognitive performances at 12 months (lower Repeatable Battery for the Assessment of Neuropsychological Status score −11.17 [−21.12, −1.22], p = .04). Smaller superior frontal lobes, thalamus, and cerebellar volumes at 3 months were associated with worse executive functioning and visual attention at 12 months. Conclusions:These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to 3 months after discharge, and that smaller brain volumes are associated with long-term cognitive impairment up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

Insulin-like growth factor-1 and delirium in critically ill mechanically ventilated patients: a preliminary investigation.

BACKGROUND Delirium occurs frequently in the intensive care unit (ICU), but its pathophysiology is still unclear. Low levels of insulin-like growth factor 1 (IGF-1), a hormone with neuroprotective properties, have been associated with delirium in some non-ICU studies, but this relationship has not been examined in the ICU. We sought to test the hypothesis that low IGF-1 concentrations are associated with delirium during critical illness. METHODS Mechanically ventilated medical ICU patients were prospectively enrolled, and blood was collected after enrollment for measurement of IGF-1 using radioimmunometric assay. Delirium and coma were identified daily using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale, respectively. The association between IGF-1 and delirium was evaluated with logistic regression. In addition, the association between IGF-1 and duration of normal mental state, measured as days alive without delirium or coma, was assessed using multiple linear regression. RESULTS Among 110 patients, the median age was 65 years (IQR, 52-75) and APACHE II was 27 (IQR, 22 -32). IGF-1 levels were not a risk factor for delirium on the day after IGF-1 measurement (p = 0.97), at which time 65% of the assessable patients were delirious. No significant association was found between IGF-1 levels and duration of normal mental state (p = 0.23). CONCLUSIONS This pilot study, the first to investigate IGF-1 and delirium in critically ill patients, found no association between IGF-1 and delirium. Future studies including serial measurements of IGF-1 and IGF-1 binding proteins are needed to determine whether this hormone has a role in delirium during critical illness.

The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors

Objective:Delirium duration is predictive of long-term cognitive impairment in intensive care unit survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and long-term cognitive impairment, we conducted this exploratory investigation of the associations between delirium duration, brain volumes, and long-term cognitive impairment. Design, Setting, and Patients:A prospective cohort of medical and surgical intensive care unit survivors with respiratory failure or shock. Measurements:Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and 3-month follow-up. Delirium was evaluated using the confusion assessment method for the intensive care unit; cognitive outcomes were tested at 3- and 12-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results:A total of 47 patients completed the magnetic resonance imaging protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio at hospital discharge (0.76, 95% confidence intervals [0.10, 1.41]; p = .03) and at 3-month follow-up (0.62 [0.02, 1.21], p = .05). Longer duration of delirium was associated with smaller superior frontal lobe (−2.11 cm3 [−3.89, −0.32]; p = .03) and hippocampal volumes at discharge (−0.58 cm3 [−0.85, −0.31], p < .001)—regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher ventricle-to-brain ratio) at 3 months was associated with worse cognitive performances at 12 months (lower Repeatable Battery for the Assessment of Neuropsychological Status score −11.17 [−21.12, −1.22], p = .04). Smaller superior frontal lobes, thalamus, and cerebellar volumes at 3 months were associated with worse executive functioning and visual attention at 12 months. Conclusions:These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to 3 months after discharge, and that smaller brain volumes are associated with long-term cognitive impairment up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

The Association between Brain Volumes, Delirium Duration and Cognitive Outcomes in Intensive Care Unit Survivors: A Prospective Exploratory Cohort Magnetic Resonance Imaging Study

Objective:Delirium duration is predictive of long-term cognitive impairment in intensive care unit survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and long-term cognitive impairment, we conducted this exploratory investigation of the associations between delirium duration, brain volumes, and long-term cognitive impairment. Design, Setting, and Patients:A prospective cohort of medical and surgical intensive care unit survivors with respiratory failure or shock. Measurements:Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and 3-month follow-up. Delirium was evaluated using the confusion assessment method for the intensive care unit; cognitive outcomes were tested at 3- and 12-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results:A total of 47 patients completed the magnetic resonance imaging protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio at hospital discharge (0.76, 95% confidence intervals [0.10, 1.41]; p = .03) and at 3-month follow-up (0.62 [0.02, 1.21], p = .05). Longer duration of delirium was associated with smaller superior frontal lobe (−2.11 cm3 [−3.89, −0.32]; p = .03) and hippocampal volumes at discharge (−0.58 cm3 [−0.85, −0.31], p < .001)—regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher ventricle-to-brain ratio) at 3 months was associated with worse cognitive performances at 12 months (lower Repeatable Battery for the Assessment of Neuropsychological Status score −11.17 [−21.12, −1.22], p = .04). Smaller superior frontal lobes, thalamus, and cerebellar volumes at 3 months were associated with worse executive functioning and visual attention at 12 months. Conclusions:These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to 3 months after discharge, and that smaller brain volumes are associated with long-term cognitive impairment up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

Deciphering spousal intentions: An fMRI study of couple communication

Several relational theories suggest that advice, particularly advice in areas important to the self, may be cognitively processed differently than other types of support (e.g., nondirective support) or low importance advice. Little is known, however, about the neurocognitive substrates of such complex social behaviors. We hypothesized that the Superior Temporal Sulcus (STS) and the Medial Prefrontal Cortex (MPFC), cortical regions previously linked to Theory of Mind (ToM), would be more active for high than low importance advice. Results indicated that high importance advice was associated with greater activation in the left MPFC and bilaterally in the STS. Similar results were obtained when compared to positive comments. These findings indicate that when given advice individuals may be attempting to infer motivation.