Statins and Brain Dysfunction A Hypothesis to Reduce the Burden of Cognitive Impairment in Patients Who Are Critically III

Center for Quality of Aging, Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN 37212, USA.
Chest (Impact Factor: 7.13). 09/2011; 140(3):580-5. DOI: 10.1378/chest.10-3065
Source: PubMed

ABSTRACT Delirium is a frequent form of acute brain dysfunction in patients who are critically ill and is associated with poor clinical outcomes, including a critical illness brain injury that may last for months to years. Despite widespread recognition of significant adverse outcomes, pharmacologic approaches to prevent or treat delirium during critical illness remain unproven. We hypothesize that commonly prescribed statin medications may prevent and treat delirium by targeting molecular pathways of inflammation (peripheral and central) and microglial activation that are central to the pathogenesis of delirium. Systemic inflammation, a principal mechanism of injury, for example, in sepsis, acute respiratory distress syndrome, and other critical illnesses, can cause neuronal apoptosis, blood-brain barrier injury, brain ischemia, and microglial activation. We hypothesize that the known pleiotropic effects of statins, which attenuate such neuroinflammation, may redirect microglial activation and promote an antiinflammatory phenotype, thereby offering the potential to reduce the public health burden of delirium and its associated long-term cognitive injury.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Since statins have pleiotropic effects on inflammation and coagulation that may interrupt delirium pathogenesis, we tested the hypotheses that statin exposure is associated with reduced delirium during critical illness, whereas discontinuation of statin therapy is associated with increased delirium. Multicenter, prospective cohort study. Medical and surgical ICUs in two large tertiary care hospitals in the United States. Patients with acute respiratory failure or shock. None. We measured statin exposure prior to hospitalization and daily during the ICU stay, and we assessed patients for delirium twice daily using the Confusion Assessment Method for the ICU. Of 763 patients included, whose median (interquartile range) age was 61 years (51-70 yr) and Acute Physiology and Chronic Health Evaluation II was 25 (19-31), 257 (34%) were prehospital statin users and 197 (26%) were ICU statin users. Overall, delirium developed in 588 patients (77%). After adjusting for covariates, ICU statin use was associated with reduced delirium (p < 0.01). This association was modified by sepsis and study day; for example, statin use was associated with reduced delirium among patients with sepsis on study day 1 (odds ratio, 0.22; 95% CI, 0.10-0.49) but not among patients without sepsis on day 1 (odds ratio, 0.92; 95% CI, 0.46-1.84) or among those with sepsis later, for example, on day 13 (odds ratio, 0.70; 95% CI, 0.35-1.41). Prehospital statin use was not associated with delirium (odds ratio, 0.86; 95% CI, 0.44-1.66; p = 0.18), yet the longer a prehospital statin user's statin was held in the ICU, the higher the odds of delirium (overall p < 0.001 with the odds ratio depending on sepsis status and study day due to significant interactions). In critically ill patients, ICU statin use was associated with reduced delirium, especially early during sepsis; discontinuation of a previously used statin was associated with increased delirium.
    Critical care medicine 05/2014; 42(8). DOI:10.1097/CCM.0000000000000398 · 6.15 Impact Factor
  • Critical Care Medicine 08/2014; 42(8):1955-1957. DOI:10.1097/CCM.0000000000000448 · 6.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effect of statins on functional status in older patients is unclear. Statins might carry a deleterious effect on muscle function leading to myopathy and therefore affecting functional recovery. We evaluated the relationship between statin exposure at in-hospital rehabilitation admission and functional outcome at discharge. This was a retrospective cohort study of older patients 70 years and older consecutively admitted to an in-hospital rehabilitation after an acute hospitalization. Statin exposure was measured at the time of rehabilitation admission. Functional status was defined with the Barthel Index score at the time of discharge. A multivariable linear regression model was used to evaluate the association between statin exposure and functional status at discharge adjusting for potential confounders through a propensity score for statin exposure. A total of 2,435 patients were included. The cohort had a mean age of 81.1 years. Of these 9% (N=220) were on statins at the time of admission. In the multivariable analysis, the use of statins at the time of admission was independently associated with an improved functional status at discharge (Point Estimate 5.2; 95% Confidence Interval: 1.5-8.9; p<0.01) after adjusting for relevant confounders; patients who were receiving statins at the time of admission had a Barthel Index score 5 points higher compared to those who were not receiving statins. The use of statins was overall safe in a group of comorbid older patients undergoing rehabilitation training after an acute hospitalization. Additionally, a possible benefit was found given the positive association between statin use and higher functional status at discharge.
    Rejuvenation Research 09/2014; DOI:10.1089/rej.2014.1604 · 3.93 Impact Factor


Available from