26 February 2010. In conversations with their patients’ loved ones, doctors may hear grumblings of how the triple bypass gave Grandpa a new heart but messed with his mind. Now, a prospective study led by William Ehlenbach and Eric Larson of the University of Washington, Seattle, seems to lend credence to such claims. “They're able to quantify and demonstrate what physicians assume and practice. That is, they demonstrate that if you're elderly and chugging along and you get hospitalized, that hospitalization can take out a piece of your cognition,” Lon Schneider, University of Southern California, Los Angeles, said of the new work, which appears in this week’s JAMA. “And if it's a hospitalization for a critical illness, it can take out twice as much of your cognition.” Specific mechanisms behind this association remain unclear; still, the authors and others hope the findings will encourage physicians to be more vigilant in detecting cognitive impairment that may develop after medical illness requiring hospitalization.
Prior research has suggested a link between critical illness and subsequent cognitive decline (e.g., Rothenhäusler et al., 2001; Hopkins et al., 2005; Sukantarat et al., 2005). The current study is the first to include cognitive evaluations done before participants ended up in the hospital bed, whereas previous studies have recruited patients during their critical illness, Ehlenbach said.
He and colleagues analyzed data from 2,929 Seattle-area elderly in an ongoing longitudinal study of aging and dementia called Adult Changes in Thought (ACT). Study subjects were cognitively normal at baseline and screened about every two years with the Cognitive Abilities Screening Instrument (CASI). With scores ranging from 0 to 100, the 40-question CASI measures several domains (e.g., attention and concentration) not covered by the slimmer Mini-Mental State Exam (MMSE), but it is less comprehensive than a full neuropsychological battery. Study participants scoring below 86 on the CASI (equivalent to a MMSE score of 25 to 26) received a full clinical evaluation for dementia.
During an average follow-up of 6.1 years, 41 people had critical illness requiring hospitalization (e.g., heart attack, stroke, acute respiratory failure), and 1,287 were hospitalized for non-critical conditions. Measuring cognition before and after hospitalization, CASI scores of critical illness patients dropped on average 2.14 points more than in the 1,601 people with no hospitalization who were assessed at similar time points. Among participants hospitalized for non-critical conditions, CASI scores fell on average 1.01 points more than in the non-hospitalized group. Furthermore, critical illness patients were more than twice as likely to develop dementia during the study, and those hospitalized for lesser reasons were 1.4 times as prone to dementia, compared to non-hospitalized study participants.
All told, the study “should remind investigators and preclinical scientists that the onset of dementia in humans is fairly complex,” Schneider said. “The expression and onset of disease is modulated by a wide variety of serious medical illness that might just push a patient who is otherwise uncompromised over the tipping point.” As such, medical illness requiring hospitalization can be seen as a “risk factor in people who don’t seem to have cognitive impairment before they go to the hospital,” Schneider told ARF. Untreated poor vision was identified as another factor contributing to late-life dementia in a study of 625 seniors published online February 11 in the American Journal of Epidemiology (Rogers and Langa, 2010).
The JAMA study authors acknowledge several limitations of their analysis, most notably the time interval between study visits. “While the longitudinal nature of this study is a strength,” they wrote, “the fact that study visits occurred every two years means that a hospitalization is only one of a number of possible significant events that could result in cognitive decline.”
Some of the critical illness hospitalizations may have been a result of fading cognition that triggered poor control of another disease, suggested Bill Thies, chief medical and scientific officer of the Alzheimer’s Association in Chicago, Illinois. “A classic example is the diabetic who arrives at the hospital in a coma because he has forgotten how to take care of his disease,” Thies mentioned in an e-mail.
Nevertheless, the study suggests that seniors surviving a critical illness may warrant more careful monitoring for potential cognitive decline that could arise after hospitalization. This becomes paramount as the Alzheimer disease field moves toward earlier diagnosis and eventually prevention trials (see ARF related news story), noted Sam Gandy, Mount Sinai School of Medicine, New York, in an e-mail to ARF. “In-hospital evaluations would provide an appropriate environment for dementia screening,” he wrote. “There has been much controversy about this topic, and it would seem to me that the inpatient setting would be a natural place to start." That controversy partly revolves around the question of whether to screen for dementia in primary care (Ashford et al., 2007; Brayne et al., 2007). Moreover, if patients do develop dementia after a critical hospitalization, recent data suggest their cognitive decline might be slowed by aggressively treating their comorbidities, Gandy wrote, citing studies on regular exercise (Rolland et al., 2007) and anti-hypertensive treatment (Saxby et al., 2008).
Ehlenbach and colleagues are designing further studies to address more specifically what underlies the link between hospitalization and subsequent cognitive impairment. “Is it certain diagnoses? Is it certain abnormalities of physiology that can occur during critical illness? This will be an important step to perhaps modify the care offered during critical illness,” Ehlenbach said.
Some of the future work will focus on understanding pathological mechanisms. Intensive-care patients routinely experience drops in blood pressure and/or oxygen levels, and recent work has raised the possibility that treatment with anesthesia could nudge people closer to AD (see ARF related news story). In addition, Ehlenbach points out, “many critical illness syndromes involve fairly dramatic whole-body inflammation that has an effect on small blood vessels everywhere in the body, including the brain.” He and others agree it’s unlikely to be one but rather many factors that contribute to cognitive decline after critical illness. However, “if we learn that one or two of these are dominant, those are potential targets for intervention,” Ehlenbach said.—Esther Landhuis.
Ehlenbach WJ, Hough CL, Crane PK, Haneuse SJ, Carson SS, Curtis JR, Larson EB. Association Between Acute Care and Critical Illness Hospitalization and Cognitive Function in Older Adults. JAMA. 2010 February 24;303(8):763-770. Abstract