Each year, up to 56 percent of all hospitalized seniors over age 65 in the United States—more than 2.5 million people—experience delirium. The condition often follows fast on the heels of surgery, anesthesia, or serious illness, complicating hospital stays and delaying patients’ return to home, family, and friends. Typically acute at onset, delirium is marked by a constellation of neuropsychiatric abnormalities, chief of which are decreased attention span and a waxing and waning state of confusion. At best, delirium reverses quickly; at worst, its symptoms trigger serious, even fatal, consequences.
Now, funded by a five-year, $11 million grant from the National Institute on Aging, a team of scientists from Harvard Medical School, the Institute for Aging Research at Hebrew SeniorLife, Beth Israel Deaconess Medical Center, and Brigham and Women’s Hospital will examine the causes and outcomes of delirium, with the goal of finding new approaches to preventing it and its long-term consequences. Called SAGES (Successful AGing after Elective Surgery), the study will follow 500 surgery patients over the age of 70 for 18 to 36 months to assess their post-surgery cognitive and functional status.
“Delirium is a common complication of surgery, but it’s also preventable, ” says co-principal investigator Sharon K. Inouye, MD, an HMS professor of medicine and director of the Aging Brain Center at the Institute for Aging Research who has studied delirium and its manifestations for more than two decades. “SAGES will advance our understanding of the short- and long-term outcomes of delirium and, ultimately, help us improve care for older surgical patients,” she adds.
Proper diagnosis is crucialThe confusion of delirium is accompanied by rapid changes in brain function. In addition to the symptoms described earlier, patients typically manifest altered levels of alertness, consciousness, and awareness. And research also has found that they show decreases in short-term memory and recall, disrupted attention, and disorganized thinking.
While delirium’s exact cause remains unknown, many experts think a variety of structural and physiological mechanisms, including multiple neurotransmitter disorders, can cause it.
“While most seniors who suffer an episode of delirium go on to a full recovery,” Inouye says, “nearly 20 percent experience complications, including death. Up to 40 percent of delirium episodes, however, are preventable, which makes taking steps to avoid or correctly diagnose this condition crucial.”
Delirium, says Edward Marcantonio, MD, an HMS associate professor of medicine at BIDMC and co-principal investigator on the study, can go unrecognized by physicians and nurses because it is episodic and often manifests simultaneously with dementia. In addition, its clinical consequences are largely underappreciated. Misdiagnosing delirium, he adds, leads to longer hospital stays, missed opportunities for treatment, unnecessary medications, or an overall poorer quality of life.
To treat delirium, physicians may look first at a patient’s medications, stopping or changing any that could contribute to the condition. Disorders that exacerbate delirium, such as anemia, low or inadequate oxygen levels in body tissues, infection, and kidney or heart failure, should be treated promptly.
Study aims to stem problems after surgeryThe SAGES study will bring together medical experts in surgery, psychiatry, anesthesiology, neurology, neuropsychology, medicine, epidemiology, and biostatistics to examine a host of delirium-related issues. Epidemiologists, for example, will examine the factors that enable a person to avoid delirium after surgery and exposure to anesthesia. Others will investigate inflammatory biomarkers and proteins to determine whether molecular changes can predict who is at risk for the condition. MRI testing, administered both pre- and postoperatively, will help determine whether delirium has long-term impacts on brain function. Investigators also will use sophisticated assessment tools to determine whether certain levels of pre-surgery cognitive and physical health protect an individual from delirium’s onset.
Inouye will assess participants 1.5 to 3 years after they’ve had elective surgery for such conditions as total hip or knee replacement, lower extremity arterial bypass, open abdominal aortic aneurysm repair, and lower extremity amputation. The evaluations will occur in the hospital or at the patient’s home.
“As the population ages and surgical interventions expand for older people, this study will advance our knowledge about delirium’s long-term effects,” says Selwyn Rogers, MD, an HMS associate professor of surgery, chief of the Division of Trauma, Burns and Surgical Critical Care at BWH, and a SAGES co-principal investigator. “By doing so, we may improve our ability to diagnose delirium in a timely manner and potentially treat it to mitigate its effects.”
Negotiating delirium’s mazeIn the late 1980s, Inouye developed the Confusion Assessment Method to help physicians identify and recognize delirium and to standardize the assessment used by clinicians who are not trained in psychiatry. In addition, Inouye developed an innovative, hospital-based approach for combating delirium. The Hospital Elder Life Program, or HELP, works to keep hospitalized older patients oriented to their surroundings and mobile within the limits of their physical condition.
Despite the considerable progress that she and her colleagues have made, Inouye says much work remains. At the Aging Brain Center, Inouye and her team are investigating whether delirium alters the course of dementia and whether it leads to longstanding cognitive impairment and pathologic changes in the brain. The SAGES study should provide insight, along with clues to interventions that can stem delirium’s damage.
This article appeared in the Fall 2010 issue of On The Brain.
HARVARD MEDICAL SCHOOL CONTACT:
Ann Marie Menting
ann_menting@hms.harvard.edu
617-432-7764
For the curious nonscientist, On The Brain deciphers how the human brain works by highlighting the leading-edge research of neuroscientists at Harvard Medical School and its affiliated teaching hospitals. The thrice-annual newsletter, produced through the Office of Communications and External Relations, is sponsored by the Harvard Mahoney Neuroscience Institute.
