Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease

The state of acute confusion and disorientation known as delirium can stem from a serious illness, surgery or infection, and often develops while patients are in the hospital.

Now a new study confirms that for patients with Alzheimer's disease, hospitalization and delirium pose a particular risk and can lead to adverse outcomes, including hastened cognitive decline, institutionalization and death.

Led by researchers at Harvard Medical School affiliates Hebrew SeniorLife and Beth Israel Deaconess Medical Center (BIDMC), the study appears in the June 19 on-line issue of the Annals of Internal Medicine.

"Evidence has shown that older patients with Alzheimer's disease [AD] are much more likely to be hospitalized than other older patients," says lead author Tamara Fong, MD, PhD, assistant scientist in the Aging Brain Center, Institute for Aging Research at Hebrew SeniorLife and Assistant Professor of Neurology at BIDMC. "Because our previous research had found that AD patients experienced a three times faster decline in mental function if they had experienced delirium, we wanted to determine if AD patients who are hospitalized are at greater risk for poor outcomes than AD patients who are not hospitalized, and if there is any additive negative outcome when hospitalized AD patients develop delirium."

The researchers, therefore, analyzed the records of 771 patients over age 65 who were examined between 1991 and 2006 at the Massachusetts Alzheimer's Disease Registry (MADRC), a clinical registry based at Massachusetts General Hospital.

"We looked at patients with and without hospitalizations who were seen at least three times in the MADRC during the study interval period," says Fong.

The authors additionally analyzed data from medical records and other data sources, including Medicare and the Social Security Death Index, to determine outcomes of hospitalization and delirium.

As predicted, their findings showed that in patients with Alzheimer's disease, any hospitalization was associated with increased risks for institutionalization, cognitive decline and death, and for those patients who developed delirium, there was an incremental increase in risk for these adverse outcomes, even after controlling for other cofactors.

"Among the hospitalized Alzheimer's patients, a substantial proportion of risk for adverse outcomes could be attributed to delirium, including 6.2 percent of deaths, 15.2 percent of institutionalization, and 20.6 percent of cognitive decline," says Fong. "The bottom line is that delirium can be a big problem for patients with AD," she adds.

There are, however, effective prevention strategies for delirium for hospitalized elders, notes Fong.

These include the Hospital Elder Life Program (HELP), a patient care program designed to prevent delirium by keeping hospitalized older people oriented to their surroundings, meeting their needs for nutrition, fluids and sleep, and keeping them mobile within the limitations of their physical conditions.

"Going forward, we plan to conduct formal studies to determine if these types of interventions can help improve outcomes for this vulnerable group of patients," she explains.

Adds senior author Sharon Inouye, MD, PhD, Director of the Aging Brain Institute at HSL, Harvard Medical School Professor of Medicine at BIDMC, "Our confirmation that hospitalization and delirium play important roles in adverse outcomes may ultimately influence care and management of patients with AD.

Interventions to prevent hospitalization and hospital-associated delirium may be appropriate for all patients with AD. The cost savings to Medicare would be far greater than the amount from current treatment options for AD."
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Fong TG, Jones RN, Marcantonio ER, Tommet D, Gross A, Habtemariam D, Schmitt E, Yap L, Inouye SK. Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease. Ann Intern Med. 19 June 2012;156(12):848-856 .

ABSTRACT

Background: Hospitalization, frequently complicated by delirium, can be a life-changing event for patients with Alzheimer disease (AD).

Objective: To determine risks for institutionalization, cognitive decline, or death associated with hospitalization and delirium in patients with AD.

Design: Prospective cohort enrolled between 1991 and 2006 into the Massachusetts Alzheimer's Disease Research Center (MADRC) patient registry.

Setting: Community-based.

Participants: 771 persons aged 65 years or older with a clinical diagnosis of AD.

Measurements: Hospitalization, delirium, death, and institutionalization were identified through administrative databases. Cognitive decline was defined as a decrease of 4 or more points on the Blessed Information-Memory-Concentration test score. Multivariate analysis was used to calculate adjusted relative risks (RRs).

Results: Of 771 participants with AD, 367 (48%) were hospitalized and 194 (25%) developed delirium. Hospitalized patients who did not have delirium had an increased risk for death (adjusted RR, 4.7 [95% CI, 1.9 to 11.6]) and institutionalization (adjusted RR, 6.9 [CI, 4.0 to 11.7]). With delirium, risk for death (adjusted RR, 5.4 [CI, 2.3 to 12.5]) and institutionalization (adjusted RR, 9.3 [CI, 5.5 to 15.7]) increased further. With hospitalization and delirium, the adjusted RR for cognitive decline for patients with AD was 1.6 (CI, 1.2 to 2.3). Among hospitalized patients with AD, 21% of the incidences of cognitive decline, 15% of institutionalization, and 6% of deaths were associated with delirium.

Limitations: Cognitive outcome was missing in 291 patients. Sensitivity analysis was performed to test the effect of missing data, and a composite outcome was used to decrease the effect of missing data.

Conclusion: Approximately 1 in 8 hospitalized patients with AD who develop delirium will have at least 1 adverse outcome, including death, institutionalization, or cognitive decline, associated with delirium. Delirium prevention may represent an important strategy for reducing adverse outcomes in this population.