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Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease

Tamara G. Fong, MD, PhD; Richard N. Jones, ScD; Edward R. Marcantonio, MD, SM; Douglas Tommet, MS; Alden L. Gross, PhD, MHS; Daniel Habtemariam, BA; Eva Schmitt, PhD; Liang Yap, PhD; and Sharon K. Inouye, MD, MPH
[+] Article, Author, and Disclosure Information

From the Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife; Beth Israel Deaconess Medical Center, Harvard Medical School; and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Acknowledgment: The authors thank Drs. John Growdon and Brad Hyman for access to the MADRC patient registry data and for providing the initial pilot grant supporting this work. They also thank Drs. Virginia Casey and Gregory Acampora for assistance with chart reviews. This work is dedicated to the memory of Joshua Bryan Inouye Helfand.

Grant Support: Funded in part by grant IIRG-08-88737 to Dr. Inouye from the Alzheimer's Association and grants P50AG005134 to Drs. Inouye and Yap, P01AG031720 to Dr. Inouye, and K24AG035075 to Dr. Marcantonio from the National Institute on Aging, as well as the Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2645.

Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Fong (e-mail, tfong@bidmc.harvard.edu).

Requests for Single Reprints: Tamara G. Fong, MD, PhD, Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA 02131; e-mail, tfong@bidmc.harvard.edu.

Current Author Addresses: Drs. Fong, Jones, Gross, Schmitt, and Inouye and Mr. Tommet and Mr. Habtemariam: Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA 02131.

Dr. Marcantonio: Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.

Dr. Yap: Massachusetts General Hospital, Warren Building, Suite 844, 55 Fruit Street, Boston, MA 02114.

Author Contributions: Conception and design: R.N. Jones, E.R. Marcantonio, S.K. Inouye.

Analysis and interpretation of the data: T.G. Fong, R.N. Jones, D. Tommet, A.L. Gross, D. Habtemariam, E. Schmitt, S.K. Inouye.

Drafting of the article: T.G. Fong, R.N. Jones, S.K. Inouye.

Critical revision of the article for important intellectual content: T.G. Fong, R.N. Jones, E.R. Marcantonio, D. Tommet, A.L. Gross, D. Habtemariam, E. Schmitt, L. Yap, S.K. Inouye.

Final approval of the article: T.G. Fong, R.N. Jones, E.R. Marcantonio, A.L. Gross, D. Habtemariam, E. Schmitt, S.K. Inouye.

Provision of study materials or patients: L. Yap.

Statistical expertise: R.N. Jones, D. Tommet, A.L. Gross, S.K. Inouye.

Obtaining of funding: S.K. Inouye.

Administrative, technical, or logistic support: D. Habtemariam, E. Schmitt, L. Yap, S.K. Inouye.

Collection and assembly of data: D. Tommet, A.L. Gross, L. Yap.

Ann Intern Med. 2012;156(12):848-856. doi:10.7326/0003-4819-156-12-201206190-00005
Text Size: A A A

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.

Primary Funding Source: National Institute on Aging and the MADRC.


Grahic Jump Location
Figure 1.

Temporal course of outcomes used in this study.

Institutionalization and death are events that happen within 1 y of hospitalization. Median days to event refers to the median length of time from one outcome to the next. MADRC = Massachusetts Alzheimer's Disease Research Center; NA = not available.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Overlap of outcomes of hospitalization and delirium combined to form the composite outcome.

The sizes of the circles and overlaps are proportional to the total number of patients with those outcomes. The dotted diamonds indicate missing data for the outcome of cognitive decline, because classification of these participants inside (or outside) of the cognitive decline circle could not be made. Some cases where the outcome of cognitive decline was not known with certainty included persons who were known to have died (n = 20), who had been institutionalized and then died (n = 24), or who were institutionalized (n = 66). An additional 181 participants were known to be alive, but their outcome of cognitive decline was not known. The total number indicated for each outcome includes those who had missing data.

Grahic Jump Location




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Hospitalization and Delirium in Dementia
Posted on July 10, 2012
Paul Regal MD, FRACP, FRCP
University of Newcastle, Australia and Wyong Hospital
Conflict of Interest: None Declared

Fong have written a useful article on adverse outcomes in Alzheimer disease [1]. The diagnosis of delirium is difficult to standardize, particularly in subjects with moderate to severe dementia. I run the Wyong Hospital Memory clinic for elderly people (mean age 83). I am often called to the emergency room to see a patient with acute confusion superimposed on dementia. Distinguishing delirium from behavioral and psychological symptoms of dementia (BPSD) is difficult. This distinction becomes far more accurate if physicians with an interest in dementia review dementia patients every six months. In view of my six-monthly measurements of several attention tests (digit span forward, 3-word registration in the Mini-Mental State Examination [2] (MMSE), spelling “WORLD” backwards in the MMSE I can compare the trajectory of these tests over the past several years with the rate of change since my last clinic visit. Since inattention is a cardinal feature of delirium, I can exclude delirium if these attention tests have not changed significantly from the last clinic visit. However, cognition fluctuates in delirium so I often repeat digit span hourly. Besides measuring MMSE every six months, I also measure Delirium Index [3] (seven questions scored from 0 no features of delirium to 21 all features of delirium).

I have never read of other centers who routinely measure delirium index as a baseline for when the patient develops acute confusion.Dementia patients reported by Fong and colleagues had six-monthly follow-up at the AD Research Center like the Wyong Memory clinic. The critical difference, however, is that the neuropsychological tests every six months in Massachusetts were not used as a baseline for analysis. For example a digit span of 3/5 represents inattention. If digit span in memory clinic two months ago was also 3/5 the inattention is old and cannot be counted towards diagnosing delirium. Dementia patients reported by Fong and colleagues did not have a whisper test performed after inserting hearing aids and eliminating background noise. Likewise Fong’s sample with impaired hearing despite hearing aids were not tested while wearing a portable amplifier with headphones. To illustrate the importance of such amplifiers in the Wyong Memory Clinic 75% of patients who score 0-4 / 5 on digit span while wearing hearing aids correct at least one point upon using a portable amplifier. Thus a digit span of 4/5 (inattention due to poor hearing rather than delirium or dementia) usually corrects to 5/5 (no inattention).


1. Fong TG, Jones RN, Marcantonio ER, Tommet D, Gross AL, Habtemariam D, Schmitt E, Yap L, Inouye SK. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Intern Med 2012;156:848-56

2. Folstein MF, Folstein SE, McHugh PE. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician J Psychiatr Res 1975;12:189-99

3. McCusker J, Cole M, Dendukuri N, Belzile E. The Delirium Index, a measure of the severity of delirium: New findings on reliability, validity, and responsiveness. J Am Geriatr Soc 2004;52:1744-1749

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Summary for Patients

Hospitalization and Delirium in Persons With Alzheimer Disease

The full report is titled “Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease.” It is in the 19 June 2012 issue of Annals of Internal Medicine (volume 156, pages 848-856). The authors are T.G. Fong, R.N. Jones, E.R. Marcantonio, D. Tommet, A.L. Gross, D. Habtemariam, E. Schmitt, L. Yap, and S.K. Inouye.


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