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Original Investigation |

Delirium and Long-term Cognitive Trajectory Among Persons With Dementia

Alden L. Gross, PhD, MHS; Richard N. Jones, ScD; Daniel A. Habtemariam, BA; Tamara G. Fong, MD, PhD; Douglas Tommet, MS; Lien Quach, MS; Eva Schmitt, PhD; Liang Yap, PhD; Sharon K. Inouye, MD, MPH
Arch Intern Med. 2012;172(17):1324-1331. doi:10.1001/archinternmed.2012.3203.
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Background  Delirium is characterized by acute cognitive impairment. We examined the association of delirium with long-term cognitive trajectories in older adults with Alzheimer disease (AD).

Methods  We evaluated prospectively collected data from a nested cohort of hospitalized patients with AD (n = 263) in the Massachusetts Alzheimer Disease Research Center patient registry between January 1, 1991, and June 30, 2006 (median follow-up duration, 3.2 years). Cognitive function was measured using the information-memory-concentration (IMC) section of the Blessed Dementia Rating Scale. Delirium was identified using a validated medical record review method. The rate of cognitive deterioration was contrasted using random-effects regression models.

Results  Fifty-six percent of patients with AD developed delirium during hospitalization. The rate of cognitive deterioration before hospitalization did not differ significantly between patients who developed delirium (1.4 [95% CI, 0.7-2.1] IMC points per year) and patients who did not develop delirium (0.8 [95% CI, 0.3-1.3] IMC points per year) (P = .24). After adjusting for dementia severity, comorbidity, and demographic characteristics, patients who had developed delirium experienced greater cognitive deterioration in the year following hospitalization (3.1 [95% CI, 2.1-4.1] IMC points per year) relative to patients who had not developed delirium (1.4 [95% CI, 0.2-2.6] IMC points per year). The ratio of these changes suggests that cognitive deterioration following delirium proceeds at twice the rate in the year after hospitalization compared with patients who did not develop delirium. Patients who had developed delirium maintained a more rapid rate of cognitive deterioration throughout a 5-year period following hospitalization. Sensitivity analyses that excluded rehospitalized patients and included matching on baseline cognitive function and baseline rate of cognitive deterioration produced essentially identical results.

Conclusions  Delirium is highly prevalent among persons with AD who are hospitalized and is associated with an increased rate of cognitive deterioration that is maintained for up to 5 years. Strategies to prevent delirium may represent a promising avenue to explore for ameliorating cognitive deterioration in AD.

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Figure. Estimated cognitive function among 263 hospitalized patients who developed delirium or did not develop delirium, showing model-implied trajectories with 95% CIs of cognitive performance at discrete time points from a random-effects regression model of the Blessed Dementia Rating Scale information-memory-concentration section (Blessed IMC) score during Massachusetts Alzheimer Disease Research Center follow-up periods. The model is adjusted for age, sex, years of education, family history of Alzheimer disease, dementia severity, number of comorbidities, and duration of Alzheimer disease symptoms before diagnosis. Missing covariate data were multiply imputed using Bayesian imputation methods with 25 data sets. The timescale depicted includes the middle 80% of study visits nearest in time to the index hospitalization (although statistical models used data up to 5 years before and 5 years after the index hospitalization). The surviving sample size is the number of patients who survived up to each year. Asterisks indicate P < .05 on test of group differences in observed annualized change in Blessed IMC score between delirium and no delirium groups.

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