Delirium and incident dementia in hospital patients in New South Wales, Australia: retrospective cohort study

Abstract

Objectives: To determine the strength and nature of the association between delirium and incident dementia in a population of older adult patients without dementia at baseline.

Design: Retrospective cohort study using large scale hospital administrative data.

Setting: Public and private hospitals in New South Wales, Australia between July 2001 and March 2020.

Participants: Data were extracted for 650 590 hospital patients aged ≥65 years. Diagnoses of dementia and delirium were identified from ICD-10 (international classification of diseases, 10th revision) codes. Patients with dementia at baseline were excluded. Delirium-no delirium pairs were identified by matching personal and clinical characteristics, and were followed for more than five years.

Main outcome measures: Cox proportional hazards models and Fine-Gray hazard models were used to estimate the associations of delirium with death and incident dementia, respectively. Delirium-outcome dose-response associations were quantified, all analyses were performed in men and women separately, and sensitivity analyses were conducted.

Results: The study included 55 211 matched pairs (48% men, mean age 83.4 years, standard deviation 6.5 years). Collectively, 58% (n=63 929) of patients died and 17% (n=19 117) had a newly reported dementia diagnosis during 5.25 years of follow-up. Patients with delirium had 39% higher risk of death (hazard ratio 1.39, 95% confidence interval 1.37 to 1.41) and three times higher risk of incident dementia (subdistribution hazard ratio 3.00, 95% confidence interval 2.91 to 3.10) than patients without delirium. The association with dementia was stronger in men (P=0.004). Each additional episode of delirium was associated with a 20% increased risk of dementia (subdistribution hazard ratio 1.20, 95% confidence interval 1.18 to 1.23).

Conclusions: The study findings suggest delirium was a strong risk factor for death and incident dementia among older adult patients. The data support a causal interpretation of the association between delirium and dementia. The clinical implications of delirium as a potentially modifiable risk factor for dementia are substantial.

Fig 1

Study design. Patients in the delirium group (index episode=orange circle) and no delirium group (index episode=green circle) were matched 1:1 according to age, gender, hospital frailty risk score, primary diagnosis, hospital length of stay and intensive care unit length of stay of index episode. Arrows to left of circles represent exclusion of previous dementia diagnosis and two year lookback for hospital frailty risk score calculation. Arrows to right of circles represent 63 month follow-up period

Fig 2

Association of delirium with death by baseline group (upper panel) and episodes of delirium recorded within first 12 months of follow-up (landmark period; lower panel). Associations presented in forest plot in lower panel were adjusted for age and gender at baseline, and number of hospital episodes recorded within landmark period. Total sample data are hazard ratio 1.36 (95% confidence interval 1.33 to 1.39) for one delirium episode, 1.67 (1.61 to 1.72) for two episodes, and 1.82 (1.74 to 1.90) for three or more episodes. Corresponding data for men only are 1.36 (1.32 to 1.40), 1.71 (1.63 to 1.79), and 1.83 (1.72 to 1.95), respectively. Corresponding data for women only are 1.36 (1.32 to 1.40), 1.63 (1.56 to 1.70), and 1.81 (1.70 to 1.91), respectively

Fig 3

Association of delirium with incident dementia by baseline group (upper panel) and episodes of delirium recorded within first 12 months of follow-up (landmark period; lower panel). Associations presented in forest plot in lower panel were adjusted for age and gender at baseline, and number of hospital episodes recorded within landmark period. Total sample data are subdistribution hazard ratio 2.81 (95% confidence interval 2.70 to 2.92) for one delirium episode, 3.70 (3.50 to 3.91) for two episodes, and 4.91 (4.57 to 5.28) for three or more episodes. Corresponding data for men only are 3.06 (2.88 to 3.25), 4.15 (3.81 to 4.52), and 5.72 (5.12 to 6.38), respectively. Corresponding data for women only are 2.64 (2.51 to 2.78), 3.42 (3.18 to 3.67), and 4.39 (3.99 to 4.83), respectively