Delirium is a neuropsychiatric syndrome characterized by an acute state of confusion, typically fluctuating over the course of a day (American Psychiatric Association, 2013). It is very common in many healthcare settings with a prevalence of 11%−42% in acute medical hospital admissions (Siddiqi et al., 2006). Delirium is often seen as a marker of underlying pathology, an epiphenomenon, and the diagnosis is frequently missed. However, delirium is independently associated with adverse outcomes, including prolonged hospitalization, increased post-discharge mortality, institutionalization, and dementia (Siddiqi et al., 2006; Witlox et al., 2010).

Delirium affects one in four acute stroke patients with rates varying between 7 and 50% (Shaw et al., 2019). Growing evidence suggests a similar pattern of increased mortality and poor outcome after post-stroke delirium (PSD) (Shaw et al., 2019; Qu et al., 2018; Shi et al., 2012; Fialho Silva et al., 2021; Dostovic et al., 2016). Infections are also common complications after stroke, with a prevalence of up to 30%, one-third consisting of post-stroke pneumonia (PSP), and another third of post-stroke urinary tract infections (PSU). PSP in particular has been linked to poor stroke outcome (Westendorp et al., 2011). PSP and PSU are also both related to PSD (Guldolf et al., 2021).

We aimed to investigate whether delirium was a predictor of prolonged hospital stay, unfavorable functional outcome, and mortality at 3 months after ischemic stroke, independent of the development of pneumonia and urinary tract infection.

The main finding of our study is that PSD is a predictor of prolonged hospital stay and poor functional outcome at 3 months, but not of mortality, independent of the development of PSP and PSU, the two most common infectious complications after AIS.

Most earlier studies had already reported that PSD was a predictor of prolonged hospital stay (Saver et al., 2021; Nydahl et al., 2017). Only Nydahl and coworkers found no association between PSD and LOHS (Nydahl et al., 2017). A partial explanation of this finding could be the inclusion of TIA patients. Most studies included mixed stroke subtypes (both ischemic and hemorrhagic) and reported only univariate analysis (Saver et al., 2021; Nydahl et al., 2017; Klimiec-Moskal et al., 2019; Oldenbeuving et al., 2011; Sheng et al., 2006). Oldenbeuving and coworkers reported a prolonged hospital stay (5.4 days longer) after adjustment for age, stroke severity, and premorbid cognitive function [Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score]. The additional value of our study is that we adjusted for age, gender, premorbid mRS, stroke severity, and, especially, PSP and PSU and that we precluded hemorrhagic stroke.

Our study also demonstrated an association between PSD and poor functional outcome at 3 months after stroke, consistent with the majority of previous research (Fialho Silva et al., 2021).

Most of the studies evaluated here included patients with mixed stroke subtypes, with the exception of Lim et al. (2017), who focused on ischemic stroke but did not adjust for potential confounders.

Two of the more recent studies also adjusted for post-stroke infections (Fialho Silva et al., 2021), PSP and PSU (Klimiec-Moskal et al., 2019).

Qu and coworkers showed an association between PSD and functional outcome as measured by Instrumental Activities of Daily Living, although this was not observed using mRS after adjustment for cofounders (Qu et al., 2018).

Oldenbeuving and coworker identified an association between PSD and the Barthel Index at 3 months, though functional outcome was not assessed using the mRS (Oldenbeuving et al., 2011).

Sheng and coworker also demonstrated an association between PSD and the Functional Independence Measure score at 12 months, but they did not evaluate functional outcome with the mRS (Sheng et al., 2006).

In our study, we found no association between PSD and mortality in multivariate analysis, including in the model with PSP and PSU. Previous studies obtained contradictory results. Some studies reported no association with early (in hospital) or late (6–12 months) mortality (Hénon et al., 1999), while others found a connection in univariate analyses but did not perform a multivariate analysis (McManus et al., 2009). Recently, a few studies did find PSD to be an independent predictor of mortality after controlling for factors like age, comorbidities, and stroke severity (Pasińska et al., 2019), although these findings are not consistent across all research (Rollo et al., 2022). Only one study adjusted for both pneumonia and urinary tract infection, despite analyzing a mixed population that included both ischemic and hemorrhagic strokes (Klimiec-Moskal et al., 2019). Variations in study populations and differences in methodology likely contribute to the ongoing uncertainty about whether PSD directly affects mortality after stroke

The strength of our study is that we studied three well-defined post-stroke complications, PSD, PSP, and PSU, within a single dataset. However, the study had several limitations. Since we used the retrospective chart review method for delirium based on DSM-5 criteria, we might have missed a couple of cases, especially for the hypoactive delirium subtype. We also did not study the delirium subtype of severity or duration. To reduce misdiagnosis, two independent evaluators reviewed independently all nursing and medical notes in the first 7 days of admission. In the first days, we had access to at least three (and often five or six) nursing notes in most patient files, including night-time notes, meaning good coverage of day and night periods. When no consensus was reached, a third independent evaluator was consulted. The same limitation is applicable to the retrospective diagnosis of PSP and PSU. However, the incidence of PSP, PSU (Westendorp et al., 2011), and PSD (Fleischmann et al., 2021) are comparable with those in prospective studies. Premorbid cognitive dysfunction was also determined retrospectively, and the 10% prevalence was likely an underestimate. Studies using the IQCODE suggest that about one-third of stroke patients have prestroke cognitive impairment (Mele et al., 2024). Another limitation of the study has to do with the extensiveness of the exclusion criteria (cf. flowchart) and the narrowness of the inclusion criteria (< 24 h after stroke onset). As a result, our findings might not be representative of the overall stroke population. In addition, we only adjusted for PSP and PSU, not for other infectious complications after stroke.

Other predictors of poor functional outcome and mortality at 3 months were age, stroke severity on admission (NIHSS), premorbid disability, and PSP. This is in line with the results of previous studies (Westendorp et al., 2011; Johnston et al., 2000).

PSU was only a predictor of prolonged hospital stay, but not of unfavorable outcome and mortality at 3 months. We speculate that this might be explained by the fact that, unlike pneumonia, most PSUs do not lead to systemic infections (Westendorp et al., 2022).

Our study demonstrates that PSD is a predictor of prolonged hospital stay and poor functional outcome at 3 months, independent of age, stroke severity, and the development of PSP and PSU, the two most frequent infectious complications in patients with AIS. This needs to be confirmed in prospective studies. Whether preventing PSD might improve stroke outcome will require further research.