Delirium in the Acute Phase of Ischemic Stroke: Incidence, Risk Factors, and Effects on Functional Outcome

  • Jianfeng Qu
    Affiliations
    Department of Neurology, Dongguan People's Hospital (Affiliated Dongguan Hospital, South Medical University), Dongguan, Guangdong Province, China
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  • Yangkun Chen
    Correspondence
    Address correspondence to Yangkun Chen Department of Neurology, Dongguan People's Hospital (Affiliated Dongguan Hospital, South Medical University), Dongguan, Guangdong Province, China.
    Affiliations
    Department of Neurology, Dongguan People's Hospital (Affiliated Dongguan Hospital, South Medical University), Dongguan, Guangdong Province, China
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  • Genpei Luo
    Affiliations
    Department of Neurology, Dongguan People's Hospital (Affiliated Dongguan Hospital, South Medical University), Dongguan, Guangdong Province, China
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  • Huohua Zhong
    Affiliations
    Department of Neurology, Dongguan People's Hospital (Affiliated Dongguan Hospital, South Medical University), Dongguan, Guangdong Province, China

    Faculty of Neurology, Guangdong Medical University, Dongguan, Guangdong Province, China
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  • Weimin Xiao
    Affiliations
    Department of Neurology, Dongguan People's Hospital (Affiliated Dongguan Hospital, South Medical University), Dongguan, Guangdong Province, China
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  • Hanpeng Yin
    Affiliations
    Department of Neurology, Dongguan People's Hospital (Affiliated Dongguan Hospital, South Medical University), Dongguan, Guangdong Province, China
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      Abstract

      Objective

      The aim of this prospective cohort study was to assess the incidence and risk factors of delirium following acute ischemic stroke, as well as its effects on functional outcome.

      Methods

      Two hundred and sixty-one patients with acute ischemic stroke were screened for delirium during the first week after admission. Delirium was diagnosed according to the Confusion Assessment Method. If delirium was present, delirium rating scale-revised-98 was used to assess its severity. Neurologic deficits were assessed with the National Institutes of Health Stroke Scale (NIHSS). Brain magnetic resonance imaging assessment quantified the infarction, white matter lesions, and medial temporal lobe atrophy. Functional outcome assessment included the modified Rankin Scale and Lawton Instrumental Activities of Daily Living scale at 3 and 6 months after the index stroke.

      Results

      Thirty-eight (14.6%) patients with acute ischemic stroke developed delirium during the first week of admission. Patients with poststroke delirium (PSD) were older, had higher NIHSS scores on admission, and were more likely to have a previous stroke, an infection, and a left cortical infarct. Furthermore, left cortical infarction, older age, severer neurological deficit and having a previous stroke increased the risk of PSD. PSD was associated with a worse functional outcome.

      Conclusion

      The incidence of delirium was 14.8% in the first week after admission with acute ischemic stroke. Age, having a previous stroke, stroke severity, and left-cortical infarction were independently predictors of PSD. PSD may result in a significantly worse functional outcome.

      Key Words

      Introduction

      Delirium is an acute confusional state that develops over a short period of time and fluctuates during the course of the day.
      American Psychiatric Association
      DSM-5 task force. Diagnostic and statistical manual of mental disorders: DSM-5.
      It is the most frequent psychiatric syndrome in hospitalized subjects,
      • Cole MG
      Delirium in elderly patients.
      and it occurs in about 10%–25% of all acute general hospital admissions and in 20%–40% of elderly patients.
      • Fick DM
      • Agostini JV
      • Inouye SK
      Delirium superimposed on dementia: a systematic review.
      Delirium is the result of the interplay between patient characteristics (eg, frailty, low cognitive reserve, and cerebral damage) and exogenous factors (eg, medication, infections, and stress).
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in acute stroke: a review.
      It has been reported to be associated with several clinical situations, including surgery, acute stroke, pulmonary infection, and intensive care.
      • Bohner H
      • Hummel TC
      • Habel U
      • et al.
      Predicting delirium after vascular surgery: a model based on pre- and intraoperative data.
      Poststroke delirium (PSD) is a common complication in the acute phase of stroke. There are only a small number of studies that have investigated the incidence of PSD, which varies from 11.8% to 66%.
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
      • Sandberg O
      • Franklin KA
      • Bucht G
      • et al.
      Sleep apnea, delirium, depressed mood, cognition, and ADL ability after stroke.
      However, these studies recruited both hemorrhagic and ischemic stroke patients and had conflicting findings. It appears critical to study a homogeneous group of subjects.
      Thus, we conducted this study to investigate the incidence, risk factors, and effects on functional outcome of PSD in Chinese patients with ischemic stroke.

      Materials and Methods

       Participants and Setting

      The study was conducted at Division I, Department of Neurology, Dongguan People's Hospital between June 1st, 2016 and June 30th, 2017. The inclusion criteria for the study were as follows: (1) aged over 18 years; (2) first or recurrent acute ischemic stroke occurring within 7 days before admission; and (3) had brain magnetic resonance imaging (MRI) examination. The exclusion criteria were as follows: (1) transient ischemic attack, cerebral hemorrhage, subdural hematoma, or subarachnoid hemorrhage; (2) central nervous system diseases other than stroke (eg, dementia, Parkinson's disease, or multiple sclerosis); and (3) severe mental disorders before the index stroke (eg, schizophrenia). The study protocol was approved by the Ethics Committee of Dongguan People's Hospital. The consent of all subjects was obtained in accordance with the Declaration of Helsinki.

       Collection of Demographic and Clinical Data

      Socio-demographic and clinical variables including age, sex, history of stroke, vascular risk factors, and treatment were recorded on a standard data collection form. The subtype of ischemic stroke was judged by neurologists during hospitalization based on the Trial of Org 10172 in Acute Stroke Treatment subtype system.
      • Adams Jr., HP
      • Bendixen BH
      • Kappelle LJ
      • et al.
      Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial TOAST. Trial of Org 10172 in acute stroke treatment.

       Assessment of PSD

      PSD was assessed by a trained neurologist Jianfeng Qu (JFQ). Each patient was screened for delirium for the first time between day 1 and 3 after admission, and for a second time between day 5 and 7. If the patient was discharged before day 5, only the first screening was performed. We aimed to screen the patients for PSD twice, as PSD can occur at any time during the hospitalization period.
      • Marcantonio ER
      Delirium in hospitalized older adults.
      Delirium was assessed using the Confusion Assessment Method (CAM).
      • Inouye SK
      • van Dyck CH
      • Alessi CA
      • et al.
      Clarifying confusion: the confusion assessment method, a new method for detection of delirium.
      If the CAM was positive, delirium was diagnosed and the severity of delirium was assessed daily with the delirium rating scale-revised-98.
      • Trzepacz PT
      • Mittal D
      • Torres R
      • et al.
      Validation of the delirium rating scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium.
      DRS-R-98 includes a 13-item severity scale and a 3-item diagnostic scale. The severity scale quantifies multiple parameters such as language, thought process, two motoric presentations, and the components of cognition. Items 1 to 14 were scored on a 4-point scale and items 15 and 16 were scored on a 3-point scale, resulting in a range for the total score from 0 to 46. The Chinese version of the DRS-R-98 has been validated.
      • Huang MC
      • Lee CH
      • Lai YC
      • et al.
      Chinese version of the delirium rating scale-revised-98: reliability and validity.
      For each PSD patient, follow-up of delirium was performed until it was cured, which was defined as having a negative CAM. The PSD patients were treated by their neurologists according to national clinical practice guidelines.
      National Clinical Guideline Centre(UK)
      Delirium: diagnosis, prevention, and management of delirium.

       Follow-Up of the Participants

      All participants were followed up for 6 months via telephone. We assessed the clinical outcomes at 3 and 6 months according to the modified Rankin Scale (mRS) and functional status. Functional status was evaluated by the Lawton Instrumental Activities of Daily Living (IADL) scale.
      • Lawton MP
      • Brody EM
      Assessment of older people: self-maintaining and instrumental activities of daily living.
      The IADL examines a person's present functional level and identifies improvement or deterioration over time. The eight domains of function measured by the IADL are using a telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medications, and handling finances. The total IADL score is calculated by summing the points obtained for each item. The maximum IADL score is 32. A higher IADL score reflects poorer IADL performance. We defined a poor outcome as an mRS score greater than or equal to 3 or an IADL total score greater than 75th percentile of the IADL total score.

       MRI Assessment

      Brain MRI scans, including T1-weighted imaging, T2-weighted imaging and diffusion-weighted imaging (DWI) were performed on each participant with a 3.0-T system (Sonata, Siemens Medical, Erlangen, Germany) within 7 days of admission. DWI spin-echo echo-planar imaging (EPI; time of repeatation/time of echo/excitation = 2162/76/1, matrix = 128 × 128, field of view [FOV] = 230 mm, slice thickness/gap = 6 mm/1 mm, EPI factor = 47, acquisition time = 25.9 seconds) with three orthogonally applied gradients was used with a b value of 0 and 1000. Axial SE T1 (TR/TE/excitation = 488/15/1, FOV = 230 mm, slice thickness/gap = 6 mm/1 mm, matrix = 256 × 256, time of acquisition = 1 minute 24.8 seconds) and TSE T2 (TR/TE/excitation = 3992/110/2, turbo factor = 15, FOV = 230 mm, slice thickness/gap = 6 mm/1 mm, matrix = 512 × 512, time of acquisition = 1 minute 55.8 seconds) images were also acquired.
      A neurologist (YKC) who was blinded to each patient's clinical information and assessment results measured the MRI variables as follows:
      • (1)
        Brain infarcts: The sites and volume of acute lesions in DWI were examined. The sites of the acute infarcts were divided into cortical regions (frontal, temporal, parietal and occipital lobes), subcortical regions (subcortical white matter, basal ganglia, and thalamus), brain stem, and cerebellum. The total area of acute infarcts on DWI was measured with manual outlines. Acute infarcts were defined as areas of restricted water diffusion identified on DWI with b values of 1000 combined with hypointensity on the corresponding apparent diffusion coefficient map. The total volume was calculated by multiplying the total area by the sum of the slice thickness and the gap.
      • (2)
        White matter lesions (WMLs): The severity of WMLs was graded using a 4-point scale developed by Fazekas et al.
        • Fazekas F
        • Chawluk JB
        • Alavi A
        • et al.
        MR signal abnormalities at 1.5T in Alzheimer's dementia and normal aging.
        Periventricular hyperintensities and deep white matter hyperintensities were scored on fluid attenuation inversion recovery images separately.
      • (3)
        Medial temporal lobe atrophy (MTLA): MTLA was evaluated using Scheltens’ scale.
        • Scheltens P
        • Leys D
        • Barkhof F
        • et al.
        Atrophy of medial temporal lobes on MRI in “probable” Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates.
        The rater judged the severity of MTLA on the coronary section based on standard MRI scans, ranging from 0 to 4 with 0 representing no atrophy and 4 representing severe atrophy.
      Intrarater reliability tests were carried out by the same MRI rater (YKC) on 10 stroke patients. The intrarater agreement of the MRI measurements was good to excellent: infarction volume intraclass coefficient, .82; WML intrarater kappa, .86; MTLA intrarater kappa, .83.

       Statistical Analysis

      The statistical analyses were carried out using SPSS for Windows (version 24.0, SPSS Inc., Chicago, IL). Descriptive data are presented as proportions, means or medians, as appropriate. A univariate analysis comparing putative risk factors between patients with and without PSD was performed. As the sample size of PSD patients was limited, risk factors with P < .005 were then analyzed using multivariate logistic regression with a forward stepwise selection strategy. If the correlations between any of the putative risk factors were greater than or equal to .50, additional correlation analyses were carried out to rule out collinearity. Subsequently, the noncollinear variables with small P values (in the univariate analysis) were entered into the logistic regression model. In the multivariate logistic regression, the odds ratio (OR) of any independent risk factor was interpreted as the risk of nonremission of PSD when all other risk factors were held constant. For the analysis of outcome data (categorical data), adjusted ORs were calculated using logistic regression with a backward elimination procedure. The significance level was set at P < .05 (2-sided).

      Results

      Three hundred and ninety-four patients with first-ever or recurrent acute ischemic stroke were consecutively admitted. Of these patients, 62 were excluded because they did not have MRI data, four were excluded because they died before the first screening, and 18 were excluded because death appeared imminent. One patient was aged <18 years, 11 had severe mental retardation, 6 had a severe language barrier, 23 were transferred to another department because of capacity problems, and 8 refused to provide informed consent. Hence, 261 patients were included in the analysis (Fig. 1).
      The baseline characteristics of the patients are summarized in Table 1. The study sample consisted of 184 men (70.5%) and 77 women (29.5%), with a mean age of 61.3 years (range, 19-91). The median NIHSS score at the time of first screening was 4 (range, 0-28).
      Table 1Demographic and clinical characteristics of the study sample
      CharacteristicsMean (SD)/Median inter quartile range/n (%) n = 261
      Age (years)61.3 (14.8)
      Men184 (70.5%)
      Hypertension175 (67.0%)
      Diabetes mellitus58 (22.2%)
      Previous stroke46 (17.6%)
      NIHSS on admission4 (2-9)
      Infectious35 (13.4%)
      Stroke subtype
      Large artery117 (44.8%)
      Small artery66 (25.3%)
      Cardioembolism29 (11.1%)
      Other etiologies11 (4.2%)
      Unknown etiologies38 (14.6%)
      Location of infarcts
      L-cortical region72 (27.6%)
      R-cortical region52 (19.9%)
      L-subcortical region95 (36.4%)
      R-subcortical region74 (28.4%)
      Brainstem54 (20.7%)
      Cerebellum27 (10.3%)
      Abbreviations: NIHSS, National Institutes of Health Stroke Scale; SD, standard deviation.

       Incidence of PSD

      Thirty-eight out of 261 (14.6%) patients developed PSD. In the PSD assessment process, three patients had delirium screening only once, as one patient died and another two were discharged within 5 days of admission. We recorded the time from the delirium onset to each patient's discharge or death as the duration of PSD. Between day 1 and 3 after admission, 35 (13.4%) patients were diagnosed with PSD and in the second screening stage (between day 5 and 7 after admission), an additional three patients (1.1%) developed PSD. The mean duration of the PSD was 4 days (range, 1-11 days).

       Univariate Analysis

      In the univariate analysis, patients with PSD were older, had higher NIHSS scores at admission and had more frequent previous strokes and infections, in comparison with their counterparts without PSD. They also had significantly more frequent left cortical infarcts, a larger infarct volume, and severer MTLA scores (Table 2).
      Table 2Comparisons of clinical and MRI variables between patients with and without PSD
      VariablesSubjects with PSD n = 38Subjects without PSD n = 223t/X2/z valueP value
      Age (years)
      Mean (SD), t test.
      69.2(16.2)60.0(14.1)13.276<.001
      Men
      n(%), chi-square test.
      28(73.7%)156(70.0%).217.641
      Hypertension
      n(%), chi-square test.
      27(71.1%)148(66.4%).323.57
      Diabetes mellitus
      n(%), chi-square test.
      5(13.2%)53(23.8%)2.114.146
      Previous stroke
      n(%), chi-square test.
      14(36.8%)32(14.3%)11.314.001
      NIHSS on admission
      M(Qu−QL), Mann-Whitney U test; L, left; R, right.
      9(5-15)4(1-7)−5.18<.001
      Infections
      n(%), chi-square test.
      14(36.8%)21(9.4%)21.03<.001
      Stroke subtype
      n(%), chi-square test.
      14.988.005
      Large artery22(57.9%)95(42.6%)
      Small artery1(2.6%)65(29.1%)
      Cardioembolism8(21.1%)21(9.4%)
      Other etiologies1(2.6%)10(4.5%)
      Unknown etiologies6(15.8%)32(14.3%)
      Location of infarcts
      n(%), chi-square test.
      L-cortical region19(50.0%)53(23.8%)11.185.001
      R-cortical region13(34.2%)39(17.5%)5.69.017
      L- subcortical region21(55.3%)74(33.2%)6.837.009
      R-subcortical region10(26.3%)64(28.7%).91.763
      Brainstem5(13.2%)49(22.0%)1.538.215
      Cerebellum5(13.2%)22(9.9%).379.538
      Infarct volume
      M(Qu−QL), Mann-Whitney U test; L, left; R, right.
      11.0(3.9-62.1)1.73(.8-7.8)−4.717<.001
      PVH
      M(Qu−QL), Mann-Whitney U test; L, left; R, right.
      2(1-3)2(1-3)−2.313.21
      DWMH
      M(Qu−QL), Mann-Whitney U test; L, left; R, right.
      1(1-2)1(1-2)−.549.583
      MTLA
      M(Qu−QL), Mann-Whitney U test; L, left; R, right.
      5(2-6)2(0-4)−3.497<.001
      Abbreviations: DWMH, deep white matter hyperintensities; MRI, magnetic resonance imaging; MTLA, medial temporal lobe atrophy; NIHSS, National Institutes of Health Stroke Scale; PSD, poststroke delirium; PVH, periventricular hyperintensities.
      low asterisk Mean (SD), t test.
      n(%), chi-square test.
      M(Qu−QL), Mann-Whitney U test; L, left; R, right.

       Multivariate Logistic Regressions

      MTLA and infarct volume were not included in the multivariate logistic regression model as they were highly correlated with age (r = .605) and NIHSS score(r = .539), respectively. Thus, age, NIHSS score at admission, previous strokes, infections, and presence of left cortical infarcts were entered into the model. Except for infections, all of the other variables were significant predictors of PSD. The presence of left cortical infarcts had an OR of 3.802 (95%CI = 1.683-8.587, P < .001) (Table 3).
      Table 3Multivariate logistic regression of risk factors for PSD
      VariableβOR (95% CI)P value
      Age.0351.036(1.008-1.065).011
      NIHSS on admission.0951.099(1.030-1.174).005
      Previous stroke1.2853.615(1.458-8.967).006
      Infections.9272.527 (.905-7.057).077
      L-cortical infarction1.3353.802(1.683-8.587).001
      Abbreviations: NIHSS, National Institutes of Health Stroke Scale; OR, odds ration; PSD, poststroke delirium.

       Effects of PSD on Clinical and Functional Outcomes

      The PSD patients had poor outcomes at 3 and 6 months, which were measured using the IADL scale. Even after adjusting for age, NIHSS score at admission and presence of a previous stroke, PSD was still associated with the 3-month IADL score, but not with the 6-month IADL score. PSD patients had significantly higher mRS scores at 3 and 6 months after stroke. However, this association became nonsignificant after adjusting for age, NIHSS score at admission, and presence of a previous stroke (Table 4). The duration and severity of PSD were not associated with mRS or IADL scores (Table 5).
      Table 4Poor outcome according to presence of PSD
      VariablePSDNo PSDβOR (95% CI)P value
      3-month mRS
      PSD group n = 33, adjusted for age, NIHSS score at admission and previous stroke.
      23(69.7%)57(27.4%).722.055(.71-5.952).184
      6-month mRS
      PSD group n = 31, adjusted for age, NIHSS score at admission and previous stroke.
      18(56.2%)51(24.8%).1841.202(.417-3.468).734
      3-month IADL
      The median of 3-month IADL score of the whole sample is 9(8-19). Adjusted for age, NIHSS score at admission and previous stroke.
      20(60.6%)33(16%)1.0652.9(1.071-7.851).036
      6-month IADL
      The median of 6-month IADL score of the whole sample is 8(8-16). Adjusted for age, NIHSS score at admission and previous stroke.
      17(54.8%)40(19.6%).5041.655(.605-4.523).326
      Abbreviations: IADL, instrumental activities of daily living; mRS, modified Rankin Scale; PSD, poststroke delirium.
      low asterisk PSD group n = 33, adjusted for age, NIHSS score at admission and previous stroke.
      PSD group n = 31, adjusted for age, NIHSS score at admission and previous stroke.
      The median of 3-month IADL score of the whole sample is 9(8-19). Adjusted for age, NIHSS score at admission and previous stroke.
      § The median of 6-month IADL score of the whole sample is 8(8-16). Adjusted for age, NIHSS score at admission and previous stroke.
      Table 5The correlations between clinical outcome and duration and severity of PSD
      VariableDuration of PSD
      Spearman correlation analyses.
      Severity of PSD(DRS-R-98)
      Spearman correlation analyses.
      rprP
      3-month mRs−.102.573−.035.848
      6-month mRs−.11.953−.188.303
      3-month IADL−.144.426.016.928
      6-month IADL−.061.746−.04.831
      Abbreviations: IADL, instrumental activities of daily living; mRS, modified Rankin Scale; PSD, poststroke delirium.
      low asterisk Spearman correlation analyses.

      Discussion

      In this prospective observational study, we found that the incidence of PSD was 14.8%, indicating that delirium was common in the acute stage of ischemic stroke. PSD was associated with age, previous stroke history, stroke severity, infection, and left cortical infarction. Furthermore, most of the delirium occurred early after stroke. Patients with PSD had a relatively poor functional outcome, suggesting that more attention should be paid to PSD by healthcare professionals. As studies attempting to investigate PSD were very limited, our study added to the knowledge of the psychiatric complications of stroke.
      The PSD incidence of 14.8% in our study is similar to the findings of previous studies (11.8%–66%).
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
      • Sandberg O
      • Franklin KA
      • Bucht G
      • et al.
      Sleep apnea, delirium, depressed mood, cognition, and ADL ability after stroke.
      ,
      • Sheng AZ
      • Shen Q
      • Cordato D
      • et al.
      Delirium within three days of stroke in a cohort of elderly patients.
      • Dunne JW
      • Leedman PJ
      • Edis RH
      Inobvious stroke: a cause of delirium and dementia.
      The various reported incidences of PSD may be due to case-mix, different definitions of delirium, different age groups included, sample size, and where and how the stroke patients were treated. As PSD may increase the length of hospitalization, mortality and poor outcomes,
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
      screening for delirium should be carried out as soon as possible for hospitalized ischemic stroke patients.
      In our study cohort, delirium was more frequent in patients with infarction in the left cortex. This finding is novel and opposes the findings of earlier studies. Some previous studies showed that PSD may correlate with issues with the right hemisphere,
      • Fick DM
      • Agostini JV
      • Inouye SK
      Delirium superimposed on dementia: a systematic review.
      right frontal straight gyrus,
      • Mori E
      • Yamadori A
      Acute confusional state and acute agitated delirium. Occurrence after infarction in the right middle cerebral artery territory.
      or medial occipito-temporal lobe.
      • Shih HT
      • Huang WS
      • Liu CH
      • et al.
      Confusion or delirium in patients with posterior cerebral arterial infarction.
      Oldenbeuving et al. found that PSD was more common in right hemispheric stroke than left hemispheric stroke.
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
      However, they recruited a patient cohort with both hemorrhagic and ischemic strokes, resulting to a heterogeneous study sample. Moreover, they used brain computed tomography scans rather than MRI scans to evaluate stroke.
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
      Lesions involving a common pathway involved in the pathogenesis of delirium may explain these differences.
      • McManus J
      • Pathansali R
      • Stewart R
      • et al.
      Delirium post-stroke.
      Regions in the dominant hemisphere, especially the limbic system and the prefrontal cortex, have a critical role in emotion, memory, and motivation.
      • Arnold MB
      Emotion, motivation, and the limbic system.
      Disturbances of emotion and memory may increase the likelihood of misinterpretation of the environment, leading to a higher risk of delirium.
      As expected, age was an important risk factor for delirium, as was found in other studies on stroke,
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
      • Carin-Levy G
      • Mead GE
      • Nicol K
      • et al.
      Delirium in acute stroke: screening tools, incidence rates and predictors: a systemic review.
      as well as in hospitalized patients with other diseases.
      • Cole MG
      Delirium in elderly patients.
      • Bohner H
      • Hummel TC
      • Habel U
      • et al.
      Predicting delirium after vascular surgery: a model based on pre- and intraoperative data.
      ,
      • McNicoll L
      • Pisani MA
      • Zhang Y
      • et al.
      Delirium in the intensive care unit: occurrence and clinical course in older patients.
      Additionally, PSD subjects often had more severe neurological deficits, in accordance with the results of previous studies.
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in acute stroke: a review.
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
      Our study showed that functional outcome (measured using the IADL scale at 3 months after the index stroke) was worse in subjects with PSD, even after adjusting for possible confounders. This finding concurred with the findings of previous studies.
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
      • Sandberg O
      • Franklin KA
      • Bucht G
      • et al.
      Sleep apnea, delirium, depressed mood, cognition, and ADL ability after stroke.
      However, when we used the mRS score as the outcome, PSD did not appear to affect it. The IADL is a comprehensive measure comprising assessments of both physical and mental function, while the mRS assesses physical deficits rather than mental disability.
      • van Swieten JC
      • Koudstaal PJ
      • Visser MC
      • et al.
      Interobserver agreement for the assessment of handicap in stroke patients.
      Thus, it is understandable that PSD, which is mainly a cognitive dysfunction, would correlate with the IADL score rather than the mRS score. In addition to the above functional outcome, mortality, hospital stay duration, and Barthel Index have also been found to be worse after delirium, according to the literature.
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
      • Miu DK
      • Yeung JC
      Incidence of post-stroke delirium and 1-year outcome.
      The advantage of our study was that we recruited a more homogenous study sample and used the brain MRI scans rather than computed tomography scans to evaluate the infarcts as well as the pre-existing brain abnormalities. As we know, MRI is more precise at locating the sites of infarction and more sensitive for detecting WMLs.
      There were also some limitations in our study. First, the sample size was relatively small. Second, we did not evaluate the cognitive status or the effects of medication in our patients, which have been found to be correlated with PSD in some studies.
      • Oldenbeuving AW
      • de Kort PL
      • Jansen BP
      • et al.
      Delirium in acute stroke: a review.
      • Klimiec E
      • Dziedzic T
      • Kowalska K
      • et al.
      PRospective Observational POLIsh Study on post-stroke delirium (PROPOLIS): methodology of hospital-based cohort study on delirium prevalence, predictors and diagnostic tools.
      However, assessment of cognitive function may not be very reliable in the acute phase of stroke. Third, we did not assess the NIHSS score at follow-up after stroke, which led to an inadequate evaluation of poststroke residual neurological deficits.
      In conclusion, we found an incidence of delirium of 14.8% in the first week after admission with acute ischemic stroke. Age, having a previous stroke, stroke severity, and left-cortical infarction were independently predictors of PSD. If delirium complicates ischemic stroke, it may result in a significantly worse functional outcome. Healthcare professionals should pay more attention to the early recognition of and intervention for delirium in stroke management.

      Author contributions

      JF and YK conceived and designed the research. JF, GP, HH and HP collected the data. JF, YK and WM analyzed the data and prepared the tables. WM revised the manuscript critically for important intellectual content.

      References

        • American Psychiatric Association
        DSM-5 task force. Diagnostic and statistical manual of mental disorders: DSM-5.
        American Psychiatric Publishing, Arlington2013: 596-601
        • Cole MG
        Delirium in elderly patients.
        Am J Geriatr Psychiatry. 2004; 12: 7-21
        • Fick DM
        • Agostini JV
        • Inouye SK
        Delirium superimposed on dementia: a systematic review.
        J Am Geriatr Soc. 2002; 50: 1723-1732
        • Oldenbeuving AW
        • de Kort PL
        • Jansen BP
        • et al.
        Delirium in acute stroke: a review.
        Int J Stroke. 2007; 2: 270-275
        • Bohner H
        • Hummel TC
        • Habel U
        • et al.
        Predicting delirium after vascular surgery: a model based on pre- and intraoperative data.
        Ann Surg. 2003; 238: 149-156
        • Oldenbeuving AW
        • de Kort PL
        • Jansen BP
        • et al.
        Delirium in the acute phase after stroke: incidence, risk factors, and outcome.
        Neurology. 2011; 76: 993-999
        • Sandberg O
        • Franklin KA
        • Bucht G
        • et al.
        Sleep apnea, delirium, depressed mood, cognition, and ADL ability after stroke.
        J Am Geriatr Soc. 2001; 49: 391-397
        • Adams Jr., HP
        • Bendixen BH
        • Kappelle LJ
        • et al.
        Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial TOAST. Trial of Org 10172 in acute stroke treatment.
        Stroke. 1993; 24: 35-41
        • Marcantonio ER
        Delirium in hospitalized older adults.
        N Engl J Med. 2017; 377: 1456-1466
        • Inouye SK
        • van Dyck CH
        • Alessi CA
        • et al.
        Clarifying confusion: the confusion assessment method, a new method for detection of delirium.
        Ann Intern Med. 1990; 113: 941-948
        • Trzepacz PT
        • Mittal D
        • Torres R
        • et al.
        Validation of the delirium rating scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium.
        J Neuropsychiatry Clin Neurosci. 2001; 2: 229-237
        • Huang MC
        • Lee CH
        • Lai YC
        • et al.
        Chinese version of the delirium rating scale-revised-98: reliability and validity.
        Compr Psychiatry. 2009; 50: 81-85
        • National Clinical Guideline Centre(UK)
        Delirium: diagnosis, prevention, and management of delirium.
        Clin Gudel. 2010; 103: 512-539
        • Lawton MP
        • Brody EM
        Assessment of older people: self-maintaining and instrumental activities of daily living.
        Gerontologist. 1969; 9: 179-186
        • Fazekas F
        • Chawluk JB
        • Alavi A
        • et al.
        MR signal abnormalities at 1.5T in Alzheimer's dementia and normal aging.
        Am J Roentgenol. 1987; 149: 351-356
        • Scheltens P
        • Leys D
        • Barkhof F
        • et al.
        Atrophy of medial temporal lobes on MRI in “probable” Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates.
        J Neurol Neurosurg Psychiatry. 1992; 55: 967-972
        • Sheng AZ
        • Shen Q
        • Cordato D
        • et al.
        Delirium within three days of stroke in a cohort of elderly patients.
        J Am Geriatr Soc. 2006; 54: 1192-1198
        • Dunne JW
        • Leedman PJ
        • Edis RH
        Inobvious stroke: a cause of delirium and dementia.
        Aust N Z J Med. 1986; 16: 771-778
        • Mori E
        • Yamadori A
        Acute confusional state and acute agitated delirium. Occurrence after infarction in the right middle cerebral artery territory.
        Arch Neurol. 1987; 44: 1139-1143
        • Shih HT
        • Huang WS
        • Liu CH
        • et al.
        Confusion or delirium in patients with posterior cerebral arterial infarction.
        Acta Neurol Taiwan. 2007; 16: 136-142
        • McManus J
        • Pathansali R
        • Stewart R
        • et al.
        Delirium post-stroke.
        Age Ageing. 2007; 36: 613-618
        • Arnold MB
        Emotion, motivation, and the limbic system.
        Ann N Y Acad Sci. 1969; 159: 1041-1058
        • Carin-Levy G
        • Mead GE
        • Nicol K
        • et al.
        Delirium in acute stroke: screening tools, incidence rates and predictors: a systemic review.
        J Neurol. 2012; 259: 1590-1599
        • McNicoll L
        • Pisani MA
        • Zhang Y
        • et al.
        Delirium in the intensive care unit: occurrence and clinical course in older patients.
        J Am Geriatr Soc. 2003; 51: 591-598
        • van Swieten JC
        • Koudstaal PJ
        • Visser MC
        • et al.
        Interobserver agreement for the assessment of handicap in stroke patients.
        Stroke. 1988; 19: 604-607
        • Miu DK
        • Yeung JC
        Incidence of post-stroke delirium and 1-year outcome.
        Geriatr Gerontol Int. 2013; 13: 123-129
        • Klimiec E
        • Dziedzic T
        • Kowalska K
        • et al.
        PRospective Observational POLIsh Study on post-stroke delirium (PROPOLIS): methodology of hospital-based cohort study on delirium prevalence, predictors and diagnostic tools.
        BMC Neurol. 2015; 15: 94