The Prognosis of Delirium

Transcription

1 PSYCHOGERIATRICS 2002: 2: REVIEW The Prognosis of Ravi S. Bhat* and Kenneth Rockwood** Received May 30,2002, accepted August 20,2002. * Centre for Older Persons Health, Mental Health Service, Australia *Department of Medicine, Dalhousie University, Canada Reprint requests to Kenneth Rockwood, Geriatric Medicine Research Unit, Capital Health, Suite 1421, 5955 Veterans Memorial Lane, Halifax, Nova Scotia B3H 2E1. CANADA. Key words: delirium, prognosis, systematic review, dementia Abstract: This paper aims to undertake a systematic review of the published experience on the prognosis of delirium. Using a standard search strategy, we identified studies and assessed them using standard criteria for validity. Seventeen cohorts were identified, with length of followup varying from hospital discharge to four years. Although delirium usually results in increased adverse outcomes in both the short and long term, the mechanism is unclear. A good case can be made, however, that, especially in older patients, delirium and dementia represent alternative expressions of the same underlying pathology. INTRODUCTION is a common problem amongst older adults, and its routine care has proved to be surprisingly difficult to implement effectively. ) Better routine care seems to be important if adverse outcomes are to be avoided, especially as the traditional conceptualisation of delirium as having a good prognosis has been questi~ned.~ An earlier metaanalysis of eight of the first systematic studies of the outcomes of delirium found most to have been of questionable validity.2) Thus, we conducted a review of all original research to assess the validity of more recent studies and examine their results. METHODS Selection of articles: The selection process involved three steps. First, MEDLINE was searched with the use of keywords delirium, aged and cohort study for all research articles published in English from January 1990 to October Second, we searched all bibliographies of relevant articles for additional references. Finally, we screened all the articles to meet the following inclusion criteria: original research, prospective study design, diagnosis of delirium based on operationalised diagnostic criteria, sample of at least 20 patients, inclusion of patients aged 60 years and above and a followup period of at least 1 week. This selection process yielded 18 articles of 17 cohorts involving 1,282 patients with delirium. (Table 1) Assessment of validity We assessed validity of each study according to the 6 criteria described by Laupacis et al5) One author first assessed all studies, and then the other reviewed his ratings. Disagreements were reviewed, so that the results here presented are a consensus view. Was a defined, representative sample of patients assembled at a common point in the course of their disease? In most studies an inception cohort was formed. Patients were those admitted to wards in a general hospital, psychogeriatric units, orthopaedic units and medicalsurgical wards. In 11 studies the sites were clearly identified as tertiary care hospitals very often university hospitals. However, it was only in 4 studies that incident and prevalent delirium was clearly identified,4.68) as this can help in clarifying certain outcomes. It appeared that in 2 studies, both of hip fracture patients, all cases were in~ident.~. ~) While it might be argued that the acuity of change makes the incidence/prevalence distinction in delirium more apparent than real, several factors suggest their differentiation to be potentially important. Conditions such as dementia following stroke and dementia with Lewy bodies can have sudden onset,1i.i2) and to, at least initially be indistinguishable from de1iri~m.l~) Moreover, the lack of recognition of delirium in usual care14) makes followup of 165

2 Bhat et al. prevalent cases more problematic. ies used some form of operationalised criteria for diagnosis of delirium. Twelve studies used the DSMIIIR criteria Was the followup long enough? for delirium 5 of them through clinical In most studies the followup was long enough to deter and the remaining based on assessment by the Confumine outcomes they were seeking to ~ b~erve.~~~~~~~,~~~~) sion Assessment Method (CAM)~,7~10~19~21~23~24,27) The study by Marcantonio et a1.2 ) used the Symptom Inter Was the followup complete? view (DS1)28) to elicit symptoms of delirium but used the In six studies it appeared that the followup was complete, 3~9~10~192124) however, in others it was not always clear whether the followups were complete. The data given in the articles was not sufficient to make this judgement. Some argue that greater than 20% loss of followup seriously threatens ~alidity.~) Were the objective outcome criteria applied in a blind fashion? While evaluating death as an outcome of delirium this criterion may not be so relevant. However, to examine outcomes such as functional decline, persistence of cognitive dysfunction, and to some extent even institutionalisation it is important that this criterion is met to minimise bias. In most studies examined the outcomes were either not examined in a blind fashion or information was not present to make judgement in that regard with the sole exception of the study by lnouye et ai.l9) If subgroups with different prognoses are identified, was there an adjustment for important prognostic factors? This was one of the major problems in the studies reviewed by Cole and Primeau.2) The outcomes of hospitalised elderly can be influenced by age, admission from a nursing preexisting cognitive dysfunctioddementia and severity of physical illness.2) Eleven of 17 studies made some adjustment for prognostic factors. More often than not the adjustment was done statistically, however, some adjusted certain prognostic factors by stratification. Was there a validation in an independent group of test set patients? None of the studies met this criterion. The only study that had a derivation and test set had had that to examine predictors for delirium rather than delirium as a prognostic factor.7, RESULTS The lack of comparable validity precluded a metaanalysis, however, we went on to examine the results. All stud CAM diagnostic algorithm for diagnosis. Four studies used DSMIII criteria and another two used DSMIV criteria. The study by Levkoff et al6) used the DSI and O Keeffe and Lavan*) established the diagnosis of delirium using the Assessment Scale (DAS).29) The overall sample size varied from 51 to 727 and that of cases carried ranged from 12 to 220. (Table 1) Mean ages were identified in all studies. The length of followup varied from in hospital to 4 years. In view of such varied periods of followup we studied them under shortterm (1nths) and longterm (2nths). Most studies had a control group except two looking at longterm outcome16*20) and one looking at the sh~rtterrn?~) In the studies comparing with controls the control group constituted of those who failed to meet criteria for delirium except one studyla) where the controls were age, sex and disease matched. The main outcomes studied were mortality, length of hospital stay, and decline and/or change in activities of daily living (ADLs) (both basic and instrumental), transfer to residential care or institutionalisation, and persistence of cognitive dysfunction or dementia. The prognostic outcomes are presented in Table 2. For ease of understanding we looked at and have presented these data under shortterm and longterm prognosis where shortterm has been defined as snths and longterm as 2nths. Shortterm prognosis The characteristics of studies that identified outcomes of patients with delirium vs. control subjects is summarised in Table 2, and the outcomes themselves in Table 3. The relationship of delirium to mortality in the shortterm appeared equivocal. (Table 3) The mortality rates at discharge from hospital ranged from 6 to 18% in patients with delirium. (Fig. 1) Only one study showed significant effects of delirium on inhospital mortality after adjusting for other prognostic factorsn (1 1 % vs. 2%). In some studies the rates were too small to derive a meaningful relati~nship.l~~~) Other studies that made these adjustments failed to find a relationship.8*21) Studies reporting without 166

3 Table 1. Characteristics of studies of prognosis of delirium in the elderly No. Study N Age in yr Diagnostic No. with Incident/ Identification Frequency of Admitting unit Control group assessment delirium prevalent of dementia followup delirium prior to onset identified? of delirium? 1 Francis et al DSMIUR ) Clinician interview 2 Levkoff et al k7.7 DSMIII 19926) symptom interview (DSI) Interview with primary nurse Daily exam of medical chart 50 No Yes Every 48 hrs 26 with until dementia discharge rating then at score Yes No Daily until 14 d then intermittently until discharge: at 3 and General medical Remaining 176 service of tertiary hospital Medical and Remaining 200 surgical units: tertiary hospital from defined institution and community 3 Koponen et al f6.4 DSMIU 70 No Yes/No Unclear Psychogeriatric ward; None Clinical exam tertiary hospital? 4 Francis et al DSMIIIR 45 No Yes 2 yrs General medical Remaining f6.1 Clinician interview 26 with service of tertiary dementia rating hospital score24 5 Pompei et al DSMIUR digit span vigilance A test Clinical assessment of confusion Confusion assessment method (CAM) 6 O Keeffe et al /82 DSMIlI assessment scale (DAS) Yes;? excluded retrospectively Yes Yes Blessed score24 or impairment in function due to cognitive impairment2 7 Georgeetal /80 DSMUI 171 All No Clinical interview prevalent confirmation later cases 8 lnouye et al _6.9 Confusion 88 No 1998 ) assessment method (CAM)/ DSMUIR Daily rating Medical and Remaining 368 until diagnosis; surgical wards; at discharge tertiary hospital and 90 d Every 48 hrs Geriatric unit: Remaining 131 and reviewed tertiary regularly? university hospital Each week: District general Age, sex 6 and hospital and diagnosis matched Yes surgical wards Within 48 hrs; Multisite Remaining 639 MMSE 3 mo tertiary care scores220 hospitals: medical and/or

4 ~~~ ~ ~~~~ 9 Henon et al. 202 Median, 75 DSMIV 1 99g9 rating scale 10 Rockwood et al. 203 Given DSMIV rating scale 49? all incident Yes Stroke unit; Remaining 153 IQCODE at tertiary care university hospital 38 Unclear Yes Once to General medical 165 Canadian measure services of study of outcome tertiary hospital health and aging dementia protocol 11 Rahkonen et al k5.4 DSMIIIR 51 No Yes 1 and 2 yr General hospital None ) Clinical interview NINCDS ADRDA criteria 12 Curtyo et al DSMIIIR 12/53 No ) Clinical interview Unclear 13 Marcantonio et al f8 symptom 52 No Yes 2006 interview (DSl)+confusion Blessed score assessment method (CAM) 24 by proxy diagnostic algorithm/ interview DSMIIIR? 14 Dolan et al / DSMIIIR 92 No Yes, but ) 80f7.4 Modified confusion excluded from ~~ assessment method analysis (CAM) 15 Galankis et al Confusion assessment 25 All incident No ) method (CAM)/DSMIIIR Every 4 mo+ 2 and 3 weeks after baseline and followup Daily until discharge; 1 and Intake; 2, 6, 12,18,24 mo From residential Remaining 41 care facility with admissions to affiliated hospitals Tertiary Remaining 74 medical centre; admissions for surgical repair of hip fractures Multisite, Remaining hospitals treating 2/3 hip fractures Preoperative; departments of tertiary care university hospital Hip surgery Remaining 80 daily patients at surgical and orthopaedic 16 ~ ~~~~ ~ Kelly et al Confusion assessment 61 Unclear No method (CAM)/ DSMIIIR Every 48 hr overall mortality in hospital at same period Acute care None until death/ nonsurgical inhospital discharge hospital for a geriatric centre mortality compared with 17 McCusker et al DSMIIIR 220 Yes Yes Enrolment; University affiliated Remaining ) Confusion assessment IQCODE 2, 6, acute primary care method (CAM) hospital 18 Rahkonenetal DSMLUR 20 Not relevant; Yes, but 3 yr initial City of Vantaa, Remaning ) range, based on community excluded from observation+ Finland 179 without 8598 retrospective clinical based study data analysis another 2 yr delirium interview and followup hospital data

5 The Prognosis of Table 2. The evidence in the shortterm prognosis (5nths) Study N Prognostic factor Outcome Time Measure Independent? rancis et al. 226 (n=50) I 99217) (remaining patients) (n=176) (n=20) (n=93) Hospital stay Hospital stay MMSE scores MMSE scores ADL decline ADL decline (n=50) (n=49) (n=176) (n=167) 4d Not known; (8%) rates too low? 14.3% Strong effect of illness severity 2d (1 Yo) 10.1% 12.1 d Yes 7.2 d 16% 12% 3.4% 5% 24.7 d 26.7 d 25% Unclear 25% evkoff et al. 325 I 9926) (n=125) community community institutional institutional In sub sample of (incident) community dwelling (n=211) Hospital stay Hospital stay Hospital stay Hospital stay 26.4% 13% 30.9 d 7.4 d 10.6 d 6.9 d 44% 7% No Yes (community: adjusted t=4.03, p=o.0001; institutional: adjusted t=4.48, p=o.o001) Yes (OR, 7.3; 95% CI, Pompei et al ) (n=64) (n=64) 90 d (n=57) (n=368) 90 d (n=359) 7d (1lYO) 6d (11%) 9d (2%) 11 d (3%) Yes No OKeeffe et al % No (in hospital: 19978' (n=94) 31?'o adjusted OR, 2.6; 5% 95% CI, ; (n=131) 15% : adjusted OR, 1.4; 95% CI, ) Hospital stay 21 d Yes (adjusted M.8, Hospital stay 11 d p<o.ool); accounted for 6.7% of variance 169

6 Bhat et al. Study N Prognostic factor Outcome Time Measure Independent? 3 Keeffe et al Complications Complications Change in functional status worse Change in functional status worse (community; n=61) (Community; n=lo4) George et al. 171 f *) (n=171) (age, sex and diagnosis matched) Readmission Readmission Mean stay Mean stay (n=47) (n=124) From hospital From hospital 56 d (60%) 44 d (34%) 12 d (26%) 15 d (1 2%) 22 d (36%) 13 d (1 3%) Yes (adjusted OR, 2.3; 95% CI, ); accounted for 5.2% of variance Yes (adjusted t=3.2, p=0.002); accounted for 2.8% of variance Yes (adjusted OR, 2.8; 95% CI, ); accounted for 2.8% of variance 19 d Not adjusted (1lYO) 53 d (31%) 65 d (38%) 6d Not adjusted (So/,) 12 d (13%) 20 d (21 Yo) 20 d Not adjusted (12%) 33 d (19YO) 40 d (23%) 5d (5%) 5d (5%) 6d (6%) 58 d Not adjusted (34%) 95 d (55%) 20 d (21%) 36 d (38%) 27 d 25 d

7 The Prognosis of Study N Prognostic factor Outcome Time lnouye et al ) (n=90) 3 mo (n=637) 3 mo 3 mo 3 mo ADL decline At 3 mo ADL decline At 3 mo Mean stay (adjusted) Mean stay (adjusted) Measure 8/90 d (9%) 24/81 d (30%) d (4%) d (12%) d (24%) d (38%) d (6%) d (11%) 36/54 d (67%) 25/47 d (53%) d (34%) d (26%) 8d 7.5 d Independent? Small Clinical but not statistical significance Yes for new NH placement (at discharge: adjusted OR, 3.0; 95% CI, ) (3 mo: adjusted OR, 3.0; 95% CI, ) Yes (at discharge: adjusted OR, 3.0; 95% CI, ; 3 mo: adjusted OR, 2.7; 95% CI, ) No Henon et al g9, (n=49) (n=153) Sentlliving at home Sentlliving at home Barthel score (0100) Barthel score (0100) (n=42) (n=29) (n=133) (n=104) 7/49 d (14.3%) 17/49 d (34.7%) d (13.1%) d (28.1%) 12/42 d (28.6%) 19/32 d (59.4%) d (49.6%) d (85.5%) 42.5 d 60 d 85 d 95 d No difference Not adjusted Not adjusted 171

8 Bhat et al. Study N Prognostic factor Outcome Time Measure Independent? Marcantonio 126 et al. 200oz1) (n=52) (n=74) ADL decline ADL decline Residential care/death Residential careldeath 1 mo 1 mo 1 mo 1 mo 1 rno 1 mo 2d (4%) 8d (15%) I d (1%) 7d (9%) 34 d (56%) 22 d (42%) 25 d (34%) 14 d (19YO) 24 d (46%) 18 d (35%) 9d (12%) 10 (14%) No Yes (1 rno: adjusted OR, 2.6; 95% CI, ; 6 rno: adjusted OR, 2.1 ; 95% CI, ) Yes (1 mo: adjusted OR, 3.0; 95% CI, ; : adjusted OR, 1.8; 95% CI, ) Galankis et al '0) (n=25) (n40) Kelly et al ) (rial) 21 complications 40% No 21 complications 28.8% 11/61 d No (18%) 1 mo d (33.3%) 3 rno 28/60 d (46.6%) No data No data )R: odds ratio, CI: confidence interval, NH: nursing home adjustment for other prognostic factors often reported significantly increased mo~tality~~.~~) where the mortality was 11 Yo and 18%, respectively. While George et compared with a control group, Kelly et al.24) compared with mortality rates for the hospital in the same period. The mean stay ranged from 8 to 30.4 days. Two studies reported median hospital of 8 and 13 days, respectively. Five studies found delirium significantly increased hospital stay compared to c~ntrois~~~~~) while two did not find any significant differen~e.'~*'~) Two studies showed that delirium patients had significantly greater inhospital complications compared to controls.8~10) Amongst patients who experience an episode of delirium, even when there is resolution of some symptoms (usually inattention) others (usually memory and disorientation) persi~t.~~~) The proportion of patients with persistent cognitive dysfunction ranged from 201 ) to 72Y0.'~) In the latter studyz4) of 214 patients admitted from a nursing home, 72% with symptom persistence at one month, and 25% had symptom persistence at three months. Similarly, in a cohort of older adults with hip fractures, 39% had persistence of their symptoms at discharge or death, 33% at one month, and 6% at six months.21) These findings are in keeping with an earlier large cohort study,@ which found that 58% of patients who developed delirium during admission still met research criteria for delirium at discharge. Similarly, a metaanalysis of eight inpatient studies,') estimated that only 55% of patients had some 172

9 Table 3. Shortterm outcomes of Datients (and control subiects) with delirium by study Study Francis et al ) Levkoff et al ) Koponen et al ) Pompei et al ) O Keeffe et al George et al ) lnouye et al ) Henon et al. 1 99g9, Marcantonio et al Galankis et al lo) Kelly et al ) Mean length of stay, days 12.1 (7.2) 18.8 (7.3) 30.4 (22.1) No data 21 (11) 27 (25) Median, 8 (7.5) Median, 13 (12) 7 (5) No data 8 (4 Rates of institutional care, YO Mortality rates, 30 ADL decline Persistence of cognitive At 1 mo 3mo 6mo At 1 mo 3mo 6mo At 3 mo dysfunction/ discharge discharge discharge dementia 14.3 (10.1) 26.4 (13.0) 31 (15) 31 (13) 67 (34) 34.7 (28.1) (9) (34) No 68% 32% 39% 20% 72%

10 Bhat et al. degree of mental recovery at one month. seems to be more robustly associated with decline in functional status and discharge or transfer to residential care or institutionalisation. There was worsening of both basic and instrumental ADLs.~~~~~~~) Decline in occurred in up to 67% of patients with delirium at discharge in one studyig) where the difference between groups was significant at three months. In two studies the decline in ADLs compared to controls was significant at six months even after adjusting for other prognostic factors.8,2i) Most studies reported that patients with delirium were significantly more likely to be transferred to residential care facilitieshursing homes upon discharge with the proportion of patients ranging from 7 to 46%. The differences remained significant at three months (RR, 2.9)19) and at six months (RR; 2.8,4.5, and 2.5, respectively).8,18,21) 50% 40% 1 30% 20% ii Longterm prognosis Characteristics of studies that addressed longterm prognosis are presented in Table 4, and their results summarised in Table 5. Two ~tudies~~.~) reported no significant relationship with mortality at twoand threeyear followups, respectively, while one reported a significant relation 30% Fig. 1. A sample graph showing inhospital mortality (in black), transfer to residential care from hospital (in white), and length of hospital stay in days (in grey). Patients with delirium are represented on positive y axis and no delirium on negative y axis. The numbers represent studies as numbered in Table 1. ship over a threeyear followup even after adjusting for month and 2 year followup^.^^^^^) confo~nders.~) The median survival time in this latter study The Rahkonen et alz5) needs to be assessed sepawas significantly reduced in people who had a diagnosis rately as it was the only populationbased study of deof deliri~m.~) lirium. The study examined the rates of delirium in the Two studies reported a significant effect of delirium on nondemented oldestold (585 years). The diagnosis of MiniMental State Examination (MMSE)3i) scores on fol delirium was made after an initial observation period of 3 lowup at nths and 2 years, ~espectively.~.~~) In the years on the surviving 199 of an initial cohort of 366 elistudy by McCusker et al4) patients with delirium only had gible subjects. There were 20 subjects with delirium and worse MMSE scores than those dementia only, but pa they were significantly more likely to develop dementia tients with delirium only showed more improvement at than those without delirium (65% vs. 26%; p=o.ool). The followup than those with dementia only. Two studies mortality rates were also higher. looked at incidence of dementia po~tdelirium.~~~~) The study by Rockwood et al3) showed an annual incidence DISCUSSION of 18.1 % for dementia in patients with delirium over a We reviewed the prognosis of patients with delirium, and threeyear followup compared to 5.6% in the control found that delirium is associated with a worse prognosis. group. also predicted institutionalisation over 12 This review has certain limitations. The studies were ini 174

11 tially selected and reviewed by one person, which may have biased the rating of each study. Moreover, we relied on the published articles themselves than getting data from the authors. Secondly, we did not assess the possibility of publication bias. It appears that delirium does have a poorer prognosis both in the shortterm and the longterm. Does delirium cause adverse outcomes or is it mostly a marker of worse physical illness, which is the real cause of the problems? The answer is not clear. In principle, a number of mechanisms can operate, and at present, none can be excluded, suggesting that some will be true for at least some patients, while in other patients, more than one mechanism is likely to be in play. In the shortterm the evidence appears to be most robust in the relationship between delirium and functional decline and transfer to residential care or institutionalisation. The data regarding mortality however is equivocal. Studies that have accounted for other factors influencing mortality such as comorbid disease and/ or illness severity have failed to find a significant association between delirium and mortality both inhospital and at shortterm fo11o~~p.~~~~~~~~~~~~) Of these in studies by Francis et ali5) and lnouye et ai.l9) the number of deaths inhospital were too small for meaningful comparisons and in the study by Levkoff et a1.6) data regarding inhospital mortality was absent. The study by Pompei et al7) was the only study to find significant association between delirium and death after adjustment for comorbid disease. Comorbidity was estimated in this study by counting the total number of discharge diagnoses and consolidating these in major diagnostic categories?) This strategy would not take into account the severity of illness; unlike the Charlson Cornorbidity Index3) (used in two studies)$21) which takes into account both the number and seriousness of illness. Few studies excluded terminally ill patients. As argued elsewhere%) the failure to do so may mean that we have systematically overestimated shortterm adverse outcomes from delirium. Most studies appear to show that cognitive dysfunction tends to persist in a substantial number of patients who have had an episode of delirium. Longterm data suggest that patients with delirium show worse cognitive performance over time and are likely to develop dementia. This raises interesting issues regarding the relationship between delirium and dementia. First concerns the definition of delirium is there a boundary between a neat, selflimited delirium that ultimately resolves, and a demen The Prognosis of tia that always goes on to get worse and a delirium that grumbles along and merges into a dementia? The second issue is that if we accept that delirium does raise the risk of dementia how does it do it? The diagnostic criteria for delirium have been criticized for taking too dogmatic a view on both the irreversibility of dementia and the reversibility of deliri~m.~~,~~) This tendency has persisted, despite substantial evidence that many older adults with delirium never recover their premorbid cognitive f ~nction.~~~~~~,~~,~~) Moreover, having identified a syndrome of reversible cognitive dysfunction (based on changes in the MMSE score) Treloar and MacDonald found that existing delirium criteria were in sensitive to such re~ersibility.~~) While their initial operationalization of the concept is, as the authors themselves note, quite flawed, any review of the prognosis of delirium must address the particular challenge posed by the finding that many people with delirium simply never show cognitive recovery. Dementia or persistent cognitive dysfunction appears to be an intriguing negative outcome of delirium. The pos sible hypotheses are: 1. causes or predisposes to dementia. 2. may serve as a marker for dementia by unmasking it. 3. and dementia are alternative expressions of a same underlying pathology. might give rise to brain injury that results in the predisposition to dementia. Indeed, if we consider that many forms of dementia may result from aberrant repair mechanisms,36) delirium may even give rise to a process that initiates dementia. Recent studies suggest that the initiating events in dementia may be preceded by decades3 ) might actually be the first presentation of an underlying dementia. There are varying strands of evidence that lend some weight to this hypothesis. First, preexisting cognitive decline has been noted as an important factor for delirium in hospitalised elderlyg) as assessed by Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).38) In this group of patients most were not considered demented and the cognitive decline was not obvious to the relatives. However, IQCODE may yield variable results for patients with deliri~m.~) The instrument asks informants to rate behavioural change that took place from over five years previously until immediately before the illness that led to the hospital admission. In such an event informants 175

12 Bhat et al. Table 4. The evidence in the longterm prognosis (2nths) Study N Prognostic factor Outcome Time Measure Independent? Koponen et at. 70 4d No ) (6Yo) 1 Yr 26 d 4 Yr (37%) 46 d (66Yo) Francis et al ) (n=50) (n=l79) (n=34 with baseline ADL) (n=146 with baseline ADL) Rockwood et al g3 (n=38) (n=165) lnstitutionalised or dependent on 1 of 4 basic ADL (1 4 deaths) lnstitutionalised or dependent on 1 of 4 basic ADL (31 deaths) MMSE MMSE Median survival time Median survival time Dementia incidence Dementia incidence 2 Yr 39% No (adjusted RR=1.4; 95% CI, ) 2 Yr 23% 2 Yr 8/20 d (40%) 2 Yr 21/115d (1 So/) d (telephone) 27.0t3.3 d 2 yr n= k4.2 d (telephone) Yes 3 Yr 30 d Yes 3 Yr (79%) 71 d (43%) Over 3 yr 510 d? Over 3 yr 1,122d Annual 18.1% Yes Annual 5.6% Rahkonen et at. 51 Dementia At beginning 14 d No 20002O (overall 28; 55%) (27%) 1 Yr 8d 2 Yr (16%) 6d (12%) 2 yr 35% Curtyo et al Yr 9d No 2001= (n=l2) (75%) 3 Yr 21 d (n=41) (51%) Dolan et al. 674 Unclear ) McCusker et at. 220f95 Neither 7/37 d 20014) dementia nor (19YO) delirium only 7/44 d Dementia only (16Yo) 12/46 d (26%) 76

13 The Prognosis of + dementia Neither dementia nor delirium only Dementia only + dementia Neither dementia nor delirium only Dementia only + dementia IADL reference IADL decline IADL decline IADL decline Barthel Index reference Barthel Index Barthel Index Barthel Index 47/121 d (39%) Od 0.63 d (2.14 to 0.88) 3.34 d (4.67 to 2.01) 4.02 d (5.22 to 2.82) Od d (28.49 to 0.70) d (26.04 to 1.23) d (41.50 to 18.67) Rahkonen et al ) (n=20) (n=179) 2 Yr 55% (after initial 3 yr of observation) 2 Yr 30% Dementia 2 Yr 65% Dementia 2 Yr 26% Vascular dementia 2 yr 35% Vascular dementia 2 yr 9% Unadjusted analysis (p=o.ool; log rank test) Unadjusted analysis (p=o.ool ) Unadjusted analysis (p=o.o09) Number of days of hospitalization beyond DRGassociated length of stay are significantly increased for patients with delirium (KruskalWallis test=27.2, 1 df, p<o.oooi. No numerical data on hospital stay. RR: relative risk Table 5. Longterm outcomes of patients (and controls) by study Study Koponen et al ) Francis et al ) George et al ) Rockwood et al Rahkonen et al. 20OO2O Curtyo et al Dolan et al ) McCusker et al ) Rates of institutional care, Yo Mortality rates, % ADL decline Persistent cognitive 1 yr 2 yr 3 yr 4yr 1 yr 2 yr 3 yr 4yr 1 yr 2 yr 3yr dysfunction dementia dementia, 39%; dementia, 26%; delirium, 16%; neither, 19% greater decline in (23) MMSE scores 38 (21) 79 60% yr (43) yr 177

14 Bhat et al. may confuse the acute behavioural changes with delirium with the longerterm changes associated with dementia. Second, studies of electroconvulsive therapy (ECT) induced delirium in elderly depressed patients have revealed that patients who developed delirium were more likely to have lesions of the basal ganglia and those with moderate to severe hyperintensities and deep white matter lesions were significantly more likely to develop an interictal Diagnostic criteria for delirium often heavily focus on inattention as a sign of delirium, however, disorientation to time is seen to be equally Age and cognitive dysfunction have been found to be important predictors of delirium. Temporal processing is often impaired with age! ) It has been hypothesised that basal ganglia play a key role in controlling an internal timekeeping process. Along with dopamine, cholinergic challenges alter accuracy as well as variability of timing and the effects are gradual. Studies also implicate a rightprefrontalinferiorparietal network in temporal ~rocessing.~~) Spiegel et al. have described temporal disorientation with bilateral medial thalamotomy, especially involving intralaminar nuclei.42) The few reports that exist on delirium following a stroke suggest greater right hemisphere strokes (reviewed elsewhereg)). Recently, a correlation was reported between disorientation to time and decreased regional cerebral glucose metabolism in the posterior cingulate gyrus bilaterally in patients with Alzheimer s disease (AD)43) and this may be the region that is affected at a very early stage in AD. ) A neuropathological study of spatial and temporal disorientation in 29 patients with AD45) has suggested spatial and temporal disorientation in AD is not related to diffuse development of pathology in AD but represent clinical expression of the disruption corticocortical connections between areas 7 and 23 and the CA1 field of the hippocampus. Thus it is possible that subtle deficits in the subcortical regions, especially in the right hemisphere, that are relevant for processing both attention and temporal orientation form the substrates on which delirium develops. It would be important to test this hypothesis by examining the role preexisting cognitive dysfunction and dysfunction in temporal processing, especially in incident cases, in predicting delirium and future cognitive dysfunction. The hypothesis that delirium and dementia are alternative expressions of a same underlying pathology was originally espoused by Engel and Blass and Gibson point that delirium and dementia have many simi larities both clinically and biologically, and that this suggests these conditions are different quantitative stages of the same process.13) They go on to argue, that both patient care and research will benefit from conceptualising these conditions as reversible cerebral insufficiency and irreversible cerebral insufficiency instead of as different entities. The second hypothesis appears to be nested within this last hypothesis in that delirium is a function of emergent dementia. Examination of these hypotheses brings us back to the idea that we need to reexamine our current conceptualisation of delirium and dementia, and that this reconceptualisation should be based on empirical ACKNOWLEDGEMENTS Kenneth Rockwood is supported by an Investigation Award from the Canadian Institute of Health Research, and by the Dalhousie Medical Research Foundation as Kathryn Allen Weldon, Professor of Alzheimer Research. REFERENCES 1. lnouye SK, Schlesinger MJ, Lydon TJ. : a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med 1999; 106: Cole MG, Primeau FJ. Prognosis of delirium in elderly hospital patients. CMAJ 1993; 149: Rockwood K, Cosway S, Carver D, et al. The risk of dementia and death after delirium. Age Ageing 1999; 28: McCusker J, Cole M, Dendukuri N, et al. in older medical inpatients and subsequent cognitive and functional status: a prospective study. 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