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Are Fluctuations in Motor Performance a Diagnostic Sign of Delirium?
Are Fluctuations in Motor Performance a Diagnostic Sign of Delirium? Giuseppe Bellelli, MD, Salvatore Speciale, MD, Sara Morghen, PsyD, Tiziana Torpilliesi, MD, Renato Turco, MD, and Marco Trabucchi, MD
Background: Although delirium is known as a mental disorder, recent evidence suggests that it is associated with short- and long-term impairment of functional status. Objective: To evaluate whether a pattern of fluctuations in motor performance are a diagnostic sign of delirium. Design: Case-controlled study with prospective evaluations of 4 groups of patients. Setting: Department of Rehabilitation and Aged Care. Methods: Fifteen patients with incident delirium alone (Del group) and 15 patients with incident delirium superimposed on dementia (DSD group) were compared with 15 patients with neither delirium nor dementia (No Del–No Dem group) and 15 patients with dementia but no delirium (Dem group), respectively. Eligibility criteria were age 65 years or older, ability on admission to maintain sitting position for at least 10 minutes, and absence of visual/hearing impairment or delirium on admission. All patients underwent a multidimensional assessment on admission and serial evaluations of motor performance using Trunk Control Test (TCT) and Tinetti scale. These assessments were fixed at 5 different times, coincident with admission (T0), predelirium (T1), onset of
Delirium is a common and devastating problem for older persons,1 which has been considered for a long time to be only a mental disorder. The clearest evidence of this notion is that diagnosis of delirium, based on current criteria, mainly depends on the demonstration of changes in cognitive functions.2–4 However, recent observations suggest that the effect of delirium may involve not only cognitive status. For Department of Rehabilitation and Aged Care, ‘‘Ancelle della Carita`’’ Hospital, Cremona, Italy (G.B., S.S., S.M., T.T., R.T.); Geriatric Research Group, Brescia, Italy (G.B., S.S., S.M., T.T., R.T., M.T.); University Tor Vergata, Rome, Italy (M.T.). Address correspondence to Giuseppe Bellelli, MD, Department of Rehabilitation and Aged Care, ‘‘Ancelle della Carita`’’ Hospital, 26100, Cremona, Italy. E-mail: [email protected] or [email protected]
Copyright Ó2011 American Medical Directors Association DOI:10.1016/j.jamda.2010.04.010 578 Bellelli et al
delirium (T2), resolution of delirium (T3), and discharge (T4). Results: Patients in the Dem, DSD, and Del groups were significantly more impaired at T0 in cognitive and functional status and motor performance compared with No Del–No Dem patients. At T1 all groups improved, although in different ways. At T2 only in the Del and DSD groups, but not in the others, there was a pattern of decline in TCT and Tinetti scores (P \ .0005 at t test for pair comparison for both tests) and a specular pattern of improvement at T3 (P \ .0005 at t test for pair comparison for both tests). Patients in the Del and DSD groups had the poorest attentive and executive performances at T2, which significantly improved at T3. In No Del–No Dem and Dem groups, attentive and executive functions did not change from T2 to T3. Conclusion: Patients with delirium exhibit a pattern of fluctuating motor performance that is chronologically related with the onset and the end of delirium, ie, they decline when delirium develops and improve when delirium ends. This pattern seems to be typical of delirium, as it is appreciable in subjects with dementia developing delirium but not in patients with dementia alone. A fluctuation of motor performance should be considered a diagnostic sign of delirium. (J Am Med Dir Assoc 2011; 12: 578–583) Keywords: Delirium; function; cognition; assessment
example, it has been demonstrated that delirium is negatively associated with regaining independence in functional status, both early5 and in the mid to long term6 after hospital discharge. Furthermore, it has been demonstrated that the longer the duration of delirium, the poorer is autonomy in activities of daily living7 and the lower the magnitude of functional recovery.8 Globally, these data seem to suggest that delirium is a phenomenon not only of the cognitive but also of the functional domain. However, a correct demonstration of this assumption requires showing that variations of functional status are not only a consequence, but also a peculiar sign of delirium itself. To our knowledge, this has never been shown in previous studies. The aim of this article was to demonstrate that, in comparison with controls, patients with delirium exhibit a pattern of JAMDA – October 2011
fluctuation in motor performance that is similar to that in cognitive performance and that this is chronologically related with the onset and the end of delirium (ie, they decline when delirium develops and improve when delirium ends). Furthermore, the study aimed at demonstrating that this pattern is typical of delirium, because it is appreciable in subjects with dementia developing delirium, but not in patients with dementia alone. METHODS
(1) acute change in mental status with a fluctuating course, (2) inattention, (3) disorganized thinking, and (4) an altered level of consciousness. Delirium is diagnosed when both CAM criteria 1 and 2 and criterion 3 or 4 are present. Diagnosis of dementia was obtained according to DSMIII-R criteria3 after a standardized approach including (1) assessment of preadmission cognitive status by interviews with caregivers, (2) reviews of previous clinical charts, and (3) consensus among 2 geriatricians and 1 neuropsychologist about the diagnosis of dementia.
Study Population and Design Patients were recruited between June 1, 2007, and December 31, 2009, from our Department of Rehabilitation and Aged Care. This is an 80-bed facility providing rehabilitation after surgical interventions, stroke, heart failure, chronic obstructive pulmonary disease, and Parkinson’s and other diseases.9 Eligibility requirements for inclusion in our study were age older than 64 years and ability to maintain sitting position for at least 10 minutes, as assessed on admission. Exclusion criteria were delirium on admission and significant visual or hearing impairment. The study design was a prospective case-control study of patients in whom incident delirium was detected (cases), compared with patients in whom delirium was not detected (controls). Only patients with hypoactive delirium were considered, because patients with hyperactive or mixed delirium would not have been reliably assessed with neuropsychological tests. The protocol of recruitment was as follows: when a patient developed delirium, another patient among those eligible without delirium was recruited and assigned to the control group. If the patient with delirium had a prior diagnosis of dementia, the recruitment of the matched control occurred by means of a random selection among patients with dementia but no delirium, taking into the account age (within 3 years) and sex. Altogether, we had 4 patient groups: those with delirium alone (Del), with delirium superimposed on dementia (DSD), with dementia alone (Dem), and with neither delirium nor dementia (No Del–No Dem). On admission to the department, informed consent was obtained directly from patients without dementia, including those in the Del groups. From patients in the DSD and Dem groups, the consent was obtained by caregivers. The protocol was approved by the Ethics Committee of Gerontological Sciences of the Geriatric Research Group, Italy. Standardized Multidimensional Assessment All eligible patients received on admission a multidimensional assessment, including demographics, nutritional (Body Mass Index and albumin serum levels), health (Charlson Index,10 number of drugs), cognitive (Mini Mental State Examination [MMSE]11 and Clinical Dementia Rating [CDR]12) and functional status (Barthel Index).13 The Confusion Assessment Method (CAM)14 was performed at enrollment and routinely 3 times a day during the period of the study. The CAM is an algorithm that is reliable and accurate in detecting delirium, which assesses 4 specific criteria: ORIGINAL STUDIES
Assessment of Motor Performance Two physiotherapists blinded to study groups assessed the changes in motor performances over time using 2 simple, performance-based instruments, the Trunk Control Test (TCT)15 and the Tinetti scale.16 The TCT examines 4 axial movements: rolling from supine position to the weak (subtest 1) and to the strong side (subtest 2), sitting up from lying-down position (subtest 3), and sitting in balanced position on the bed’s edge with feet off the ground for 30 seconds (subtest 4). The score of each subtest ranges from 0 (unable to move without help) to 25 (able to move) and total score is the sum. The Tinetti scale evaluates balance and gait, ranging from 0 (maximum impairment) to 28 (best performances). Balance is evaluated while sitting, arising from and sitting on a chair, in the standing position, with eyes closed, while turning, when nudged on the sternum, and when turning the neck while standing. Gait is evaluated as initiation of gait, step height, length, symmetry, and continuity, path deviation, trunk stability, and turning while walking. The TCT and Tinetti scales were performed on admission (T0) and every week until discharge. The same tests were repeated at T2 (ie, at the detection of delirium in cases and on the day of enrollment in controls) and at T3 (ie, at the resolution of delirium in cases and during the same day in controls). The last TCT and Tinetti scores obtained by patients in the weekly assessment that preceded T2 were also recorded for analyses (T1). Delirium was considered resolved when CAM was negative at least 3 times consecutively in a day. A final assessment with TCT and Tinetti scales was performed in all groups at discharge (T4). Neuropsychological Assessment At T2 and at T3, an assessment of attentive and executive functions was provided in all groups using the Clock Drawing Test,17 the Digit Span Task,18 the Cognitive Estimation test,19 and a verbal abstraction task.20 Rehabilitation Training From admission until discharge, all patients underwent a standardized rehabilitation program of 2 daily sessions (60 minutes per day of physiotherapy, 6 days per week), including strengthening, transferring, postural and gait training, and adaptive equipment training. For reasons of equality, the physiotherapy was stopped from T2 to T3 in all groups. Bellelli et al 579
Statistics All analyses were performed using the SPSS (Statistical Package for Social Sciences, SPSS inc., Chicago, IL) software tool, version 11.5. Significance between variables was checked using 1-way analysis of variance (ANOVA) for continuous or chi square for categoric variables. Where significant group effects were detected, Bonferroni test indicated significant post hoc differences between individual groups. The changes in TCT and Tinetti scores and in neuropsychological tests were detected using t test for paired samples. RESULTS During the study enrollment period, 2445 patients were eligible for this study, of whom there were 327 (13.3%) with prevalent and 65 (2.6%) with incident delirium. In the incident group, there were 38 patients with hypoactive delirium. Of these, 18 had a prior diagnosis of dementia and 20 did not. During the course of the study, 3 patients in the DSD group and 5 patients in the Del group did not complete the study protocol because of a transfer to hospital for acute illness. Therefore, these 8 patients and 8 controls matched to them (3 in the Dem and 5 in the No Del–No Dem groups) were excluded from the study. Thus, the final sample included 30 patients as cases (15 persons in the Del and 15 in the DSD group) and 30 patients (15 persons in the No Del–No Dem and 15 in the Dem group) as controls. Table 1 presents the characteristics at enrollment of the 4 groups. There were significant differences with respect to cognitive and functional status, but not to demographics, nutritional status, and length of stay. Although their primary diagnoses were similar, the level of comorbidity was significantly higher in patients with DSD if compared with patients with Table 1.
No Del–No Dem. On average, the time from T1 to T2 was 3.9 days in cases and 4.1 days in controls (P 5.82), whereas the time from T2 to T3 was 3.5 days both in cases and controls. Figures 1 and 2 show the changes over time among the 4 study groups in the TCT and Tinetti scores, respectively. Patients in the Dem, DSD, and Del groups were more impaired at T0 in TCT and Tinetti scores with respect to patients in the No Del–No Dem group. The comparison between groups at the ANOVA show that patients did not differ in TCT scores (P 5 .07), whereas Tinetti score was higher in patients with No Del–No Dem in comparison with DSD (P 5 .001), Del (P 5 .03), and Dem (P 5 .04) groups (data not shown). In all patients there was an improvement from T0 to T1 in TCT and Tinetti scores, but only in the Del and DSD groups was there a pattern of steep decline from T1 to T2 and a specular pattern of improvement from T2 to T3. At T4, all groups showed a further improvement in these tests, probably as a result of successful rehabilitation. Table 2 presents the mean values and the results of pairwise comparison for the 4 study groups with regard to neuropsychological tests. It should be noted that patients in the Del and DSD groups had poorer attentive and executive performances at T2 in comparison with controls, probably as an effect of delirium. However, only in the Del and DSD groups, but not in their controls, we observed a significant improvement from T2 to T3, indirectly suggesting a similar pattern of fluctuating motor and cognitive performances in delirious patients. DISCUSSION This study shows that patients with hypoactive delirium exhibit a pattern of fluctuation in motor performance that is chronologically related to the onset and the end of
Baseline Characteristics of the 4 Study Groups
Demographics Age, y Female, n (%) Education, y Living alone, n (%) Biological and somatic health status Body Mass Index, kg/m2 Albumin serum levels, g/dL No. of drugs on admission Charlson comorbidity index Primary diagnosis, n (%) Postorthopedic surgery Neurological and musculoskeletal gait disorders Cardiologic and respiratory diseases Mini Mental State Examination (0–30) Clinical Dementia Rating Scale (0–5) Barthel Index on admission (0–100) Total length of rehabilitation stay, days
Delirium Alone (n 5 15)
DSD (n 5 15)
No Del–No Dem (n 5 15)
Dementia Alone (n 5 15)
81.4 6.2 11 (73.3) 5.8 3.3 3 (20.0)
84.8 6.8 10 (66.7) 5.7 2.1 3 (20.0)
79.3 4.6 10 (66.7) 6.2 2.8 8 (53.3)
83.2 5.6 12 (80.0) 4.4 1.4 6 (40.0)
.06 .82 .22 .14
23.9 4.0 3.3 0.3 6.0 2.0 2.0 1.9
22.7 4.2 3.3 0.5 6.5 2.0 3.6 1.8c
25.8 3.6 3.6 0.3 5.9 2.2 1.3 1.4b
24.4 4.6 3.2 0.9 6.0 3.0 2.8 1.8
.25 .20 .89 .007
2 (13.3) 2 (13.3)
3 (20.0) 3 (20.0)
3 (20.0) 1 (6.7)
11 (73.3) 23.2 2.4b,c,d 0.7 0.6b 49.0 25.6c 40.2 11.6
9 (60.0) 12.0 4.8a,c,d 2.1 1.0a,c 34.7 23.6c,d 38.4 14.3
11 (73.3) 27.2 1.2a,b,d 0.031.2b,d 79.9 12.1a,b 31.2 7.6
1 (6.7) 1 (6.7) 13 (86.7) 17.8 4.4a,b,c 1.4 0.9c 64.5 17.4b 35.8 10.8
P
.74
\.005 \.005 \.005 .16
DSD, delirium superimposed on dementia; No Del–No Dem, no delirium nor dementia; data are presented as mean SD, unless otherwise specified. P denotes significance on analysis of variance for continuous or chi square for categoric variables. Where significant group effects were detected, Bonferroni test indicated significant post hoc differences between individual groups, as follows: a, significant difference to the group with delirium alone; b, significant difference to the group with DSD; c, significant difference to the group with no delirium–no dementia; d, significant difference to the group with only dementia. 580 Bellelli et al
JAMDA – October 2011
Delirium alone
DSD
Dementia alone
No De l No D e m
120 100
T C T
80
s c o r e
60 40 20 0 T0
T1
T2
T3
T4
Time of assessment
p-value
T0
T1
T2
T3
T4
p*
p**
p***
p****
Delirium alone
55.0±32.7
74.2±24.9
33.4±25.7
71.7±25.4
78.4±26.5
0.04
<0.0005
<0.0005
0.18
DSD
46.6±27.3
58.2±26.8
29.4±23.6
60.2±29.4
61.9±30.9
0.78
<0.0005
0.01
0.42
Dementia alone
64.9±23.1
69.9±23.8
73.4±25.1
78.6±25.6
82.8±19.8
0.02
0.04
0.10
1.00
No Del – No Dem
70.7±20.8
82.7±19.3
86.2±17.9
89.6±14.0
89.6±14.9
0.03
0.30
0.16
0.13
Fig. 1. Mean values and results of pairwise comparison in TCT scores over time among the 4 study groups.
delirium, ie, they decline when delirium develops and improve when delirium ends. This pattern seems to be similar to what occurs for cognitive performance and it is not appreciable in control groups (ie, patients with dementia alone and patients with neither dementia nor delirium).
Delirium alone
DSD
On the basis of these results, we suggest considering the fluctuations of motor performance as a diagnostic correlate for hypoactive delirium. Some researchers have sensed the importance of evaluating motor characteristics of delirium by developing instruments that consider not only the
No De l No Dem
Dementia alone
30 T i 25 n e t 20 t i 15 s 10 c o 5 r e 0 T0
T1
T2
T3
T4
Time of assessment
p-value
T0
T1
T2
T3
T4
p*
p**
p***
p****
Delirium alone
10.9±8.1
14.6±7.5
5.9±6.1
12.2±6.7
17.3±8.6
<0.0005
<0.0005
<0.0005
0.10
DSD
8.2±5.7
11.0±4.7
5.0±3.4
11.8±5.0
13.4±6.1
<0.0005
<0.0005
0.001
0.42
Dementia alone
15.2±6.8
17.3±7.0
18.2±5.6
18.5±6.7
20.2±4.3
1.0
0.04
0.10
1.0
No Del – No Dem
18.1±6.6
21.0±5.1
21.0±4.4
21.5±4.8
22.5±2.9
0.23
0.30
0.16
0.13
Fig. 2. Mean values and results of pairwise comparison in Tinetti scores over time among the 4 study groups. ORIGINAL STUDIES
Bellelli et al 581
Data are presented as mean SD, unless otherwise specified. P denotes significance at t test pair for paired samples. DSD, delirium superimposed on dementia; No Del–No Dem, no delirium nor dementia; T2, assessment at detection of delirium for DSD and Delirium alone groups, and after recruitment in the study for No Del–No Dem and Dementia alone groups; T3, assessment at resolution of delirium for DSD and Delirium alone groups and in the same day for No Del–No Dem and Dementia alone groups.
.81 .58 .95 .29 .51 2.0 2.7 3.7 0.8 2.0 0.4 2.6 1.4 0.9 1.1 2.1 3.0 3.8 0.9 2.0 0.2 2.2 1.1 1.1 1.0 .11 .10 .67 .79 .58 6.8 3.2 4.5 0.7 2.7 0.8 4.2 1.1 3.8 1.6 5.5 3.6 4.5 0.7 2.6 0.7 4.3 0.9 3.7 1.7 .60 .002 .009 .009 .01 1.4 2.1 3.3 1.5 1.4 1.1 1.5 1.1 1.6 1.5 1.0 2.0 2.0 1.4 0.6 0.7 0.7 0.7 0.5 0.5 .002 .01 .02 .04 .004 2.5 1.8 4.2 0.7 1.6 1.2 2.5 1.3 1.7 1.4 0.6 1.0 3.4 0.9 1.0 1.0 1.9 1.2 0.8 1.0 Clock drawing Digit span forward Digit span backward Cognitive estimation test Verbal abstraction task
P T3 T2 T2 T3
P T2
T3
P
T2
T3
P
Dementia Alone (n 5 15) No Del–No Dem (n 5 15) DSD (n 5 15) Delirium Alone (n 5 15)
Cognitive Performances of the 4 Study Groups at T2 and at T3 Table 2. 582 Bellelli et al
cognitive domain. However, most of them are useful to describe the clinical picture of delirium, but are only partially useful for diagnostic purposes. For example, both the Delirium Rating Scale20 and the Memorial Delirium Assessment Scale,21 2 widely used tools assessing delirium’s psychomotor behaviors, do not measure if these behaviors develop at the onset of delirium and do not put them in association with the clinical hallmarks of delirium (ie, fluctuating course, inattention, and disorganized thinking). Accordingly, assessing psychomotor behaviors with these instruments does not add useful information in diagnosing delirium. Our findings extend those of previous studies demonstrating that delirium is associated with functional consequences5–6 and subsequent dementia,22 and suggest that fluctuation in motor performance is a unique sign of delirium itself. In fact, this pattern occurs synchronically with cognitive fluctuations and is not evident in patients with a competing condition of delirium, ie, it is appreciable in DSD patients but not in controls with dementia alone. A pathophysiological explanation of these results may involve the networks between cortical and subcortical brain structures. As underlined by Snijders et al,23 postural stability and normal walking rely not only on sensorimotor systems, but also critically depend on executive functions. Because acetylcholine, serotonin, and dopamine serum levels derange with delirium23–25 and are also altered in attentive and executive dysfunctions,26 it could be hypothesized that motor fluctuations of delirium may be related to an imbalance in key central neurotransmitters that leads to attentive and executive dysfunction and therefore to the inability in planning and sustaining movements.25,26 There are some clinical implications of this study that need to be underscored. As it has been repeatedly underlined, recognition of DSD is a challenge in clinical practice, which can account for a relative underestimation of this condition.27–30 In fact, current diagnostic criteria for delirium requires a demonstration of an acute change in cognition, a decline in attention, and/or incoherence of thought. However, these functions may be already impaired in demented individuals, partially explaining why DSD may be misattributed to dementia’s behavioral disorders.31 On the contrary, fluctuations in motor performance, which are easy to detect and do not require sophisticated instruments, could provide additional information and therefore may assume a specific diagnostic utility. For example, the observation of an unexpected failure to sitting up from the bed in patients who were previously able to do it could be helpful in detecting delirium even in demented patients. Therefore, if further studies will confirm our results, it could be hypothesized that the combination of motor and cognitive assessment may improve accuracy in the diagnosis of hypoactive delirium. Moreover, because the assessment of a change in cognitive functions may depend on the ability of physicians to detect it,24 while a change in motor performance can be more immediate and quick to detect, we suggest that this approach can be appropriate especially for patients with DSD, in whom distinguishing an acute confusional status from a condition of dementia is often challenging. JAMDA – October 2011
A strength of this study is its design, which allows a comparison in a chronological relationship of the fluctuations of motor and cognitive performances in delirious and nondelirious patients. A second strength is the use of performance-based instruments to measure changes in motor performance over time. Some limitations of this study should be acknowledged. First, one could argue that physiotherapists may have grasped the meaning of requests of assessment at T2 and therefore may have unconsciously misattributed the TCT and Tinetti scores. However, 1 of the 4 study groups included patients with dementia, a competing condition of delirium, and it is thus unlikely that physiotherapists have misattributed TCT and Tinetti scores only to Del and DSD and not to demented patients. A second limitation is that patients of the 4 study groups had different TCT and Tinetti scores on admission, raising the question if their pattern of motor performances are attributable to a selection bias. Although we cannot completely exclude that baseline differences may have influenced the TCT and Tinetti scores at discharge, we would like to emphasize that only DSD and Del patients showed a peculiar pattern, indirectly suggesting a strict relationship of delirium with motor fluctuations. The third limitation is that we have not carried out the neuropsychological assessment at T0, T1, and T4 in all patient groups. However, this would have been too time-consuming and not feasible in routine clinical practice. The last limitation is that we included only patients with hypoactive, and not those with hyperactive or mixed delirium. However, these 3 subtypes of delirium probably reflect different pathophysiologic substrates32 and therefore may require separate studies. In conclusion, this study shows that a pattern of fluctuating motor performances occurs synchronically and in parallel with fluctuations of cognitive performance in delirious patients. The clinical implications of these findings are particularly useful to diagnose delirium superimposed on dementia. ACKNOWLEDGMENTS Sincere appreciation is due to Prof. Alessandro Padovani, Dr. Fabio Guerini, Dr. Alessandra Marre`, and Dr. Marco Pagani for their support in collecting data. REFERENCES 1. Flaherty JH, Rudolph J, Shary K, et al. Delirium is a serious and underrecognized problem: Why assessment of mental status should be the sixth vital sign. J Am Med Dir Assoc 2007;8:273–275. 2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd edition revised. Washington, DC: American Psychiatric Association; 1987. 3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition, Text Revision. Washington, DC: American Psychiatric Association; 2000. 4. International Statistical Classification of Diseases and Health Related Problems, 10th Revision. Geneva: The World Health Organization, 1993. 5. Marcantonio ER, Flacker JM, Resnick NM, et al. Delirium is independently associated with poor functional recovery after hip fracture. J Am Geriatr Soc 2000;48:618–624. 6. McCusker J, Cole M, Dendukuri N, et al. Delirium in older medical inpatients and subsequent cognitive and functional status: a prospective study. CMAJ 2001;165:575–583.
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7. Marcantonio ER, Simon SE, Bergamm MA, et al. Delirium symptoms in post-acute care: prevalent, persistent and associated with poor functional recovery. J Am Geriatr Soc 2003;51:4–9. 8. Speciale S, Bellelli G, Lucchi E, et al. Delirium and functional recovery in elderly patients. J Gerontol A Biol Sci Med Sci 2007;62:107–108. 9. Bellelli G, Magnifico F, Trabucchi M. Outcomes at 12 months in a population of elderly patients discharged from a rehabilitation unit. J Am Med Dir Assoc 2008;9:55–64. 10. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373–383. 11. Folstein MF, Folstein SE, McHugh PR. ‘‘Mini-Mental State’’: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198. 12. Hughes CP, Berg L, Danziger WL, et al. A new clinical scale for the staging of dementia. Br J Psychiatr 1982;140:566–572. 13. Mahoney FI, Barthel DW. Functional evaluation: The Barthel Index. Md State Med J 1965;14:61–65. 14. Inouye SK, Van Dyck CH, Horwitz RI, et al. Clarifying confusion: the Confusion Assessment Method. Ann Intern Med 1990;113:941–948. 15. Franchignoni FP, Tesio L, Ricupero C, et al. Trunk control test as an early predictor of stroke rehabilitation outcome. Stroke 1997;28:1382–1385. 16. Tinetti ME. Performance-oriented assessment of mobility problems in elderly patients. J Am Geriatr Soc 1986;119–126. 17. Adamis D, Morrison C, Martin CF, et al. The performances of the Clock Drawing Test in elderly medical inpatients: Does it have utility in the identification of delirium? J Geriatr Psychiatry Neurol 2005;18:129–133. 18. Miller GA. The magic number seven, plus or minus two: some limits to our capacity for processing information. Psych Rev 1956;63:81–93. 19. Lezak MD. Neuropsychological Assessment. 3rd ed. New York: Oxford University Press; 1995. 20. Trzepacz PT. The Delirium Rating Scale. Its use in consultation liaison research. Psychosomatics 1999;40:193–204. 21. Breitbart W, Rosenfeld B, Roth A. The Memorial Delirium Assessment Scale. J Pain Symptom Manage 1997;13:128–137. 22. Fong TG, Jones RN, Shi P, et al. Delirium accelerates cognitive decline in Alzheimer disease. Neurology 2009;72:1570–1575. 23. Snijders AH, van de Warrenburg BP, Giladi N, et al. Neurological gait disorders in elderly people: Clinical approach and classification. Lancet Neurol 2007;6:63–74. 24. Young J, Inouye SK. Delirium in older people. BMJ 2007;334:824–826. 25. Hshieh TT, Fong TG, Marcantonio ER, et al. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol A Biol Sci Med Sci 2008;63A:764–772. 26. Behl P, Bocti C, Swartz RH, et al. Strategic subcortical hyperintensities in cholinergic pathways and executive function decline in treated Alzheimer patients. Arch Neurol 2007;64:266–272. 27. Fick DM, Agostini JV, Inouye SK. Delirium superimposed on dementia: A systematic review. J Am Geriatr Soc 2002;50:1723–1732. 28. Fick DM, Hodo DM, Lawrence F, Inouye SK. Recognizing delirium superimposed on dementia: Assessing nurses’ knowledge using case vignettes. J Gerontol Nurs 2007;33:40–47. 29. Bellelli G, Frisoni GB, Turco R, et al. Delirium superimposed on dementia predicts 12-month survival in elderly patients discharged from a postacute rehabilitation facility. J Gerontol Med Sci 2007;62A:1306–1309. 30. Voyer P, Richard S, Doucet L, Carmichael PH. Detecting delirium and subsyndromal delirium using different diagnostic criteria among demented long-term care residents. J Am Med Dir Assoc 2009;10:181–188. 31. Morandi A, Solberg LM, Habermann R, et al. Documentation and management of words associated with delirium among elderly patients in postacute care: A pilot investigation. J Am Med Dir Assoc 2009;10:330–333. 32. Yang FM, Marcantonio ER, Inouye SK, et al. Phenomenological subtypes of delirium in older persons: Patterns, prevalence and prognosis. Psychosomatics 2009;50:248–254.
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Background: Although delirium is known as a mental disorder, recent evidence suggests that it is associated with short- and long-term impairment of functional status. Objective: To evaluate whether a pattern of fluctuations in motor performance are a diagnostic sign of delirium. Design: Case-controlled study with prospective evaluations of 4 groups of patients. Setting: Department of Rehabilitation and Aged Care. Methods: Fifteen patients with incident delirium alone (Del group) and 15 patients with incident delirium superimposed on dementia (DSD group) were compared with 15 patients with neither delirium nor dementia (No Del–No Dem group) and 15 patients with dementia but no delirium (Dem group), respectively. Eligibility criteria were age 65 years or older, ability on admission to maintain sitting position for at least 10 minutes, and absence of visual/hearing impairment or delirium on admission. All patients underwent a multidimensional assessment on admission and serial evaluations of motor performance using Trunk Control Test (TCT) and Tinetti scale. These assessments were fixed at 5 different times, coincident with admission (T0), predelirium (T1), onset of
Delirium is a common and devastating problem for older persons,1 which has been considered for a long time to be only a mental disorder. The clearest evidence of this notion is that diagnosis of delirium, based on current criteria, mainly depends on the demonstration of changes in cognitive functions.2–4 However, recent observations suggest that the effect of delirium may involve not only cognitive status. For Department of Rehabilitation and Aged Care, ‘‘Ancelle della Carita`’’ Hospital, Cremona, Italy (G.B., S.S., S.M., T.T., R.T.); Geriatric Research Group, Brescia, Italy (G.B., S.S., S.M., T.T., R.T., M.T.); University Tor Vergata, Rome, Italy (M.T.). Address correspondence to Giuseppe Bellelli, MD, Department of Rehabilitation and Aged Care, ‘‘Ancelle della Carita`’’ Hospital, 26100, Cremona, Italy. E-mail: [email protected] or [email protected]
Copyright Ó2011 American Medical Directors Association DOI:10.1016/j.jamda.2010.04.010 578 Bellelli et al
delirium (T2), resolution of delirium (T3), and discharge (T4). Results: Patients in the Dem, DSD, and Del groups were significantly more impaired at T0 in cognitive and functional status and motor performance compared with No Del–No Dem patients. At T1 all groups improved, although in different ways. At T2 only in the Del and DSD groups, but not in the others, there was a pattern of decline in TCT and Tinetti scores (P \ .0005 at t test for pair comparison for both tests) and a specular pattern of improvement at T3 (P \ .0005 at t test for pair comparison for both tests). Patients in the Del and DSD groups had the poorest attentive and executive performances at T2, which significantly improved at T3. In No Del–No Dem and Dem groups, attentive and executive functions did not change from T2 to T3. Conclusion: Patients with delirium exhibit a pattern of fluctuating motor performance that is chronologically related with the onset and the end of delirium, ie, they decline when delirium develops and improve when delirium ends. This pattern seems to be typical of delirium, as it is appreciable in subjects with dementia developing delirium but not in patients with dementia alone. A fluctuation of motor performance should be considered a diagnostic sign of delirium. (J Am Med Dir Assoc 2011; 12: 578–583) Keywords: Delirium; function; cognition; assessment
example, it has been demonstrated that delirium is negatively associated with regaining independence in functional status, both early5 and in the mid to long term6 after hospital discharge. Furthermore, it has been demonstrated that the longer the duration of delirium, the poorer is autonomy in activities of daily living7 and the lower the magnitude of functional recovery.8 Globally, these data seem to suggest that delirium is a phenomenon not only of the cognitive but also of the functional domain. However, a correct demonstration of this assumption requires showing that variations of functional status are not only a consequence, but also a peculiar sign of delirium itself. To our knowledge, this has never been shown in previous studies. The aim of this article was to demonstrate that, in comparison with controls, patients with delirium exhibit a pattern of JAMDA – October 2011
fluctuation in motor performance that is similar to that in cognitive performance and that this is chronologically related with the onset and the end of delirium (ie, they decline when delirium develops and improve when delirium ends). Furthermore, the study aimed at demonstrating that this pattern is typical of delirium, because it is appreciable in subjects with dementia developing delirium, but not in patients with dementia alone. METHODS
(1) acute change in mental status with a fluctuating course, (2) inattention, (3) disorganized thinking, and (4) an altered level of consciousness. Delirium is diagnosed when both CAM criteria 1 and 2 and criterion 3 or 4 are present. Diagnosis of dementia was obtained according to DSMIII-R criteria3 after a standardized approach including (1) assessment of preadmission cognitive status by interviews with caregivers, (2) reviews of previous clinical charts, and (3) consensus among 2 geriatricians and 1 neuropsychologist about the diagnosis of dementia.
Study Population and Design Patients were recruited between June 1, 2007, and December 31, 2009, from our Department of Rehabilitation and Aged Care. This is an 80-bed facility providing rehabilitation after surgical interventions, stroke, heart failure, chronic obstructive pulmonary disease, and Parkinson’s and other diseases.9 Eligibility requirements for inclusion in our study were age older than 64 years and ability to maintain sitting position for at least 10 minutes, as assessed on admission. Exclusion criteria were delirium on admission and significant visual or hearing impairment. The study design was a prospective case-control study of patients in whom incident delirium was detected (cases), compared with patients in whom delirium was not detected (controls). Only patients with hypoactive delirium were considered, because patients with hyperactive or mixed delirium would not have been reliably assessed with neuropsychological tests. The protocol of recruitment was as follows: when a patient developed delirium, another patient among those eligible without delirium was recruited and assigned to the control group. If the patient with delirium had a prior diagnosis of dementia, the recruitment of the matched control occurred by means of a random selection among patients with dementia but no delirium, taking into the account age (within 3 years) and sex. Altogether, we had 4 patient groups: those with delirium alone (Del), with delirium superimposed on dementia (DSD), with dementia alone (Dem), and with neither delirium nor dementia (No Del–No Dem). On admission to the department, informed consent was obtained directly from patients without dementia, including those in the Del groups. From patients in the DSD and Dem groups, the consent was obtained by caregivers. The protocol was approved by the Ethics Committee of Gerontological Sciences of the Geriatric Research Group, Italy. Standardized Multidimensional Assessment All eligible patients received on admission a multidimensional assessment, including demographics, nutritional (Body Mass Index and albumin serum levels), health (Charlson Index,10 number of drugs), cognitive (Mini Mental State Examination [MMSE]11 and Clinical Dementia Rating [CDR]12) and functional status (Barthel Index).13 The Confusion Assessment Method (CAM)14 was performed at enrollment and routinely 3 times a day during the period of the study. The CAM is an algorithm that is reliable and accurate in detecting delirium, which assesses 4 specific criteria: ORIGINAL STUDIES
Assessment of Motor Performance Two physiotherapists blinded to study groups assessed the changes in motor performances over time using 2 simple, performance-based instruments, the Trunk Control Test (TCT)15 and the Tinetti scale.16 The TCT examines 4 axial movements: rolling from supine position to the weak (subtest 1) and to the strong side (subtest 2), sitting up from lying-down position (subtest 3), and sitting in balanced position on the bed’s edge with feet off the ground for 30 seconds (subtest 4). The score of each subtest ranges from 0 (unable to move without help) to 25 (able to move) and total score is the sum. The Tinetti scale evaluates balance and gait, ranging from 0 (maximum impairment) to 28 (best performances). Balance is evaluated while sitting, arising from and sitting on a chair, in the standing position, with eyes closed, while turning, when nudged on the sternum, and when turning the neck while standing. Gait is evaluated as initiation of gait, step height, length, symmetry, and continuity, path deviation, trunk stability, and turning while walking. The TCT and Tinetti scales were performed on admission (T0) and every week until discharge. The same tests were repeated at T2 (ie, at the detection of delirium in cases and on the day of enrollment in controls) and at T3 (ie, at the resolution of delirium in cases and during the same day in controls). The last TCT and Tinetti scores obtained by patients in the weekly assessment that preceded T2 were also recorded for analyses (T1). Delirium was considered resolved when CAM was negative at least 3 times consecutively in a day. A final assessment with TCT and Tinetti scales was performed in all groups at discharge (T4). Neuropsychological Assessment At T2 and at T3, an assessment of attentive and executive functions was provided in all groups using the Clock Drawing Test,17 the Digit Span Task,18 the Cognitive Estimation test,19 and a verbal abstraction task.20 Rehabilitation Training From admission until discharge, all patients underwent a standardized rehabilitation program of 2 daily sessions (60 minutes per day of physiotherapy, 6 days per week), including strengthening, transferring, postural and gait training, and adaptive equipment training. For reasons of equality, the physiotherapy was stopped from T2 to T3 in all groups. Bellelli et al 579
Statistics All analyses were performed using the SPSS (Statistical Package for Social Sciences, SPSS inc., Chicago, IL) software tool, version 11.5. Significance between variables was checked using 1-way analysis of variance (ANOVA) for continuous or chi square for categoric variables. Where significant group effects were detected, Bonferroni test indicated significant post hoc differences between individual groups. The changes in TCT and Tinetti scores and in neuropsychological tests were detected using t test for paired samples. RESULTS During the study enrollment period, 2445 patients were eligible for this study, of whom there were 327 (13.3%) with prevalent and 65 (2.6%) with incident delirium. In the incident group, there were 38 patients with hypoactive delirium. Of these, 18 had a prior diagnosis of dementia and 20 did not. During the course of the study, 3 patients in the DSD group and 5 patients in the Del group did not complete the study protocol because of a transfer to hospital for acute illness. Therefore, these 8 patients and 8 controls matched to them (3 in the Dem and 5 in the No Del–No Dem groups) were excluded from the study. Thus, the final sample included 30 patients as cases (15 persons in the Del and 15 in the DSD group) and 30 patients (15 persons in the No Del–No Dem and 15 in the Dem group) as controls. Table 1 presents the characteristics at enrollment of the 4 groups. There were significant differences with respect to cognitive and functional status, but not to demographics, nutritional status, and length of stay. Although their primary diagnoses were similar, the level of comorbidity was significantly higher in patients with DSD if compared with patients with Table 1.
No Del–No Dem. On average, the time from T1 to T2 was 3.9 days in cases and 4.1 days in controls (P 5.82), whereas the time from T2 to T3 was 3.5 days both in cases and controls. Figures 1 and 2 show the changes over time among the 4 study groups in the TCT and Tinetti scores, respectively. Patients in the Dem, DSD, and Del groups were more impaired at T0 in TCT and Tinetti scores with respect to patients in the No Del–No Dem group. The comparison between groups at the ANOVA show that patients did not differ in TCT scores (P 5 .07), whereas Tinetti score was higher in patients with No Del–No Dem in comparison with DSD (P 5 .001), Del (P 5 .03), and Dem (P 5 .04) groups (data not shown). In all patients there was an improvement from T0 to T1 in TCT and Tinetti scores, but only in the Del and DSD groups was there a pattern of steep decline from T1 to T2 and a specular pattern of improvement from T2 to T3. At T4, all groups showed a further improvement in these tests, probably as a result of successful rehabilitation. Table 2 presents the mean values and the results of pairwise comparison for the 4 study groups with regard to neuropsychological tests. It should be noted that patients in the Del and DSD groups had poorer attentive and executive performances at T2 in comparison with controls, probably as an effect of delirium. However, only in the Del and DSD groups, but not in their controls, we observed a significant improvement from T2 to T3, indirectly suggesting a similar pattern of fluctuating motor and cognitive performances in delirious patients. DISCUSSION This study shows that patients with hypoactive delirium exhibit a pattern of fluctuation in motor performance that is chronologically related to the onset and the end of
Baseline Characteristics of the 4 Study Groups
Demographics Age, y Female, n (%) Education, y Living alone, n (%) Biological and somatic health status Body Mass Index, kg/m2 Albumin serum levels, g/dL No. of drugs on admission Charlson comorbidity index Primary diagnosis, n (%) Postorthopedic surgery Neurological and musculoskeletal gait disorders Cardiologic and respiratory diseases Mini Mental State Examination (0–30) Clinical Dementia Rating Scale (0–5) Barthel Index on admission (0–100) Total length of rehabilitation stay, days
Delirium Alone (n 5 15)
DSD (n 5 15)
No Del–No Dem (n 5 15)
Dementia Alone (n 5 15)
81.4 6.2 11 (73.3) 5.8 3.3 3 (20.0)
84.8 6.8 10 (66.7) 5.7 2.1 3 (20.0)
79.3 4.6 10 (66.7) 6.2 2.8 8 (53.3)
83.2 5.6 12 (80.0) 4.4 1.4 6 (40.0)
.06 .82 .22 .14
23.9 4.0 3.3 0.3 6.0 2.0 2.0 1.9
22.7 4.2 3.3 0.5 6.5 2.0 3.6 1.8c
25.8 3.6 3.6 0.3 5.9 2.2 1.3 1.4b
24.4 4.6 3.2 0.9 6.0 3.0 2.8 1.8
.25 .20 .89 .007
2 (13.3) 2 (13.3)
3 (20.0) 3 (20.0)
3 (20.0) 1 (6.7)
11 (73.3) 23.2 2.4b,c,d 0.7 0.6b 49.0 25.6c 40.2 11.6
9 (60.0) 12.0 4.8a,c,d 2.1 1.0a,c 34.7 23.6c,d 38.4 14.3
11 (73.3) 27.2 1.2a,b,d 0.031.2b,d 79.9 12.1a,b 31.2 7.6
1 (6.7) 1 (6.7) 13 (86.7) 17.8 4.4a,b,c 1.4 0.9c 64.5 17.4b 35.8 10.8
P
.74
\.005 \.005 \.005 .16
DSD, delirium superimposed on dementia; No Del–No Dem, no delirium nor dementia; data are presented as mean SD, unless otherwise specified. P denotes significance on analysis of variance for continuous or chi square for categoric variables. Where significant group effects were detected, Bonferroni test indicated significant post hoc differences between individual groups, as follows: a, significant difference to the group with delirium alone; b, significant difference to the group with DSD; c, significant difference to the group with no delirium–no dementia; d, significant difference to the group with only dementia. 580 Bellelli et al
JAMDA – October 2011
Delirium alone
DSD
Dementia alone
No De l No D e m
120 100
T C T
80
s c o r e
60 40 20 0 T0
T1
T2
T3
T4
Time of assessment
p-value
T0
T1
T2
T3
T4
p*
p**
p***
p****
Delirium alone
55.0±32.7
74.2±24.9
33.4±25.7
71.7±25.4
78.4±26.5
0.04
<0.0005
<0.0005
0.18
DSD
46.6±27.3
58.2±26.8
29.4±23.6
60.2±29.4
61.9±30.9
0.78
<0.0005
0.01
0.42
Dementia alone
64.9±23.1
69.9±23.8
73.4±25.1
78.6±25.6
82.8±19.8
0.02
0.04
0.10
1.00
No Del – No Dem
70.7±20.8
82.7±19.3
86.2±17.9
89.6±14.0
89.6±14.9
0.03
0.30
0.16
0.13
Fig. 1. Mean values and results of pairwise comparison in TCT scores over time among the 4 study groups.
delirium, ie, they decline when delirium develops and improve when delirium ends. This pattern seems to be similar to what occurs for cognitive performance and it is not appreciable in control groups (ie, patients with dementia alone and patients with neither dementia nor delirium).
Delirium alone
DSD
On the basis of these results, we suggest considering the fluctuations of motor performance as a diagnostic correlate for hypoactive delirium. Some researchers have sensed the importance of evaluating motor characteristics of delirium by developing instruments that consider not only the
No De l No Dem
Dementia alone
30 T i 25 n e t 20 t i 15 s 10 c o 5 r e 0 T0
T1
T2
T3
T4
Time of assessment
p-value
T0
T1
T2
T3
T4
p*
p**
p***
p****
Delirium alone
10.9±8.1
14.6±7.5
5.9±6.1
12.2±6.7
17.3±8.6
<0.0005
<0.0005
<0.0005
0.10
DSD
8.2±5.7
11.0±4.7
5.0±3.4
11.8±5.0
13.4±6.1
<0.0005
<0.0005
0.001
0.42
Dementia alone
15.2±6.8
17.3±7.0
18.2±5.6
18.5±6.7
20.2±4.3
1.0
0.04
0.10
1.0
No Del – No Dem
18.1±6.6
21.0±5.1
21.0±4.4
21.5±4.8
22.5±2.9
0.23
0.30
0.16
0.13
Fig. 2. Mean values and results of pairwise comparison in Tinetti scores over time among the 4 study groups. ORIGINAL STUDIES
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Data are presented as mean SD, unless otherwise specified. P denotes significance at t test pair for paired samples. DSD, delirium superimposed on dementia; No Del–No Dem, no delirium nor dementia; T2, assessment at detection of delirium for DSD and Delirium alone groups, and after recruitment in the study for No Del–No Dem and Dementia alone groups; T3, assessment at resolution of delirium for DSD and Delirium alone groups and in the same day for No Del–No Dem and Dementia alone groups.
.81 .58 .95 .29 .51 2.0 2.7 3.7 0.8 2.0 0.4 2.6 1.4 0.9 1.1 2.1 3.0 3.8 0.9 2.0 0.2 2.2 1.1 1.1 1.0 .11 .10 .67 .79 .58 6.8 3.2 4.5 0.7 2.7 0.8 4.2 1.1 3.8 1.6 5.5 3.6 4.5 0.7 2.6 0.7 4.3 0.9 3.7 1.7 .60 .002 .009 .009 .01 1.4 2.1 3.3 1.5 1.4 1.1 1.5 1.1 1.6 1.5 1.0 2.0 2.0 1.4 0.6 0.7 0.7 0.7 0.5 0.5 .002 .01 .02 .04 .004 2.5 1.8 4.2 0.7 1.6 1.2 2.5 1.3 1.7 1.4 0.6 1.0 3.4 0.9 1.0 1.0 1.9 1.2 0.8 1.0 Clock drawing Digit span forward Digit span backward Cognitive estimation test Verbal abstraction task
P T3 T2 T2 T3
P T2
T3
P
T2
T3
P
Dementia Alone (n 5 15) No Del–No Dem (n 5 15) DSD (n 5 15) Delirium Alone (n 5 15)
Cognitive Performances of the 4 Study Groups at T2 and at T3 Table 2. 582 Bellelli et al
cognitive domain. However, most of them are useful to describe the clinical picture of delirium, but are only partially useful for diagnostic purposes. For example, both the Delirium Rating Scale20 and the Memorial Delirium Assessment Scale,21 2 widely used tools assessing delirium’s psychomotor behaviors, do not measure if these behaviors develop at the onset of delirium and do not put them in association with the clinical hallmarks of delirium (ie, fluctuating course, inattention, and disorganized thinking). Accordingly, assessing psychomotor behaviors with these instruments does not add useful information in diagnosing delirium. Our findings extend those of previous studies demonstrating that delirium is associated with functional consequences5–6 and subsequent dementia,22 and suggest that fluctuation in motor performance is a unique sign of delirium itself. In fact, this pattern occurs synchronically with cognitive fluctuations and is not evident in patients with a competing condition of delirium, ie, it is appreciable in DSD patients but not in controls with dementia alone. A pathophysiological explanation of these results may involve the networks between cortical and subcortical brain structures. As underlined by Snijders et al,23 postural stability and normal walking rely not only on sensorimotor systems, but also critically depend on executive functions. Because acetylcholine, serotonin, and dopamine serum levels derange with delirium23–25 and are also altered in attentive and executive dysfunctions,26 it could be hypothesized that motor fluctuations of delirium may be related to an imbalance in key central neurotransmitters that leads to attentive and executive dysfunction and therefore to the inability in planning and sustaining movements.25,26 There are some clinical implications of this study that need to be underscored. As it has been repeatedly underlined, recognition of DSD is a challenge in clinical practice, which can account for a relative underestimation of this condition.27–30 In fact, current diagnostic criteria for delirium requires a demonstration of an acute change in cognition, a decline in attention, and/or incoherence of thought. However, these functions may be already impaired in demented individuals, partially explaining why DSD may be misattributed to dementia’s behavioral disorders.31 On the contrary, fluctuations in motor performance, which are easy to detect and do not require sophisticated instruments, could provide additional information and therefore may assume a specific diagnostic utility. For example, the observation of an unexpected failure to sitting up from the bed in patients who were previously able to do it could be helpful in detecting delirium even in demented patients. Therefore, if further studies will confirm our results, it could be hypothesized that the combination of motor and cognitive assessment may improve accuracy in the diagnosis of hypoactive delirium. Moreover, because the assessment of a change in cognitive functions may depend on the ability of physicians to detect it,24 while a change in motor performance can be more immediate and quick to detect, we suggest that this approach can be appropriate especially for patients with DSD, in whom distinguishing an acute confusional status from a condition of dementia is often challenging. JAMDA – October 2011
A strength of this study is its design, which allows a comparison in a chronological relationship of the fluctuations of motor and cognitive performances in delirious and nondelirious patients. A second strength is the use of performance-based instruments to measure changes in motor performance over time. Some limitations of this study should be acknowledged. First, one could argue that physiotherapists may have grasped the meaning of requests of assessment at T2 and therefore may have unconsciously misattributed the TCT and Tinetti scores. However, 1 of the 4 study groups included patients with dementia, a competing condition of delirium, and it is thus unlikely that physiotherapists have misattributed TCT and Tinetti scores only to Del and DSD and not to demented patients. A second limitation is that patients of the 4 study groups had different TCT and Tinetti scores on admission, raising the question if their pattern of motor performances are attributable to a selection bias. Although we cannot completely exclude that baseline differences may have influenced the TCT and Tinetti scores at discharge, we would like to emphasize that only DSD and Del patients showed a peculiar pattern, indirectly suggesting a strict relationship of delirium with motor fluctuations. The third limitation is that we have not carried out the neuropsychological assessment at T0, T1, and T4 in all patient groups. However, this would have been too time-consuming and not feasible in routine clinical practice. The last limitation is that we included only patients with hypoactive, and not those with hyperactive or mixed delirium. However, these 3 subtypes of delirium probably reflect different pathophysiologic substrates32 and therefore may require separate studies. In conclusion, this study shows that a pattern of fluctuating motor performances occurs synchronically and in parallel with fluctuations of cognitive performance in delirious patients. The clinical implications of these findings are particularly useful to diagnose delirium superimposed on dementia. ACKNOWLEDGMENTS Sincere appreciation is due to Prof. Alessandro Padovani, Dr. Fabio Guerini, Dr. Alessandra Marre`, and Dr. Marco Pagani for their support in collecting data. REFERENCES 1. Flaherty JH, Rudolph J, Shary K, et al. Delirium is a serious and underrecognized problem: Why assessment of mental status should be the sixth vital sign. J Am Med Dir Assoc 2007;8:273–275. 2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd edition revised. Washington, DC: American Psychiatric Association; 1987. 3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition, Text Revision. Washington, DC: American Psychiatric Association; 2000. 4. International Statistical Classification of Diseases and Health Related Problems, 10th Revision. Geneva: The World Health Organization, 1993. 5. Marcantonio ER, Flacker JM, Resnick NM, et al. Delirium is independently associated with poor functional recovery after hip fracture. J Am Geriatr Soc 2000;48:618–624. 6. McCusker J, Cole M, Dendukuri N, et al. Delirium in older medical inpatients and subsequent cognitive and functional status: a prospective study. CMAJ 2001;165:575–583.
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