Medical Research Council, Neurochemical Pathology Unit, Newcastle upon Tyne
Human Cognitive Neuroscience Department, University of Northumbria
University of California
Department of Old Age Psychiatry, University of Newcastle upon Tyne
Correspondence: C. G. Ballard, Medical Research Council, Neurochemical Pathology Unit, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK. Tel: 0191273 5251; fax: 0191272 5291; e-mail: c.g.ballard{at}ncl.ac.uk
Declaration of interest None; source of funding: Medical Research Council.
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ABSTRACT |
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Aims To determine the value of two rating scales to measure fluctuating confusion.
Method The agreement between the clinician-rated scale and the scale completed by a non-clinician was determined. Correlations between the two scales were calculated; variability in attention was calculated on a computerised cognitive assessment and variability in delta rhythm on an electroencephalogram (EEG).
Results The Clinician Assessment of Fluctuation and the computerised cognitive assessment were completed for 155 patients (61 Alzheimer's disease, 37 dementia with Lewy bodies, 22 vascular dementia, 35 elderly controls). A subgroup (n=40) received a further evaluation using the One Day Fluctuation Assessment Scale and an EEG. The two scales correlated significantly with each other, and with the neuropsychological and electrophysiological measures of fluctuation.
Conclusions Both scales are useful instruments for the clinical assessment of fluctuation in dementia.
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INTRODUCTION |
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METHOD |
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One Day Fluctuation Assessment Scale (Appendix 2)
This consists of seven items of confusional behaviour (falls, fluctuation,
drowsiness, attention, disorganised thinking, altered level of consciousness,
communication), scores for which are summed to provide a severity score for
fluctuating confusion ranging from 0 to 21. It is based on a validated
delirium assessment scale (Inouye et
al, 1990), with additional items selected from the Barthel
index (communication question) (Mahoney
et al, 1965) and the fluctuation component
of the DLB clinical diagnostic criteria
(McKeith et al,
1996). In the current study, the scale was completed by a
postgraduate researcher (M.W.), blind to the operationalised clinical
diagnosis and the Clinician Fluctuation Assessment score. This scale focuses
upon fluctuating confusion over the day before the assessment, and takes
approximately 15 minutes to administer.
Subjects and assessment
Patients were recruited from a dementia case register of consecutive
referrals to old age psychiatry services in Tyneside (UK), and the spouses of
the patients are recruited as healthy elderly volunteers. All patients were
assessed by a structured psychiatric history (History and Aetiology Schedule;
Dewey et al, 1992),
the Mini-Mental State Examination (MMSE;
Folstein et al, 1975),
a standardised physical examination which incorporated the Unified Parkinson's
Disease Rating Scale (UPDRS; Fahn et
al, 1987) and a validated instrument to evaluate psychotic
symptoms (Columbia University Scale for psychopathology in Alzheimer's
disease; Devanand et al,
1992), and fluctuating confusion was evaluated by the Clinician
Assessment of Fluctuation.
Diagnosis was undertaken separately, several months after the assessments were completed, at a consensus meeting between the three senior clinicians (I.McK., J.O'B., C.B.). Patients with DLB were diagnosed according to the internationally agreed consensus criteria (McKeith et al, 1996), patients with Alzheimer's disease were diagnosed according to the guidelines of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (McKhann et al, 1984), an operationalised clinical diagnosis of vascular dementia was made using the criteria of the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (Roman et al, 1993).
All participants also received a computerised neuropsychological assessment using the COGDRAS-D battery (Simpson et al, 1991). The main parameters used in the present study were choice reaction time (each time YES or NO was presented in the centre of the screen the participant was required to press the corresponding YES or NO button as quickly as possible) and digit vigilance reaction time (a digit was displayed constantly on the right-hand side of the screen and 90 digits were serially presented in the middle of the screen; participants were required to press YES every time the central digit matched the right-hand side digit). Within-trial variability (standard deviation) of these measures was assessed in single trials, all lasting approximately 90 seconds. The choice reaction time and vigilance reaction time trials were administered at another visit, separate from the diagnostic assessment, by a different rater (M.W.).
As it was not feasible with the available staff resources to complete a more comprehensive evaluation for all patients, a subgroup of 40 subjects (15 with DLB, 15 with Alzheimer's disease and 10 healthy elderly volunteers) from this sample received a more detailed assessment. This included an additional evaluation of fluctuation with the One Day Fluctuation Assessment Scale and an evaluation of EEG delta-band frequency (0-3.9 Hz) variability over 90 seconds. Seventeen primary channel electrodes were used, placed according to the international 10-20 system, which recorded EEG from Fp1, Fp2, Fz, F3, F4, Cz, C3, C4, Pz, P3, P4, T3, T4, T5, T6, O1 and O2 linked to mastoid electrodes. Eye movement compensation was derived from nasion-linked mastoid electrodes. Signals were amplified using a SynAmps and NeuroscanTM acquisition system. The mean spectral frequency was obtained resting with eyes open and resting with eyes closed. The variability (s.d.) in frequency from this mean was used as a measure of fluctuating electrocortical activity. In these patients the attention tasks, the EEG and the One Day Fluctuation Assessment Scale were all assessed on the same day.
The tests were approved by the Joint Ethics Committee of Newcastle and North Tyneside Health Authority and the University of Newcastle upon Tyne. Following full explanation and discussion of the study, the patients and the healthy volunteers gave their consent to the assessment, with additional assent from the next of kin for all patients with cognitive impairments.
Analysis of data
Non-parametric statistical analysis was applied, since the rating scale
yielded ordinal data. A Spearman's rank-order correlation was used in the
assessment of associations between the two assessment scales for fluctuation.
Cronbach's was used to assess internal consistency of the Fluctuation
Assessment Scale. Optimal cut-off values were obtained following a receiver
operating characteristics (ROC) analysis according to the method of Altman
(1995), and used to calculate
the sensitivity and specificity with which the different groups could be
distinguished, both in the overall sample and in the subsample with the more
detailed evaluation. All analyses were performed using the SPSS package
(SPSS, 1992).
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RESULTS |
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One hundred and fifty-five people were studied (61 with Alzheimer's disease, 37 with DLB, 22 with vascular dementia, 35 elderly controls). The age, gender and performance on the MMSE schedule for the different diagnostic groups are shown in Table 1.
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In the total sample of 155 patients, the Clinician Assessment of Fluctuation score was strongly correlated with the neuropsychological measures of fluctuation (choice reaction time variability and Clinician Assessment of Fluctuation r=0.73, P<0.0001; vigilance reaction time variability and Clinician Assessment of Fluctuation r=0.50, P<0.001). In the subgroup of 40 patients who received a more detailed evaluation, the Clinician Assessment of Fluctuation correlated significantly with the electrophysiological measures of fluctuations in delta-band frequency on EEG (resting, eyes open, r=0.52, P<0.001; resting, eyes closed, r=0.43, P<0.006), and correlated strongly with the independently rated One Day Fluctuation Assessment Scale (r=0.88, P<0.0001).
In this group of 40 patients, the One Day Fluctuation Assessment Scale also correlated strongly with the neuropsychological and electrophysiological measures of fluctuation (choice reaction time variability and One Day Fluctuation Assessment Scale r=0.70, P<0.0001; vigilance reaction time variability and One Day Fluctuation Assessment Scale r=0.52, P<0.001; fluctuation in delta-band frequency and One Day Fluctuation Assessment Scale: resting, eyes open r=0.60, P<0.0001; resting, eyes closed r=0.38, P<0.01).
A reliability coefficient analysis between the seven items of confusional
behaviour on the One Day Fluctuation Assessment Scale indicated good internal
consistency (Cronbach's =0.78).
Distinguishing diagnostic groups
In the subsample of 40 patients, an ROC analysis identified an optimal
cut-off value of 5 for the Clinician Assessment of Fluctuation (see
Fig. 1). Using this threshold,
all 15 DLB patients, but none of the controls of Alzheimer's disease
sufferers, had significant fluctuation (DLB v. Alzheimer's disease,
sensitivity 100%). A further analysis, using the same cut-off point in the
total sample of 155 patients, indicated that 30 (81%) of the DLB patients,
four (18%) of the vascular dementia patients and five (8%) of the Alzheimer's
disease patients had significant fluctuation (DLB v. Alzheimer's
disease, sensitivity 81%, 95% CI 73.2-88.8; specificity 92%, 95% CI 86.6-97.4;
DLB v. vascular dementia, sensitivity 81%, 95% CI 71-91; specificity
82%, 95% CI 72.2-91.8).
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In the subgroup of 40, an ROC was also used to determine the optimal
threshold for the One Day Fluctuation Assessment Scale
(Fig. 2). A score of 6
achieved the best discrimination, with 14 of the 15 (93%) DLB patients, but
only two (13%) of the Alzheimer's disease sufferers and none of the controls,
scoring above this threshold (sensitivity 93%, 95% CI 83.9-100, specificity
87%, 95% CI 75-99).
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Direct agreement between scales
A 90% agreement was achieved for the presence of significant fluctuating
confusion between the expert clinicianrated scale and the One Day Fluctuation
Assessment.
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DISCUSSION |
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Two clinical assessment instruments
The two scales are brief and easy to administer, and complement each other
well. The Clinician Assessment of Fluctuation evaluates fluctuating confusion
over the month prior to the interview, on the basis of an interview with an
informant, and needs to be completed by an experienced clinician. It provides
a method for standardising the clinical decision-making process. The One Day
Fluctuation Assessment Scale evaluates fluctuating confusion over the 24 hours
prior to the assessment, again on the basis of an interview with an informant.
It can be completed by a variety of mental health professionals or research
staff, and hence is well suited to research studies. The scoring system gives
it good face validity for measuring change during intervention trials.
Future studies
Interrater reliability has not yet been determined for either scale,
although the structured nature of the instrument should have advantages over
expert clinical judgement alone. Within the current study, extensive
discussion took place between the three raters, working through previously
assessed cases in order to achieve consistent scores. The same procedure is
recommended for groups of clinicians intending to use the Clinician Assessment
of Fluctuation, as an aid to clinical evaluation.
Potential value for differential diagnosis
A preliminary evaluation was also undertaken to assess the potential value
of the two scales in distinguishing between the different dementia groups.
Just on the basis of fluctuation assessments, both scales were able to achieve
a sensitivity and specificity in excess of 80%. Although there is a potential
tautology for the Clinician Assessment of Fluctuation, as this information was
used as part of the diagnostic procedure, the One Day Fluctuation Assessment
Scale was completed independently of, and blind to, the diagnostic process, by
a separate rater. It is therefore suggested that using this method to
standardise the evaluation of fluctuating confusion, within the framework of
the consensus clinical criteria for DLB, could have a significant impact upon
diagnostic accuracy. This is potentially important, as poor sensitivity for
the diagnosis of DLB has been a problem in some studies
(Mega et al, 1996;
Litvan et al, 1998),
with the accurate identification of fluctuating confusion highlighted as a
major difficulty. This is also highly relevant to everyday clinical practice,
as good case identification is essential to optimise clinical management and
to avoid neuroleptic sensitivity reactions.
APPENDIX I. CLINICIAN ASSESSMENT OF FLUCTUATION
Fluctuating confusion or impaired consciousness
are identified by a positive answer to either one or both of the following
questions.
If a positive rating of fluctuating confusion is present, a severity rating should be made.
Frequency of fluctuating confusion: Total score index
APPENDIX 2. ONE DAY FLUCTUATION ASSESSMENT SCALE
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Clinical Implications and Limitations |
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LIMITATIONS
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Received for publication August 2, 1999. Revision received February 22, 2000. Accepted for publication February 24, 2000.