The British Journal of Psychiatry (2009)
194, 34–39. doi: 10.1192/bjp.bp.108.052050
Diagnostic accuracy of 123I-FP-CIT SPECT
in possible dementia with Lewy bodies
John T. O’Brien, Ian G. McKeith, Zuzana Walker, Klaus Tatsch, Jan Booij, Jacques Darcourt,
Moritz Marquardt and Cornelia Reininger for the DLB Study Group*
Background
123
I-FP-CIT SPECT (single photon emission computed
tomography) can help in the differential diagnosis of probable
dementia with Lewy bodies (Lewy body dementia) and
Alzheimer’s disease.
Aims
Our aim was to determine the accuracy of 123I-FP-CIT SPECT
in diagnosing people with possible dementia with Lewy
bodies.
non-Lewy body dementia (16%) and for 18 individuals it
remained possible dementia with Lewy bodies (41%). Of the
19 who at follow-up were diagnosed with probable dementia
with Lewy bodies, 12 had abnormal scans at baseline
(sensitivity 63%); all 7 individuals with a possible diagnosis
who were diagnosed as having Alzheimer’s disease at followup had normal scans (specificity 100%).
Method
We undertook a 12-month follow-up of 325 individuals with
probable or possible Lewy body or non-Lewy body dementia
who had previously undergone 123I-FP-CIT SPECT. A
consensus panel, masked to SPECT findings, established
diagnosis at 12 months in 264 people.
Conclusions
Our findings confirm the diagnostic accuracy of 123I-FP-CIT
SPECT in distinguishing Lewy body from non-Lewy body
dementia and also suggest a clinically useful role in
diagnostically uncertain cases, as an abnormal scan in a
person with possible dementia with Lewy bodies is strongly
suggestive of dementia with Lewy bodies.
Results
Of 44 people with possible dementia with Lewy bodies at
baseline, at follow-up the diagnosis for 19 people was
probable dementia with Lewy bodies (43%), in 7 people
Declaration of interest
At the time of the study, M.M. and C.R. were GE Healthcare
employees. J.O’B, I.McK, Z.W., K.T., J.B. and J.D. have
received consultancy payments from GE Healthcare.
Early accurate diagnosis of dementia with Lewy bodies, especially
its differentiation from Alzheimer’s disease, is important for
optimum management, including provision of appropriate
information to patients and carers, initiation of effective treatments and avoidance of potentially life-threatening antipsychotic
drugs.1 Consensus clinical diagnostic criteria have high specificity
for diagnosis of probable dementia with Lewy bodies but poor
sensitivity;2 data for possible dementia with Lewy bodies are not
available. Ancillary investigations, such as neuroimaging, may be
important in enhancing accuracy of diagnosis. Nigrostriatal
degeneration, accompanied by profound reductions in the striatal
dopamine transporter is found in dementia with Lewy bodies.3 It
is possible to assess the dopamine transporter in vivo with specific
ligands, such as [123I]-2b-carbomethoxy-3b-(4-iodophenyl)-N(3-fluoropropyl)nortropane (123I-FP-CIT).4 A phase III multicentre study investigating 123I-FP-CIT SPECT (single photon
emission computed tomography) in dementia with Lewy bodies
reported a sensitivity of 77.7% for detecting probable dementia
with Lewy bodies and a specificity of 90.4% for excluding nonLewy body dementia (primarily Alzheimer’s disease).5 123I-FPCIT SPECT has been incorporated into the revised diagnostic
criteria1 and is recommended by the National Institute for Health
and Clinical Excellence (NICE) for use to assist with the diagnosis
of dementia with Lewy bodies (www.nice.org.uk).
Studies showing high diagnostic accuracy for 123I-FP-CIT
SPECT5–7 have compared imaging against clinical diagnosis of
probable dementia with Lewy bodies. Arguably, imaging investigations have greater potential to help clinicians where there is
less diagnostic certainty – that is, in individuals with possible
*Investigators in the DLB study group are listed in an online supplement.
(one core feature – fluctuation, recurrent visual hallucinations
or spontaneous parkinsonism) as opposed to probable (two or
more core features) dementia with Lewy bodies. Studies in such
groups require subsequent verification of diagnosis, either
through autopsy or by further follow-up when disease progression
clarifies the diagnosis.
We undertook a 12-month follow-up study of people with
Lewy body or non-Lewy body dementia who had taken part in
a previous study of 123I-FP-CIT SPECT in dementia, focusing
on the outcome of the individuals with possible dementia with
Lewy bodies who were not part of the primary outcome in the
previous report.5 Our aim was to assess the ability of 123I-FPCIT SPECT to differentiate between people with Lewy body or
non-Lewy body dementia with an initial uncertain clinical
diagnosis of possible dementia with Lewy bodies.
Method
Participants
We undertook a 12-month follow-up assessment of participants
previously enrolled to the McKeith et al phase III multicentre
study.5 For full inclusion criteria, please see that paper. Briefly,
participants were aged 55–90 years, met the criteria for dementia
detailed in DSM–IV and fulfilled at least one of the following:
consensus criteria6 or NINCDS–ADRDA (National Institute of
Neurological and Communicative Diseases and Stroke, and the
Alzheimer’s Disease and Related Disorders Association) criteria
for probable or possible Alzheimer’s disease,8 or NINDS–AIREN
(National Institute of Neurological Disorders and Stroke, and
Association Internationale pour la Recherche et l’Enseignement
en Neurosciences) criteria for probable or possible vascular
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123
dementia.9 A Mini-Mental State Examination (MMSE) score of 10
or more was required to ensure individuals could complete assessments.10 Participants with dementia who developed parkinsonism
more than 1 year before the onset of dementia were deemed to
have Parkinson’s disease with dementia and were not included.11
Those with structural imaging findings indicative of infarction
in the region of the basal ganglia, including the internal capsule,
were excluded. Use of medication known or suspected to interact
with striatal binding of 123I-FP-CIT was not permitted.
The study was done in accordance with the current revision of
the Declaration of Helsinki and the Good Clinical Practice:
Consolidated Guideline approved by the International Conference
on Harmonisation and applicable to national and local laws and
regulations. At every participating site, the study protocol and
all amendments were approved by an institutional review board
or independent ethics committee. All participants and caregivers
gave written informed consent.
Following inclusion in the initial study, we invited participants
for re-assessment at 12 months.
Procedures
Clinical diagnosis at baseline, as previously reported, was
established by an independent consensus panel of three specialist
clinicians, who were provided with a participant profile compiled
from quality-assured clinical data from the on-site investigators’
case record forms and copies of on-site original source data. The
same panel reconvened to consider the baseline and the 12-month
follow-up data to arrive at a second and final consensus diagnosis.
The following were undertaken at baseline and follow-up:
MMSE, Unified Parkinson’s Disease Rating Scale (UPDRS) III
(motor section),12 modified Hoehn and Yahr staging,13 Clinical
Assessment of Fluctuation (CAF) scale,14 the Cambridge Cognitive Examination–revised version (CAMCOG–R),15 Neuropsychiatric Inventory with caregiver input (NPI–D),16 Visual
Object and Space Perception (VOSP) battery17 and Clinical
Dementia Rating (CDR).18 The Cornell Scale for Depression in
Dementia19 and the investigator’s estimation of the person’s IQ
level were completed at baseline, but not at follow-up. Results of
magnetic resonance imaging and computed tomography scans
and the on-site investigators’ clinical diagnosis before imaging
were also available. The consensus panel did not at any stage have
access to 123I-FP-CIT SPECT findings and was unaware of the
participants’ identities, the names of the centre and the investigators. Before any participants were diagnosed, the consensus panel
was asked to diagnose ten patients (separate to the study) for
whom autopsy diagnosis was independently available. There was
100% concordance between the diagnoses made by the panel
and at autopsy.5 Individual panel members reviewed each study
case, including the baseline consensus panel diagnosis and all subsequent information, before meeting to agree a final clinical diagnosis
of probable dementia with Lewy bodies, possible dementia with
Lewy bodies or non-Lewy body dementia. Participants in the nonLewy body dementia category were further allocated to probable
or possible Alzheimer’s disease, probable or possible vascular
dementia or other.
Within a few weeks of the baseline clinical diagnosis, SPECT
images were acquired on a two- or three-headed camera 3–6 h
after a single intravenous injection of 111-185 MBq of I-FPCIT20 (the radiotracer was supplied by GE Healthcare). See
McKeith et al for details.5 Participants underwent standard thyroid
blocking. Single photon emission computed tomography imaging
was not repeated at follow-up. As previously described, three
nuclear medicine physicians assessed scans, masked to diagnosis,
using a 4-point scale (0, normal uptake; 1, unilateral putamen
I-FP-CIT SPECT to diagnose possible dementia with Lewy bodies
loss; 2, bilateral putamen loss; 3, virtually absent uptake);5 we used
only the dichotomous division of normal (0) v. abnormal (1–3)
images for analysis.
Statistical analysis
We analysed data with SAS software (version 9.1) for Windows for
binomially distributed data, using w2 tests to assess differences
among the diagnostic groups (probable dementia with Lewy
bodies, possible dementia with Lewy bodies, non-Lewy body dementia) with respect to participants’ characteristics. We used an
analysis of variance (ANOVA) for normally distributed data; if
normality could not be established, we used the non-parametric
Kruskal–Wallis test.
Our aim was to compare the results of the visual assessment
(normal or abnormal scan) in individuals with probable Lewy
body or non-Lewy body dementia as determined by the final
(12-month follow-up) consensus panel diagnosis. We were
particularly interested in individuals reported by McKeith et al5
to have possible dementia with Lewy bodies, and the ability of
123
I-FP-CIT imaging at baseline to predict the final consensus
panel diagnosis 12 months later.
Results
Figure 1 shows the participant profile. Of 325 participants invited
for follow-up at 12 months, information was obtained for 264
(81%). Completer status varied slightly between diagnostic
groups, with 129 of 147 (88%) in the non-Lewy body dementia
group returning for follow-up compared with 72 of 94 (77%) in
the probable dementia with Lewy bodies group and 46 of 57
(81%) in the possible dementia with Lewy bodies group. Of 28
(61%) participants with no initial diagnosis, 17 were followedup. Age and gender did not differ between completers and noncompleters. Of 264 participants who completed the 12-month
follow-up assessment, 29 were excluded from the analysis (Fig. 1).
Follow-up diagnoses for the 235 participants available for the
efficacy analysis were probable dementia with Lewy bodies (n=86),
possible dementia with Lewy bodies (n=25) and non-Lewy body
326 people assessed with
123
I-FP-CIT at baseline
1 died
8
6
325 invited for
12-month follow-up
61 did not complete 12-month
follow-up assessment
13 had died
10 did not consent to follow-up
34 lost to follow-up
4 other, e.g. disease worsening
8
6
264 completed
follow-up assessment
29 excluded from efficacy analysis
22 consensus panel unable to
establish a follow-up diagnosis
(15 already excluded at baseline
8
consensus panel assessment)
7 unreadable images at baseline
because of on-site acquisition
problems and/or camera-related
reasons or patient movement
6
235 available for
efficacy analysis
Fig. 1
Trial profile.
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O’Brien et al
dementia (n=124; of which 84 were diagnosed as probable
Alzheimer’s disease, 29 possible Alzheimer’s disease, 1 probable
vascular dementia, 9 possible vascular dementia and 1 dementia
post-surgery).
Diagnostic groups at follow-up were similar in terms of mean
age (probable dementia with Lewy bodies, 73.7 years; possible
dementia with Lewy bodies, 76.0; non-Lewy body dementia,
74.2; no diagnosis, 69.8) with, as expected, more men in the
dementia with Lewy bodies groups (percentage of men with
probable dementia with Lewy bodies, 62%; possible dementia with
Lewy bodies, 67%; non-Lewy body dementia, 50%; no diagnosis,
64%). Table 1 shows the clinical characteristics of the groups at
baseline and follow-up. Groups were well matched for baseline
MMSE and CAMCOG; participants in all three dementia groups
showed evidence of cognitive decline over 12 months. Patients
with dementia with Lewy bodies also showed evidence of
worsening motor symptoms over the follow-up period.
Table 1
Behavioural disturbance – as judged by the neuropsychiatric
inventory and fluctuation scales – showed relatively few differences
over time, although as anticipated dementia with Lewy bodies
groups had a greater degree of behavioural disturbance, more fluctuations and more parkinsonian symptoms than did individuals
with non-Lewy body dementia.
There were no significant differences noted for participants
with and without follow-up data with respect to MMSE
(mean=21.2 (s.d.=4.3) v. 19.2 (s.d.=4.3), P=0.99), UPDRS
(mean=14.0 (s.d.=14.3) v. 20.5 (s.d.=14.7), P=0.76), CAMCOG–R
(mean=64.6 (s.d.=16.2) v. 57.2 (s.d.=17.6), P=0.41), CAF (mean=2.8
(s.d.=4.2) v. 3.4 (s.d.=4.2); P=0.83) and severity of dementia
(mean=1.22 (s.d.=0.67) v. 1.48 (s.d.=0.69), P=0.81).
Table 2 shows the comparison between consensus panel
diagnosis at follow-up and baseline. Of the 68 individuals with
probable dementia with Lewy bodies diagnosed at baseline, most
retained their diagnosis at follow-up. In only five people (7%)
Clinical characteristics of participants at baseline and follow-up according to diagnosis a
Probable DLB
Possible DLB
Non-DLB
No diagnosis
Mini-Mental State Examination
Baseline, mean (s.d.)
Follow-up, mean (s.d.)
20.9 (4.3)
17.4 (6.5)
20.8 (4.4)
19.0 (7.1)
21.7 (4.3)
19.4 (6.1)
22.5 (2.9)
19.8 (6.4)
Cambridge Cognitive Examination–revised version
Baseline, mean (s.d.)
Follow-up, mean (s.d.)
63.0 (17.0)
53.9 (20.5)
63.3 (16.6)
55.9 (23.4)
66.4 (15.5)
60.1 (20.4)
69.1 (12.7)
64.1 (17.9)
Baseline, mean (s.d.)
Follow-up, mean (s.d.)
28.3 (14.5)
36.0 (16.4)
17.4 (11.1)
18.7 (11.6)
5.7 (7.7)
6.5 (6.6)
16.6 (14.2)
20.4 (22.2)
Hoehn and Yahr staging
Baseline, mean (s.d.)
Follow-up, mean (s.d.)
2.44 (0.98)
2.96 (1.07)
1.57 (1.02)
1.69 (1.14)
0.22 (0.71)
0.27 (0.81)
1.12 (1.36)
1.43 (1.51)
Neuropsychiatric Inventory
Baseline, mean (s.d.)
Follow-up, mean (s.d.)
22.1 (16.2)
22.1 (17.7)
15.7 (11.2)
17.8 (13.3)
10.1 (11.0)
12.3 (12.8)
12.5 (10.8)
10.7 (6.5)
Clinician Assessment of Fluctuation
Baseline, mean (s.d.)
Follow-up, mean (s.d.)
6.6 (4.2)
6.1 (4.2)
3.0 (4.3)
1.8 (3.0)
0.3 (1.2)
0.4 (1.7)
2.6 (4.1)
1.0 (2.2)
Visual hallucinations
Baseline, n (%)b
Follow-up, n (%)
55 (64)
58 (67)
11 (44)
9 (36)
5 (4)
2 (1.6)
Psycholepticsc
Baseline, n (%)
Follow-up, n (%)
31 (33)
35 (39)
20 (35)
12 (44)
20 (14)
22 (18)
10 (36)
9 (43)
Psychoanalepticsd
Baseline, n (%)
Follow-up, n (%)
69 (73)
75 (84)
44 (77)
17 (63)
106 (72)
107 (85)
20 (71)
21 (100)
Unified Parkinson’s Disease Rating Scale
N/A
N/A
DLB, dementia with Lewy bodies; N/A, not available.
a. Unless otherwise stated, group sizes at baseline: probable DLB, n=72; possible DLB, n=46; non-DLB, n=129; no diagnosis, n=17. Group sizes at follow-up: probable DLB, n=89;
possible DLB, n=27; non-DLB, n=126; no diagnosis, n=22.
b. Group size at baseline: probable DLB, n=86; possible DLB, n=25; non-DLB, n=124.
c. Psycholeptics: hypnotic and antipsychotic drugs.
d. Psychoanaleptics: anti-dementia drugs and antidepressants.
Table 2
Changes in diagnosis over time
Clinical diagnosis at follow-up (n=235), n (%)
Clinical diagnosis
main assessment
n
Probable DLB
68
63
(93)
5
(7)
0
Possible DLB
44
19
(43)
18
(41)
7
(16)
Non-DLB
116
2
(2)
1
(1)
113
(97)
Other
5
1
(20)
1
(20)
3
(60)
No diagnosis
2
1
(50)
0
1
(50)
Probable DLB
DLB, dementia with Lewy bodies.
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Possible DLB
Non-DLB
123
was the diagnosis revised to possible dementia with Lewy bodies.
Similarly, the diagnosis of non-Lewy body dementia showed
relative stability. Possible dementia with Lewy bodies was, as
anticipated, a more unstable diagnosis. Of the 44 individuals in
this group, only 18 (41%) still had a diagnosis of possible
dementia with Lewy bodies 1 year later, 26 had a clearer diagnosis
at follow-up, 19 of probable dementia with Lewy bodies (43%)
and 7 (16%) with non-Lewy body dementia.
Table 3 shows results of 123I-FP-CIT SPECT ratings against
final clinical diagnosis. Sensitivity ranged between 73.8 and
81.3% (mean=78) and specificity between 91.8 and 95.0%
(mean=93.1). These findings are similar to those reported in
the initial study (sensitivity mean, 77.7%; specificity, 90.4%).5
The results of the scan ratings and final panel diagnoses are
shown in Table 4. Of note is the possible dementia with Lewy
bodies group, which was not included in the primary analysis
of the baseline data. Nineteen participants diagnosed with possible dementia with Lewy bodies at baseline had their diagnosis
revised to probable dementia with Lewy bodies at follow-up. Of
these, 12 had an abnormal scan (as rated by at least two of the
raters). By contrast, seven individuals were diagnosed with nonLewy body dementia at follow-up, and all had normal scans.
Although numbers are small, it is striking that 2 of the 3 individuals diagnosed with non-Lewy body dementia initially but
who at follow-up were diagnosed with probable dementia with
Lewy bodies had abnormal scans v. only 3 of 116 whose diagnosis of non-Lewy body dementia remained at follow-up. Similarly, only 1 of the 5 (20%) individuals in the probable
dementia with Lewy bodies group who became a possible at
follow-up had an abnormal scan, compared with 42 of 63
(67%) participants who remained in the probable dementia
with Lewy bodies group. An abnormal scan, therefore, was predictive of an individual either keeping a diagnosis of dementia
with Lewy bodies or the diagnosis becoming probable dementia
with Lewy bodies.
Table 3
Sensitivity and specificity of
1 23
I-FP-CIT SPECT to diagnose possible dementia with Lewy bodies
Discussion
Differential diagnosis of Lewy body from non-Lewy
body dementia
Our results, using follow-up diagnosis, confirm the high diagnostic accuracy of 123I-FP-CIT SPECT imaging in discriminating
Lewy body from non-Lewy body dementia we previously reported
using the baseline diagnosis. The 12-month follow-up was a
powerful way of validating diagnosis in the uncertain group of
people with possible dementia with Lewy bodies, since diagnosis
became clearer in almost 60% of participants. At baseline, individuals with possible dementia with Lewy bodies had a bimodal
distribution of 123I-FP-CIT uptake,5 suggesting that the diagnosis
reflected a heterogeneous population. The consensus panel’s
diagnoses at follow-up were not influenced by 123I-FP-CIT
imaging results, as they relied solely on rating scores and
information about symptoms from the site investigators.
Strikingly, of the seven individuals with possible dementia with
Lewy bodies deemed to be non-Lewy body dementia (all
Alzheimer’s disease) at follow-up, none had had an abnormal
scan. By contrast, of the 19 people diagnosed with probable
dementia with Lewy bodies at follow-up that had been categorised
as possible dementia with Lewy bodies at baseline, 12 (63%) had
abnormal 123I-FP-CIT scans. These results (63% sensitivity, 100%
specificity), albeit in a small sample, mirror the overall results
obtained for probable dementia with Lewy bodies. 123I-FP-CIT
imaging, therefore, appears to have similar accuracy in discriminating Lewy body from non-Lewy body dementia in individuals
with a possible diagnosis as it does in those with a probable
diagnosis, and is likely to offer greatest diagnostic value when
clinicians are most in need of support – namely, for accurate
and timely diagnosis in clinically uncertain cases of individuals
who have just one of the three core dementia with Lewy bodies
features. These findings also support recent NICE guidelines for
I-FP-CIT SPECT v. follow-up clinical diagnosis
Parameter
Reader
Participants with
rateable scans, n
Participants with
abnormal scans, n
Accuracy, % (95% CI)
Sensitivity
A
B
C
80
80
80
65
59
63
81.3 (71.0–89.1)
73.8 (62.7–83.0)
78.8 (68.2–87.1)
Specificity
A
B
C
121
122
120
115
112
111
95.0 (89.5–98.2)
91.8 (85.4–96.0)
92.5 (86.2–96.5)
SPECT, single photon emission computed tomography.
Table 4
Changes in consensus panel diagnoses over time with the corresponding
12 3
I-FP-CIT SPECT findings
Number of SPECT readers with image finding ‘abnormal’ per participants, n (%)
Clinical diagnosis main
assessment
Clinical diagnosis 12-month
follow-up
n
Probable DLB
n
3
2
1
0
68
Probable DLB
Possible DLB
Non-DLB
63
5
0
42 (67)
1 (20)
0
3 (5)
0
0
9 (14)
2 (40)
0
9 (14)
2 (40)
0
Possible DLB
44
Probable DLB
Possible DLB
Non-DLB
19
18
7
11 (58)
1 (6)
0
1 (5)
4 (22)
0
2 (11)
1 (6)
0
5 (26)
12 (67)
7 (100)
Non-DLB
121
Probable DLB
Possible DLB
Non-DLB
3
2
116
2 (67)
0
3 (3)
0
0
5 (4)
1 (33)
0
6 (5)
0
2 (100)
102 (88)
DLB, dementia with Lewy bodies. SPECT, single photon emission computed tomography.
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O’Brien et al
dementia, which suggest that 123I-FP-CIT SPECT imaging may be
particularly helpful when the diagnosis of dementia with Lewy
bodies is in doubt.
Stability of disease over time
The stability of the diagnosis of probable Alzheimer’s disease is
well recognised. However, far less attention has been given to
longitudinal stability of a diagnosis of dementia with Lewy bodies.
Our results show that, over 1 year, probable dementia with Lewy
bodies is a stable diagnosis, as would be expected for a diagnosis
with high specificity and positive predictive value as judged by
clinicopathological studies.2,21 The outcome of possible dementia
with Lewy bodies has not previously been reported. In our study,
only 40% of individuals with possible dementia with Lewy bodies
at baseline remained in the possible category 12 months later. Our
study did not include further assessments, so we cannot determine
the proportion of participants whose diagnosis might be clear at 2
years. However, it is noteworthy (Table 4) that the proportion of
abnormal 123I-FP-CIT scans in the possible dementia with Lewy
bodies group had fallen in the year between baseline and followup. This finding is consistent with the view that most individuals
diagnosed with possible dementia with Lewy bodies who did
actually have dementia with Lewy bodies became apparent within
1 year.
Strengths and limitations
Strengths of this study include rigorous and quality-assured
assessment of comprehensive clinical, cognitive and psychiatric
ratings at baseline and follow-up, inclusion of multiple European
sites, and use of a masked independent consensus panel for
clinical diagnosis and independent masked readers for
123
I-FP-CIT rating. A limitation is that, as with baseline findings,
the gold standard for image validation was a clinical rather than a
pathological diagnosis. However, the validity of the probable
dementia with Lewy bodies diagnosis has been established in
clinicopathological series,2 and also in terms of 123I-FP-CIT
changes both in our baseline and in other independent
studies.5–7
suggests that 123I-FP-CIT imaging may be more accurate than
clinical diagnosis in distinguishing Lewy body from non-Lewy
body dementia.
The latest revision of the International Consensus Criteria for
dementia with Lewy bodies diagnosis incorporates abnormal
123
I-FP-CIT imaging as a feature that, in addition to a single core
feature, allows a diagnosis of probable dementia with Lewy bodies
to be made.1 Results reported here confirm this is an appropriate
and sensible amendment. Other investigations that may
potentially assist with distinguishing dementia with Lewy bodies
from Alzheimer’s disease include 18F-flurodopa positron emission
tomography (PET), which assesses the integrity of the nigrostriatal
pathway,24,25 18F-FDG PET, used to assess metabolic deficits, and
abnormal MIBG (meta-iodobenzylguanidine) imaging, which
assesses sympathetic cardiac denervation.26,27 Other differences
of less certain diagnostic value include changes in cerebrospinal
fluid measures of amyloid and tau,28 occipital hypoperfusion on
SPECT or PET29 and preservation of medial temporal lobe
structures on structural imaging.30 It may be that particular diffusion31 and spectroscopic32 changes associated with dementia with
Lewy bodies will emerge that can help distinguish it from
Alzheimer’s disease. However, currently 123I-FP-CIT SPECT
imaging has the greatest evidence base. Several single-site studies
and a large multicentre study have all demonstrated its utility for
dementia with Lewy bodies diagnosis.5 Our results confirm this
position and demonstrate the diagnostic value of 123I-FP-CIT in
clinically uncertain (possible) cases.
John T. O’Brien, DM, Ian G. McKeith, FMedSci, Institute for Ageing and Health,
Newcastle University, Newcastle upon Tyne, UK; Zuzana Walker, MD, Department of
Mental Health Sciences, University College London, UK; Klaus Tatsch, MD,
Department of Nuclear Medicine, Ludwig Maximilians University Hospital, Munich,
Germany; Jan Booij, MD, Department of Nuclear Medicine, Academic Medical
Centre, Amsterdam, Netherlands; Jacques Darcourt, MD, Department of Nuclear
Medicine, Medical Faculty, University of Nice Sophia-Antipolis, Nice, France;
Moritz Marquardt, Cornelia Reininger, MD, GE Healthcare, Clinical Research and
Development, Munich, Germany
Correspondence: John T. O’Brien, Institute for Ageing and Health, Wolfson
Research Centre, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE,
UK. Email: j.t.o’brien@ncl.ac.uk
First received 5 Mar 2008, final revision 11 Jun 2008, accepted 10 Jul 2008
Clinical implications
Assuming that our results can be extrapolated to the wider
population of individuals with possible dementia with Lewy
bodies, an abnormal 123I-FP-CIT scan in a person who fulfils
possible dementia with Lewy bodies criteria strongly suggests a
diagnosis of probable dementia with Lewy bodies and that the
person should be managed as having dementia with Lewy bodies.
The converse does not necessarily apply, since around 20% of
individuals with probable dementia with Lewy bodies appear to
have normal 123I-FP-CIT scans. There are a number of possible
explanations for this finding. The clinical diagnosis may be
inaccurate, some people with dementia with Lewy bodies may
have normal dopaminergic function or the technique may be
unable to detect subtle transporter loss (which might be more
readily detected with partial volume effect correction).22 Further
research needs to determine the proportion, clinical correlates
and outcome in people with probable dementia with Lewy bodies
who have normal 123I-FP-CIT imaging. This will require studies
with repeat imaging (to determine at what point in the illness
123
I-FP-CIT abnormalities may become apparent) as well as more
studies involving autopsy verification. Of note, in the expanded
series reported by Walker et al,23 123I-FP-CIT imaging was in
agreement with autopsy diagnosis in the vast majority of cases
(19/20), and was more precise than clinical diagnosis. This finding
Acknowledgements
The sponsor (GE Healthcare) financially supported the collection, analysis and interpretation
of data. The study was initiated by the principal investigators who drafted and approved
the manuscript. The first author had full access to all the data in the study and wrote
and approved the manuscript.
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