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SUPPLEMENTARY MATERIAL
APPENDICES
Appendix 1. Early features
SUPPLEMENTARY TABLE LEGENDS
Supplementary Table 1. Cases by site
Supplementary Table 2. 1998 Consensus criteria for bvFTD (Neary et al., 1998)
Supplementary Table 3. First and last clinical diagnoses
SUPPLEMENTARY FIGURE CAPTIONS
Supplementary Figure 1: Sensitivity of bvFTD criteria by age of onset: (A) Sensitivity of
FTDC and 1998 criteria (B) FTDC diagnostic features. Clear bars show percent of cases with
early onset (before age 65), black bars show percent of cases with late onset (after 65); *
p<.05.
Supplementary Figure 2: 1998 criteria supportive features. Frequency is shown as percent
of cases in the 1998 criteria sample (clear bars) or the common sample (black bars).
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Appendix 1
To help establish the optimal duration for criteria involving “early” presentations (i.e.,
disinhibition, apathy, loss of empathy, perseverative behaviors), raters were asked to provide
the timing of symptom onset when available. Table 1 shows symptom onset findings in
patients who met criteria for Possible bvFTD and were ascertained for both FTDC and 1998
criteria (n=118). Symptom onset ratings were only available for a subset of these patients.
Since FTDC criteria require the presence of 3 or more diagnostic features, a sample of patients
with 3 or more symptom onset ratings (n=96) was used to determine the optimal temporal cutoff for fulfillment of Possible bvFTD. Please refer to the subsequent text for information on
samples and criteria.
Table 1: Symptom onset and temporal fulfillment of criteria for Possible bvFTD (n=118)
Cumulative percent by time course (years from onset)
Patients
0 yrs
with onset
1 yr
2yrs
3yrs
> 3yrs
(onset)
ratings
Early disinhibition
92
65
87
93
98
100
Early apathy / inertia
98
70
90
95
97
100
Early loss of empathy
81
49
90
96
100
100
Early perseverative / compulsive
74
42
73
88
97
100
Meet criteria for Possible bvFTD
96
41
83
93
97
100
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In this sample, “early” symptoms are present in 97-100% of patients within the first three
years. Based on these limited observations, a cut-off of 3 years is suggested as a general
guideline for the onset of these features. Prospective studies are needed to determine the
optimal temporal cut-off for symptom onset and fulfillment of criteria.
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Supplementary Table 1
Site
# Patients
Rotterdam
25
Johns Hopkins
23
Mayo
17
Western Ontario
17
UCSF
14
Sydney/Cambridge
14
UCL Institute of Neurology
13
UCSD
11
U Penn
10
UCLA
10
Sunnybrook
7
Northwestern
4
Harvard
4
Munich
3
Lille
2
VU Amsterdam
2
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Supplementary Table 2
I. Core diagnostic features
A. Insidious onset and gradual progression
B. Early decline in social interpersonal conduct
C. Early impairment in regulation of personal conduct
D. Early emotional blunting
E. Early loss of insight
II. Supportive diagnostic features
A. Behavioral disorder
1. Decline in personal hygiene and grooming
2. Mental rigidity and inflexibility
3. Distractibility and impersistence
4. Hyperorality and dietary changes
5. Perseverative and stereotyped behavior
6. Utilization behavior
B. Speech and language
1. Altered speech output
2. Stereotypy of speech
3. Echolalia
4. Perseveration
5. Mutism
C. Physical signs
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1. Primitive reflexes
2. Incontinence
3. Akinesia, rigidity, and tremor
4. Low and labile blood pressure
D. Investigations
1. Neuropsychology: significant impairment on frontal lobe tests in the absence of
severe amnesia, aphasia, or perceptuospatial disorder
2. Electroencephalography: normal on conventional EEG despite clinically evident
dementia
3. Brain imaging (structural and/or functional): predominant frontal and/or anterior
temporal abnormality
III. Supportive features (common to clinical syndromes of FTLD)
A. Onset before 65: positive family history of similar disorder in first-degree relative
B. Bulbar palsy, muscular weakness and wasting, fasciculations (associated motor neuron
disease present in a minority of patients)
IV. Diagnostic exclusion features (common to clinical syndromes of FTLD)
A. Historical and clinical
1. Abrupt onset with ictal events
2. Head trauma related to onset
3. Early, severe amnesia
4. Spatial disorientation
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5. Logoclonic, festinant speech with loss of train of thought
6. Myoclonus
7. Corticospinal weakness
8. Cerebellar ataxia
9. Choreoathetosis
B. Investigations
1. Brain imaging: predominant postcentral structural or functional deficit, multifocal
lesions on CT or MRI
2. Laboratory tests indicating brain involvement or inflammatory disorder such as MS,
syphilis, AIDS and herpes simplex encephalitis
V. Relative diagnostic exclusion features (common to clinical syndromes of FTLD)
A. Typical history of chronic alcoholism
B. Sustained hypertension
C. History of vascular disease (e.g., angina, claudication)
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Supplementary Table 3
First diagnosis
Last diagnosis
n
n
bvFTD
122
112
AD
26
18
FTD / ALS
13
27
Other
13
5
DLB
2
5
CBS
0
1
PNFA
0
2
PSP
0
2
SD
0
2
Don’t Know
0
2
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ACKNOWLEDGEMENTS
Work undertaken at UCLH/UCL received a proportion of funding from the UK Department
of Health’s NIHR Biomedical Research Centres funding scheme. The UCL Dementia
Research Centre is an Alzheimer’s Research UK Co-ordinating Centre and has also received
equipment funded by Alzheimer’s Research UK. Drs. Fox and Rossor have received support
from the NIHR and the MRC; Dr. Warren is supported by a Wellcome Senior Clinical
Fellowship. Dr. Piguet is supported by a National Health and Medical Research Council
Clinical Career Development Award fellowship (#510184). Dr. David Salmon is supported
by NIH grant P50-AG05131. Dr. Black’s research is supported by the Canadian Institutes of
Health Research (MT-13129).