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Journal of the International Neuropsychological Society (1996),
2,
5
J1
-524.
Copyright
©
1996 INS. Published
by
Cambridge University Press. Printed
in the
USA.
Nonfluent progressive aphasia and semantic dementia:
A comparative neuropsychological study
JOHN
R.
HODGES
1
AND
KARALYN PATTERSON
2
'University Neurology Unit, University
of
Cambridge, Cambridge CB2 2QQ,
UK
2
MRC Applied Psychology Unit, Cambridge CB2 2EF,
UK
(RECEIVED
August 14, 1995;
REVISED
January 24, 1996;
ACCEPTED
February 7, 1996)
Abstract
Two patients with nonfluent progressive aphasia,
who
have been studied longitudinally,
are
contrasted with
a
group
of 5 patients with fluent progressive aphasia
or
semantic dementia.
The
most prominent feature
of
the nonfluent
syndrome
is the
severe distortion
of
speech output with phonological errors
and
agrammatic sentence structure. This
contrasts with
the
fluent, well articulated
and
syntactically correct,
but
empty, anomic speech found
in
semantic
dementia. Performance
on
tests
of
comprehension separates
the
patient groups: The nonfluent patients show normal
single-word comprehension,
but
marked impairment
on
tests
of
syntactic comprehension, while those with semantic
dementia demonstrate
(he
opposite pattern. Category fluency
is
severely defective
in
semantic dementia,
but
initial
leitcr-bascd fluency
is
more impaired
in the
nonfluent syndrome. Performance
on
nonverbally mediated tests
of
semantic knowledge
is
impaired
in
semantic dementia only.
The 2
forms
of
progressive aphasia have
in
common
the
sparing
of
perceptual
and
visuospatial skills, nonverbal problem solving abilities,
and
day-to-day (episodic) memory.
Neuroradiological investigations have shown marked selective
and
striking inferolateral left temporal lobe atrophy
in
all 5
patients with semantic dementia.
The
changes
in
nonfluent progressive aphasia appear
to be
less focal
and
involve left perisylvian structures more diffusely. These
2
forms
of
progressive aphasia are,
we
argue, distinct
in
their manifestations. {JINS, 1996,
2,
511-524.)
Keywords: Nonfluent progressive aphasia. Semantic dementia
INTRODUCTION
In 1982 Mcsulam drew attention
to the
clinical syndrome
of "slowly progressive aphasia without generalised demen-
tia"
by
reporting
6
patients with
a 5- to
10-year history
of
insidiously worsening aphasia in the absence
of
signs of more
generalized cognitive failure.
One of
the
6
patients under-
went
a
brain biopsy, which revealed nonspecific changes
only.
Ten
years later,
on the
basis
of
both their own inves-
tigations
and a
review
of
the literature, Mesulam
and
Wein-
traub (1992) were able to propose clearer diagnostic criteria
for primary progressive aphasia,
as
follows:
a
progressive
deterioration
of
language with preservation
of
the activities
of daily living
for
at least 2 years, and evidence
of
relatively
normal nonverbal abilities
on
neuropsychological testing.
Reprint requests
to:
John
R.
Hodges. Department
of
Neurology.
Uni-
versity
of
Cambridge Clinical School. Addcnbrooke's Hospital. Hills
Road, Cambridge. UK. CB2
2QQ.
There have
now
been over
30
papers reporting some
80
patients who fulfill the criteria for primary progressive apha-
sia (e.g., Kirshner et al., 1984; Poeck
&
Luzzatti, 1988; Tyr-
rell
et
al., 1990; Weintraub
et
al., 1990; Caselli
et
al.,
1992;
Hodges
ct
al.. 1992a; Mesulam & Weintraub, 1992; Snowden
et al., 1992; Karbc
et
al., 1993; Scheltens
et
al., 1994).
The
major focus
of
these studies
has
concerned
the
nosological
status
of
progressive aphasia
in
relationship
to
Alzheimer's
and Pick's diseases,
the
neuropathology,
and the
radiologi-
cal features
of
the syndrome. The detailed nature
of
the
lan-
guage disorder has received little attention. From review
of
the published case descriptions, however,
it
seems clear that,
although the language disorder in progressive aphasia is het-
erogeneous, two broad groups
can be
identified: fluent
and
nonflucnl progressive aphasia.
In the
fluent patients,
syn-
tax, phonology
and
articulation
are
relatively preserved,
speech remains fluent and well articulated, but becomes pro-
gressively devoid
of
content words. Anomia
is the
most
prominent feature
on
clinical testing,
and
semantic naming
errors may occur. Comprehension
is
also impaired. By con-
51
512
J.R.
Hodges and K. Patterson
trast, many other cases with progressive aphasia are de-
scribed as having a nonfluent aphasic syndrome: Of the 63
cases reviewed by Mesulam and Weintraub (1992), 28 were
classified as nonfluent aphasics, 31 as fluent aphasics, and
5 mixed. The nature of the nonfluent language disorder is
itself apparently somewhat heterogeneous: Whereas in some
instances speech appears to be disrupted by severe anomia,
producing hesitancy without disturbance of phonology or
syntax, other cases have shown features more typically as-
sociated with Broca's type aphasia, such as phonological
paraphasias, or agrammatism, or both.
Despite the fact that the nonfluent form was the first to
be described under the sobriquet of progressive aphasia, it
is the fluent variety that has received the most detailed ex-
perimental analysis of language and other cognitive func-
tions.
This is particularly so for a subgroup of patients
recently accorded the label of "semantic dementia" (Snowden
etal., 1989; Hodges etal., 1992a, 1994; Saffran& Schwartz,
1994;
Moss et al., 1995) to encapsulate the key component
of the syndrome: progressive breakdown in semantic mem-
ory. Such losses are often observed in both verbal and non-
verbal abilities, although the former typically dominates the
clinical picture. Less \s known about the deficits in nonflu-
ent progressive aphasia as, with very few exceptions (e.g.
Weintraub et a!., 1990), such patients have not been the sub-
ject of formal neuropsychological and linguistic analysis.
The aim of this article is to describe the clinical and neuro-
psychological features of a variety of nonfluent progressive
aphasia that has the following characteristics:
(1) presentation with an insidiously progressive impair-
ment in speech fluency,
(2) the occurrence of phonological errors in spontane-
ous speech or confrontation naming, or both,
(3) deficits in the production and comprehension of
syntax,
(4) relative preservation of single-word comprehension,
(5) normal perceptual skills and nonverbal problem solv-
ing abilities; and
(6) relatively preserved autobiographical and day-to-
day (episodic) memory.
Two patients with this syndrome who have been followed
longitudinally are described, and are contrasted with a group
of 5 patients with semantic dementia.
NONFLUENT PROGRESSIVE APHASIA
Case Reports
In neither case was there a family history of dementia, a
background of alcoholism or other ctiologically relevant fac-
tors.
Physical signs (including frontal release phenomena)
were absent, and detailed investigations for causes of de-
mentia were negative.
Case 1
PG, a 74-year-old, right-handed ex-secretary, presented in
1991 with a 2-year history of progressive loss of speech
fluency. She complained of an inability to converse due to
hesitancy, word finding difficulty and distortion of her
speech. Her reading and writing abilities were unaffected,
and memory for recent and past events was excellent. She
was living independently, and had no difficulty perform-
ing the activities of daily life, including driving to visit
friends and family.
Spontaneous speech was poorly articulated, with abnor-
mal prosody and frequent phonemic errors. She was rarely
able to produce phrases of greater than four or five words,
and conversation was punctuated by word finding diffi-
culty. The degree of anomia on confrontational naming was
initially mild (see below). Comprehension of single words
was normal but she had difficulty understanding syntacti-
cally complex sentences. Repetition of short words was in-
tact, but on multisyllabic words and phrases she produced
phonological errors. In contrast to her language impair-
ment, her visuospatial abilities were markedly well pre-
served; copies of complex geometric shapes were executed
flawlessly.
A magnetic resonance imaging (MRI) scan in 1991 re-
vealed minimal left cerebral atrophy, with widening of the
sylvian fissure, but no focal lobar
atrophy.
A 99mTc-HMPAO
SPECT scan was normal.
On followup over the subsequent 3 years there has been
little change in her general cognitive abilities. Despite hav-
ing relocated to be nearer to her son, she continues to live
on her own without assistance. She remains immaculately
groomed, is a conscientious housekeeper, and drives short
distances alone. In contrast, her language has deteriorated
progressively and dramatically. She volunteers almost no
spontaneous speech, but will give appropriate one- or two-
word replies to direct questions. Many of her utterances are
now incomprehensible. She sometimes perseverates a pre-
viously used word in place of the currently sought one,
without necessarily seeming aware of her error. Her com-
prehension of sentences is severely impaired and she now
often has difficulty understanding even single words. A
repeat MRI in October 1994, using a three-dimensional ac-
quisition program, revealed a more obvious degree of gen-
eralized cerebral atrophy, with marked widening of the left
sylvian fissure, but no focal lobar atrophy (see Figure 1).
A sample of conversational speech with PG in 1994 is
given below:
Ex: where did you go last week?
PG: oh yes, oh the urn, Maybank* cr the um Sunny-
bank*
Ex: and who lives there?
•TJicsc arc villages names (which have been changed to protect the
patient's anonymity).
Primary progressive aphasia
Fig. 1 Coronal MR1 scan (Tl weighted images) at the level ot the antenoi temporal lobes tiom a patient with nontlucni
progressive aphasia
(P(~>)
showing a degree of generalized cerebral atrophy that is more marked on the left, and in-
volves particularly the inferior frontal region, with widening of the sylvian fissure
PC: oh yes the the the er /dn/ /daivin/ (driving
j
(gestures
driving a ear)
Ex: so you drove there did you','
/*(/:
yes (hand on chest) mm
Ex: do you like to drive'?
PG: no (smiling, shaking head, pantomiming driving)
driving er the /ba'vmon/
Case
2
LM, a 76-year-old, right-handed retired clerk of the works
presented in 1991 with an 18-month history of difficult)
speaking. Like PG, he complained o\" an inability to con-
verse due to hesitancy, word-finding difficulty and dis-
torted speech. His autobiographical and everyday memory
remained good; he could give a good (though aphasic) ac-
count of his past life, and of recent family events. He had
no difficulty performing the activities of daily life and re-
mained a keen gardener. There had been no change in per-
sonality or social behavior. His retained insight into the
difficulties resulted in understandable anxiety.
Spontaneous speech was nonfluent. poorly articulated and
contained numerous phonemic errors. EM never produced
phrases of longer than four or five words, and abnormal pros-
ody and severe word finding difficulties were apparent. Con-
frontational naming revealed a moderate degree ot anomia
with phonemic errors (see below ). Comprehension and rep-
etition were identical to Case I t/'C/h Tests of attention and
orientation, recall ot'simple verbal material and copying ot
three-dimensional drawings were all performed
w
ithout error.
An MRI scan demonstrated a mild degree of cerebral at-
rophy with accentuation in the left perisyhian region. A
SPHCT scan showed extensive left parietotemporal hypo-
perfusion.
On follow up over the subsequent 2 years there has been
little change in his general cognitive abilities. He remains
completely self-caring, still takes care of his garden, does
odd jobs about the house and drives short distances. In
contrast, his spontaneous speech is telegramnuuic. lacking
all but the simplest grammatical morphemes; his speech is
also often unintelligible because ol phonological parapha-
sias.
although stereotyped, high-frequency phrases (such
as "all right") are still very dear. He is often able to make
himself understood by the use ol gestures and pointing when
unable to speak. His comprehension of connected speech
is now severely disrupted, and even his family are finding
it difficult to communicate with him. In 1
1
>
c
>3. EM devel-
oped carcinoma of the prostate. Although we have kept in
contact, we have been unable to collect further follow up
data.
A sample of conversational speech with EM in 1W3 is
tiiven below;
E.\: could you tell me something about your holiday in
N'orw ay'.'
EM: er /naid// mint
1
iJa\si (holding up nine tinners>
and (points to the window )
an /Kr//oo//nd/ (aeroplane) have How and /o/ nond/
/b;endolon// and /o/ the
when we came out (pointing down) a coach (point-
ing down) and took /.xl/us all round (gesturing "all
round*") /o/
/
\es
>
/hood31/
(fune11
three days ami er (holds up three fingersi
we /\V coach /»i/ two days
i
holds up two fingers)
and /nsplip/ and /out/ five days (holds up five fin
gers)
/'n// /a/ (mimes sleeping) /;>// like (laughs)
it's alright (gi\e\ '•thumbs up" sign)
514
J.R.
Hodges and K. Patterson
Neuropsychological Test Results
The results of standard clinical neuropsychological tests at
the time of presentation are shown in Table 1. In both cases,
there was a discrepancy between verbal and performance
IQ in favor of the latter. Impairments were most marked on
the Digit Span and Arithmetic verbal subtests. Nonverbal
problem-solving intelligence, as judged by performance on
the Raven's Colored Progressive Matrices (Raven, 1962),
was within the expected range for the patients' ages. Evi-
dence of preserved constructional ability is provided by the
normal copies of the Rcy Complex Figure. Performance
within the normal range was also observed for both PG and
Table 1. Basic neuropsychological data collected at the time of
presentation (PG: July 1991; LM: October 1991)
Measure
MMSE (30)
DRS (144)
WAIS subiest scores (age scaled)
Information
Digit Span
Vocabulary
Comprehension
Arithmetic
Similarities
Picture Completion
Block Design
Digil Symbol
Picture Arrangement
Verbal IQ
Performance IQ
Rey Figure Copy (36)
Recall
Raven's Colored Matrices (36)
Judgment of Line Orientation (30)
VOSP subtests
Fragmented letters (20)
Cube analysis (10)
Bcnton Face Matching (54)
Object Matching Test (40)
Digit Span
Forward
Backward
Logical Memory WMS
Immediate (25)
30-min delayed
RMT
Words (50)
Faces(50)
Patient's test score
PG
28
116
8
6
7
-
5
6
9
10
10
8
78
98
29
13
28
29
20
10
51
37
4
4
6.5
7.25
46
36
LM
25
123
9
4
9
10
7
8
10
10
9
10
86
95
34
10
28
29
19
10
45
38
3
2
4
2.5
43
37
MMSE = Mini-Mental State Test (Folstcin
c!
al., 1975), DRS = Demen-
tia Rating Scale (Mattis, 1988), VOSP = Visual Object and Space Percep-
tion Battery (Warrington & James, 1991), WMS = Wcchslcr Memory
Scale-Revised (Wcchslcr.
1987),
RMT = Recognition Memory
Test
(War-
rington, 1984). Figures in parentheses indicate maximum scores.
LM on two of the subtests from the Visual Object and Space
Perception Battery (VOSP; Warrington & James, 1991), on
the Judgment of Line Orientation Test (JLO; Benton et al.,
1983a), and on the Face Recognition Test (Benton et a!.,
1983b), which requires subjects to match photographs of
the same person taken with different lighting conditions, and
from different angles.
Digit span both forward and backward was clearly im-
paired. Assessment of longer-term verbal memory was con-
founded by the expressive language disorder. Case 1 (PG)
showed reasonable immediate recall of the prose passage
from the Wechslcr Memory Scale-Revised (WMS-R; Wech-
sler, 1987), but Case 2 (LM) performed below his expected
level. Delayed recall of the passages (as a proportion of the
initial score) was, however, normal in both PG and LM (111
and 65% of immediate recall, respectively). Nonverbal mem-
ory assessed by recall of the Rey Complex Figure was pre-
served, although both patients showed weak memory for new
faces,
with (surprisingly) somewhat better recognition mem-
ory for words (Recognition Memory
Test;
Warrington, 1984).
Picture description using the "Cookie Theft" picture from
the BDAE (Goodglass & Kaplan, 1976) produced nonfiu-
ent, poorly articulated, and occasionally agrammatic dis-
course, punctuated by frequent word finding difficulty and
occasional phonemic paraphasias. PCs and LM's "Cookie
Theft" attempts in 1991 are shown below.
PG: O well., en.urn., on the steps., and the cookie ...
things ... and er girl on the sher ... no the cookie ...
things and er... furniture and the curtains and the ...
outside urn ... and the mu ... mother is washing up ..
oh ... that's right... yes ... the tap is gone ... the cup
... cups arc there ... and the plat.. and the cupboards
.. and cr . II.. think the gate really ... and urn ... the
flowers and things ... the pth .. and yeah ... mmmm
... that's right.
LM: Well.. the first thing .. er.. the sink is overflowed ..
water down to cupboards .. and .. where you walk
and ... er.. the boy is on .. er.. chair and .. three legs
... and his ... cr.. gu .. er... cookie ... jar is ... getting
one for his sister ... and he's fillin ... fallin over the
... the chair wos he's on ,. and the mother is step-
ping on the water and she' s drying the plates .. and
as I said ... the sink ... is overflowed
Results of language testing are shown in Table 2. For the
nonstandard tests we compared the performance of the pa-
tients with 24 age- and education-matched normal controls
selected from the MRC Applied Psychology Unit's subject
panel. Both patients were given three picture naming tests
ranging in difficulty from the rigorous Graded Naming Test
(McKenna & Warrington, 1983) to the easier Boston Nam-
ing Test (BNT) (Kaplan ct al., 1983). PG was initially only
mildly impaired at object naming, while LM showed severe
anomia even at presentation. Apart from omissions, naming
errors were predominantly phonemic in type. A fuller anal-
ysis of
the
pattern of naming errors on a wide range of single-
word processing tasks is presented elsewhere (Croot ct al.,
Primary progressive aphasia
515
Table 2. Results of the principal language tests collected at the
time of presentation (PG: July 1991; LM: October 1991)
Measure
Fluency:
Letter (F,A,S)
Category (animals)
Naming: number correct
GNT (30)
SBNT (48)
BNT (60)
Token Test (36)
TROG
Total score (80)
Blocks passed (20)
Word-picture matching test
from PALPA (40)
Word and nonword repetition
from ADA (80)
Phoneme discrimination (100)
Reading
Regular (126)
Exception (126)
Writing (36)
Language test scores
for patients and controls
PG
li
12
9
39
41
30
60
9
40
12
79
126
122
35
LM
9
6
2
27
24
16
55
7
39
13
74
118
87
28
Controls
M
44.6
17.5
-
43.6
54.5
35.7
78.8
19.0
38.9
-
-
125.2
123.6
35.3
SD
10.2
4.0
2.3
5.2
0.5
1.8
1.3
2.2
2.7
3.1
0.9
GNT = Graded Naming Test (McKcnna & Warrington, 1983), SBNT =
Semantic Bailcry Naming Test (Hodges ctai.. 1992b), BNT = Boston Nam-
ing Test (Kaplan ct al., 1983), TROG = Test for the Reception of Gram-
mar (Bishop,
1989),
ADA = Action for Dysphasic Adults Battery (Franklin
ct al., 1992). Figures in parentheses indicate maximum scores.
in press). On the BNT, neither patient's naming perfor-
mance was significantly enhanced by the provision of ei-
ther semantic or phonemic cues.
On comprehension tests, both patients showed a marked
discrepancy between performance on tests designed to mea-
sure single-word lexical-semantic comprehension via word-
picture matching, and tests intended to assess syntactic
comprehension in phrases or sentences using very simple
vocabulary. PG and LM were severely impaired on both the
shortened Token Test (Dc Renzi & Faglioni, 1978) and the
Test for the Reception of Grammar (TROG; Bishop, 1989—
for more details of this lest sec below). In contrast, simple
lexicosemantic comprehension was normal in both cases,
as evidenced by their near perfect performance on the word-
picture matching test from the Psycholingustic Assess-
ments of Language Processing in Aphasia battery (PALPA;
Kay ct al,, 1992), in which subjects arc required to point to
the named target picture from an array of five pictures: the
target, two scmantically related alternatives, one visual, and
one unrelated foil. To investigate single word comprehen-
sion more extensively in LM, we administered a word-
picture matching test including all 260 items from the
Snodgrass and Vandenvart corpus (Snodgrass & Vander-
wart, 1980). Each target item must be selected from an ar-
ray of four pictures from the same semantic category (e.g.,
four birds, four types of fruit, etc.). LM made only 4 errors
(1.5%) on this test.
Word and nonword repetition was assessed formally using
a test from the Action for Dysphasic Adults (ADA) battery
(Franklin et al., 1992); LM correctly repeated 23% of the
words and 10% of the nonwords, while PG correctly re-
peated 50% of the words and 10% of the nonwords. As the
normal controls achieved mean scores of 95 and 78% cor-
rect on the words and nonwords respectively, it is clear that
the performance of both patients was severely impaired. Al-
though repetition performance was doubtless depressed by
the patients' speech production difficulties, it is likely—on
the grounds of other evidence—that their impaired repeti-
tion also reflects a deficit in processing spoken words. First
of all, both patients were well outside normal limits on the
Nottingham Four-Alternative Auditory Feature Test (Foster
& Haggard, 1987) of phoneme discrimination, in which the
patient must select one of four written words to match a
single spoken word, each choice differing from the target
by a single phoneme. Secondly, LM was given two further
word-based tests, neither of which requires speech produc-
tion but only a yes-no decision for which a "thumbs-up-
down" response was adequate, and both of which can be
administered with either spoken or written presentation. The
two tests from the ADA battery (Franklin et al., 1992) are
lexical decision and synonym matching (these results are
not listed in Table 2 because comparable data are not avail-
able for PG). In both cases, LM achieved normal scores when
the stimulus words were presented in written form (lexical
decision: 78/80; synonym matching: 73/80), but markedly
deficient scores when the stimuli were spoken words (42/80
and 51/80, respectively, for lexicality and synonym judg-
ments),
indicating a specific deficit in processing spoken
words (see, e.g., Howard & Franklin, 1988).
At the time of this initial assessment, PG showed no def-
icits in either single-word reading or writing. The reading
test was designed (by Patterson & Hodges, 1992) to detect
surface dyslexia, a form of reading impairment signalled by
a marked disadvantage in oral reading of words with "ex-
ceptional" spelling-sound correspondences (e.g., "pint") with
contrastingly normal accuracy in reading "regular" words
(e.g., "mint"). PG's scores of 100 and 97%, respectively, on
regular and exception words were entirely within the nor-
mal range, as was her accuracy in writing to dictation of a
subset of words from the reading list. LM, on the other hand,
had a mild impairment in writing to dictation and in reading
of regular words, and a more substantial deficit in reading
exception words.
Followup Neuropsychological Assessment
As shown in Tables 3 and 4, longitudinal testing has re-
vealed a relentless decline in both the receptive and expres-
sive aspects of language in both PG and LM. When last
516
J.R.
Hodges and K. Patterson
Table 3. Longitudinal neuropsychological data from Case 1 (PG)
Measure
MMSE (30)
Raven's Colored
Matrices (36)
Rcy Figure Copy (36)
Judgment of Line
Orientation (30)
Bcnton Face Matching (54)
Object Matching Test (40)
Digit Span
Forward
Backward
Logical Memory WMS
Immediate (24)
RMT:
Words (50)
Faces (50)
Fluency:
Letter (F,A,S)
Category (Living x 4)
Naming:
Pictures Sem Battery (48)
To verbal description (24)
Token Test (36)
TROG
Total score (80)
Word-picture matching tests
From PALPA (40)
From Sem battery (48)
Reading
Regular (126)
Exception (126)
Writing (36)
July
91
28
28
29
29
51
-
4
4
6.5
46
36
11
37
39
-
30
60
40
48
126
122
35
Test score
Jan
92
23
26
31
23
45
37
5
4
4.0
-
35
11
27
38
19
27
59
40
47
122
118
—
at time of measurement
June
92
25
23
29
27
47
37
5
2
4.0
23
31
12
29
34
15
23
60
40
45
124
118
32
April
93
18
24
28
25
-
39
3
3
2.5
18
29
10
21
31
9
4
53
38
45
118
no
31
Fcb
94
9
18
29
0
—
34
0
0
-
-
-
2
8
14
2
-
43
33
37
79
60
13
Aug
94
4
12
26
0
34
26
0
0
-
-
—
-
0
8
0
-
29
31
27
70
50
—
MMSE = Mini-Mcnia! Stale Test (Folstcin ct al., 1975), WMS = Wcchslcr Memory Scale-Revised
(Wechsler,
1987),
RMT = Recognition Memory Test (Warrington, 1984), Sem Battery = Semantic Test
Battery (Hodges et al.,
1992b),
TROG = Test for the Reception of Grammar (Bishop, 1989). Figures in
parentheses indicate maximum scores.
assessed, neither patient managed to name a single object
from verba! description, and the trajectory of their scores
for naming in response to pictures suggests that this ability,
too,
is rapidly approaching zero. Single-word reading and
writing skills, which were initially well maintained in PG,
and only mildly deficient for LM, have been subject to dra-
matic deterioration in both cases. The first 2 years of lon-
gitudinal data in the case of PG, and the first year in LM,
mirrored the original pattern of performance on the tests of
lexicosemantic and syntactic comprehension; that is, intact
scores on the former, impaired on the latter. Thereafter, per-
formance also began to decline on single-word comprehen-
sion, though even at latest assessment, both patients showed
an advantage for semantic as compared to syntactic com-
prehension. By contrast, patients with fluent progressive
aphasia (see below) are characterized by the opposite pat-
tern; namely, an advantage for syntactic over semantic com-
prehension.
Because of their profound comprehension problems, it was
difficult to judge the patients' abilities in other areas of cog-
nition, especially on tests that entail complex instructions.
For example, PCs inability to score at all on the Judgement
of Line Orientation (JLO) Test in February, 1994 (follow-
ing adequate performance in April, 1993) was clearly at-
tributable to her failure to comprehend the instructions. Even
with this proviso, however, nonlinguistic competence docs
appear to have deteriorated, particularly for PG, as evi-
denced by declining scores on Raven's Colored Progressive
Matrices and the object matching "unusual views" test. Both
patients' level of performance on more basic visuospatial
Primary progressive aphasia 517
Table
4.
Longitudinal neuropsychological data from Case
2 (LM)
Measure
MMSE
(30)
Raven's Colored
Matrices
(36)
Rcy
Figure Copy
(36)
Judgment
of
Line
Orientation
(30)
Object Matching Test
(40)
Digit Span
Forward
Backward
Logical Memory
WMS
Immediate
(24)
Fluency:
Letter (F,A,S)
Category (Living
x 4)
Naming:
Pictures from
Sem
Battery
(48)
From verbal description
(24)
Token Test
(36)
TROG
Total score
(80)
Word-picture matching tests
From PALPA
(40)
From
Sem
battery
(48)
Reading
Regular
(126)
Exception
(126)
Writing
(36)
Oct
91
25
24
34
29
38
3
2
4
9
15
27
11
16
55
39
47
118
87
28
Test score
at
time
of
measurement
Feb
92
23
-
36
27
39
4
2
4
7
16
27
11
19
64
40
47
110
88
25
Sept
92
22
22
36
-
36
3
2
2
7
17
15
3
-
53
39
47
98
58
18
July
93
20
19
35
25
35
2
2
1
10
10
9
-
-
41
31
44
80
50
14
MMSE = Mini-Mental State Test (Folsleinetal.,
1975),
WMS = Wcchslcr
Memory Scale-Revised (Wechsler, 1987), RMT = Recognition Memory
Test (Warrington, 1984). Sem Battery = Semantic Test Battery (Hodges et
al.,
1992b), TROG = Test for the Reception of Grammar (Bishop, 1989).
Figures in parenthesis indicate maximum scores.
tasks,
such as copying the Rey Complex Figure, was none-
theless still largely preserved, even when last assessed.
SEMANTIC DEMENTIA
The 5 patients with semantic dementia (2 men and 3 women;
mean age 60.8 ± 8.7 years, mean education 11.0 ± 2.9 years)
presented with rather homogeneous histories, and have al-
most identical findings on examination. We shall therefore
provide one illustrative case history, and summarize the oth-
ers in Table 5. One of the patients (JL) has previously been
reported elsewhere (Hodges et al., 1992a, 1995).
Illustrative Case History
AM, a 64-year-old retired chemical engineer, presented in
April 1994 with a 5- to
8-year
history of difficulty remem-
bering the names of people and things. This word finding
problem had progressed slowly but, by the time of his as-
sessment in Cambridge, AM's conversation had become very
disrupted by word finding pauses and recurrent cliches ("one
of those things"). These problems had prompted him to em-
bark on a series of mental exercises that consisted of look-
ing up, in an encyclopedia, the names of flowers, household
items and so forth, and rehearsing the lists daily. As far as
we were able to determine, these exercises had not en-
hanced his spontaneous word finding ability. His wife had
noted problems in his comprehension of words that had for-
merly been well within his vocabulary, for instance, the
names of flowers (he had previously been a keen gardener).
Despite these difficulties, his day-to-day and autobiograph-
ical memory remained relatively intact. He was still play-
ing golf with proficiency, and driving his car. His family
suggested that there had also been subtle changes in per-
sonality, amounting to an exaggeration of his premorbid ex-
trovert tendencies.
Table
5.
Summary
of
demographic
details,
presenting features
and
radiological
abnormalities
in
five patients with semantic dementia
Age/sex
Length
of
history
Presenting features
MR1
atrophy
SPECT hypoperfusion
AM
63/M
8yrs
WFD
Anomia
Comph
Bilat temp
L>R
Bilat temp
L>R
JL
60/M
2 yrs
WFD
Anomia
Comph
Bilat temp
R>L
Bilat Fr-temp
R> L
PS
58/F
2 yrs
WFD
Anomia
L
temp
Ltcmp
BM
48/M
6 yrs
WFD
Anomia
Face deficit
OCD
Bilat temp
R >L
Bilat Fr-tcmp
R>L
DC
73/F
lyr
WFD
Anomia
Ltemp
L
Temp-par
WFD = word finding difficulties. Comph = comprehension deficit, face deficit = deficit in recognizing faces,
OCD - obsessive-compulsive disorder. Bilat temp = bilateral temporal. Fr-tcmp - fronto-tcmporal. Temp-
par = tcmporo-parictal lobe.
518
J.R.
Hodges and K. Patterson
MltUCiM's 1 "mil !"vM!
n!l.:'-l
lM..'j!apliu ;il ilv-Kni-. \\a-> i.-Vn.'lu'iii Di.iwmg o! geometric
figures could not be faulted.
MRI revealed striking focal atrophy of the inferolateral
temporal lobes with relative sparing of the hippocampal com-
plex, more marked on the left, which was particularly evi-
dent on the coronal slices (Figure 2). A SPECT scan also
showed markedly reduced perfusion in the anterior and mid-
dle portions of the left temporal lobe, with less marked re-
duction in the right temporal pole.
COMPARISON OF NONFLUENT
PROGRESSIVE APHASIA AND
SEMANTIC DEMENTIA
To compare the performance of the 2 patients with nonflu-
ent progressive aphasia to that of the group of 5 patients
with semantic dementia across a range of tasks, we per-
formed a standardization conversion using a simple linear
scaling technique, based on the controls' mean score and
standard deviation (SD) [(control mean - subject mean)/
controls* SD]. In this way, scores were calculated using each
patient's test results and for the subgroups, at the time of
presentation, with reference to data obtained from 24 age-
and education-matched control participants selected from
the MRC Applied Psychology Unit's subject panel (18
women and 6 men, mean age 69.7 ±7.8 years, mean edu-
cation 10.7 ± 2.2 years). The calculations used were iden-
tical to those applied when deriving z scores, but in this
instance we have refrained from using this term, since the
controls' scores on many tasks were not normally distrib-
uted. All patients and controls were administered the fol-
lowing standard clinical neuropsychological tests: (1) digit
span (WMS-R, Wechsler, 1987), (2) the Rey Complex Fig-
ure Test (CFT, Rey, 1941), (3) Judgment of Line Orienta-
tion (Benton et al., 1983a), and (4) verbal fluency for the
letters F, A and S (FAS). In addition we used a number of
more experimental tasks described below.
Experimental Neuropsychological Tests
Semantic test battery of Hodges et al. (1992b)
This battery of
tests,
all employing one consistent set of stim-
ulus items, and designed to assess input to, and output from,
central representational knowledge about the same group of
items via different sensory modalities, has been described
in detail elsewhere (Hodges et al., 1992a, 1992b). It con-
tains 48 items, chosen from the corpus of line drawings by
Snodgrass and Vanderwart (1980), representing three cat-
egories of animals (land animals, sea creatures and birds),
and three categories of manufactured items (household items,
vehicles, and musical instruments) matched for category pro-
totypicality and word frequency. In
brief,
the six subtests
consist of:
1.
Category fluency for each of the six main categories, plus
two lower order categories (breeds of dog and types of
boat).
Fig. 2 Coronal MRI scan (TI weighted images) at the level of the anterior and midtemporal lohe from a patient with
semantic dementia (AM) showing striking and relatively selective atrophy of the temporal lobes
t
left • • right) that
involves particularly the inferolateral gyri. Note sparing of the hippocampus in right panel.
Primary
progressive aphasia
519
2.
Naming of all 48 line drawings, without cues.
3.
Naming in response to verbal description (e.g., "What
do we call the large African animal with a curved horn
on its head?").
4.
Semantic feature questions: For each of the 48 items, we
designed eight questions such that four questions ex-
plore knowledge of physical features (size, shape, color
etc.) and four tap knowledge of nonperceptual attributes
(habitat, diet, uses etc.). Half of the questions posed
should receive "yes" answers, and the other half "no"
answers (e.g., "Does a zebra have stripes?", "Does a ze-
bra eat meat?", etc.).
5.
Picture sorting at three levels: superordinate (living or
man made), category (land animal or bird or water crea-
ture,
household item or vehicle or musical instrument)
and subordinate (e.g., fierce or nonfierce animal, kitchen
ot nonkitchen item etc.).
6. Picture-word matching in response to a spoken word
using within-catcgory picture arrays. For example, for
the target word "zebra," all picture alternatives are land
animals. The original battery had arrays of six pictures,
but this has now been expanded to eight, each array con-
taining two additional within-category foils not other-
wise included in the test battery.
Test for the Reception of Grammar
In this test, the patient is asked to point to one of four pic-
tures in response to phrases or sentences of increasing syn-
tactic complexity, in which the vocabulary remains very
simple (e.g., "The boys pick the apples." "The boy is chased
by the dog." "The pencil is on the book that is yellow," etc.).
In total, there are 80 arrays, which are divided into 20 blocks,
each of which tests comprehension of a particular syntactic
structure (e.g., plurality, gender, locative prepositions, neg-
atives,
reversible active, reversible passive, postmodified
subject, relative and embedded sentences).
Nonverbal tasks
1.
The Pyramids and Palm Trees 7<?.?/-three-picture ver-
sion (Howard & Patterson, 1992) was chosen as a non-
verbal test of semantic knowledge. Subjects are required
to match conceptually related pictures. For instance, the
target picture of an Egyptian pyramid is presented above
two drawings depicting a palm tree and a fir tree, and the
individual is asked to judge which one goes with the pyr-
amid. Other examples arc spectacles with eye and ear,
and saddle with goat and horse. The test comprises a to-
tal of 52 triads.
2.
The Object Decision Test (Riddoch & Humphreys, 1987)
assesses the integrity of stored structural descriptions of
objects. In this task, test takers are required to judge
whether each of a series of pictures represents a real or
an unreal object; half of the 64 pictures arc line draw-
ings of real objects (e.g., a pair of scissors, a tiger),
whereas the other half are chimeric objects (e.g., the body
of a tiger with the head of a mouse, the blades of a pair
of scissors on the handle of a screwdriver).
3.
The Object Matching
Test
(Humphreys & Riddoch, 1984)
was selected as a test of perceptual ability that does not
entail access to semantic knowledge. The subject is pre-
sented with an array of three photographs consisting of a
target object photographed from a conventional angle,
presented above two response alternatives: the same tar-
get object photographed from a different (unusual) view,
and a photo of
a
different but visually similar object. The
subject is asked to indicate which of the lower two photo-
graphs is of the same object as that shown above. The 40
items in the test are divided into those in which the cor-
rect alternative represents a foreshortened view of the
object
(H
= 20), and those classified as a minimal fea-
ture view {n = 20).
RESULTS
As shown in Figure 3, both patient groups obtained normal
scores on the tests of visuoperceptual and spatial ability (JLO,
Complex Figure and Object Matching). By contrast, on the
Nonfiuent vs. Semantic Dementia Cases
JLO
Complex Figure test
Object matching
Object decision
Digits forwards
FAS
Category fluency
Picture naming
Name to description
Word-picture matching
Sort level I
Sort level III
SFQ
Pyramids
&.
Palm trees
Nonfiuent PA
Semantic dementia
0
« 8 12 16
standardised score (negative values)
Fig. 3 A comparison of the performance of the two patient groups
(nonfiuent progressive aphasics [/» = 2], and semantic dementia
[n = 51) across a range of neuropsychological tests showing the
groups' standardized scores [(control mean - subject mean)/
(controls' SD)] with reference to 24 age- and education-matched
controls. JLO = Judgment of Line Orientation Test, FAS = verbal
fluency for the letters F. A, and S combined, Son Level I and III
refer to the picture sorting test from the semantic memory test bat-
tery. SFQ = semantic features questions from the same battery,
TROG = Test for the Reception of Grammar.
520
J.R.
Hodges and K. Patterson
object decision test, the semantic dementia patients ob-
tained defective scores, while the nonfluent aphasic pa-
tients were unimpaired. Digit span was abnormal only in
the nonfluent
cases.
Performance on the verbal fluency task
presents further evidence of dissociation: Initial-letter-
based (FAS) fluency was more impaired in the nonfluent
cases,
whereas the semantic dementia group fared consid-
erably worse on the semantic-category-based fluency tests.
Naming was impaired in both patient groups regardless of
the modality of input (pictures or verbal descriptions), but
the semantic dementia cases were more severely anomic.
One of the most striking differences between the groups
was the preservation of single-word comprehension (word-
picture matching) in the nonfluent aphasics, which con-
trasts with the grossly impaired performance of the semantic
dementia group on this and other tests of semantic knowl-
edge,
including picture sorting at a subordinate level (Sort
Level III in Figure 3), and answering semantic feature ques-
tions.
The deficit in semantic memory in the latter group
extended to nonverbal knowledge, as witnessed by their poor
performance on the three-picture version of the Pyramids
and Palm Trees Test. On the syntactic comprehension task,
TROG, the nonfluent cases (as indicated above) were se-
verely impaired, while the semantic dementia patients
achieved an average score just outside the normal range.
DISCUSSION
The two patients with nonfluent progressive aphasia re-
ported here presented with a progressive and relatively pure
breakdown in the phonological and syntactic aspects of lan-
guage processing, contrasting sharply with the progressive
fluent aphasia observed in 5 cases of semantic dementia.
The discussion will focus firstly upon the neuropsycholog-
ical and radiological features that characterize and distin-
guish these two varieties of progressive aphasia, and secondly
on the possible relation of these disorders to dementia of
Alzheimer's type (DAT).
The most prominent clinical feature of nonfluent progres-
sive aphasia is the distortion of speech output, with dis-
turbed articulation and prosody, phonological errors, word
finding pauses, and agrammatic sentence
structure.
The strik-
ing dysfluency results in practical communication difficul-
ties that are obvious to the patient and
observers.
With disease
progression, speech becomes unintelligible. Comprehen-
sion, except for syntactically complex constructions, is rel-
atively spared in the early stages of the disease, but a
progressive decline in phonological processing gradually
compromises speech comprehension as well as production.
Eventually, patients are "locked in" by their failure to com-
municate, and become socially isolated, although able to
perform the activities of daily life. On formal testing, con-
frontational naming is impaired, but may be only mildly
affected in comparison to the obvious breakdown in con-
versational language ability. Naming errors include many
phonemic approximations, suggesting that the patient has
often accessed the appropriate "location" in phonological
space but is unable to retrieve or produce all of the correct
phonological segments in the correct order (see Patterson
et al., 1994, for further discussion). Repetition and short-
term auditory-verbal memory are also severely disrupted.
Semantic dementia presents, in many ways, the mirror
image of nonfluent progressive aphasia. The cognitive and
linguistic deficits in semantic dementia can be explained on
the basis of a profound and pervasive semantic deteriora-
tion, producing an aphasic syndrome in which lexical-
semantic aspects of speech comprehension and production
are compromised while phonology and syntax remain rela-
tively preserved (see Hodges et al., 1992a, 1992b; Hodges
et al., 1995). Patients present with a progressive loss of vo-
cabulary, both receptive and expressive, typically complain-
ing of difficulty in "remembering" the names of people,
places and things. Word finding difficulty is usually appar-
ent, but in some cases may fail to be detected in casual ob-
servation, because spoken language remains fluent, well
articulated, prosodic, and lacking in phonological or syn-
tactic abnormalities. Later, speech output becomes highly
stereotyped, with repetitive cliches and often semantic par-
aphasias. Confrontational naming is severely affected from
an early stage, but is highly frequency dependent (see War-
rington,
1975;
Patterson & Hodges, 1992; Parkin, 1993).
Unlike patients with nonfluent progressive aphasia, those
with semantic dementia are more anomic on formal testing
than would be predicted from informal assessment. Errors
may be predominantly omissions ("don't know"), while er-
rors of commission are typically semantic in type, consist-
ing of within-category errors (e.g., "violin" for accordion)
and superordinate terms ("animal" for fox). Patients with
semantic dementia never produce phonemic naming errors
of the sort observed in the nonfluent progressive aphasics.
Performance on tests of comprehension separates pa-
tients with these two forms of progressive aphasia. In non-
fluent progressive aphasia, relatively spared comprehension
of even low frequency nomjnal terms contrasts with the
marked impairment on tests of syntactic comprehension, such
as the TROG (Bishop, 1989). It is possible that the nonflu-
ent patients' impaired auditory-verbal short-term memory
contributed to their poor performance on these tasks, but
analysis of their errors showed no clear relationship be-
tween the length of test phrase on the TROG and success at
picture-pointing. Patients with semantic dementia exhibit the
opposite pattern: Matching of object names to pictures is
impaired early in the course of the disease, while compre-
hension of even complex syntactic structures—provided that
they contain only simple, high-frequency nouns and verbs—
remains relatively intact until later stages of the disease.
An early and consistent feature in both conditions is im-
pairment on word generation tasks, but with a relative dou-
ble dissociation between letter-based fluency (generating
words beginning with a given letter of the alphabet) and
semantic-category-based verbal fluency (generating names
of animals, musical instruments, etc.). In nonfluent progres-
sive aphasia, there is an exaggeration of the normal pattern,
Primary progressive aphasia 521
that is, relatively fewer correct responses in letter than in
category fluency. Patients with semantic dementia demon-
strate the reverse: considerably worse performance on cat-
egory fluency. Identical executive or supervisory processes
are involved in the initiation and monitoring of both tasks,
but effective performance on tests of category fluency also
depends on the integrity of semantic knowledge. Letter flu-
ency, by contrast, requires access to the phonological level
of word representation, but not the semantic system (see Ran-
dolph et al., 1993; Rosser & Hodges, 1994). It should be
stressed that this relative dissociation is apparent in the early
stages, and as the diseases progress, performance on both
forms of fluency task falls dramatically.
The fluent cases showed deficits not only on subtests of
the semantic memory battery, most of which rely heavily
on language abilities, but also on both a nonverbal test of
semantic knowledge—the three-picture version of the Pyr-
amids and Palm Trees Test—and on an object decision task
that assesses the integrity of stored structural descriptions.
The nonfluent cases, by contrast, were substantially im-
paired only on semantic tests requiring speech production.
The mild, but significant, impairment on the semantic fea-
tures questionnaire (in which subjects are asked to answer
questions such as "Does a rhinoceros eat meat... live in
Africa?", etc.) may be secondary to their auditory verbal
short-term memory and syntactic comprehension deficits.
On the Wechsler Adult Intelligence Scale (WAIS; Wech-
sler, 1981), both disorders cause impairment in verbal rel-
ative to performance
IQ.
Semantic dementia primarily affects
WAIS subtests that are dependent on word knowledge (In-
formation, Similarities and Vocabulary), and spares arith-
metic skills and Digit Span. In nonfluent aphasics, the
knowledge-dependent subtests are least affected, whereas
digit span is significantly reduced.
In both groups, formal assessment of verbal memory, es-
pecially for stories, presents considerable difficulty be-
cause of impairment in speech production or comprehension,
or both. Clinical evidence suggests that personal autobio-
graphical and practical day-to-day components of memory
are preserved in both patient groups, certainly in the early
stages of the disorder. In keeping with this observation, tem-
poral orientation is invariably preserved. Most of the pa-
tients showed some ability to learn new verbal material and,
in contrast to patients with DAT (Butters et al., 1988; Welsh
et al., 1991), the proportion retained after a delay was nor-
mal. Memory for nonverbal material is, on the whole, mod-
erately well preserved in both the fluent and nonfluent cases.
For example, recall of the Rey Complex Figure was within
normal limits in all patients. For reasons that are unclear,
both of our nonfluent cases performed poorly on the faces
component of Warrington's Recognition Memory Test. One
of the striking and consistent features of both disorders was
the preservation of complex visuospatial skills and percep-
tual abilities: In addition to good performance on Block De-
sign, all of the patients at presentation performed within normal
limits on Ravens Colored Progressive Matrices, tests of face
matching ability, JLO, and copy of the Rey Complex Figure.
The radiological findings in the two disorders appear dis-
tinct. The present semantic dementia cases, in common with
previous reports (Snowden et
al.,
1989; Hodges et
al.,
1992a),
showed focal temporal lobe atrophy on MRI involving the
left temporal lobe in 2 and bilateral structures in 3, the pole,
inferior and middle temporal gyri being most affected. Func-
tional brain imaging by SPECT also implicated the left tem-
poral region in all 5 patients. This localization to the left
temporal neocortex is in keeping with that found in patients
with selective impairment of semantic memory in the con-
text of nonprogressive brain damage (e.g., Warrington &
Shallice, 1984; Pietrini et al., 1988; Sartori & Job, 1988).
The two patients with nonfluent aphasia have, by contrast,
shown both less severe and less localized changes on MRI,
including widening of the left sylvian fissure, but no focal
lobar atrophy. In one case, functional imaging by SPECT
scan (at presentation, when her degree of aphasia was mild)
was normal; the other case showed extensive reduction in
the left parietal and temporal regions.
Regarding the relationship between progressive aphasia
and DAT, although the patterns of cognitive deficit in DAT
have been extensively investigated (Becker et al., 1988;
Sagar & Sullivan, 1988; Spinnler & Delia Sala, 1988; Mor-
ris etal., 1989; Hodges etal.,
1990,1991;
Welsh etal., 1992),
relatively few studies have provided histological confirma-
tion of the diagnosis (Neary et al., 1986; Morris et al., 1988;
Price et al.,1993). However, findings from studies both with
and without pathology suggest that the most salient feature
of DAT is a profound deficit of anterograde memory. For
instance, Price et al. (1993) state that "our observations, as
well as others, show that the typical clinical correlate of
AD,
probably seen in 95% to 99% of
cases,
is a progressive am-
nesic dementia" (p. 936). Language deficits are also com-
mon, and in the aforementioned study were found in 17 of
20 cases. The characteristic language impairment in DAT is
a breakdown in the semantic component of language, re-
sulting in anomia with predominantly semantic errors (Bay-
les&Tolmoeda,
1983;
Huff etal.,
1986;
Hodges etal., 1991),
reduced category fluency (Ober et al., 1986; Butters et al.,
1987;
Hodges et al., 1990), and other features of impaired
semantic knowledge even fairly early in the course of the
disease (Chertkow & Bub, 1990; Hodges et al., 1992b;
Hodges & Patterson, 1995). By contrast, basic phonologi-
cal and syntactic processing are typically spared in DAT (see
Hart, 1988; Kempler et al., 1990). It is worth noting, how-
ever, that a few cases of confirmed Alzheimer's disease have
presented atypically, with circumscribed deficits other than
anterograde amnesia, such as progressive right parietal lobe
dysfunction (Crystal et al., 1982), Balint's syndrome (Hof
et al., 1990), or even progressive aphasia (Pogacar & Wil-
liams,
1984; Green etal., 1990; Kempler etal., 1990; Green
et al., in press).
Given that DAT can, albeit very rarely, present as pro-
gressive aphasia, it is not possible to exclude absolutely the
possibility that the fluent and nonfluent aphasic patients re-
ported here will turn out to have Alzheimer's disease. Our
reasons for considering this unlikely include the following.
522
J.R.
Hodges
and K.
Patterson
First, the majority of patients with progressive aphasia reach-
ing autopsy have been shown to have non-Alzheimer pathol-
ogy, cither Pick's disease or nonspecific changes (Mesulam
& Weintraub, 1992; Snowden et al., 1992; Scheltens ct al.,
1994).
Second, to our knowledge, there have still been no re-
ported cases with features of semantic dementia who have been
shown to have pathologically verified
DAT.
One of ourcases
of semantic dementia (JL) has subsequently died; patholog-
ical examination showed severe neural loss with spongiform
change and gliosis, with occasional intraneuronal inclusions
characteristic of Pick's disease (for
details,
see Hodges et al.,
1995).
A similar patient reported by Graff-Radford et al.
(1990) also showed Pick's pathology, and 2 of Warrington's
(1975) original patients with semantic dementia were later
shown to have Pick's disease on autopsy (personal commu-
nication, 1992), Finally, each of the 4 patients with proven
Alzheimer's disease presenting with progressive aphasia had
more extensive neuropsychological deficits when formally
tested, even if theirhistories suggested a long prodrome of
rel-
atively pure aphasia (Pogacar & Williams, 1984; Green
et al., 1990; Kempleretal., 1990; Green etal., in press).
In conclusion, we have presented more detailed data than
available elsewhere on the neuropsychological profile of 2
patients with nonfluent progressive aphasia. Although we
agree with Tyrcll et al. (1990) that the syndrome of progres-
sive aphasia is heterogeneous, our study suggests that there
are at least two clearly identifiable subtypes within this gen-
eral rubric, each with distinctive clinical, radiological, and
perhaps neuropathological features. There are also several
reports of patients who display features of both fluent and
nonfluent aphasia (Snowden et al., 1992). Further detailed
study of patients with progressive language disorders will
undoubtedly define other syndromes of clinical and theo-
retical importance.
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