Harold Wilson, Lord Mountbatten, Ronald Reagan). Patient P. P. has been the subject of an intensive longitudinal study (1. R. Hodges and K. E. Patterson ...
Brain
(1992), 115, 1783- 1806
SEMANTIC DEMENTIA PROGRESSIVE FLUENT APHASIA WITH TEMPORAL LOBE A TROPHY by
JOHN R. HODGES
KARAL YN PATTERSON~ 2 SUSAN OXBURy
and
ELAINE FUNNELL University of Cambridge Clinical School , Addenbrooke s Hospital, and the 2 MRC Applied Psychology Unit , Cambridge, the 3Department of Neuropsychology, Radcliffe Infirmary, Oxford and the 4Department of Psychology, Royal Holloway College , University of London , London, UK)
(From the
SUMMARY We report five patients with a stereotyped clinical syndrome characterized by fluent dysphasia with severe anomia , reduced vocabulary and prominent impairment of single-word comprehension , progressing to a stage of virtually complete dissolution of the semantic components of language. A marked reduction in the ability to generate exemplars from restricted semantic categories (e. g. animals , vehicles , etc. ) was a consistent and early feature. Tests of semantic memory demonstrated a radically impoverished knowledge about a range of living and man-made items. In contrast , phonology and grammar of spoken language were largely preserved , as was comprehension of complex syntactic commands. Reading showed a pattern of surface dyslexia. Autobiographical and day- to- day (episodic) memory were relatively retained. Non-
verbal memory, perceptual and visuospatial abilities were also strikingly preserved. In some cases, behavioural and personality changes may supervene; one patient developed features of the Kluver-Bucy Syndrome. Radiological investigations have shown marked focal temporal atrophy in all five patients , and functional imaging by single positron emission tomography and positron emission tomography (one case) have implicated the dominant temporal lobe in all five. In the older literature , such cases would have been subsumed under the rubric of Pick' s disease. Others have been included in series with progressive aphasia. et at. (1989), to designate this clinical We propose the term semantic dementia , first coined by Snowden syndrome.
INTRODUCTION
Selective impairment of semantic memory was first clearly delineated by Warrington (1975), who described three patients with cerebral atrophy presenting with progressive anomia and impaired word comprehension. Detailed neuropsychological testing revealed a loss of receptive and expressive vocabulary, and impoverished knowledge of a wide range of living things and inanimate objects affecting particularly specific subordinate attributional knowledge. Other aspects of spoken language (e. g. phonology and syntax) and perceptual skills were relatively intact. Such a deficit would previously have been assimilated under the rubric of associative agnosia. Warrington , drawing a distinction made by Tulving (1972 , 1983), identified the deficit as one of semantic memory. The term semantic memory is applied to the component of long- term memory containing knowledge of objects , facts and concepts as well as words and their meaning (Tulving, 1972 , 1983). In short , semantic memory gives meaning to our sensory experience. In contrast to episodic or event memory, semantic memory is culturally Correspondence to: Dr J. R. Hodges , Department of Neurology, Addenbrooke s Hospital , Hills Road , Cambridge CB2 2QQ, UK, (9
Oxford University Press
1992
1784
1. R. HODGES AND OTHERS
shared , not temporally specific and to a large extent acquired early in life. There is evidence to suggest that semantic memory is stored in a highly structured and hierarchical
fashion. Tasks dependent on semantic memory include object naming, generation of definitions for spoken words , word- picture and picture- picture matching and the generation of exemplars on category fluency tests (e. g. animals , vegetables , etc. ). Patients with dementia of Alzheimer type (DA T) are characteristically impaired on these tests; most authors interpreted these impairments as a breakdown in the structure of semantic memory as the disease progresses (Bayles and Tomoeda , 1983; Martin and Fedio , 1983; et ai. 1990 , 1991 , 1992), but others support the concept Huff et ai. 1986; Hodges of a primary disturbance in access to information rather than a loss of knowledge
per
Nebes , 1989). Although semantic memory impairment occurs in DAT , there is virtually always accompanying severe impairment of episodic memory, and eventually disruption of many other cognitive domains , including visuospatial and frontal execution function. Since the seminal report of Warrington (1975), a number of other patients with selective semantic memory impairment have been reported. The majority have occurred in the context of extensive neocortical damage , for instance following herpes simplex virus et ai. 1987; Pietrini et al. encephalitis (e. g. Warrington and Shallice , 1984; De Renzi 1988; Sartori and Job , 1988), but some of these patients have had additional complicating cognitive deficits. se (see
Other examples of semantic memory impairment have been subsumed within the category of primary progressive aphasia. The latter term was originally introduced by Mesulam (1982) to describe a syndrome , clearly distinct from semantic memory loss, characterized by non-fluent language output with phonemic paraphasic errors progressing in many instances to complete mutism , but sparing comprehension. As is often the case following the description of an apparently new syndrome the term progressive aphasia has been widened to embrace any progressive disorder of language. Hence , patients very different to the original cases of non- fluent aphasia have been reported under the title of progressive aphasia (e. g. Basso et ai. 1988; Poeck and Luzzatti , 1988; Tyrrell et al. 1990). The pattern of deficits in these latter cases has been one of undoubted semantic memory loss causing deficits both in word production and comprehension but with relative sparing of other components oflanguage (i. e. syntax and phonology). Poeck and Luzzatti (1988) drew attention to the fact that Pick (1892 , 1904) and Rosenfeld
(1909) deserve credit for publishing the first descriptions
of slowly progressive
circumscribed neuropsychological symptoms due to focal brain atrophy, including clear-cut cases of progressive aphasia , with all the hallmarks of primary semantic memory impairment. The pathological basis of progressive aphasia is still debated. In the patients
with the Mesulam non- fluent variety, the disorder appears to remain confined to the dominant hemisphere and a number of autopsies have demonstrated non- Alzheimer et al. 1987). In patients with progressive et ai. 1987; Mehler pathology (Kirshner semantic memory impairment , modern neuropathological data are limited , although two very similar cases have shown the changes of Pick' s disease (Cummings and Duchen et ai. 1990; also patient A. B. from Warrington , 1975). 1981; Graff- Radford The introduction of the term semantic dementia (Snowden
to add further to the nosological confusion. It does ,
et al. 1989) may be thought however , have the advantage of
brevity, avoids pathological assumptions and implies a cognitive deficit affecting
--
~"-- ~.~~~---
0. ._._~-
SEMANTIC DEMENTIA
1785
fundamental aspects of language , memory and object recognition. In this paper we describe five cases with semantic dementia which , we suggest , is a clinically recognizable syndrome with the following characteristics: (i) selective impairment of semantic memory causing severe anomia , impaired spoken and written single-word comprehension reduced generation of exemplars on category fluency tests and an impoverished fund
of general knowledge; (ii) relative sparing of other components of language output and comprehension , notably syntax and phonology; (iii) normal perceptual skills and nonverbal problem-solving abilities; (iv) relatively preserved autobiographical and day- today (episodic) memory; (v) a reading disorder with the pattern of surface dyslexia.
addition , we report the results of a test battery specifically designed to assess input to and output from , semantic memory which is useful in the evaluation of such cases. CASE REPORTS In none of the five cases was there a family history of dementia , a background of alcoholism or other aetiologically relevant factors. Physical signs (including frontal release phenomena) were absent and detailed investigations for causes of dementia were negative. The major clinical features are summarized in Table I.
TABLE I. SUMMARY OF MAJOR CLINICAL FEATURES. LANGUAGE AND OTHER COGNITIVE DEFICITS IN FIVE PATIENTS WITH SEMANTIC DEMENTIA J.L. Age/sex Length of history
68/F
54/F
2 yrs
I yr
Presenting feature
WFD , comph . alexia
WFD
42/F 3 yrs
WFD, comph
60/M
62/F
I yr WFD+anomia
WFD+anomia
I yr
Language (clinical assessment) Naming Spontaneous output
Phonology Articulation Word finding Paraphasias (semantic)
Paraphasias (phonemic)
Syntax
Comprehension Syntactic Semantic
Repetition (words and sentences) Reading: surface dyslexia
+(a)
Writing: surface dysgraphia
Orientation Episodic memory (informal clinical assessment) Visuospatial skills
Personality change CT scan atrophy MRI atrophy SPECT or PET- hypoperfusion N = normal ,
Bilat T lobe L perisylvian LF-
Late
Early
Bilat T Lobe L ;0. R
LT Lobe
LT lobe LF-
Bilat T Lobe R ;0. L Bilat T Lobe
LT Lobe
LF-
0 = absent; + = deficit present; NP = not performed; "= = deficit occasionally present; WFD = word finding difficulty; comph = comprehension deficit; (a) = also letter-by- letter reader; LT = left temporal; LF- T = left fronto- temporal; Bilat T Lobe = bilateral temporal lobe.
,'
1786
,'
g. '
J. R. HODGES AND OTHERS
Case 1
, a 68-yr-old , right- handed ex- clerical officer and secretary presented in 1990 with a 2 yr history of progressive loss of memory for names of people , places and things , together with impaired comprehension
of nominal terms. She has also complained from the onset of problems recognizing even very familiar people from sight , voice or description. Her fund of general knowledge was radically impoverished. When asked Have you ever been to America?' , she replied ' what's America?' , or asked What s your favourite food?' , she replied ' food , food , I wish I knew what that was ' - Despite this profound deficit in semantic memory her day- to- day memory remained fairly good. She could remember appointments and keep track of family events. Sadly, she retained insight into her deficit and at times became severely depressed. There
had been no deterioration in self-care. Spontaneous speech was well articulated with normal prosody. She was able to produce fluent and grammatically correct sentences, but conversation was punctuated by severe word- finding difficulty and frequent semantic paraphasias. Phonemic errors were never observed. The degree of anomia is such that she has never correctly named a single item , either on informal testing or on a number of formal naming tests (see below). Comprehension of simple questions about personal events was maintained (e. how are you today?'; ' is your mother well?' ), but there was a profound deficit in understanding of all but very common nominal terms (Le. mother , today, home , etc. ), to such an extent that she was unable to point to very common objects. Repetition of single words and even of grammatically complex sentences was normal. Reading was severely disrupted with letter- by- Ietter alexia , but she could identify, from oral spelling, words with regular spelling- to-sound correspondence. Similarly, she managed to write to dictation some regular words. She was able to do simple mental arithmetic. In contrast to her profound language impairment her visuospatial abilities were remarkably well preserved; copies of complex geometric shapes were executed flawlessly (see Fig. 1). Computerized tomography (CT) and magnetic resonance imaging (MRI) scans revealed a moderate degree of cerebral atrophy, more marked in the left hemisphere , particularly around the sylvian fissure. A positron emission tomography (PET) study, performed at the Hammersmith Hospital , revealed hypometabolism
in the left inferior frontal and temporo-parietal areas. On follow-up over the subsequent 12 mths there has been only moderate change in her general abilities. She is still self-caring and is able to do very simple housework but when shopping she no longer knows which items to choose , and similarly her cooking ability deteriorated because of a lack of understanding of the fundamental processes and utensils involved. She enjoys seeing family members and her visits to Cambridge. Language has deteriorated further. Her spontaneous speech now contains virtually no nouns
FIG. 1. Copy of the Rey- Osterrieth figure by patient P. P. at presentation (August 1990) which contrasts with her profound anomia and comprehension deficit.
SEMANTIC DEMENTIA
1787
, and she tends to produce grammatically correct and few verbs other than general ones like ' come ' and ' and fluent stereotyped phrases such as ' Oh dear , I wish I could think what I wanted to say . Insight into
her predicament is maintained. Eating habits , table manners , grooming and toileting are all normal and she has not exhibited any unusual or anti-social behaviour.
Case
, a left- handed, 54- yr-old care assistant in an old people s home presented in April 1991 with a 12 mth history of ' memory problems , specifically affecting her ability to recall the names of people and
things. This first became apparent when she realized that she could not tell the residents of the home what foods were available on the meal trolley. She also experienced great difficulty in naming family members friends and famous personalities. Despite this problem , her day-to-day and personal autobiographical memory were unaffected. She gave an accurate history of her past life , work , recent family events and visits to the hospital. Family members confirmed that there has been no change in personality, behaviour comportment or practical skills. She continued running the house without difficulty. Spontaneous speech was fluent with normal syntax and phonology. Word-finding difficulty was apparent in conversation but no paraphasic errors were noted. Comprehension of three-stage commands was normal. Repetition of words and sentences was unimpaired. Naming was severely disrupted , however , with circumlocutions and semantic paraphasias. Reading of passages and regular words was normal , but she gave regularized pronunciations of some irregular words. Copying of complex geometric shapes and representational figures was normal. Memory for simple verbal material (e. g. recall of a name and address) was normal , even after a delay. Whilst on the ward she showed no evidence of spatial disorientation.
A CT brain scan revealed no abnormalities , but a 99m Tc-HM-PAO single positron emission tomography
(SPECT) scan showed reduction in perfusion to the left temporal regions. An MRI scan with temporal lobe orientated horizontal and coronal cuts showed striking focal atrophy of the left temporal neocortex with preservation of the hippocampus (Fig. 2). Case
, a 42- yr-old ex- biology teacher presented with a 2- 3 yr history of word- finding difficulty and impaired comprehension. She first noticed problems helping her children with their homework. Later her family observed that comprehension , especially of proper nouns and names , was poor , and that her speech contained semantic errors. Her spelling was also poor. Despite these problems , her everyday memory was good , she was able to remember appointments and organize her family s complex schedules. No change in personality or social behaviour had been noted. Insight was well maintained. Spontaneous speech was fluent and well articulated with normal prosody, but with occasional spontaneous semantic paraphasias. Naming was severely impaired. Comprehension of syntax was normal as judged by her ability to obey complex three-stage commands. Repetition of words and sentences was likewise unimpaired. She had difficulty reading words with irregular spelling-to-sound correspondence , making phonologically plausible errors. Written and oral spelling were below her expected pre-morbid level. She was fully orientated in time and place , and performed serial seven subtractions and mental arithmetic quickly and accurately. Copying of simple geometric and representational shapes (interlocking pentagons and a house) were extremely good.
A CT brain scan was within normal limits and a SPECT scan using 500 M Bq Tc- 99m Exametazime showed no abnormality. On follow-up over the subsequent 12 mths , there has been a marked deterioration in all cognitive
abilities dependent upon semantic memory. Spontaneous speech is still fluent
and
grammatically correct but lacking in content and punctuated by frequent circumlocutions. Comprehension has further deteriorated and she is unable to name even very common everyday items. She tends to use stereotyped phrases such as ' I wish I knew what you meant . Writing skills are maintained but the content parallels spoken language. Reading of sentences is retained , but regularization errors on irregular words are common. Despite the precipitous decline in semantic memory, her day- to- day memory remains fairly good; she recalls family events and keeps track of appointments. Visuospatial skills are maintained.
In addition to the rapid decline in aspects of cognition , there has also been a change in personality and behaviour. She has become very irritable and irascible , and at times verbally aggressive to members of her family. She has become obsessively tidy, vacuuming the house several times a day and brushing the
1788
J. R. HODGES AND OTHERS
carpet until the pile is aligned. Features of the Kluver- Bucy syndrome have also appeared including sexual disinhibition and indiscriminate eating of discarded food , scraps and even occasionally non- food items such as cigarette ends. No physical signs have developed. A CT scan with temporal lobe orientated horizontal cuts now shows obvious bilateral temporal pole atrophy more marked on the left (Fig. 3). A repeat SPECT scan also revealed left fronto-temporal hypoperfusion.
(above) FIG. 2. T -weighted MRI scan images in patient F. : two coronal (below) and two horizontal slices orientated through the temporal lobes demonstrating marked focal left temporal neocortical atrophy with relative sparing of the hippocampal formation.
SEMANTIC DEMENTIA
1789
Case
J.L. , a 60-yr-old company director , presented in April 1991 with difficulty remembering the names of people and places. More recently, his vocabulary had diminished causing word- finding difficulty. The
family had noted problems understanding the meaning of words which had previously been well within
,I'
FIG. 3. Computerized tomography scan images in patient M. : two sequential horizontal cuts orientated through the temporal lobes at the level of the midbrain showing focal left neocortical atrophy.
1790
J. R. HODGES AND OTHERS
his vocabulary, for instance the names of foods. He was no longer familiar with the names of the local villages in the region where he had lived all his life. The deficit also affected his ability to recognize people by face , name or description. He had also exhibited problems identifying real objects and animals , for instance he had been frightened by finding a snail in the backyard and thought that a goat was a strange creature. Despite these difficulties ,
his day- to- day
and autobiographical memory remained relatively
very good.
His family suggested that there had also been subtle changes in personality, behaviour and judgement. Having previously been very financially shrewd and adept , he had made a number of recent disastrous deals as a result of which his sons have taken over the company. Also , he had become uncharacteristically generous , giving money to charities and offering his holiday home to relative strangers. Spontaneous speech was fluent with normal articulation and grammar. Occasional word- finding difficulties
were apparent , but no paraphasic errors were noted. Confrontational naming was moderately impaired. Comprehension of conversation and of syntactically complex three-part commands was normal. In contrast understanding of nominal terms was impaired. Repetition of words and sentences was normal. Reading of prose passages was unimpaired , but he made regularization errors to low frequency irregular words. Writing was poorer than expected with numerous spelling errors , especially for irregular words. He was fully orientated in time and place. Recall of simple verbal material was good. Drawing of geometric and representational figures could not be faulted.
A CT scan suggested atrophy of the anterior pole of the temporal lobes. This was confirmed on MRI which showed striking focal atrophy of the temporal region , more marked on the right , which was particularly evident on the coronal slices (see Fig. 4). A 99m Tc-HM- PAO SPECT scan also showed bilateral
hypoperfusion confined to the temporal lobes. Case
, a 62-yr-old , ex-middle school maths teacher , presented in November 1989 with a 12 mth history of word- finding difficulty. She complained of particular problems naming people and things including categories offood , animals and inanimate objects. Her family had noted impaired comprehension of nominal terms and that she tended to use general labels. For instance , the word ' container ' was used for cups, glasses , bottles , etc. , and ' machine ' implied anything mechanical. In addition , her writing abilities had deteriorated due to very poor spelling. She was a keen folk dancer and had no difficulty with the complex routines , but was unable to remember the names of the individual dances. Her autobiographical and everyday
memory remained good; she remembered appointments , and could give a good account of her past life and of recent family events. She remained able to drive and perform housework. She is an accomplished dressmaker and can carry out the instructions in complicated knitting and sewing patterns. There had been no change in personality or social behaviour. Her retained insight into the difficulties produced understandable anxiety . Spontaneous speech was fluent with normal syntax , phonology and prosody, but was punctuated by frequent problems with word finding. Confrontational naming of even common items (e. g. watch , pen , keys , etc. revealed considerable difficulty. Although she had no problem following syntactically complex three-stage commands , pointing to items in arrays was impaired. Word and sentence repetition presented no difficulty.
Tests of attention and orientation and recall of simple verbal material (e. g. name and address) were also normal. She was able to copy three- dimensional drawings without error. Apraxic errors were not observed nor were features of tactile or visual neglect. A CT scan demonstrated focal atrophy of the left temporal lobe. A SPECT scan using 500 MB 2 Tc- 99m Exametazime revealed hypometabolism of the left fronto-
temporal region. On follow-up over 18 mths , no deterioration in performance has been observed in any test of psychological function , including those investigating semantic memory, naming, reading and writing, short- term memory and attention.
NEUROPSYCHOLOGICAL TEST DATA
The results of standard clinical neuropsychological tests are shown in Table 2. all five cases , there was a discrepancy between Verbal and Performance IQ in favour of the latter. Although the severity of verbal intellectual impairment varied from mild
SEMANTIC DEMENTIA
1791
(E. ) t.o profound (P. ), the pattern of Wechsler Adult Intelligence Scale (WAIS) sub- test scores (Wechsler , 1955) was consistent across patients. In all instances impairments were most marked on Vocabulary, Information and Similarities. Digit span was strikingly preserved in all five. Arithmetic was normal in the more mildly impaired
cases and only became marginally reduced in the most deteriorated patient (P. ). Of the Performance sub- tests , Block Design and Digit Symbol were relatively well preserved in all. Picture Completion was impaired in three of the more impaired patients probably
FiG. 4. T -weighted MRI scan images in patient J. L.: two coronal (below) and two horizontal slices (above) orientated through the temporal lobes demonstrating bilateral temporal neocortical atrophy which in this case is more marked on the right side.
1. R. HODGES AND OTHERS
1792
TABLE 2. BASIC NEUROPSYCHOLOGICAL DATA IN THE FIVE PATIENTS
Me.
J.L.
E.P.
W AIS subtest scores (age scaled)
Information Digit span
Vocabulary Arithmetic Similarities Picture Completion Block Design
Digit Symbol Verbal IQ Performance IQ
116
101
Rey Figure Copy (36)
45 min delay recall
19.
12.
Raven s Coloured Matrices (36) Face Recognition Test (54)
Judgement of Line Orientation (30)
Digit span forward Digit span backward Logical Memory WMS Immediate (21) 30 min delayed
PALT WMS Immediate (21) 30 min delayed
BVRT
Normal
Normal
Normal
Normal
WRMT Faces (50)
NT = not tested; WMS = Weschler Memory Scale; PALT = Paired Associate Learning Test; BVRT = Benton Visual Recognition Test; WRMT = Warrington Recognition Memory Test. Figures in brackets indicate maximum possible scores.
due to failure to comprehend the stimuli , as evidenced by performance on the object decision test
(see below).
Further evidence of preserved constructional ability is provided by the normal copies of the complex Rey- Osterrieth figure (Osterrieth , 1944). Perceptual skills were also normal. All five patients performed within the normal range on the Face Recognition Test (Benton et al. 1983), which requires subjects to match photographs of the same person taken with different lighting conditions and from different angles. Performance on the Benton Test of Line Orientation Judgement (Benton et al. 1983) was also within the normal range. The dissociation . of vi suo- perceptual ability and semantic memory
was strikingly illustrated in P.
; she performed within the normal range
on the
Humphreys and Riddoch (1987) object matching test in which one photograph , showing a prototypical view of a common object (e. g. comb , knife , hammer , etc. ), is presented
along with an atypical view of the target object (e. g. from above or one end) and a different but visually similar item; but she could not name or identify any of the objects. All three patients over 60 yrs performed within the normal range on Raven s Colour
SEMANTIC DEMENTIA
1793
Matrices (Raven , 1962) and the performance of the younger patients was also considered
normal by extrapolation from the normal data for elderly subjects. Assessment of verbal memory was confounded by the language disorder. All but the most deteriorated patient (P. ) demonstrated some recall of the prose passage from the Wechsler Memory Scale (Wechsler , 1945), but all scores were below average and significantly below the expected level based on presumed pre-morbid ability. The same was true of learning of verbal pairs tested with the Paired Associate Learning Test (PAL T). Delayed recall of the passages ranged from normal in M. C. (85 % of immediate
recall) to varying degrees of impairment (44% in F. ). Given preserved perceptual and visuospatial abilities , non-verbal memory could be more reliably assessed. This was within normal limits for age on all tests used for E. , M. c. and F. , but memory for new faces (Recognition Memory Test; Warrington , 1984) was impaired in P.
and J. To assess remote memory for personal episodic and semantic information , we gave the Autobiographical Memory Interview to two patients (F. M. and J. L.) (Kopelman et ai. 1989). This test requires subjects to produce standard factual information from three life epochs (childhood , young adult and recent), such as names of school friends teachers , colleagues; details of schools attended , first job , wedding, etc. , and to relate personally experienced episodes from the same periods which are then scored in a standard
fashion for detail. F. M. and J. L. scored above the cut-off levels for impairment
on
each epoch for autobiographical episodes. Conversely, both were impaired on the personal semantic information scores from each era tested (see Table 3).
Language testing (Table 4) showed a highly consistent pattern across the patients although the degree of impairment varied according to the stage of the disease. Picture description using the ' cookie theft scene ' from the Boston Diagnostic Aphasia Examination (Goodglass and Kaplan , 1983) produced fluent , normally articulated and grammatically
correct but factually empty discourse , punctuated by frequent word- finding difficulty and , in the more severely impaired patients , semantic paraphasias. Performance on naming ranged from moderately to profoundly impaired. Apart from omissions , naming errors were semantic in type , being either within-category (e. g. hippopotamus for rhinoceros; violin for accordion), superordinate (e. g. animal , musical instrument) or circumlocations. Phonemic and visually based errors were not observed. In all cases there was a marked frequency effect , such that any correctly named items came from the high frequency end of the range. On comprehension tests , there was a marked discrepancy between those dependent upon semantic and on syntactic comprehension. On the shortened Token Test (De Renzi and Faglioni , 1978), four of the patients performed nearly perfectly. In the case of P. , her reduced vocabulary limited understanding of the colour names , but on a modified version using only black and white shapes , she was able to follow all of the appropriate commands. Simil~rly, on the Test for the Reception of Grammar (TRaG) (Bishop, 1989) on which subjects point to one syntactic complexity while vocabulary remains very simple (e. g. the boys pick the apples; the dog the boy is chasing is brown , etc. ), the only significant impairment was in P. , who made a large number of lexically based errors (e. g. boy- girl , cat- dog) as well as some grammatical errors. The other patients ' performances were virtually faultless. In contrast , lexico-semantic comprehension was impaired in all cases. This will be discussed further in the context of four pictures in response to statements of increasing
J. R. HODGES AND OTHERS
1794
TABLE 3. PERFORMANCE OF PATIENTS J. L. AND F. M. ON THE AUTOBIOGRAPHICAL MEMORY INTERVIEW SHOWING THE CUT- OFF FOR IMPAIRMENT IN EACH EPOCH Personal semantic
F.M.
Epoch Childhood Young adult Recent
J.L.
Cut-off
Autobiographical episodes
Max.
F.M.
J.L.
Cut-off
.::: 12
12.
29.
Overall score
.::: 15 .::: 18
.:::4 .:::4 .:::6
.:::48
.::: 13
The test method of Kopelman
et al.
Max.
(1989) was used.
TABLE 4. RESULTS OF THE PRINCIPAL LANGUAGE TESTS IN THE FIVE PATIENTS M.e.
J.L.
E.P.
Normal
Normal
Normal
Naming: number correct Oldfield- Wingfield (36) CNT (48) BNT (60) Token Test (36)
TROG (errors out of total 80) Repetition *
Normal*** 22** Normal
Normal
Fluency Letter (F ,
A,
S)
Category (animals)
NT = Not tested; CNT = Category Naming Test (Hodges et al. 1992); BNT = Boston Naming Test; TROG = Test for the Reception of Grammar (Bishop, 1989). *Single word and sentences from BDAE (Goodglass and Kaplan 1983); ** errors predominantly lexical (i. e. girl/boy, dog/cat) rather than syntactic; *** modified because of reduced vocabulary. Figures in brackets indicate maximum scores.
of the semantic test battery below. Repetition of single words and of phrases from the Boston Diagnostic Aphasia Examination (Goodglass and Kaplan , 1983) was normal in all cases. Verbal fluency tests (see Table 4) showed a disproportionate impairment of category, rather than letter- based fluency. In the less impaired patients (E. , P. , J. , M. c.), letter fluency was reduced to approximately 50% of normal performance , but generation of exemplars from semantic categories (e. g. animals) was reduced to less than 20% of normal Hodges (see et al. 1990). P. P. was unable to generate any category exemplars from a wide range of semantic categories , but still produced a few items on letter fluency testing. On tests of oral reading, all five patients showed a pattern of surface dyslexia , i.e. a superiority for regular words and non-words over exception words and a strong tendency to produce phonologically plausible (regularization) errors on the exception words (e. PINT pronounced to rhyme with ' mint'). This has been investigated in detail in several of the patients and will be the subject of a further report (Patterson and Hodges , 1992). In addition , P. P. had features of pure alexia with letter- by- letter reading. The surface dyslexia caused difficulty reading the words of the New Adult Reading Test (NART) (Nelson , 1982) which if not spotted by the examiner would lead to fallaciously low
g. '
SEMANTIC DEMENTIA
1795
estimates of pre morbid IQ. Writing ability paralleled reading; execution of writing was well preserved without dyspraxia , and grammar was retained but the spelling of exception words was often incorrect , though almost always phonologically plausible. Semantic memory test battery
This battery of tests , all employing one consistent set of stimulus 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 at. 1992). It contains 48 items chosen to represent three categories of animals (land animals , sea creatures and birds) and three categories of man-made items (household items , vehicles and musical instruments) matched for category prototypically. They were chosen from the corpus of line- drawings by Snodgrass and Vanderwart (1980). In brief , the five sub- tests consist of: (i) category fluency for each of the six main categories plus two lower order categories (breeds of dog and types of boat); (ii) naming of all 48 line- drawings; (iii) picture sorting at superordinate , category and subordinate levels; (iv) picture pointing to spoken word using within-category arrays; (v) generation
of verbal definitions in response to the spoken name of the item. The results are shown in Table 5. Category fluency was severely reduced in all five patients in each of the semantic categories tested. In keeping with the concept of progressive disintegration of semantic knowledge (i.e. preservation of superordinate with loss of more specific knowledge), none of the patients produced any items from the lowest order categories comprising breeds of dog and types of boat. By comparison
normal subjects produce an average of more than 10 items from each of the latter categories. Naming was impaired to a very severe degree in all five patients. This is a relatively easy naming test as evidenced by the near ceiling performance of the normal controls. There was no clear category-specificity, in that all patients were severely impaired at naming line- drawings of both living and man-made items. The results of the picture sorting test showed a very interesting pattern. All the patients even the most impaired , were perfectly capable of sorting the 48 cards at the highest order (living versus man-made), demonstrating preservation ofthis broad concept , and
additionally establishing that they could follow the instructions involved in the test. At the category level , subjects are required to sort the man-made items into one of three categories (household item versus musical instrument versus vehicle) and the living items
into one of three categories (land animal versus sea creature versus bird). Four of the five showed no impairment , their scores falling within two standard deviations of normal.
The most profoundly affected patient , P. , did show significant impairment at this level , although her performance was still above chance (0. 72 versus a chance level of 33). The lowest order of sorting requires subjects to sort the animals according to subordinate or attributional judgements (British versus foreign animal; fierce versus non- fierce animal , etc. ) and the household items according to similar attributes (kitchen versus non- kitchen item; electrical versus non-electrical item , etc. ). At this third level scores for all five patients were more than three standard deviations below the normal controls. The test was modified for P.
, who had difficulty comprehending the concepts
involved; she was asked to choose from arrays of five pictures , three demonstrating the desired attribute (e. which of these five are foreign animals?' etc.
g. '
,'
,'
1. R. HODGES AND OTHERS
1796
TABLE 5. PERFORMANCE ON THE SEMANTIC TEST BATTERY Normal controls (n
FM.
Me.
J.L.
= 26)
Mean
(1) Category fluency
47.
Animals (three categories)a Dogs Man-made items (three categories) Boats
10.
49. 11.6
(2) Naming
46.4
Total (48)
1.I
23. 23.
Living (24) Man-made (24) (3) Picture sorting
Level I: living versus man-made (48) Level II: category (48) Level III: subordinate (72)
27*
48. 45. 69.4
1.2
(4) Picture pointing to spoken word 47. 23. 24.
Total (48)
Animals (24) Man-made (24)
0.4 0.4
(5) Definitions (n = 12)
Adequate Inadequate Containing major errors
12.
*Test modified to multiple choice format , see text; atotal for three categories (animals , sea creatures and birds); b total for three categories (household items , musical instruments and vehicles); c number of items for which adequate (i. detailed and factually correct) definitions were provided; d number containing substantial factual errors. The test was from Hodges
et al.
(1992).
Picture pointing in response to spoken word confirmed that semantic comprehension was impaired in all patients. For normal subjects this is extremely easy (mean score 47. 9, SD = 0.4 , out of a maximum of 48), hence the scores in the patients , with the exception of F .
, reflect a profound deficit in this test which requires words and pictures In the definitions test all patients
to be processed and matched via the semantic system.
and controls were given 12 standard names of items in the battery to define. Normals produce adequate (i. e. detailed and factually correct) definitions for nearly all ofthese. The only occasional errors produced are perseverative. By contrast , the patients definitions were frequently grossly impoverished (e. g. rhinoceros is it an animal?') or contained numerous factual intrusive errors (e. g. deer animal , it gives milk , like a sheep ). Examples are given in Table 6. As reported by Warrington (1975), superordinate knowledge was often demonstrated in the absence of any further information (e. an animal but I don t know what kind' , etc. In
summary, the results of the semantic test battery confirm substantial impairment
in semantic knowledge in all five patients , apparent on category fluency, naming, picture pointing, sorting of pictures and generation of verbal definitions. Superordinate knowledge was better preserved than subordinate knowledge , although it is noteworthy that the
SEMANTIC DEMENTIA
1797
TABLE 6. EXAMPLES OF EMPTY OR ERRONEOUS DESCRIPTIONS GIVEN BY PATIENTS ON DEFINITIONS TEST Lion:
Is it an animal? . . . it has little legs and big ears, they sleep alot , see them in shops. (M. An animal , quite tall , can t think of anything else. (F. Rhinoceros: No idea , is it living? (E. No idea. (M. Is it an animal? (J. L.) Deer: Animal , gives milk, like sheep. (E.
Is it an animal? (M. Violin:
A music thing, can t think. (M. It it an instrument? I think it s made of metal. (J. L.) Guitar:
Play music with it , can t remember , it's big you play with an arrow. (E. It's what you do music with , put on your shoulder and put a bit across- like that (mimes bowing). (F. Spinning wheel:
Don t know. (E.
Never heard of it. (M. I think I've heard of it , can
t think. (F.
Eagle:
A bird , it stands up, has big eyes , does things at night. (F. No idea. (P.
nonnal control subjects showed the same pattern , albeit at a superior level of perfonnance. Category level differences may therefore reflect differences in the difficulty of the task. Tests of visual semantic knowledge
In order to test semantic knowledge without the possible confounding influences of word comprehension or production , we also administered a range of non-verbal semantic memory tests to the three most recently studied patients (P. , J. , F. On an object decision test (Humphreys and Riddoch , 1987) subjects are presented with line- drawings of either real items (animals and tools) or unreal chimeric items made by combining two incongruous halves of real items (e. g. a head of a mouse with the body of a lion), and are asked to classify each as a real or unreal item. All three patients
were impaired: P. P. scored at chance on a set of 32 of the easiest items;
F. M.
and
L. scored 101 (79%) and 96 (75 %), respectively, out of a total of 128 items. By contrast
normal subjects score virtually perfectly on this task. The Pyramids and Palm- trees Test (Howard and Orchard- Lisle , 1984; Howard and Patterson , 1992) requires subjects to match conceptually related pictures (the word version was not used in this study). For instance , the target picture of an Egyptian pyramid is presented above two drawings depicting a palm- tree and a fir- tree , and the subject is asked to judge which one goes with the pyramid. Other examples are spectacles with eye and ear ,
saddle with goat and horse. P.
s performance was at chance , F. M. and
g. '
1798
1. R. HODGES AND OTHERS
L. scoted42 (81 %) and 36 (69%),
respectively, out ofa total of 52. Normal controls
make a maximum of three errors. P. and J. L. were also tested for their knowledge of famous personalities. On a modified version of a famous faces test previously described (Hodges and Ward , 1989), both patients were at chance at distinguishing famous from non- famous faces and were
unable to access any knowledge
even concerning the most famous faces (e. Harold Wilson , Lord Mountbatten , Ronald Reagan). Patient P. P. has been the subject of an intensive longitudinal study (1. R. Hodges and K. E. Patterson , unpublished data). She shows severe impairment on tests of environment sound-picture matching and in demonstrating the use of real household items.
DISCUSSION
The five patients reported here all presented with a neuropsychological syndrome understandable in terms of a progressive and relatively pure breakdown in semantic knowledge; in keeping with the report by Snowden
et at.
(1989), we have called this
semantic dementia. We prefer this term to progressive aphasia because the deficit affects more than language processes. Semantic dementia conveys the concept of profound and pervasive semantic deterioration which disrupts language , factual memory and knowledge and object recognition. The discussion will focus on (i) the neuropsychological features which characterize this distinctive clinical syndrome , (ii) aspects which resemble or contrast with the deficits found in other degenerative brain diseases , namely Alzheimer and Pick' s disease , (Hi) the relationship of semantic dementia to primary progressive aphasia , and (iv) the possible anatomical basis.
The most prominent neuropsychological feature of this syndrome is a striking loss of vocabulary, both receptive and expressive , affecting particularly nouns. This explains the frequent presenting complaint of difficulty ' remembering ' the names of people , places and things. In the early stages of the disorder , patients also complain of word- finding difficulty and exhibit marked circumlocutions. Later , speech is punctuated by frequent pauses and often semantic paraphasias. Initially, informal conversation may not reveal any impairment of comprehension and only if single-word comprehension for relatively uncommon items is tested will the true extent of the input deficit become apparent. Naming , however , severely affected from an early stage. This too is highly frequency dependent. In these patients , phonemic cueing typically does not facilitate naming. Errors may be predominantly omissions (don t know), while errors of commission are typically semantic violin ' for accordion), superordinate in type , consisting of within-category errors (e. terms (' animal' for fox) or circumlocutions. Another early and consistent feature resulting from vocabulary loss is a severe impairment in the generation of exemplars from semantic categories (such as animals musical instruments , etc. ) on verbal fluency testing. Patients with more advanced disease like the case of P. P. reported here , may be totally unable to generate examples from any category. In contrast , letter fluency (generating words (excluding proper names) beginning with a given letter of the alphabet) is much less impaired. The former task depends upon generating systematic strategies to search an intact semantic network. The latter can be performed at a lexical level without recourse to the semantic system et ai. 1990). (Hodges
SEMANTIC DEMENTIA
1799
The semantic test battery employed in this study was designed to assess input to and output from semantic memory via different modalities in patients with dementia of Alzheimer type (DAT) (Hodges et ai. 1992). The pattern of results here parallels that found in DAT , but indicates a more profound deficit. The most telling findings include: (i) grossly impaired category fluency, with complete failure on lower order categories such as types of boat or dog; (ii) severely impaired naming; (iii) defective sorting according to specific attributes coupled with largely intact sorting at a category level; (iv) errors matching pictures of the items to their spoken names; (v) difficulty generating verbal definitions of the items. The pattern of breakdown involving lower order subordinate or attributional knowledge with retention of superordinate category knowledge is identical to that described by Warrington , Shallice and others (e. Warrington , 1975; Warrington and Shallice , 1984; Shallice , 1988) in patients with loss of semantic memory due to non-progressive focal brain damage. The errors made on the definitions test were particularly revealing in the milder patients whose expressive and receptive language can appear relatively normal on casual conversation. Evidence of the patients ' pervasive deficit in semantic memory, affecting not just naming and word comprehension but also more fundamental aspects of knowledge about living and man-made things , comes from their performance on the picture sorting test in the semantic battery. In addition , more extensive tests of non-verbal semantics were given to three patients (P. , J. , F. ). All three showed marked impairment on an object decision test requiring subjects to judge the veracity of real and non-real chimeric objects and animals , and on the Pyramids and Palm-
,I'
trees Test (Howard
and
Orchard- Lisle , 1984; Howard and Patterson , 1992) which requires the matching of conceptually linked drawings. Detailed longitudinal study of P. P. has demonstrated a gross impairment in her use of real household items and in matching pictures to environmental sounds. In P. P. and J. L. an early spontaneous complaint was in recognizing people from sight , sound or description. Both have been shown to be severely impaired at picking out famous faces from arrays containing photos of famous and non-famous individuals , in accessing any semantic information from faces and in recognizing famous names. In contrast to the progressive breakdown in the semantic components of language syntax and phonology are preserved at least as assessed by conventional explicit tasks. Even in the advanced stages , as in patient P. , sentences are well articulated and grammatically correct , although simplified and repetitious in content. Similarly, comprehension of even fairly complex syntax can be normal , as evidenced by the near perfect performance of most of the patients on the Token Test (De Renzi and Faglioni , 1978) and on the Test for the Reception of Grammar (TRaG) (Bishop, 1989). Repetition of single words and sentences was also normal in all patients. Schwartz
et at.
(1979) reported
a patient showing similar preservation of syntax and phonology accompanying severe lexical impairments. The breakdown in semantic memory appears to have a consistent impact on reading. The patients all showed an impairment in oral reading of words with irregular spellingto-sound correspondence , making phonologically plausible (or regularization) errors on these items: The pattern of surface dyslexia arises because of disruption in the lexical/semantic procedure of whole-word reading, so that increasing reliance is placed upon sub-word correspondence between spelling and sound (Ellis and Young, 1988;
1800
J. R. HODGES AND OTHERS
McCarthy and Warrington , 1990). A full discussion of the relevance of these findings to the controversy concerning the putative existence of a whole-word non-semantic route
of reading is beyond the scope of this paper. The characterization
of the reading
impairment has been investigated in more detail in several of these patients and is the subject of a further report (Patterson and Hodges , 1992). One patient , P. , also exhibited features of pure alexia with letter- by- letter reading (Patterson and Kay, 1982). Written picture descriptions paralleled spoken language , in that grammatical structure was retained but frequent semantic errors occurred on nouns and specific verbs. Writing of single words to dictation paralleled reading performance , with errors in spelling irregular words a pattern described as surface (or lexical) agraphia (Beauvois and Derousne , 1981; Hatfield and Patterson , 1983). The difficulty in reading irregular words has practical implications for the interpretation of the widely used New Adult Reading Test (NART) (Nelson , 1982). The ability to read irregular words is usually regarded as a retained skill , even in advanced dementia (Nelson and McKenna , 1975; Hart , 1988), which can therefore be used to predict pre-morbid verbal IQ. Since the NART consists almost exclusively of irregular words the surface dyslexia typically seen in semantic dementia means that the NART may lead to erroneously low predictions of pre-morbid intellectual level if the examiner does not recognize the dyslexia. A better estimate of pre-morbid intellect in these patients comes from the Block Design sub- test from the W AIS and Raven s Coloured Matrices on which performance was preserved even in the patients with the most profound semantic dementia. Turning to theW AIS results in semantic dementia, the most consistent and in some cases , profound , impairment was noted in the Verbal sub-tests dependent upon word knowledge , notably Information , Similarities and Vocabulary. By contrast arithmetic
skills were reasonably well retained and digit span was invariably normal. Of the Performance sub-tests , Block Design and Digit Symbol , which do not rely on any semantic knowledge , were within normal limits for all five of our cases , whilst Picture Completion was impaired in the most advanced cases due to the loss of meaning of the stimulus pictures. The clinical evidence suggests that personal autobiographical and practical day-today memory is preserved , certainly in the early stages of the disorder. This dissociation
offers support for the episodic-semantic dichotomy first proposed by Tulving (1972 1983). This distinction is most clear in the area ofremote memory; despite the often profound loss of semantic memory, patients are able to remember past family events and outings , and accurately relate details of their autobiography. This discrepancy was demonstrated quantitatively in two of the patients (F. , J. L.) using the Autobiographical et al. 1989). Even P. P. , in whom comprehension of nominal Interview (Kopelman terms and naming ability was virtually absent , could still relate some basic family events albeit anomically and with frequent semantic substitutions (such as sister for daughter), and seems to recall visits to Cambridge. In keeping with this observation , temporal
orientation is also preserved. The laying down of new episodic memories is likely to be seriously impaired as the semantic deficit progresses since semantic memory must ultimately subserve other memory processes (see Mayes , 1988). Formal assessment of verbal memory presents considerable difficulty because of impairment in word meaning. However , most ofthe patients showed some ability to learn new verbal material
SEMANTIC DEMENTIA
and , in contrast to patients with DAT (Butters after a delay was normal in some patients.
et ai.
1801
1988), the proportion retained
Memory of non-verbal material is on the whole very well preserved. Recall of the Rey- Osterrieth Complex Figure was within normal limits in four of the five patients. Performance on the Benton Visual Retention Test (Benton , 1974) was also normal in
the four patients tested. However , memory for faces on the Warrington Recognition Memory Test (Warrington , 1984) was less consistent , being normal in two patients and impaired in two others. Visuospatial skills were unequivocally preserved even in advanced
cases: in addition to good performance on Block Design , all of the patients performed within normal limits on Raven s Coloured Matrices , and copy of the Rey- Osterrieth Figure was executed without substantial error in all five. In addition , performance on a test of face-matching ability and judgement of line orientation (Benton
et ai. 1983)
were also well within normal limits for age in all five patients. Although the typical pattern of cognitive deficit in DA T is now fairly well established (Corkin , 1982; Huppert and Tym , 1986; Hart , 1988; Sagar and Sullivan , 1988; Spinnler and Della Sala , 1988; Hodges et ai. 1990 , 1991), it is also recognized that atypical cases occur (e. g. Crystal et ai. 1982; Pogacar and Williams , 1984; Jagust et al. 1990). It is , therefore , conceivable that these patients represent a subgroup ofDAT. Certainly the progressive disruption in semantic memory is compatible with that hypothesis. In DAT there is anomia with predominantly semantic errors (Bayles and Tomoeda , 1983; Huff et ai. 1986; Hodges et ai. 1991), reduced category fluency (Ober et ai. 1986; Butters et al. 1987; Hodges et al. 1990) and other features of impaired semantic memory even fairly early in the course of the disease (Chertkow and Bub , 1990; Hodges et ai. 1992). However , there is also almost invariably a profound loss of episodic memory and early impairment in visuo-perceptual skills. These features contrast with those found in semantic dementia. To our knowledge , there have been no reported cases with features of semantic dementia who have been shown to have pathologically verified DA T. In addition , functional brain- imaging studies , PET and SPECT , in our cases have not shown the bilateral posterior occipito-parietal deficits characteristic ofDAT (Haxby et al. 1986; Johnson et ai. 1987; Neary et ai. 1987). The demonstration of focal and often
asymmetric temporal lobe atrophy on CT and/or MRI in four patients is also against this diagnosis. Until pathological confirmation or the development of specific
in vivo
diagnostic methods , DAT cannot be absolutely excluded , but appears unlikely. The development of changes in personality and behaviour which were marked in one patient with features of the Kluver- Bucy Syndrome , together with the SPECT and MRI findings , suggest that semantic dementia may herald the onset of Pick' s disease. As reported by Poeck and Luzzatti (1988), Pick' s first case (1892) had a severe language disorder in association with focal atrophy of the left temporal pole. He subsequently described further cases with circumscribed temporal atrophy (1904), and only later (1906) the frontal atrophy which has become , incorrectly, synonomous with Pick' s disease. The older literature contains other patients with predominant aphasia and lobar atrophy (Serieux , 1893; Rosenfeld , 1909 (as described by Luzzatti and Poeck, 1991); Mingazzini 1914; Stertz , 1926; Malamud and Boyd , 1940). More recently, patients with relatively pure language disorders of semantic type , focal cerebral atrophy and the pathological changes of Pick' s disease have also been reported (Wechsler et ai. 1982; Holland et ai. 1985; Graff- Radford et ai. 1990). It is also noteworthy that two of Warrington s (1975)
1802
J. R. HODGES AND OTHERS
original patients with selective impairment of semantic memory were later shown to have Pick' s disease on autopsy (E. K. Warrington , personal communication) and one developed features of Kluver-Bucy syndrome (Cummings and Duchen , 1981). Although
the histological diagnosis in our patients is uncertain , the syndrome is more in keeping with Pick' s disease than DAT. Turning to the difficult issue of the relationship between semantic dementia and primary progressive aphasia , it is important to consider the evolving use of the latter diagnostic term. Mesulam , in his seminal article of 1982 , drew attention to the clinical syndrome of ' slowly progressive aphasia without generalized dementia . This was characterized by progressive anomic aphasia, sometimes with eventual impairment of reading, writing and comprehension , but with sparing of ' other areas of comportment' even on prolonged follow-up over 5- 10 yrs. Excluding one highly atypical case (a 17- yr-old with pure word deafness and normal naming), four of the five older patients had a severe nonoutput with impaired syntactic production and repetition , but relatively normal fluent auditory comprehension. Following this report , a number of authors reported further similar cases under various headings including non- familial dysphasic dementia (Mehler et ai. 1987), slowly progressive aphasia (Poeck and Luzzatti , 1988; Kempler et al. et ai.
1990), progressive language impairment without dementia (Basso
1988) and
1990). Many of these cases share the core characteristics of the original Mesulum cases , namely progressive nonaphasia with impaired syntax but good comprehension. However , some patients fluent present with a radically different picture of language impairment , with afluent aphasia and preserved syntax , phonology and repetition , but severely impaired semantic comprehension (e. g. Basso et al. 1988; Poeck and Luzzatti , 1988; Graff- Radford et al. 1990; Kempler et al. 1990 , Case 3). As a result of this variability in the use of the diagnostic term , and lack of any operational criteria , considerable controversy has arisen regarding the nosological status progressive aphasia due to focal atrophy (Tyrrell
et ai.
of progressive aphasia and particularly its relationship to established dementing diseases. Some authors favour a continuum between progressive aphasia and general dementia (e. g. Kirshner et al. 1984; Poeck and Luzzatti , 1988; Green et al. 1990). Others support a dichotomous view , with progressive aphasia as a clinically and pathologically distinct syndrome (Mesulum , 1982; Weintraub et al. 1990). Two reports containing pathological confirmation of the diagnosis have supported the latter view (Kirshner et al. 1987; Mehler et al. 1987). In both reports , each containing two patients , unique pathological changes not typical of either Alzheimer s or Pick' s disease were found. It should be noted , however , that these four patients all had a progressive non-fluent dysphasia as described by Mesulam. The situation has also been further clarified by the latest report from Mesulam s group (Weintraub et ai. 1990) in which , for the first time , operational
clinical criteria for primary progressive aphasia have been applied as follows: (i) at least a 2-yr history of progressive decline in language; (ii) prominent language deficits with normal or relatively preserved performance on tests of other mental functions; (iii) independence in activities of daily living. Their four patients fulfilled these criteria but most importantly, again , all had a non-fluent picture with hesitant , often dysprosodic speech , frequent phonemic paraphasias , impaired syntax , poor repetition and preserved comprehension. Clearly, the features of the language impairment in these cases contrasts
sharply with those found in our patients.
SEMANTIC DEMENTIA
1803
We tentatively suggest that the term primary progressive aphasia should be applied non-fluent dysphasia in which the deficit affects very predominantly the output of language but spares word comprehension and causes no impairment in non-verbal semantic knowledge. For the patients we described here we therefore prefer the designation semantic dementia. Review of the literature also suggests that progression of non- fluent primary progressive aphasia is typically slow
only to those patients with a progressive
over many years. In several of our patients the decline was precipitous. Finally, what conclusions can be drawn regarding the locus of pathology in semantic dementia? The evidence from previous cases with selective impairment of semantic memory in the context of non-progressive brain damage implicates the temporal neocortex et al. 1988; Sartori and Job , 1988). (e. g. Warrington and Shallice , 1984; Pietrini Similarly, in other patients with the fluent type of progressive aphasia suggesting semantic breakdown , selective and often asymmetric atrophy of the temporal lobes has been et al. 1990; Kempler et al. 1990). reported (Poeck and Luzzatti , 1988; Graff- Radford In three of our patients ,
strikingly focal left temporal lobe atrophy was present on CT and/or MRI imaging; the other two had bilateral temporal atrophy. Functional brain imaging has also implicated the left temporal region in our patients. In the PET scanning et al. study reported by Tyrrell (1990), the patients with progressive fluent dysphasia
all had reduced metabolism most marked in the left anterior temporal lobe. The two et al. (1990) with progressive fluent dysphasia , also had
patients reported by Kempler
focal areas of hypometabolism in the left temporo-parietal region. Examination by SPECT et al. ' (1989) patients with semantic dementia have shown deficits scans in Snowden less clearly localized , but always maximal in the left temporo- parietal region. From the evidence , it would seem that this syndrome results from extensive temporal neocortical
damage which can , at least initially, be confined to the dominant hemisphere. ACKNOWLEDGEMENTS We wish to thank Dr Kim Jobst for providing follow-up information on patient M. , Dr Nagui Antoun Drs Basil Shepstone and Philip Wraight who performed the SPECT scans in Oxford and Cambridge , respectively, and Drs Guy Sawle and Richard Wise for performing the PET study on patient P. P. We also wish to thank Linda Pallister who provided invaluable secretarial assistance. for radiological assistance ,
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