semantic dementia · case reports in none of the five cases was there a family history of dementia,...

Brain (1992), 115, 1783- 1806

SEMANTIC DEMENTIA

PROGRESSIVE FLUENT APHASIA WITH TEMPORAL LOBE A TROPHY

by JOHN R. HODGES KARALYN PATTERSON~2 SUSAN OXBURy andELAINE FUNNELL

(From the University of Cambridge Clinical School, Addenbrooke s Hospital, and the 2MRC AppliedPsychology Unit, Cambridge, the 3Department of Neuropsychology, Radcliffe Infirmary, Oxford and

the 4Department of Psychology, Royal Holloway College , University of London , London, UK)

SUMMARY

We report five patients with a stereotyped clinical syndrome characterized by fluent dysphasia with severeanomia , reduced vocabulary and prominent impairment of single-word comprehension , progressing to astage of virtually complete dissolution of the semantic components of language. A marked reduction inthe ability to generate exemplars from restricted semantic categories (e.g. animals , vehicles , etc. ) wasa consistent and early feature. Tests of semantic memory demonstrated a radically impoverished knowledgeabout a range of living and man-made items. In contrast , phonology and grammar of spoken languagewere largely preserved , as was comprehension of complex syntactic commands. Reading showed a patternof 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-BucySyndrome. Radiological investigations have shown marked focal temporal atrophy in all five patients , andfunctional 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 beensubsumed under the rubric of Pick' s disease. Others have been included in series with progressive aphasia.We propose the term semantic dementia, first coined by Snowden et at. (1989), to designate this clinicalsyndrome.

INTRODUCTION

Selective impairment of semantic memory was first clearly delineated by Warrington(1975), who described three patients with cerebral atrophy presenting with progressiveanomia and impaired word comprehension. Detailed neuropsychological testing revealeda loss of receptive and expressive vocabulary, and impoverished knowledge of a widerange of living things and inanimate objects affecting particularly specific subordinateattributional knowledge. Other aspects of spoken language (e. g. phonology and syntax)and perceptual skills were relatively intact. Such a deficit would previously have beenassimilated under the rubric of associative agnosia. Warrington , drawing a distinctionmade by Tulving (1972 , 1983), identified the deficit as one of semantic memory.

The term semantic memory is applied to the component of long-term memorycontaining knowledge of objects , facts and concepts as well as words and their meaning(Tulving, 1972 , 1983). In short , semantic memory gives meaning to our sensoryexperience. 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 isevidence to suggest that semantic memory is stored in a highly structured and hierarchicalfashion. Tasks dependent on semantic memory include object naming, generation ofdefinitions for spoken words, word-picture and picture-picture matching and thegeneration of exemplars on category fluency tests (e.g. animals , vegetables , etc. ). Patientswith dementia of Alzheimer type (DA T) are characteristically impaired on these tests;most authors interpreted these impairments as a breakdown in the structure of semanticmemory as the disease progresses (Bayles and Tomoeda , 1983; Martin and Fedio , 1983;Huff et ai. 1986; Hodges et ai. 1990, 1991 , 1992), but others support the conceptof a primary disturbance in access to information rather than a loss of knowledge perse (see Nebes , 1989). Although semantic memory impairment occurs in DAT, thereis virtually always accompanying severe impairment of episodic memory, and eventuallydisruption of many other cognitive domains , including visuospatial and frontal executionfunction.

Since the seminal report of Warrington (1975), a number of other patients with selectivesemantic memory impairment have been reported. The majority have occurred in thecontext of extensive neocortical damage , for instance following herpes simplex virusencephalitis (e.g. Warrington and Shallice , 1984; De Renzi et ai. 1987; Pietrini et al.1988; Sartori and Job , 1988), but some of these patients have had additional complicatingcognitive deficits.

Other examples of semantic memory impairment have been subsumed within thecategory of primary progressive aphasia. The latter term was originally introduced byMesulam (1982) to describe a syndrome , clearly distinct from semantic memory loss,characterized by non-fluent language output with phonemic paraphasic errors progressingin many instances to complete mutism , but sparing comprehension. As is often the casefollowing the description of an apparently new syndrome the term progressive aphasiahas been widened to embrace any progressive disorder of language. Hence , patientsvery different to the original cases of non-fluent aphasia have been reported under thetitle of progressive aphasia (e. g. Basso et ai. 1988; Poeck and Luzzatti , 1988; Tyrrellet al. 1990). The pattern of deficits in these latter cases has been one of undoubtedsemantic memory loss causing deficits both in word production and comprehensionbut 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 progressivecircumscribed neuropsychological symptoms due to focal brain atrophy, includingclear-cut cases of progressive aphasia , with all the hallmarks of primary semantic memoryimpairment. The pathological basis of progressive aphasia is still debated. In the patientswith the Mesulam non-fluent variety, the disorder appears to remain confined to thedominant hemisphere and a number of autopsies have demonstrated non-Alzheimerpathology (Kirshner et ai. 1987; Mehler et al. 1987). In patients with progressivesemantic memory impairment , modern neuropathological data are limited , although twovery similar cases have shown the changes of Pick' s disease (Cummings and Duchen1981; Graff-Radford et ai. 1990; also patient A. B. from Warrington, 1975).

The introduction of the term semantic dementia (Snowden et al. 1989) may be thoughtto add further to the nosological confusion. It does , however , have the advantage ofbrevity, avoids pathological assumptions and implies a cognitive deficit affecting

- - 0. ._._~- ~"--~.~~~---

SEMANTIC DEMENTIA 1785

fundamental aspects of language , memory and object recognition. In this paper wedescribe five cases with semantic dementia which , we suggest , is a clinically recogniz-able syndrome with the following characteristics: (i) selective impairment of semanticmemory causing severe anomia , impaired spoken and written single-word comprehensionreduced generation of exemplars on category fluency tests and an impoverished fundof general knowledge; (ii) relative sparing of other components of language output andcomprehension , notably syntax and phonology; (iii) normal perceptual skills and non-verbal problem-solving abilities; (iv) relatively preserved autobiographical and day-to-day (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 toand 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 otheraetiologically relevant factors. Physical signs (including frontal release phenomena) were absent and detailedinvestigations for causes of dementia were negative. The major clinical features are summarized in Table I.

TABLE I. SUMMARY OF MAJOR CLINICAL FEATURES. LANGUAGE AND OTHERCOGNITIVE DEFICITS IN FIVE PATIENTS WITH SEMANTIC DEMENTIA

J.L.

Age/sex 68/F 54/F 42/F 60/M 62/FLength of history 2 yrs I yr 3 yrs I yr I yrPresenting feature WFD , comph . alexia WFD WFD, comph WFD+anomia WFD+anomia

Language (clinical assessment)

Naming

Spontaneous outputPhonologyArticulationWord findingParaphasias (semantic)

Paraphasias (phonemic)Syntax

ComprehensionSyntacticSemantic

Repetition (words and sentences)

Reading: surface dyslexia +(a)

Writing: surface dysgraphia

OrientationEpisodic memory (informal

clinical assessment)Visuospatial skillsPersonality change Late EarlyCT scan atrophy Bilat T lobe Bilat T Lobe L ;0. R LT Lobe LT Lobe

MRI atrophy L perisylvian LT lobe Bilat T Lobe R ;0. LSPECT or PET-hypoperfusion LF- LF- Bilat T Lobe LF-

N = normal , 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 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 historyof progressive loss of memory for names of people , places and things , together with impaired comprehensionof nominal terms. She has also complained from the onset of problems recognizing even very familiarpeople from sight , voice or description. Her fund of general knowledge was radically impoverished. Whenasked

, '

Have you ever been to America?' , she replied ' what's America?' , or asked

, '

What s your favouritefood?' , she replied ' food , food , I wish I knew what that was ' - Despite this profound deficit in semanticmemory her day-to-day memory remained fairly good. She could remember appointments and keep trackof family events. Sadly, she retained insight into her deficit and at times became severely depressed. Therehad been no deterioration in self-care.

Spontaneous speech was well articulated with normal prosody. She was able to produce fluent andgrammatically correct sentences, but conversation was punctuated by severe word-finding difficulty andfrequent semantic paraphasias. Phonemic errors were never observed. The degree of anomia is such thatshe has never correctly named a single item , either on informal testing or on a number of formal namingtests (see below). Comprehension of simple questions about personal events was maintained (e.

g. '

howare you today?'; ' is your mother well?' ), but there was a profound deficit in understanding of all but verycommon nominal terms (Le. mother , today, home , etc. ), to such an extent that she was unable to pointto very common objects. Repetition of single words and even of grammatically complex sentences wasnormal. 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 someregular words. She was able to do simple mental arithmetic. In contrast to her profound language impairmenther visuospatial abilities were remarkably well preserved; copies of complex geometric shapes were executedflawlessly (see Fig. 1).

Computerized tomography (CT) and magnetic resonance imaging (MRI) scans revealed a moderate degreeof cerebral atrophy, more marked in the left hemisphere , particularly around the sylvian fissure. A positronemission tomography (PET) study, performed at the Hammersmith Hospital , revealed hypometabolismin 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 knowswhich items to choose , and similarly her cooking ability deteriorated because of a lack of understandingof the fundamental processes and utensils involved. She enjoys seeing family members and her visits toCambridge. 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 herprofound anomia and comprehension deficit.


and few verbs other than general ones like ' come ' and ' , and she tends to produce grammatically correctand fluent stereotyped phrases such as ' Oh dear , I wish I could think what I wanted to say . Insight intoher predicament is maintained. Eating habits , table manners , grooming and toileting are all normal andshe 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 a12 mth history of ' memory problems , specifically affecting her ability to recall the names of people andthings. This first became apparent when she realized that she could not tell the residents of the home whatfoods were available on the meal trolley. She also experienced great difficulty in naming family membersfriends and famous personalities. Despite this problem , her day-to-day and personal autobiographical memorywere unaffected. She gave an accurate history of her past life , work , recent family events and visits tothe hospital. Family members confirmed that there has been no change in personality, behaviourcomportment or practical skills. She continued running the house without difficulty.

Spontaneous speech was fluent with normal syntax and phonology. Word-finding difficulty was apparentin 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, withcircumlocutions and semantic paraphasias. Reading of passages and regular words was normal , but shegave regularized pronunciations of some irregular words. Copying of complex geometric shapes andrepresentational 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 temporallobe orientated horizontal and coronal cuts showed striking focal atrophy of the left temporal neocortexwith 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 andimpaired comprehension. She first noticed problems helping her children with their homework. Later herfamily observed that comprehension , especially of proper nouns and names , was poor , and that her speechcontained semantic errors. Her spelling was also poor. Despite these problems , her everyday memorywas good , she was able to remember appointments and organize her family s complex schedules. No changein personality or social behaviour had been noted. Insight was well maintained.

Spontaneous speech was fluent and well articulated with normal prosody, but with occasional spontaneoussemantic paraphasias. Naming was severely impaired. Comprehension of syntax was normal as judgedby her ability to obey complex three-stage commands. Repetition of words and sentences was likewiseunimpaired. She had difficulty reading words with irregular spelling-to-sound correspondence , makingphonologically plausible errors. Written and oral spelling were below her expected pre-morbid level. Shewas fully orientated in time and place , and performed serial seven subtractions and mental arithmetic quicklyand accurately. Copying of simple geometric and representational shapes (interlocking pentagons and ahouse) were extremely good.

A CT brain scan was within normal limits and a SPECT scan using 500 M Bq Tc-99m Exametazimeshowed no abnormality. On follow-up over the subsequent 12 mths , there has been a marked deteriorationin all cognitive abilities dependent upon semantic memory. Spontaneous speech is still fluent andgrammatically correct but lacking in content and punctuated by frequent circumlocutions. Comprehensionhas further deteriorated and she is unable to name even very common everyday items. She tends to usestereotyped phrases such as ' I wish I knew what you meant . Writing skills are maintained but the contentparallels spoken language. Reading of sentences is retained , but regularization errors on irregular wordsare common. Despite the precipitous decline in semantic memory, her day-to-day memory remains fairlygood; 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 andbehaviour. She has become very irritable and irascible , and at times verbally aggressive to members ofher family. She has become obsessively tidy, vacuuming the house several times a day and brushing the


carpet until the pile is aligned. Features of the Kluver-Bucy syndrome have also appeared including sexualdisinhibition and indiscriminate eating of discarded food , scraps and even occasionally non-food itemssuch as cigarette ends. No physical signs have developed. A CT scan with temporal lobe orientated horizontalcuts now shows obvious bilateral temporal pole atrophy more marked on the left (Fig. 3). A repeat SPECTscan also revealed left fronto-temporal hypoperfusion.

FIG. 2. T -weighted MRI scan images in patient F. : two coronal (below) and two horizontal slices (above)

orientated through the temporal lobes demonstrating marked focal left temporal neocortical atrophy with relative sparingof the hippocampal formation.


Case

J.L. , a 60-yr-old company director, presented in April 1991 with difficulty remembering the names ofpeople and places. More recently, his vocabulary had diminished causing word-finding difficulty. Thefamily 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 throughthe temporal lobes at the level of the midbrain showing focal left neocortical atrophy.


his vocabulary, for instance the names of foods. He was no longer familiar with the names of the localvillages in the region where he had lived all his life. The deficit also affected his ability to recognize peopleby face , name or description. He had also exhibited problems identifying real objects and animals , forinstance he had been frightened by finding a snail in the backyard and thought that a goat was a strangecreature. Despite these difficulties , his day- to-day and autobiographical memory remained relativelyvery 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 disastrousdeals as a result of which his sons have taken over the company. Also, he had become uncharacteristicallygenerous , giving money to charities and offering his holiday home to relative strangers.

Spontaneous speech was fluent with normal articulation and grammar. Occasional word-finding difficultieswere 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 contrastunderstanding of nominal terms was impaired. Repetition of words and sentences was normal. Readingof 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 wasfully orientated in time and place. Recall of simple verbal material was good. Drawing of geometric andrepresentational figures could not be faulted.

A CT scan suggested atrophy of the anterior pole of the temporal lobes. This was confirmed on MRIwhich showed striking focal atrophy of the temporal region , more marked on the right , which was particularlyevident on the coronal slices (see Fig. 4). A 99m Tc-HM-PAO SPECT scan also showed bilateralhypoperfusion confined to the temporal lobes.

Case

, a 62-yr-old , ex-middle school maths teacher , presented in November 1989 with a 12 mth historyof word-finding difficulty. She complained of particular problems naming people and things includingcategories offood , animals and inanimate objects. Her family had noted impaired comprehension of nominalterms 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 haddeteriorated due to very poor spelling. She was a keen folk dancer and had no difficulty with the complexroutines , but was unable to remember the names of the individual dances. Her autobiographical and everydaymemory remained good; she remembered appointments , and could give a good account of her past lifeand of recent family events. She remained able to drive and perform housework. She is an accomplisheddressmaker and can carry out the instructions in complicated knitting and sewing patterns. There had beenno change in personality or social behaviour. Her retained insight into the difficulties produced understandableanxiety .

Spontaneous speech was fluent with normal syntax, phonology and prosody, but was punctuated by frequentproblems 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-stagecommands , 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 alsonormal. She was able to copy three-dimensional drawings without error. Apraxic errors were not observednor were features of tactile or visual neglect. A CT scan demonstrated focal atrophy of the left temporallobe. A SPECT scan using 500 MB2 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 psychologicalfunction , including those investigating semantic memory, naming, reading and writing, short-term memoryand 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 favourof the latter. Although the severity of verbal intellectual impairment varied from mild


(E. ) t.o profound (P. ), the pattern of Wechsler Adult Intelligence Scale (WAIS)sub-test scores (Wechsler, 1955) was consistent across patients. In all instancesimpairments were most marked on Vocabulary, Information and Similarities. Digit spanwas strikingly preserved in all five. Arithmetic was normal in the more mildly impairedcases and only became marginally reduced in the most deteriorated patient (P. ). Ofthe Performance sub-tests , Block Design and Digit Symbol were relatively well preservedin 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) orientatedthrough the temporal lobes demonstrating bilateral temporal neocortical atrophy which in this case is more markedon the right side.


TABLE 2. BASIC NEUROPSYCHOLOGICAL DATA IN THE FIVE PATIENTS

Me. J.L. E.P.

W AIS subtest scores (age scaled)

InformationDigit span

VocabularyArithmeticSimilarities

Picture CompletionBlock Design

Digit Symbol

Verbal IQPerformance 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 forwardDigit span backward

Logical Memory WMSImmediate (21)30 min delayed

PALT WMSImmediate (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 = BentonVisual Recognition Test; WRMT = Warrington Recognition Memory Test. Figures in brackets indicate maximum possiblescores.

due to failure to comprehend the stimuli , as evidenced by performance on the objectdecision test (see below).

Further evidence of preserved constructional ability is provided by the normal copiesof the complex Rey-Osterrieth figure (Osterrieth , 1944). Perceptual skills were alsonormal. All five patients performed within the normal range on the Face RecognitionTest (Benton et al. 1983), which requires subjects to match photographs of the sameperson taken with different lighting conditions and from different angles. Performanceon the Benton Test of Line Orientation Judgement (Benton et al. 1983) was also withinthe normal range. The dissociation . of vi suo-perceptual ability and semantic memorywas strikingly illustrated in P. ; she performed within the normal range on theHumphreys and Riddoch (1987) object matching test in which one photograph , showinga prototypical view of a common object (e.g. comb , knife , hammer , etc. ), is presentedalong with an atypical view of the target object (e. g. from above or one end) and adifferent 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


Matrices (Raven , 1962) and the performance of the younger patients was also considerednormal by extrapolation from the normal data for elderly subjects.

Assessment of verbal memory was confounded by the language disorder. All but themost deteriorated patient (P. ) demonstrated some recall of the prose passage fromthe Wechsler Memory Scale (Wechsler , 1945), but all scores were below average andsignificantly below the expected level based on presumed pre-morbid ability. The samewas 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 immediaterecall) to varying degrees of impairment (44% in F. ). Given preserved perceptualand visuospatial abilities , non-verbal memory could be more reliably assessed. Thiswas within normal limits for age on all tests used for E. , M. c. and F. , but memoryfor new faces (Recognition Memory Test; Warrington , 1984) was impaired in P.and J.

To assess remote memory for personal episodic and semantic information , we gavethe Autobiographical Memory Interview to two patients (F.M. and J.L.) (Kopelmanet ai. 1989). This test requires subjects to produce standard factual information fromthree life epochs (childhood , young adult and recent), such as names of school friendsteachers , colleagues; details of schools attended , first job , wedding, etc. , and to relatepersonally experienced episodes from the same periods which are then scored in a standardfashion for detail. F.M. and J.L. scored above the cut-off levels for impairment oneach epoch for autobiographical episodes. Conversely, both were impaired on the personalsemantic information scores from each era tested (see Table 3).

Language testing (Table 4) showed a highly consistent pattern across the patientsalthough the degree of impairment varied according to the stage of the disease. Picturedescription using the 'cookie theft scene ' from the Boston Diagnostic Aphasia Examination(Goodglass and Kaplan , 1983) produced fluent , normally articulated and grammaticallycorrect but factually empty discourse , punctuated by frequent word-finding difficultyand , in the more severely impaired patients , semantic paraphasias. Performance onnaming ranged from moderately to profoundly impaired. Apart from omissions , namingerrors were semantic in type , being either within-category (e.g. hippopotamus forrhinoceros; violin for accordion), superordinate (e.g. animal , musical instrument) orcircumlocations. Phonemic and visually based errors were not observed. In all casesthere was a marked frequency effect , such that any correctly named items came fromthe high frequency end of the range. On comprehension tests , there was a markeddiscrepancy between those dependent upon semantic and on syntactic comprehension.On the shortened Token Test (De Renzi and Faglioni , 1978), four of the patientsperformed nearly perfectly. In the case of P. , her reduced vocabulary limited under-standing of the colour names , but on a modified version using only black and whiteshapes , she was able to follow all of the appropriate commands. Simil~rly, on the Testfor the Reception of Grammar (TRaG) (Bishop, 1989) on which subjects point to oneof four pictures in response to statements of increasing syntactic complexity whilevocabulary remains very simple (e. g. the boys pick the apples; the dog the boy is chasingis brown , etc. ), the only significant impairment was in P. , who made a large numberof 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-semanticcomprehension was impaired in all cases. This will be discussed further in the context


TABLE 3. PERFORMANCE OF PATIENTS J. L. AND F. M. ON THE AUTOBIOGRAPHICALMEMORY INTERVIEW SHOWING THE CUT-OFF FOR IMPAIRMENT IN EACH EPOCH

Personal semantic Autobiographical episodes

F.M. J.L. Cut-off Max. F.M. J.L. Cut-off Max.

Epoch

Childhood .::: 12 .:::4Young adult .::: 15 .:::4Recent 12. .::: 18 .:::6

Overall score 29. .:::48 .::: 13

The test method of Kopelman et al. (1989) was used.

TABLE 4. RESULTS OF THE PRINCIPAL LANGUAGE TESTS IN THE FIVE PATIENTS

M.e. J.L. E.P.Naming: number correctOldfield-Wingfield (36)CNT (48)BNT (60)Token Test (36) Normal***TROG (errors out of total 80) 22**Repetition * Normal Normal Normal Normal Normal

FluencyLetter (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 Kaplan1983); ** errors predominantly lexical (i.e. girl/boy, dog/cat) rather than syntactic; ***modified because of reducedvocabulary. Figures in brackets indicate maximum scores.

of the semantic test battery below. Repetition of single words and of phrases from theBoston Diagnostic Aphasia Examination (Goodglass and Kaplan , 1983) was normal inall 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 generationof exemplars from semantic categories (e. g. animals) was reduced to less than 20%of normal (see Hodges et al. 1990). P. P. was unable to generate any category exemplarsfrom a wide range of semantic categories , but still produced a few items on letter fluencytesting.

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 tendencyto produce phonologically plausible (regularization) errors on the exception words (e.PINT pronounced to rhyme with ' mint'). This has been investigated in detail in severalof 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 surfacedyslexia 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


estimates of pre morbid IQ. Writing ability paralleled reading; execution of writing waswell preserved without dyspraxia , and grammar was retained but the spelling of exceptionwords 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 designedto assess input to , and output from , central representational knowledge about the samegroup 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 (householditems , vehicles and musical instruments) matched for category prototypically. Theywere 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 maincategories plus two lower order categories (breeds of dog and types of boat); (ii) namingof all 48 line-drawings; (iii) picture sorting at superordinate , category and subordinatelevels; (iv) picture pointing to spoken word using within-category arrays; (v) generationof 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 fivepatients in each of the semantic categories tested. In keeping with the concept ofprogressive disintegration of semantic knowledge (i.e. preservation of superordinatewith loss of more specific knowledge), none of the patients produced any items fromthe lowest order categories comprising breeds of dog and types of boat. By comparisonnormal subjects produce an average of more than 10 items from each of the lattercategories.

Naming was impaired to a very severe degree in all five patients. This is a relativelyeasy 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 atnaming line-drawings of both living and man-made items.

The results of the picture sorting test showed a very interesting pattern. All the patientseven the most impaired , were perfectly capable of sorting the 48 cards at the highestorder (living versus man-made), demonstrating preservation ofthis broad concept , andadditionally establishing that they could follow the instructions involved in the test. Atthe category level , subjects are required to sort the man-made items into one of threecategories (household item versus musical instrument versus vehicle) and the living itemsinto one of three categories (land animal versus sea creature versus bird). Four of thefive showed no impairment , their scores falling within two standard deviations of normal.The most profoundly affected patient , P. , did show significant impairment at thislevel , 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 tosubordinate or attributional judgements (British versus foreign animal; fierce versusnon-fierce animal , etc. ) and the household items according to similar attributes (kitchenversus non-kitchen item; electrical versus non-electrical item , etc. ). At this third levelscores for all five patients were more than three standard deviations below the normalcontrols. The test was modified for P. , who had difficulty comprehending the conceptsinvolved; she was asked to choose from arrays of five pictures , three demonstratingthe desired attribute (e.

g. '

which of these five are foreign animals?' etc.


TABLE 5. PERFORMANCE ON THE SEMANTIC TEST BATTERY

Normal controls(n = 26)

FM. Me. J.L. Mean

(1) Category fluency

Animals (three categories)a 47.Dogs 10.

Man-made items (three categories) 49.Boats 11.6

(2) NamingTotal (48) 46.4 1.ILiving (24) 23.Man-made (24) 23.

(3) Picture sorting

Level I: living versus man-made (48) 48.Level II: category (48) 45. 1.2

Level III: subordinate (72) 27* 69.4

(4) Picture pointing to spoken wordTotal (48) 47. 0.4Animals (24) 23. 0.4Man-made (24) 24.

(5) Definitions (n = 12)

Adequate 12.

InadequateContaining major errors

*Test modified to multiple choice format , see text; atotal for three categories (animals , sea creatures and birds); btotalfor three categories (household items , musical instruments and vehicles); cnumber of items for which adequate (i.detailed and factually correct) definitions were provided; dnumber containing substantial factual errors. The test wasfrom Hodges et al. (1992).

Picture pointing in response to spoken word confirmed that semantic comprehensionwas impaired in all patients. For normal subjects this is extremely easy (mean score47.9, SD = 0.4 , out of a maximum of 48), hence the scores in the patients , with theexception of F . , reflect a profound deficit in this test which requires words and picturesto be processed and matched via the semantic system. In the definitions test all patientsand controls were given 12 standard names of items in the battery to define. Normalsproduce adequate (i. e. detailed and factually correct) definitions for nearly all ofthese.The only occasional errors produced are perseverative. By contrast, the patientsdefinitions were frequently grossly impoverished (e.g. rhinoceros

, '

is it an animal?')or contained numerous factual intrusive errors (e. g. deer

, '

animal , it gives milk , likea 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.

g. '

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, picturepointing, sorting of pictures and generation of verbal definitions. Superordinate knowledgewas better preserved than subordinate knowledge , although it is noteworthy that the


TABLE 6. EXAMPLES OF EMPTY OR ERRONEOUS DESCRIPTIONS GIVEN BY PATIENTS ONDEFINITIONS 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 ofword comprehension or production , we also administered a range of non-verbal semanticmemory 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 madeby combining two incongruous halves of real items (e. g. a head of a mouse with thebody of a lion), and are asked to classify each as a real or unreal item. All three patientswere 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 contrastnormal 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 versionwas not used in this study). For instance , the target picture of an Egyptian pyramidis presented above two drawings depicting a palm-tree and a fir-tree , and the subjectis asked to judge which one goes with the pyramid. Other examples are spectacles witheye and ear , saddle with goat and horse. P. s performance was at chance , F.M. and


L. scoted42 (81 %) and 36 (69%), respectively, out ofa total of 52. Normal controlsmake a maximum of three errors.

P. and J. L. were also tested for their knowledge of famous personalities. On amodified 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 wereunable 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. Hodgesand K. E. Patterson , unpublished data). She shows severe impairment on tests ofenvironment sound-picture matching and in demonstrating the use of real household items.

DISCUSSION

The five patients reported here all presented with a neuropsychological syndromeunderstandable in terms of a progressive and relatively pure breakdown in semanticknowledge; in keeping with the report by Snowden et at. (1989), we have called thissemantic dementia. We prefer this term to progressive aphasia because the deficit affectsmore than language processes. Semantic dementia conveys the concept of profound andpervasive semantic deterioration which disrupts language , factual memory and knowledgeand object recognition. The discussion will focus on (i) the neuropsychological featureswhich characterize this distinctive clinical syndrome , (ii) aspects which resemble orcontrast with the deficits found in other degenerative brain diseases , namely Alzheimerand Pick' s disease , (Hi) the relationship of semantic dementia to primary progressiveaphasia , and (iv) the possible anatomical basis.

The most prominent neuropsychological feature of this syndrome is a striking lossof vocabulary, both receptive and expressive , affecting particularly nouns. This explainsthe frequent presenting complaint of difficulty ' remembering ' the names of people , placesand things. In the early stages of the disorder , patients also complain of word-findingdifficulty and exhibit marked circumlocutions. Later , speech is punctuated by frequentpauses and often semantic paraphasias. Initially, informal conversation may not revealany impairment of comprehension and only if single-word comprehension for relativelyuncommon 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 bepredominantly omissions (don t know), while errors of commission are typically semanticin type , consisting of within-category errors (e.

g. '

violin ' for accordion), superordinateterms (' animal' for fox) or circumlocutions.

Another early and consistent feature resulting from vocabulary loss is a severeimpairment in the generation of exemplars from semantic categories (such as animalsmusical instruments , etc. ) on verbal fluency testing. Patients with more advanced diseaselike the case of P. P. reported here , may be totally unable to generate examples fromany category. In contrast , letter fluency (generating words (excluding proper names)beginning with a given letter of the alphabet) is much less impaired. The former taskdepends 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(Hodges et ai. 1990).


,I'

The semantic test battery employed in this study was designed to assess input to andoutput from semantic memory via different modalities in patients with dementia ofAlzheimer type (DAT) (Hodges et ai. 1992). The pattern of results here parallelsthat found in DAT , but indicates a more profound deficit. The most telling findingsinclude: (i) grossly impaired category fluency, with complete failure on lower ordercategories such as types of boat or dog; (ii) severely impaired naming; (iii) defectivesorting according to specific attributes coupled with largely intact sorting at a categorylevel; (iv) errors matching pictures of the items to their spoken names; (v) difficultygenerating verbal definitions of the items. The pattern of breakdown involving lowerorder subordinate or attributional knowledge with retention of superordinate categoryknowledge is identical to that described by Warrington , Shallice and others (e.Warrington , 1975; Warrington and Shallice , 1984; Shallice , 1988) in patients with lossof semantic memory due to non-progressive focal brain damage. The errors made onthe definitions test were particularly revealing in the milder patients whose expressiveand receptive language can appear relatively normal on casual conversation.

Evidence of the patients ' pervasive deficit in semantic memory, affecting not justnaming and word comprehension but also more fundamental aspects of knowledge aboutliving and man-made things , comes from their performance on the picture sorting testin the semantic battery. In addition , more extensive tests of non-verbal semantics weregiven to three patients (P. , J. , F. ). All three showed marked impairment onan object decision test requiring subjects to judge the veracity of real and non-real chimericobjects and animals, and on the Pyramids and Palm-trees Test (Howard andOrchard-Lisle, 1984; Howard and Patterson , 1992) which requires the matching ofconceptually linked drawings. Detailed longitudinal study of P.P. has demonstrated agross impairment in her use of real household items and in matching pictures toenvironmental sounds. In P.P. and J.L. an early spontaneous complaint was in recognizingpeople from sight , sound or description. Both have been shown to be severely impairedat picking out famous faces from arrays containing photos of famous and non-famousindividuals , in accessing any semantic information from faces and in recognizing famousnames.

In contrast to the progressive breakdown in the semantic components of languagesyntax 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, com-prehension of even fairly complex syntax can be normal , as evidenced by the near perfectperformance 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 ofsingle words and sentences was also normal in all patients. Schwartz et at. (1979) reported

a patient showing similar preservation of syntax and phonology accompanying severelexical 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 spelling-to-sound correspondence , making phonologically plausible (or regularization) errorson these items: The pattern of surface dyslexia arises because of disruption in thelexical/semantic procedure of whole-word reading, so that increasing reliance is placedupon sub-word correspondence between spelling and sound (Ellis and Young, 1988;


McCarthy and Warrington , 1990). A full discussion of the relevance of these findingsto the controversy concerning the putative existence of a whole-word non-semantic routeof reading is beyond the scope of this paper. The characterization of the readingimpairment has been investigated in more detail in several of these patients and is thesubject of a further report (Patterson and Hodges , 1992). One patient, P. , also exhibitedfeatures of pure alexia with letter-by-letter reading (Patterson and Kay, 1982). Writtenpicture descriptions paralleled spoken language , in that grammatical structure was retainedbut frequent semantic errors occurred on nouns and specific verbs. Writing of singlewords to dictation paralleled reading performance , with errors in spelling irregular wordsa 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 interpretationof the widely used New Adult Reading Test (NART) (Nelson , 1982). The ability toread 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 predictpre-morbid verbal IQ. Since the NART consists almost exclusively of irregular wordsthe surface dyslexia typically seen in semantic dementia means that the NART maylead to erroneously low predictions of pre-morbid intellectual level if the examiner doesnot recognize the dyslexia. A better estimate of pre-morbid intellect in these patientscomes from the Block Design sub-test from the W AIS and Raven s Coloured Matriceson which performance was preserved even in the patients with the most profound semanticdementia.

Turning to theW AIS results in semantic dementia, the most consistent and in somecases , profound , impairment was noted in the Verbal sub-tests dependent upon wordknowledge , notably Information , Similarities and Vocabulary. By contrast arithmeticskills were reasonably well retained and digit span was invariably normal. Of thePerformance sub-tests , Block Design and Digit Symbol , which do not rely on any semanticknowledge , were within normal limits for all five of our cases , whilst Picture Completionwas impaired in the most advanced cases due to the loss of meaning of the stimuluspictures.

The clinical evidence suggests that personal autobiographical and practical day-to-day memory is preserved , certainly in the early stages of the disorder. This dissociationoffers support for the episodic-semantic dichotomy first proposed by Tulving (19721983). This distinction is most clear in the area ofremote memory; despite the oftenprofound loss of semantic memory, patients are able to remember past family eventsand outings , and accurately relate details of their autobiography. This discrepancy wasdemonstrated quantitatively in two of the patients (F. , J. L.) using the AutobiographicalInterview (Kopelman et al. 1989). Even P. P. , in whom comprehension of nominalterms and naming ability was virtually absent , could still relate some basic family eventsalbeit anomically and with frequent semantic substitutions (such as sister for daughter),and seems to recall visits to Cambridge. In keeping with this observation , temporalorientation is also preserved. The laying down of new episodic memories is likely tobe seriously impaired as the semantic deficit progresses since semantic memory mustultimately subserve other memory processes (see Mayes , 1988). Formal assessmentof verbal memory presents considerable difficulty because of impairment in wordmeaning. However , most ofthe patients showed some ability to learn new verbal material


and , in contrast to patients with DAT (Butters et ai. 1988), the proportion retained

after a delay was normal in some patients.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 inthe four patients tested. However , memory for faces on the Warrington RecognitionMemory Test (Warrington , 1984) was less consistent , being normal in two patients andimpaired in two others. Visuospatial skills were unequivocally preserved even in advancedcases: in addition to good performance on Block Design , all of the patients performedwithin normal limits on Raven s Coloured Matrices , and copy of the Rey-OsterriethFigure was executed without substantial error in all five. In addition , performance ona 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; Spinnlerand Della Sala , 1988; Hodges et ai. 1990 , 1991), it is also recognized that atypicalcases 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. Certainlythe progressive disruption in semantic memory is compatible with that hypothesis. InDAT 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 memoryeven 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 memoryand early impairment in visuo-perceptual skills. These features contrast with those foundin semantic dementia. To our knowledge , there have been no reported cases with featuresof semantic dementia who have been shown to have pathologically verified DA T. Inaddition , functional brain-imaging studies , PET and SPECT , in our cases have not shownthe bilateral posterior occipito-parietal deficits characteristic ofDAT (Haxby et al. 1986;Johnson et ai. 1987; Neary et ai. 1987). The demonstration of focal and oftenasymmetric temporal lobe atrophy on CT and/or MRI in four patients is also againstthis 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 MRIfindings , suggest that semantic dementia may herald the onset of Pick' s disease. Asreported by Poeck and Luzzatti (1988), Pick' s first case (1892) had a severe languagedisorder in association with focal atrophy of the left temporal pole. He subsequentlydescribed 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); Mingazzini1914; Stertz , 1926; Malamud and Boyd , 1940). More recently, patients with relativelypure language disorders of semantic type , focal cerebral atrophy and the pathologicalchanges 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)


original patients with selective impairment of semantic memory were later shown tohave Pick' s disease on autopsy (E. K. Warrington , personal communication) and onedeveloped features of Kluver-Bucy syndrome (Cummings and Duchen , 1981). Althoughthe histological diagnosis in our patients is uncertain, the syndrome is more in keepingwith Pick's disease than DAT.

Turning to the difficult issue of the relationship between semantic dementia and primaryprogressive aphasia , it is important to consider the evolving use of the latter diagnosticterm. Mesulam , in his seminal article of 1982 , drew attention to the clinical syndromeof ' slowly progressive aphasia without generalized dementia . This was characterizedby progressive anomic aphasia, sometimes with eventual impairment of reading, writingand comprehension , but with sparing of ' other areas of comportment' even on prolongedfollow-up over 5- 10 yrs. Excluding one highly atypical case (a 17-yr-old with pureword deafness and normal naming), four of the five older patients had a severe non-

fluent output with impaired syntactic production and repetition , but relatively normalauditory comprehension. Following this report , a number of authors reported furthersimilar cases under various headings including non-familial dysphasic dementia (Mehleret ai. 1987), slowly progressive aphasia (Poeck and Luzzatti , 1988; Kempler et al.1990), progressive language impairment without dementia (Basso et ai. 1988) and

progressive aphasia due to focal atrophy (Tyrrell et ai. 1990). Many of these casesshare the core characteristics of the original Mesulum cases , namely progressive non-

fluent aphasia with impaired syntax but good comprehension. However , some patientspresent with a radically different picture of language impairment, with afluent aphasiaand preserved syntax , phonology and repetition , but severely impaired semantic com-prehension (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 anyoperational criteria , considerable controversy has arisen regarding the nosological statusof 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 supporta dichotomous view , with progressive aphasia as a clinically and pathologically distinctsyndrome (Mesulum, 1982; Weintraub et al. 1990). Two reports containing pathologicalconfirmation of the diagnosis have supported the latter view (Kirshner et al. 1987;Mehler et al. 1987). In both reports , each containing two patients , unique pathologicalchanges not typical of either Alzheimer s or Pick' s disease were found. It should benoted , however , that these four patients all had a progressive non-fluent dysphasia asdescribed by Mesulam. The situation has also been further clarified by the latest reportfrom Mesulam s group (Weintraub et ai. 1990) in which , for the first time , operationalclinical criteria for primary progressive aphasia have been applied as follows: (i) atleast a 2-yr history of progressive decline in language; (ii) prominent language deficitswith normal or relatively preserved performance on tests of other mental functions;(iii) independence in activities of daily living. Their four patients fulfilled these criteriabut most importantly, again , all had a non-fluent picture with hesitant , often dysprosodicspeech , frequent phonemic paraphasias , impaired syntax , poor repetition and preservedcomprehension. Clearly, the features of the language impairment in these cases contrastssharply with those found in our patients.


We tentatively suggest that the term primary progressive aphasia should be appliedonly to those patients with a progressive non-fluent dysphasia in which the deficit affectsvery predominantly the output of language but spares word comprehension and causesno impairment in non-verbal semantic knowledge. For the patients we described herewe therefore prefer the designation semantic dementia. Review of the literature alsosuggests that progression of non-fluent primary progressive aphasia is typically slowover many years. In several of our patients the decline was precipitous.

Finally, what conclusions can be drawn regarding the locus of pathology in semanticdementia? The evidence from previous cases with selective impairment of semanticmemory in the context of non-progressive brain damage implicates the temporal neocortex(e. g. Warrington and Shallice , 1984; Pietrini et al. 1988; Sartori and Job , 1988).

Similarly, in other patients with the fluent type of progressive aphasia suggesting semanticbreakdown , selective and often asymmetric atrophy of the temporal lobes has beenreported (Poeck and Luzzatti , 1988; Graff-Radford et al. 1990; Kempler et al. 1990).In three of our patients , strikingly focal left temporal lobe atrophy was present on CTand/or MRI imaging; the other two had bilateral temporal atrophy. Functional brainimaging has also implicated the left temporal region in our patients. In the PET scanningstudy reported by Tyrrell et al. (1990), the patients with progressive fluent dysphasiaall had reduced metabolism most marked in the left anterior temporal lobe. The twopatients reported by Kempler et al. (1990) with progressive fluent dysphasia , also hadfocal areas of hypometabolism in the left temporo-parietal region. Examination by SPECTscans in Snowden et al. ' (1989) patients with semantic dementia have shown deficitsless clearly localized , but always maximal in the left temporo-parietal region. Fromthe evidence , it would seem that this syndrome results from extensive temporal neocorticaldamage 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 Antounfor radiological assistance , Drs Basil Shepstone and Philip Wraight who performed the SPECT scans inOxford and Cambridge , respectively, and Drs Guy Sawle and Richard Wise for performing the PET studyon patient P. P. We also wish to thank Linda Pallister who provided invaluable secretarial assistance.

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(Received April 6, 1992. Accepted May 13, 1992)

semantic dementia · case reports in none of the five cases was there a family history of dementia,...

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