BRAIN AND LANGUAGE 5, 103- 118 (1978) Speech Disturbances in Presenile Dementia Related to Local Cerebral Blood Flow Abnormalities in the Dominant Hemisphere LARS GUSTAFSON, Bo HAGBERG, AND DAVID H. INGVAR University Hospital, Lund, Sweden Ten female patients, age 50-70 years, suffering from presenile dementia and showing signs of defective speech function were analyzed. All patients underwent measurements of regional cerebral blood flow (rCBF) by the xenon clearance technique using a 32-detector piece of equipment, and all showed a marked reduction of the hemisphere mean blood flow level. In addition, regional decreases of blood flow of the gray matter was demonstrated. Patients with a marked reduction in the temporo-parieto-occipital regions showed signs of receptive aphasia including alexia and agraphia. Patients with a marked frontal reduction showed signs of expressive aphasia of various types including stereotyped language, voluble speech, echolalia, and mutism in later stages. The results give further support to our previous conclusion that subsymptoms of presenile dementia, apparently also speech disturbances, can be related to local degenerative changes in the brain, which in their turn are accompanied by local reductions of the blood flow of the gray matter. There is pathoanatomical evidence to support this conclusion. INTRODUCTION Speech disturbance is a frequent symptom in organic dementia. In dementia such symptoms have been related to the localization of the degenerative changes of the cerebral neurons in post mortem examinations (Sjogren, Sjogren, & Lindgren, 1952; Mansvelt, 1954; McMenemy, 1963). On the whole, however, these studies have not established that the degenerative brain changes have a distribution to be expected from the vast literature on the morphological basis of speech disturbances (Nielsen, 1947; Critchley, 1953; Brain, 1961; Luria, 1966, 1970, 1973). With the 133-xenon intraarterial technique for regional cerebral blood flow (rCBF) measurements (Lassen & Ingvar, 1972) it is possible to presenile This study was supported by the Swedish Medical Research Council (Projects 25-3950, 61-4568, 14-10, and 14&I), the Wallenberg Foundation, and the Thuring Foundation in Stockholm. The authors are indebted to Professor Lennart Nilsson for aiding the present study in many respects. Miss Uhika Serin gave efficient secretarial help. Requests for reprints should be sent to Prof. David H. Ingvar, Department of Clinical Neurophysiology, University Hospital, Lund, 5, Sweden, S-221 85. 103 0093-934x/78/0051-0103$02.00/0 Copyright All rights 0 1978 by Academic Press, Inc. of reproduction in any form reserved. 104 GUSAFSON, HAGBERG, AND INGVAR measure the functional level of mainly the lateral structures of one hemisphere. In presenile dementia it has been shown that various rCBF parameters show a reduction which is most marked in those regions in which the cortical degenerative changes are pronounced (Brun, Gustafson, & Ingvar, 1975), and hence that the rCBF pattern in viva reflects the distribution of the neuronal degeneration. The present investigation includes 10 presenile patients with symptoms of aphasia in which the rCBF was measured in the dominant hemisphere. The purpose was to relate the rCBF findings to symptoms of aphasia, i.e., to investigate whether speech disturbances, like other subsymtoms in organic dementia, show a relationship to a reduced functional level, i.e., to low rCBF values in certain brain regions (Gustafson & R&berg, 1974; Gust&son & Hagberg, 1975; Hagberg & Ingvar, 1976). MATERIALS AND METHODS Ten females with speech disturbances were selected from a group of fifty presenile patients described elsewhere (Ingvar & Gustafson, 1970; Gustafson & Risberg, 1974). None of them had abused alcohol or drugs, had chronic psychosis, endogenous intoxications, severe head injuries, or major strokes with gross neurological symptoms. The age of the patients ranged from 59 to 70 years and the duration of symptoms from 4 to 8 years. The clinical diagnoses were Alzheimer’s disease in seven cases, and diffuse cortical atrophy with frontotemporal predominance, probably Pick’s disease, in three cases. Clinical Investigations All patients went through complete somatic and neurologic examination including EEG and neuroradiological studies (see case histories below). Psychiatric and Psychometric Investigations The psychiatric investigation of the patients was performed according to a formalized rating scale for symptoms of mental dysfunction, emotional disturbances, and behavior changes in dementia. The psychiatric rating, which after the first investigation was repeated at regular intervals, has been described elsewhere (Gustafson, 1975). The patients were tested with a conventional battery for cognitive deficits. It included tests for verbal performance, immediate memory, logic-inductive ability, and spatial ability. The word list, paired associates (Cronholm & Molander, 1957), and Kohs’ block (Matarazzo & Wechsler, 1958) were scored in stanine points (mean = 5, SD = 2) and memory for design (Graham & Kendall, 1960)in three categories, “reproduction,” “copy,” and “cannot copy,” the last category being equated with constructional apraxia. Examination for aphasia was made according to Eisenson (1954) in a slightly modified version, and in this context the evaluation of verbal performance is reported upon. Following Weisenberg and McBride (1935), Eisenson (1954), Lhermitte and Gautier (1%9), and Luria (1973) the speech analysis was divided into two major lines, related to expressive and receptive disturbances. Expressive disturbances were examined with items of successively increasing complexity, starting with verbal repetition of numbers, words, and sentences. Then items followed for automatic speech (counting, enumeration of the alphabet, the days of the week, and the months), naming of body parts, real objects, and on the conceptual level, simple word LOCAL CEREBRAL BLOOD FLOW STUDIES 105 finding, sentence completion, opposites, and similarities (abstract word finding). Care was taken not to include aspects in the evaluation other than just the ability for expressive verbal communication. Receptive disturbances were likewise examined at levels of increasing complexity. Simple comprehension required an adequate response to simple propositions (“Sit down, please”; “Point at your nose”) and simple questions (“What do people wear on their heads?“). The latter type of items was followed by multiple-choice answers suggested verbally to the patients. For evaluating complex comprehension a paragraph was read to the patient, and he was then questioned about its content. Also here care was taken to avoid including in the evaluation things other than comprehension of verbal communication. The following further aphasia items were made the object of special rating: Dysarthria: indistinct, slurred speech. Logorrhea: rapid, voluble speech. Echolalia: meaningless imitation and repetition of the speech of other people. Mutism: absence of spontaneous speech. Stereotyped speech: frequent, unwarranted repetition of phrases and words. Verbal perservation: involuntary continuation or repetition of phrases and sentences related to preceding questions or topics. Emotional speech retained: inability to give an ordinary understandable verbal contact except when provoked, or in effect, a retention of simple, emotionally loaded expressions. Pharaphasia: incorrect substitution of words or parts of them. Jargon aphasia: fluent speech consisting of a mixture of neologistic, paraphasic, and appropriate words. The symptoms of aphasia were related as absent (0), present to a slight amount (+), and definitely present (+ +). In addition, the patients were rated as to: Recent memory: memory for events during the past 6 months. Remote memory: memory for previous events from childhood and later up to the last year. Momentary confabulation: the tendency to hide memory failure and to fill the memory lacunes with false statements (“Verlegenheits-Konfabulation,” “confabulation of embarrassment”; Bonhoeffer, 1901, 1904; Berlyne, 1972). Fantastic confabulation: spontaneous fabrication of adventurous, fantastic experiences. The rCBF Technique The rCBF was determined at rest (i.e., with silence in the laboratory and the patient wearing eye pads) by means of the intra-arterial-133-xenon injection technique using a computer-operated 32-detector piece of equipment (Ingvar & Gus&&on, 1970; Sveinsdottir, Torlof, Risberg, Ingvar, & Lassen, 1971). The theoretical background and the clinical application of this method have been described elsewhere (Lassen, Hoedt-Rasmussen, Sorenssen, Skinhoj, Crongvist, Bodforss, & Ingvar, 1963; Sveinsdottir et al., 1971; Lassen & Ingvar, 1972; Risberg & Ingvar, 1973). By this method the level of the blood flow (function) is measured mainly in the lateral part of one hemisphere. Subcortical and medial parts of the hemisphere are seen less well by the detectors due to tissue absorption. All the present patients were measured in the left (dominant) hemisphere with the 32-detector system. The positions of the detectors were localized on a lateral skull X ray. The blood flow parameter of main interest in the present context isfinlt, calculated from the initial slope of the clearance curves. This parameter is mainly determined by the level of activity of the gray matter. 106 GUSAFSON, HAGBERG, AND INGVAR RESULTS General Findings At the time of the rCBF study, all 10 patients showed signs of advanced intellectual deterioration. Their principal symptoms and psychometric performance are summarized in Table 1. TABLE AGE 1 PARAMETERS, CLINICAL SYMPTOMS, COGNITIVE FUNCTIONS, AND ABNORMALITIES IN 10 PATIENTS WITH PRESENILE DEMENTIA Case No. (Yew Duration (yea@ I U.P. 60 8 Age 2 J.K. 3 T.Q. 4 F.G. 62 62 63 4 6 4 Clinical findings Cognitive functions’ Slightly euphoric but preserved insight Bewildered, confused Recent memory strongly reduced Remote memory reduced Slight momentary confabulation Test: v 1 st. My 0 Completely disorientated Aspontaneous Slow, stiff gait Facial masking and coarse manual tremor Recent memmy strongly reduced Remote memory moderately reduced Momentary confabulation Silent, sometimes indistinct speech with stereotyped phrases Test: V 0 M, I 0 0 Restless, irritable Confused, perseverating Emotional labile Facial masking Recent memory strongly reduced Remote memory moderately affected Slow, slurred speech Test: V I st. MI 0 Restless Disorientation as to time Easily tired Slightly euphoric and emotionally labile Recent memory strongly reduced Remote memory moderately reduced Slow, indistinct speech with stereotyped fragment&d phrases and words Test: V I St. M, 1 st. I 0 M, reproduces Agraphia, ideational and motoric Acalculia Apraxia, dressing I 0 Ms cannot copy Agraphia, alexia Acalculia Apraxia, constructional MS COPY Acalculia Apraxia, ideomotor Right-left disorientation Agnosia, tactile I 0 MS COPY Acalculia Agnosia, auditive SPEECH Speech abnormalities Expressive: sentence completion, abstract word finding Receptive: comprehension of complex meaning Expressive: abstract word finding Receptive: slightly disturbed complex comprehension Expressive: naming Receptive: comprehension of complex meaning Expressive: naming, sentence completion, abstract word finding Receptive: slightly disturbed complex comprehension LOCAL CEREBRAL TABLE Case No. (Years) Duration w%wS) 5 H.Q. 59 9 AiT BLOOD FLOW 107 STUDIES 1 (Continued) Clinical findings Cognitive functions” Speech abnomnlities Confused, bewildered Anxiously restless Emotional labile Recent and remote memory strongly reduced Slight momentary confabulation Test: V 0 M\ 0 Test: V 0 Mr 0 I 0 MS 0 Agraphia Al&a Acalculia Apraxia, ideomotor and constructional Right-let? disorientation Agnosia, general Expressive: repetitive, automatic, naming, sentence completion, abstract word finding Receptive: disturbance of complex comprehension Test: V 0 M, 0 I 0 ‘44s cannot copy Agrapbia Apraxia, ideomotor and constNctional Agnosia, tactile Expressive: naming, sentence completion, abstract word finding Not testable Not testable Test: V 0 U” I 0 0 Ms cannot copy Agraphia, ideational Acalculia Agnosia, visual Expressive: repetitive, automatic, naming, sentence completion, abstract word finding Receptive: simple and complex comprehension Not testable Not testable 6 K.F. 64 7 Anxiously restless Completely disorientated Irritable, emotionally labile Facial grimacing Severe global amnesia Slight momentary confabulation Sluned, “stuttering” speech Can recognize familiar voices 7 H.H. 70 7 (1967) Euphoria Logorrhea, slight dysarthria Recent memory severely reduced Remote memory preserved Fantastic confabulation I 0 MS cannot copy Agraphia Alexis Acalculia Apraxia, constructional Agnosia, audit& Expressive: automatic speech, naming, sentence completion, abstract word finding Receptive: comprehension of complex meaning (1971) Akin&a Amimia Mutism Spells of crying Seems to understand simple comments 8 H.K. 64 9 (1%9) Euphoria, bulemia Hyperorality Severe general amnesia Fantastic confabulation Voluble, stereotyped speech (1972) Restless, amimia No spontaneous speech, but echolaliaand echopraxis Perseverating, stereotyped writing Some simple practical abilities retained 108 GUSAFSON, HAGBERG, TABLE Case No. (Y-m Duration (Years) 9 H.O. 50 5 “be 10 B.D. 63 8 AND INGVAR 1 (Continued) Clinical findings Cognitive functions’ Speech abnormalities (1970) Restlessly walking around Completely disorientated Total emotional indifference Global amnesia No verbal contact but preserved simple uttemces Test: V 0 M, 0 I 0 MS COPY Agraphia, ideational Acalculia Apraxia, ideomotor Agnosia, general Expressive: repetitive, automatic, nanling, sentence completion, abstract word finding Receptive: simple and complex comprehension Slight leftsided hemiparesis Aspontaneous, agitated Amimia Hyperorality Bulimia Anarthria Not testable Not testable Euphoric, restless Recent and remote me”twy severely reduced Voluble, stereotyped speech Paraphasic, neologistic jargon Test: V 0 M, 0 I 0 MS cannot copy Agmphia Alexia Acakulia Apraxia, general Agnosia, general Expressive: automatic, nanling, sentence completion, abstract word finding Receptive: simple and complex comprehension (I Symbols: V = verbal function, M, = verbal immediate memory, I = logic-inductive function, MS = spatial immediate memory or spatial function. Points are given in stat&e, St., with m = 5.0 and SD = 2.0. 0 = adequate attempt but failure in perfomxmce; 0 = not capable of attempt. According to our previous analyses (Gustafson & Hagberg, 1975; Hagberg & Ingvar, 1976), the patients could be classified as having either: a general intellectual and verbal reduction including anomia, acalculia, and disturbed but retained spatial ability (group C 4 according to Hagberg & Ingvar, 1976); or a general intellectual and verbal reduction with aphasia, agnosia, and apraxia, as well as a distorted spatial ability (group C 5). All patients showed memory failure, verbal perseveration, disorientation, and impairment of thinking, speech, and motor behavior. They also showed personality alterations with emotional shallowness, or indifference, euphoria, and in some cases, uninhibited behavior. Emotional lability was common with easily provoked catastrophic reactions or spells of aggressive behavior. The symptoms of speech disturbances are presented in Table 2. Apart from symptoms of dementia including speech disturbance, none of the 10 patients showed other neurological abnormalities, except case 9 who showed a slight left-sided hemiparesis. The mean rCBF parameters of the 10 patients together with values from 109 LOCAL CEREBRAL BLOOD FLOW STUDIES. TABLE 2 SYMFTOMS Patient No. Patient code Expressive functions Repetitive Automatic Naming Sentence completion Abstract word finding Logorrhea Echolalia Mutism Stereotyped speech Preserved emotional speech Dysarthria Receptive functions Simple Complex OF SPEECH DISTURBANCE 1 2 3 U.P. J.K. T.Q. - - - ++ - 4 5 6 F.G. H.Q. K.F. - ++ ++ ++ - ++ + ++ ++ ++ ++ ++ ++ 7 ++ ++I’ ++” ++” ++ ++ ++ ++” ++ ++ - ++I’ ++ ++ + ++ ++ - - ++ ++ ++ ++ ++I’ ++” ++ ++ + - + ++I’ + + ++ + - + ++ + ++ + + ++ ++ 9 10 H.O. B.D. ++ ++ ++ ++ ++I’ ++ - - 8 H.H. H.K. ++ - Symbols: -, absence of symptom; +, slight or intermittent presence of the symptom: + +, presence of the symptom; l/, evaluation refers to stage prior to the final mutistic one. a control group are shown in Table 3. The significant differences are easily seen. Individual Findings The 10 patients will be described individually with regard to symptoms, test performance, and rCBF measurements. The rCBF distribution refers only to&, values (Fig. 1). TABLE 3 MEAN HEMISPHERE 10 PATIENTS rCBF VALUES WITH IN CONTROLS PRESENILE DEMENTIA 10 F 41 + 4 35 + 6 AND IN Age Patients Patients with presenile dementia P value (one-tailed t test) Control group (Ingvar et al., 1975) No. (years) 10 62-e5 15 4625 lF,14M 40?2 34 2 5 54 + 7 43 r 4