Dissociation of numbers and objects in corticobasal degeneration and semantic dementia C.H. Halpern, BA; G. Glosser, PhD†; R. Clark, PhD; J. Gee, PhD; P. Moore, BA; K. Dennis, BA; C. McMillan, BA; A. Colcher, MD; and M. Grossman, MD
Abstract—Background: Semantic memory is thought to consist of category-specific representations of knowledge that may be selectively compromised in patients with neurodegenerative diseases, but this has been difficult to demonstrate reliably across object categories. Methods: The authors evaluated performance on several simple measures requiring number representations (including addition and magnitude judgments of single digits), and on a task that requires object representations (an object naming task) in patients with corticobasal degeneration (CBD; n ⫽ 13) and semantic dementia (SD; n ⫽ 15). They also examined regional cortical atrophy using voxel-based morphometric analyses of high resolution structural MRI in subgroups of five CBD patients and three SD patients. Results: CBD patients were consistently more impaired on simple addition and magnitude judgment tasks requiring number representations compared to object representations. Impaired performance with numbers in CBD was associated with cortical atrophy in right parietal cortex. By comparison, SD patients demonstrated a greater impairment on a naming task requiring object representations relative to their performance on measures involving number representations. This was associated with left anterior temporal cortical atrophy. Conclusion: The cognitive and neuroanatomic dissociations between CBD and SD are consistent with the hypothesis that number and object representations constitute distinct domains in semantic memory, and these domains appear to be associated with distinct neural substrates. NEUROLOGY 2004;62:1163–1169
Semantic memory refers to the long-term store of representations for facts, concepts, and objects, as well as the processes that allow us to organize and retrieve these representations.1 Recent investigations of patients with neurodegenerative diseases have focused on the dissociation of categories of knowledge in semantic memory. Perhaps the most frequently examined distinction involves selective difficulty with natural kinds like ANIMALS (we use capitals to indicate a concept) or manufactured artifacts like TOOLS.2,3 Controversies nevertheless persist in our understanding of category-specific representations in semantic memory,4,5 possibly because of the difficulties associated with distinguishing these complex object concepts, and when category-specific effects are found, demonstrating these dissociations in a reliable manner. In the present study, we sought to sharpen our understanding of semantic memory by focusing on the dissociation of a different set of categories—those concerned with number and object representations. Moreover, we used evidence from high resolution structural MRI to examine the hypothesis that each of these semantic categories is maintained in part by a distinct neural substrate.
Semantic dementia (SD) is a rare neurodegenerative condition where naming is impaired early in the disease course, and comprehension of single words becomes compromised over time.6,7 Several reports document a relative deficit with object categories like ANIMALS or TOOLS,8,9 or difficulty with object categories like these relative to ABSTRACT categories.10,11 This deficit appears to be associated with left temporal lobe atrophy.12,13 Number knowledge is a distinct domain of semantic memory involving features that are quite different from the attributes of objects.14,15 We know about the meaning of “five” as a quantity independent of the objects (e.g., dolls, books, hours) that happen to be used to illustrate the concept of “fiveness,” for example, and this concept can be equally represented by arbitrary symbols such as “5” and “V.” Number concepts like “zero” emphasize that this domain does not depend on the integrity of the visual-perceptual system. Evidence to support the dissociation of number representations and object representations comes from two reported case studies with object naming difficulty relative to preserved number representations.16,17 Cases of relatively isolated acalculia are
†Deceased. From the Departments of Neurology (C.H. Halpern, P. Moore, K. Dennis, and C. McMillan, and Drs. Glosser, Clark, Colcher, and Grossman) and Radiology (Dr. Gee), University of Pennsylvania, Philadelphia. Supported in part by the US Public Health Service (AG15116, AG17586, and NS35867). Portions of this work were presented at the meeting of the Cognitive Neuroscience Society; New York, NY; April 2003. Received July 10, 2003. Accepted in final form December 2, 2003. Address correspondence and reprint requests to Dr. Murray Grossman, Department of Neurology–2 Gibson, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283; e-mail:
[email protected] Copyright © 2004 by AAN Enterprises, Inc.
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extraordinarily rare.18-21 In a recent study of corticobasal degeneration (CBD), we reported an impairment on tasks such as dot counting and oral calculations that require number representations.22 Whereas some CBD patients have naming difficulty, there is little evidence of object comprehension impairment.23,24 Based on clinical features such as cortical sensory loss and apraxia,25,26 and clinical neuroimaging observations,27,28 the cortical component of this neurodegenerative disease appears to be centered in the parietal lobe. Neuroanatomic correlations,29,30 and functional neuroimaging work,31,32 have implicated parietal cortex in number representations. The number deficit in CBD thus appears to be associated primarily with parietal lobe atrophy. In the present study, we examined cognitive and neuroanatomic dissociations of number and object representations in CBD and SD. We hypothesized that CBD patients would be more impaired on tasks requiring number representations than object representations, and that this would be related to cortical atrophy in a parietal distribution. SD patients were expected to encounter more difficulty on a measure involving object representations compared to performance on tasks requiring number representations, and we expected this to be related to atrophy of temporal cortex. Methods. Cognitive study. Subjects. We examined patients with the diagnosis of CBD (n ⫽ 13; 7 men, 6 women; age ⫽ 66.76 ⫾ 10.15 years; education ⫽ 15.15 ⫾ 4.58 years; disease duration ⫽ 50.46 ⫾ 20.86 months; Mini-Mental State Examination33 [MMSE] score ⫽ 19.62 ⫾ 5.09) or SD (n ⫽ 15; 9 men, 6 women; age ⫽ 67.73 ⫾ 8.75 years; education ⫽ 16.39 ⫾ 3.28 years; disease duration ⫽ 56.64 ⫾ 20.81 months; MMSE score ⫽ 22.87 ⫾ 3.72) recruited from the outpatient clinic of the Department of Neurology at the Hospital of the University of Pennsylvania. These patient groups were matched for age [t(26) ⫽ 0.73; NS], education [t(26) ⫽ 0.42; NS], disease duration [t(26) ⫽ 0.45; NS], and MMSE [t(26) ⫽ 0.06; NS]. The clinical diagnosis was made by a board-certified neurologist (M.G.) with expertise in the diagnosis of neurodegenerative conditions. Seven unselected CBD patients included in this study participated in our previous study.22 There are no published consensus criteria for the clinical diagnosis of CBD, although experts have suggested specific clinical features that are important in diagnosing CBD.34 The criteria we developed, based on a review of the literature examining clinicalpathologic diagnosis of CBD and our personal experience,35 include insidious onset and gradual progression of higher cortical functioning, including apraxia, alien hand syndrome, and cortical sensory loss. Some of these patients may also have visual perceptual-spatial difficulty or anomia, depending on the laterality of their disease. Additional diagnostic criteria include the presence of an asymmetric akinetic-rigid disorder involving gait instability, dystonia, and myoclonus, but little resting tremor. There was no evidence for an ocular motility disorder, and these patients did not show evidence of neglect. All CBD patients presented with extrapyramidal motor features that were somewhat bilateral, including 9 of 13 CBD patients with extrapyramidal motor features primarily on the left, 3 of 13 patients with extrapyramidal features more prominently on the right, and 1 CBD patient with fairly symmetric involvement. The basis for the clinical diagnosis of SD was the LundManchester criteria36 for frontotemporal dementia, modified by McKhann et al.37 The SD subgroup of frontotemporal dementia patients demonstrated fluent, circumlocutory speech with frequent word-finding pauses, semantic paraphasias, difficulty naming objects in the examination room, and a comprehension deficit.38 Structural and functional neuroimaging were consistent with 1164
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the clinical diagnosis in all patients. Other causes of dementia were excluded by history, physical examination, serum studies, and brain imaging, including other neurodegenerative conditions such as Alzheimer disease (AD), structural neurologic disease such as stroke or hydrocephalus, primary psychiatric disease such as major depression or psychosis, and medical conditions that can interfere with cognitive functioning. Although most of the patients (CBD, n ⫽ 10; SD, n ⫽ 14) were taking cholinergic-supplementing agents (e.g., donepezil, galantamine) and some (CBD, n ⫽ 6; SD, n ⫽ 7) were taking modest dosages of serotonin-specific reuptake inhibitor antidepressants (e.g., sertraline), our patients were not taking sedating medications at the time of assessment. This study was approved by the Institutional Review Board of the University of Pennsylvania, and all patients and caregivers participated in the informed consent procedure. Materials. Pencil-and-paper tests assessing number and object representations were presented to all patients. Arabic numeral magnitude judgment. Patients were shown two different Arabic numerals printed in large black digits on a white page while they were read aloud by the experimenter, and were asked to judge which number was greater in magnitude. We presented patients with 36 pairs of vertically arrayed numbers, one at a time, in a fixed, random order, including six pairs with only small single digits (1–3), six with only medium-sized single digits (4 – 6), and six with only larger single digits (7–9). We also presented patients with six pairs of small and medium-sized single digits, six pairs of small and larger single digits, and six pairs of medium-sized and larger single digits. The smaller digit was presented in the upper position and read first in half of each type of pair. The same pairs of numbers were used in all of the following tasks. In this task and the tasks described below, patients were allotted 45 seconds to respond with an answer, and failure to respond within this time was marked as incorrect. For all tasks, we evaluated patient accuracy and the latency to make a correct decision. Dot array magnitude judgment. Patients were shown 36 vertically aligned pairs of boxes in a fixed, random order, one pair at a time. Each box contained a randomly arranged array of filled circles (1 cm diameter) or “dots.” Patients were asked to judge which box contained the greater number of dots. Arabic numeral addition. Patients were shown 36 vertically arrayed addition problems in a fixed, random order. Patients were asked to read along as the experimenter aurally presented each addition problem, and then were asked to respond with the answer. Dot array addition. We presented patients with 36 vertically arranged pairs of boxes, each containing a randomly arranged array of dots. Patients were asked to determine the total quantity of dots by adding the two arrays together. These problems were presented in a fixed, random order. Object naming. We assessed object naming with a visual confrontation naming task. We used a measure of object naming rather than object associative knowledge because longitudinal studies of SD patients suggest that performance on associative knowledge tasks is determined in large part by disease severity.39 We assessed mildly demented SD patients in this study to minimize the confound of overall disease severity. Patients were presented with 65 black-and-white line drawings of familiar, everyday objects one at a time.40 This included frequency- and familiarity-matched sets of manufactured artifacts and natural kinds. Patients were asked to name the object in the picture and were allotted 10 seconds to respond with an answer. Failure to respond in 10 seconds was marked as incorrect. We report patient accuracy. The entire protocol, intermixed with other measures, was administered individually in one session lasting about 1 hour and 30 minutes. Patients were given frequent rest periods. The components of this protocol were administered in a fixed order, beginning with object naming, and followed by the measures involving number representations. Statistical analysis. To minimize the confound of overall task difficulty, we performed analyses of individual patient performance profiles by converting each patient’s performance on each task to a z-score based on the performance of the entire patient sample. To obtain a single measure reflecting performance with representations of number, we averaged the z-scores across the four measures of number magnitude judgment and addition in
each patient. We were unable to use healthy control subjects as a reference group for these analyses because healthy seniors scored at ceiling on all measures. Structural MRI study. Subjects. We examined the regional distribution of gray matter atrophy in subgroups of five CBD patients (left laterality: n ⫽ 4; right laterality: n ⫽ 1) and three SD patients obtained within 3 months of the above study. We used a volumetric, high spatial resolution, structural MRI, and compared these to the images of 12 age-matched healthy seniors. We were able to assess only eight patients for a variety of reasons (e.g., claustrophobia, pacemaker, technical difficulty at the time of scanning, intercurrent illness). Imaging protocol. All images were acquired by a GE Horizon Echospeed 1.5-T MRI scanner (GE Medical Systems, Milwaukee, WI). Each study began with a rapid sagittal T1-weighted image to determine patient position. Next, high resolution T1-weighted three-dimensional spoiled gradient echo images were acquired in a transaxial orientation with a repetition time (TR) of 35 msec, an echo time (TE) of 6 msec, a slice thickness of 1.3 mm, a flip angle of 30 degrees, a matrix size of 128 ⫻ 256, and a rectangular field of view giving an in-plane resolution of 0.9 ⫻ 0.9 mm. The brain volumes were normalized by registration to the SPM99 T1 template of 305 averaged brains41 using 12-parameters affine registration, nonlinear registration with 12 nonlinear iterations, and 7 ⫻ 8 x 7 basis functions. SPM9942 was used to segment the brain volumes into four tissue types (gray matter, white matter, CSF, and other) with minimal inhomogeneity correction. The segmentation algorithm in SPM99 calculates a Bayesian probability for each voxel of each tissue group in the volume, based on a priori MRI information. Finally, using SPM99, the gray matter volume was smoothed with a 12 mm FWHM Gaussian filter to minimize individual gyral variations. Statistical analysis. SPM99 was used for all statistical analyses. This included a two-sample t-test routine to compare the gray matter volume of each patient group to the control group of 12 healthy seniors. A proportional analysis threshold was used to include only voxels with ⱖ40% of gray matter. Implicit masking was used to ignore zeros, and global calculation was based on the mean voxel value. We set our statistical threshold for the atrophy studies at a value of p ⬍ 0.001, and we accepted only clusters comprised of 100 or more adjacent voxels as significant.
Results. Behavioral study. Twelve of 13 individual CBD patients were more impaired on the averaged measure of number representations compared to object naming (p ⬍ 0.05, according to the McNemar test). This pattern was seen consistently across each of the number measures relative to object naming: 10 of 13 CBD patients encountered more difficulty on the arabic numeral magnitude judgment task; 10 of 13 patients were more impaired on the dot array magnitude judgment task; 11 of 13 CBD patients were more impaired on the arabic numeral addition task; and 11 of 13 patients were more impaired on the dot addition task. SD patients, by comparison, were more impaired on the object confrontation naming task relative to measures of number representations. This performance pattern was seen consistently across the various number tasks: 12 of 15 SD patients encountered more difficulty on the naming task compared to the arabic numeral magnitude judgment task; 12 of 15 patients were more impaired on the naming task than on the dot magnitude judgment task; 10 of 15 SD patients were more impaired on the naming task relative to the arabic numeral addition task; and 14 of 15 patients had a greater naming impairment relative to the dot addition task. Averaging across the measures of number representations, 12 of 15 SD patients were more impaired on the object naming task than on tasks of number representations (p ⬍ 0.05, according to the McNemar test). A 2 test was used to assess the relative impairment of individual CBD and SD patients on the averaged measures
Figure 1. Impairment in number knowledge and object naming in corticobasal degeneration (CBD) and semantic dementia (SD). Histogram indicates the percent of patients with a relatively greater impairment in number knowledge (black bar) or object knowledge (gray bar). Asterisks indicate individual patient difference scores for z-scores, where ⬍0.0 indicates a relative number deficit and ⬎0.0 indicates a relative object deficit. of number representations compared to the object naming task. We found a significant difference in the proportions of impaired performance on measures involving number and object representations in patients with CBD and SD [2(1) ⫽ 14.65; p ⬍ 0.001]. As summarized in figure 1, CBD patients have relatively impaired number representations, while SD patients were more compromised on a naming task requiring object representations. Groupwide means, standard deviations, and medians for accuracy and latency are summarized in table 1. CBD patients were significantly worse than SD patients in their performance on three of the four measures involving number representations. SD patients were worse than CBD patients in their performance on the object naming task, but this difference was not significant (p ⬍ 0.20). Structural MRI study. The anatomic distribution of atrophy in CBD is illustrated in figure 2A, and the loci of the peaks, according to Talairach and Tournoux43 coordinates, are summarized in table 2. Gray matter volume differed significantly in CBD patients relative to 12 healthy seniors in right lateral parietal and bilateral medial parietal distributions, although some atrophy was also found in two adjacent areas of right ventral temporal cortex. Figure 2B illustrates the anatomic distribution of cortical atrophy in SD. As summarized in table 2, the peak distribution of cortical atrophy was in anterior and ventral portions of the left temporal lobe.
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Table 1 Mean ⫾ SD (median) accuracy* and latency† on measures requiring number representations and object representations in corticobasal degeneration (CBD) and semantic dementia Measures
Corticobasal degeneration
Semantic dementia
Arabic numeral magnitude judgment 93.59 ⫾ 13.39 (100)
Accuracy, %
2.05 ⫾ 2.07
Latency, sec‡
99.81 ⫾ 0.72 (100) 1.00 ⫾ 0.00
Dot array magnitude judgment 89.32 ⫾ 13.60 (94.44)
Accuracy, %‡
3.41 ⫾ 2.74
Latency, sec‡
99.63 ⫾ 0.98 (100) 1.88 ⫾ 0.78
Arabic numeral addition 71.58 ⫾ 39.50 (91.67)
Accuracy, %‡
4.19 ⫾ 4.28
Latency, sec‡
97.78 ⫾ 3.51 (100) 1.56 ⫾ 0.81
Dot array addition 48.50 ⫾ 32.07 (47.22)
Accuracy, %‡
5.74 ⫾ 2.79
Latency, sec
95.00 ⫾ 5.67 (100) 5.32 ⫾ 1.53
Object confrontation naming 74.10 ⫾ 24.11 (83.33)
Accuracy, %
60.22 ⫾ 31.55 (70.00)
* Mann-Whitney U tests were used to compare performance accuracy because patients with semantic dementia were at or near ceiling on every measure requiring number representations. † t-Tests were used to compare performance latency between CBD and semantic dementia patients, with a minimum latency of 1 sec. ‡ Significant difference between groups at least at the p ⬍ 0.05 level, except for the Arabic numeral magnitude judgment task, where the groups differed at the p ⬍ 0.059 level.
between CBD and SD. SD patients exhibited a strong dissociation between impaired naming and normal number knowledge. Their deficit on a naming task emphasizes their difficulty with object representations, and most of these individual patients were more impaired on this task than on measures
Figure 2. Gray matter atrophy in (A) corticobasal degeneration and (B) semantic dementia. 1166
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requiring number representations. Previous case studies of SD patients have shown a single dissociation between impaired object representations and preserved representations of abstract nouns,10,11 and two cases of SD had impaired representations of objects relative to preserved numbers.16,17 By comparison, CBD patients demonstrated a weaker dissociation between an impairment on measures of number magnitude and simple addition that depend in large part on number representations and a milder deficit on a confrontation naming task that depends on object representations. Other observations of difficulty on tasks requiring number representations are consistent with the hypothesis that this is a coherent semantic domain.18,21 Examination of subgroups of these CBD and SD patients also suggested a neuroanatomic basis for this dissociation in semantic memory. Patients with CBD had significant atrophy that is most prominent in right parietal cortex, while SD patients showed atrophy in left temporal cortex. The distinct cognitive performance profiles, together with selective distributions of gray matter atrophy in subgroups of these patients, are consistent with a model of semantic memory that implicates dissociable domains of knowledge for objects and numbers that depend in part on distinct neuroanatomic substrates. We discuss each group of patients in more detail below. Occasional clinical descriptions of single patients with CBD have mentioned difficulty on calculation tasks requiring number representations.27,44 Our previous report quantified this difficulty, showing a significant deficit on oral calculations involving
Table 2 Anatomic distribution and extent of regional gray matter atrophy in corticobasal degeneration and semantic dementia Coordinates* Anatomic region (Brodmann area)
x
y
z
No. voxels
z-Score
Corticobasal degeneration (n ⫽ 5) Right lateral parietal (BA 7, 40) Bilateral medial parietal (BA 7, 23)
56
⫺30
48
2,193
4.20
8
⫺70
38
1,052
4.09
Right ventral temporal (BA 20)
46
⫺36
⫺26
275
3.52
Right ventral temporal (BA 19)
32
⫺46
⫺2
104
3.47
⫺46
4
⫺38
3,570
4.79
Semantic dementia (n ⫽ 3) Left ventral-lateral temporal (BA 20, 21, 36, 35)
* Peak anatomic coordinates refer to the neuroanatomic atlas of Talairach and Tournoux.43
addition, subtraction, multiplication, and division relative to AD and frontotemporal dementia.22 In the present study, we confirmed significant difficulty with simple addition of single digits in a mildly demented cohort of CBD patients. This deficit was present in all but one of the individual CBD patients we assessed. Concurrent visual, executive, or language deficits have been proposed to account for difficulty on measures requiring number representations, but it is unlikely that these accounts can fully explain the deficit we observed in CBD. Visual perceptualspatial impairments have been documented in CBD,45,46 and a study of 14 patients with autopsyconfirmed CBD reported visual or sensory neglect.47 However, a visual perceptual-spatial deficit alone is unlikely to explain comparable levels of impaired addition for dot arrays and Arabic numerals, particularly since the problems were administered aurally as well as visually, and the potential impact of lateralized neglect was minimized by arraying stimulus materials vertically. Several studies have associated calculations with executive resources such as working memory.48,49 While some CBD patients appear to have executive resource limitations,25,50 and while they required significantly more time than SD patients to add Arabic numerals, an executive impairment is unlikely to account for a number deficit involving the simplest of calculation processes— addition—with single digit numbers and very small dot arrays, and there was no evidence for a speedaccuracy trade-off. To confirm impaired number representations in CBD in a manner that minimizes the resource demands associated with calculation, we also assessed their magnitude judgments of pairs of Arabic numerals and pairs of dot arrays. Although the deficit was less pronounced than their calculation performance, almost all of the individual CBD patients experienced difficulty in their judgments of relative magnitude. Some aspects of number representations have been hypothesized to depend on verbal mediation,15 but we observed consistently milder difficulty on a visual confrontation naming task than performance on tasks requiring number representa-
tions. While performance of CBD patients and SD patients as groups did not differ significantly on the object naming task, most individual CBD patients had greater difficulty with tasks requiring numbers than objects, and the number of individual CBD patients relatively impaired with numbers compared to objects differed significantly from the number of individual SD patients with this impairment profile. Naming difficulty has been reported in clinical series26 and autopsy-proven cases47,51 of CBD, but impaired naming does not appear to be a constant feature,24,52 comprehension of single words seems to be less severe than their naming difficulty,53,54 and aphasia is said to be uncommon.23,26 Our histopathologic analysis emphasizes the wide distribution of disease in CBD,35 perhaps explaining a mild naming deficit in CBD related to the temporal lobe involvement seen in the voxel-based morphometric (VBM) analyses.55 Studies of number deficits in patients that also report imaging for neuroanatomic correlation,19,29,30 and functional neuroimaging work in healthy adults,31,32 link number representations primarily to parietal cortex, although prefrontal regions have been implicated in patient22,56 and functional neuroimaging studies57,58 of number processing that requires greater resource demands. For example, our previous study associated frontal cortex with calculations that require working memory such as division.22 CBD appears to affect several cortical regions, making the clinical diagnosis of CBD relatively difficult.59 However, structural and functional neuroimaging studies in clinically diagnosed cases of CBD,27,28 and neuropathologic reports of CBD including an analysis of the neuroanatomic distribution of disease,35,47,53 often emphasize involvement of parietal cortex. VBM analyses of volumetric structural MRI in five of the CBD patients in this study showed significant gray matter atrophy in a parietal distribution. We are aware that VBM has advantages and disadvantages relative to approaches used in other studies of regional cortical atrophy.60,61 However, we used VBM because it is investigator-independent, fully automated, and statistically rigorous. The small April (1 of 2) 2004
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number of patients we studied limits the generalizability of our findings, and direct histopathologic evidence is needed to confirm the diagnosis of CBD in these patients. Nevertheless, the parietal locus of cortical atrophy in these patients is consistent with functional neuroimaging work reporting parietal activation during calculation performance in healthy young adults.31,32 SD patients, in contrast to CBD patients, performed all measures requiring number representations with minimal difficulty. SD patients also required a relatively brief amount of time to perform these number-related tasks, except on the dot array addition task where SD and CBD patients both were burdened with counting dots in order to add them. Our observations are consistent with two previously reported cases describing the relative preservation of number representations despite a severe impairment for object representations.16,17,21 A hallmark of SD is a deficit for object naming.6,7 Longitudinal studies of SD emphasize that the comprehension deficit for single words emerges in most of these patients as they become more demented over time.39 To avoid the confound of differing levels of overall dementia severity that would be needed to demonstrate a deficit on a single word comprehension measure in SD relative to CBD, we elected to use a measure of confrontation naming that depends on object representations. Additional work will be needed to develop a measure of semantic memory showing a statistically significant impairment that is selective for patients with mild SD. Whereas there appear to be several competing explanations for the impairment of object representations in SD, the deficit for concrete nouns relative to abstract nouns in SD—so-called reversal of the concreteness effect—suggests degradation of the visual-perceptual features important for object representations during tasks like naming.10,11 Visual-perceptual difficulty has been observed in SD,6,38 but this is unlikely to fully account for the naming deficit.39 For example, the present study showed that visual-perceptual processing is sufficiently intact in SD that it does not interfere with magnitude judgments and addition of dot arrays. Although executive difficulties evident in some patients with frontotemporal dementia62,63 may contribute to the impairments we observed, the SD subgroup of frontotemporal dementia patients generally performs measures of executive functioning and working memory in a near-normal fashion.6 SD is said to be the “temporal variant” of frontotemporal dementia. Structural neuroimaging studies associate SD with cortical atrophy of anterior and ventral portions of the left temporal lobe.12,64 Atrophy in this distribution appears to be correlated with their semantic memory performance.13 Functional neuroimaging work in patients with SD65 also associates difficulty on measures involving object representations with left temporal cortex. We too observed atrophy in a left temporal distribution, although we were able to study only a small number of patients in 1168
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NEUROLOGY 62
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Dissociation of numbers and objects in corticobasal degeneration and semantic dementia C. H. Halpern, G. Glosser, R. Clark, et al. Neurology 2004;62;1163-1169 DOI 10.1212/01.WNL.0000118209.95423.96 This information is current as of April 12, 2004 Updated Information & Services
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