Archives of Clinical Neuropsychology, Vol. 13, No. 8, pp.

721735, 1998
Copyright 1998 National Academy of Neuropsychology
Printed in the USA. All rights reserved
0887-6177/98 $19.00 .00

PII S0887-6177(98)00010-9

Neuropsychological Similarities and

Differences Among Huntingtons Disease,
Multiple Sclerosis, and Cortical Dementia

Meryl A. Butters, Gerald Goldstein, Daniel N. Allen, and Wendy Jo Shemansky

VA Pittsburgh Healthcare System and School of Medicine, University of Pittsburgh

A comparison of cognitive function was made among patients with Huntingtons disease, multi-
ple sclerosis, and cortical dementia. Utilizing indexes from the Wechsler Adult Intelligence Scale
and the HalsteadReitan Battery, it was found that there was substantially more severe cognitive
deficit in the Huntingtons disease patients than in the multiple sclerosis patients, and the level of
impairment was similar between the Huntingtons disease and cortical dementia groups. Quali-
tative differences, particularly involving amount and type of perseveration, were noted among
the three groups. It was concluded that subcortical dementia is not necessarily characterized by
mild cognitive impairment, and there appear to be important qualitative differences between
cortical and subcortical dementia. Results are discussed in terms of the usefulness of the pres-
ently conceptualized distinction between cortical and subcortical dementia. 1998 National
Academy of Neuropsychology. Published by Elsevier Science Ltd

To investigate the validity and utility of the corticalsubcortical dementia distinction,

some researchers have compared the performances of patient groups that have a prototypic
cortical dementia (e.g., Alzheimers disease) with those that have a prototypic subcortical
dementia, such as Huntingtons disease (HD; Heindel, Salmon, Shults, Walicke, & Butters,
1989; Huber, Shuttleworth, Paulson, Bellchambers, & Clapp, 1986; Stern, Richards, Sano,
& Mayeux, 1993). Results of these studies suggest that neuropsychological deficits char-
acteristic of patients with cortical dementia are aphasia, amnesia, agnosia, and apraxia,
whereas deficits associated with subcortical disease are bradyphrenia, defective recall,
poor abstraction and strategy formation, and mood abnormalities (Cummings, 1990; Hu-
ber & Paulson, 1985; Huber, Shuttleworth, Paulson, Bellchambers, & Clapp, 1986).
Attempts to differentiate cortical and subcortical dementias are predicated in part on
the assumption that each of these two general categories of dementia contain distinct
and homogeneous patterns of neuropsychological deficits. In fact, this assumption may
be inappropriate. For example, recent studies have reported a pattern of cognitive defi-
cits in cortical dementia of the frontal type that differs markedly from deficits observed

Indebtedness is expressed to the Department of Veterans Affairs for support of this research and to Sania E.
Hamilton for assistance with this research.
Address correspondence to Address correspondence to: Gerald Goldstein, VA Pittsburgh Healthcare System
(151R), 7180 Highland Drive, Pittsburgh, PA 15206.

721
722 M. A. Butters et al.

in dementia of the Alzheimers type (Mann, South, Snowden, & Neary, 1993; Neary,
1990). Presumably, these distinct neuropsychological patterns may be explained by dif-
ferences in neuroanatomical dysfunction in the two disorders, at least in the early and
middle stages of the disease processes. Moreover, several investigators have found dis-
tinct deficit profiles within a single type of cortical dementia (i.e., dementia of the Alz-
heimers type) leading them to distinguish between different subtypes of the disorder
(Becker, 1988; Butters, Lopez, & Becker, 1996; Kurz, Haupt, Pollmann, & Romero,
1992). The term cortical dementia is also somewhat misleading because Alzheimers dis-
ease, the most frequently used prototype of cortical dementia produces pathology out-
side of the cerebral cortex, notably in the nucleus basalis of Meynert and the locus ce-
ruleus. Furthermore, studies have shown that 1825% of samples of patients with
Alzheimers disease show pathological and clinical changes characteristic of Parkinsons
disease (Adams & Victor, 1989).
A focus of discussion within the literature on subcortical dementia concerns whether
the wide range of disorders that involve degeneration of various subcortical structures
should be grouped together under the term subcortical dementia. This term encompasses
diseases that cause dysfunction or degeneration of the brainstem, thalamus, and basal
ganglia. These distinct patterns of degeneration may result in equally distinct patterns of
neurobehavioral deficits. Furthermore, it may not be the case that the cognitive profiles
found in at least some of the subcortical dementias differ substantially from those seen
in cortical dementia. As a result, some authors conclude that the term subcortical de-
mentia is not a useful distinction (Mayeux, Stern, Rosen, & Benson, 1983).
Although few studies have directly compared the neuropsychological profiles of pa-
tients with different forms of subcortical dementia, there are reasons to believe that the
deficits will vary across disorders (Caine, Bamford, Schiffer, Shoulson, & Levy, 1986).
Structural involvement of the subcortex varies, and different subcortical structures have
different efferent and afferent connections to different regions of the cortex (Alexander,
DeLong, & Strick, 1986). In an attempt to address this debate concerning brain-behavior
relationships in various forms of dementia, the present study compared various aspects
of neuropsychological performance of patients who have different subcortical disorders
arising from different etiologies with distinct patterns of involvement of subcortical
structures and patients with cortical dementia.
The subcortical disorders selected for comparison were HD and multiple sclerosis
(MS). We selected these disorders because they affect different subcortical structures
and thus may result in different clusters of neuropsychological deficits. The neuropathol-
ogy of HD primarily involves degeneration of the caudate nucleus. There is often frontal
lobe involvement because of the heavy connections between the caudate nucleus and
the frontal lobes. Neuropsychological studies of patients with HD typically reveal im-
pairments in memory, conceptual reasoning, and mechanical aspects of language. On the
other hand, demyelinization in MS may occur anywhere within the central nervous sys-
tem, but it most often affects the white matter in periventricular areas (Rao, 1990). Fre-
quent symptoms include partial paralysis, disturbances of vision, and cognitive deficits
involving memory and conceptual reasoning. Symbolic language and verbal intelligence
are relatively spared, although there may be mechanical difficulties with speech produc-
tion (Goldstein & Shelly, 1974). Both HD and MS are progressive disorders, and so the
term subcortical dementia may be misleading with regard to individual cases. Patients
with early HD may not meet diagnostic criteria for dementia, but many patients with MS
do not develop dementia until very late in the progression of their illnesses. However,
many early HD and MS patients have neuropsychological deficits, although their perva-
siveness and severity may not constitute frank dementia.
 Cortical and Subcortical Disorders 723

The frequently made observation that patients with different disorders often perform
quantitatively similarly on standard neuropsychological measures has led to the study of
qualitative differences, or distinct error patterns, produced by various patient groups
(Bayles, Trosset, & Tomoeda, 1993; Jacobs, Salmon, Troster, & Butters, 1990). Identify-
ing distinct qualitative performance patterns is useful for a number of reasons. First, it
may help in the diagnosis of disorders that are otherwise difficult to differentiate using
exclusively quantitative methods. Second, specifying qualitative differences between pa-
tient groups helps contribute to the understanding of brain-behavior relationships.
Third, findings from these types of studies may help elucidate or offer support for cur-
rent psychological models of specific cognitive activities. Thus, the present study em-
ploys qualitative as well as quantitative indexes in the investigation of the neuropsycho-
logical performance of patients with HD, MS, and cortical dementia.

METHOD

Participants
Participants were selected from a large pool of patients who had received neuropsy-
chological testing at three VA medical facilities. They included 36 male patients with a
diagnosis of MS, 16 male patients with HD, and 18 male patients with Alzheimers dis-
ease or other progressive cortical dementias. All participants in the HD group had a
medical diagnosis of HD, a documented positive family history (with the exception of
one patient), and the presence of choreiform movements. Participants in the MS group
met the criteria for clinically definite MS suggested by Poser et al. (1983). The cortical
dementia group consisted of patients with definitive evidence of cortical atrophy. In five
cases, the diagnosis of Alzheimers disease was made. Two cases were diagnosed as hav-
ing Picks disease. One case was diagnosed as Alzheimers-Picks disease, and one pa-
tient had Creutzfeldt-Jakob disease. In the remaining cases, dementia in association with
cortical atrophy was diagnosed, but the specific etiology was not specified. The patients
ranged in age from 30 to 65 years, with a mean of 45.6 years (SD 7.7) for the MS
group, 48.1 years (SD 10.7) for the HD group, and 53.97 years (SD 11.86) for the
cortical dementia group. The difference in age, F(2, 77) 5.37, p .01, was statistically
significant. In the MS group, education ranged from 3 to 18 years, with a mean of 12.8
years (SD 3.8). The range for the HD group was from 8 to 16 years of education, with
a mean of 11.6 years (SD 2.5). The range for the cortical dementia group was 4 to 18
years, with a mean of 12.04 years (SD 4.11). The difference in education, F(2, 77)
0.71, p .05, was not statistically significant. All participants may be characterized as be-
ing in the middle stages of their illnesses in consideration of their ages, the existence of
sufficient severity and number of symptoms to make a diagnosis, and the need for hospi-
talization for evaluation or extended treatment.

Materials
All participants were administered a battery of neuropsychological tests that included
the 11 subtests of the Wechsler Adult Intelligence Scale (WAIS; Wechsler, 1955) and
most of the tests that make up the HalsteadReitan Neuropsychological Battery
(HRNB; Reitan & Wolfson, 1993), including the Halstead Category, Tactual Perfor-
mance, Speech Perception, Finger Tapping, Seashore Rhythm, Trail Making, Aphasia
Screening, and Grooved Pegboard Tests. These procedures assess a variety of problem
solving, language, and psychomotor skills.
724 M. A. Butters et al.

Treatment of Data
To evaluate profile and individual test differences among the HD, MS, and cortical
dementia samples, scores on the WAIS subtests and the HRNB tests were compared uti-
lizing one-way analyses of variance. It was anticipated that there would be age and level
of performance differences among the three groups. To demonstrate possible pattern
differences separated from general level of impairment, we used a method employed
previously by Russell and Polakoff (1993) in which indexes of general level of perfor-
mance are subtracted out from scores on individual subtests, thereby equating groups
for level of performance. In the case of the WAIS, the mean scaled score was used as the
index of global impairment, and the Average Impairment Rating, an impairment index
described by Russell, Neuringer, and Goldstein (1970), was used for the component tests
of the HRNB. We also performed analyses of covariance for each measure, with age and
Average Impairment Rating as covariates. Multiple comparisons among groups were
made utilizing the Scheff Test (p .05). In addition, various numerical measures of
qualitative features of performance on both WAIS and HRNB were developed. Some of
the qualitative indexes were taken from the WAIS-Revised-Neuropsychological Instru-
ment (WAIS-R-NI; Kaplan, Fein, Morris, & Delis, 1991) manual. In addition, we devel-
oped other indexes derived from concepts discussed within the neuropsychological liter-
ature in general and by the authors of the WAIS-R-NI. We developed test-based
indexes for perseveration, meta-learning, abstract conceptualization, impulsivity, loss of
set, and stimulus-bound behavior. Descriptions of the qualitative indexes follow.

Sequencing: The Picture Arrangement Sequence Score is the sum of squares of the
number of junctures in each group of correctly placed cards. The Picture Arrange-
ment Sequence index, the score used here, is the sum of the sequence scores di-
vided by the sum of the maximum possible sequence scores based on the number of
items presented.
Perseverations: Perseverations were scored for the WAIS Vocabulary, Information,
and Similarities subtests when a response was inappropriately influenced by a pre-
vious stimulus. For example, if a patient responded South America to the ques-
tion Where is Brazil? and gave the same response to the subsequent question
Where is Egypt? then the response was recorded as a perseveration. For the Vo-
cabulary subtest, perseverations of both key content words and general words
were scored. Key content words referred to specific aspects of responses or defini-
tions. For example, if the stimulus word cavern was defined as a place of conceal-
ment, the term concealment was recorded as a perseveration from the previous
item What does conceal mean? General words were defined as terms that may be
used in any definition or response. Examples include something and someone. Per-
severations of general words were scored when more than two presentations ap-
peared in sequential responses or when a perseveration occurred more than five
times within the subtest.
Meta-Learning: A learning component was derived utilizing Category Test Subtests
V and VI. These subtests involve the same concept; thus comparing scores on these
subtests should reflect degree of learning. The Category Difference score was cal-
culated by subtracting the number of errors on Subtest VI from the number on V
and then adding the difference to 50 to avoid negative numbers. Thus, a score over
50 shows learning took place, whereas a score below 50 reflects the absence of
learning.
The Abstract Conceptualization Index: The percentage of total points received for
the three proverbs included in the WAIS Comprehension subtest.
 Cortical and Subcortical Disorders 725

Loss of Set: Failure to maintain or shift set appropriately. A loss of set was re-
corded for Part B of the Trail Making Test whenever the patient stayed within the
numerical or alphabetical sequence without alternating (12 rather than 1A, etc.).
For the WAIS Similarities subtest, loss of set was recorded whenever any of the fol-
lowing occurred: (a) differences were reported instead of similarities, (b) the re-
sponse focused exclusively on one stimulus of the pair (e.g., when asked In what
way are an orange and a banana alike? the response was They are both yellow.),
or (c) the response did not contain a similarity. For example, They are opposites
or They go together.
Impulsivity: For Trails A, impulsive errors occurred when instead of drawing a line
from a number (n) to the next consecutive number in the series (n 1), a line was
drawn to a number that is greater in value by two (n 2) and that was in closer
physical proximity than the next correct consecutive number. For Trail Making-B,
impulsive errors occurred when instead of drawing a line to the next item in the se-
quence (regardless of whether it was a letter or number), a line was drawn to an
item in closer proximity, without a shift between number and letter sequences. Im-
pulsivity was also scored for Item 5 of the Comprehension subtest (What should
you do if while in the movies you were the first person to see smoke and fire?).
The response yell fire, or its equivalent, was scored as an impulsive response.
Stimulus Bound: Stimulus-bound errors were scored for the WAIS Similarities and
Vocabulary subtests. A response was considered stimulus bound when it inappro-
priately focused on the stimulus. On the Similarities subtest, an error was consid-
ered stimulus bound when two words were chained or linked together simplisti-
cally. For example, for the item In what way are a table and a chair alike?, the
response A chair goes next to a table was considered stimulus bound. For the Vo-
cabulary subtest, a stimulus-bound error was recorded when part of the stimulus
word influenced a response; for example, defining journey for the stimulus word
travesty was considered stimulus bound. It was reasoned that the patient was re-
sponding to the syllable trav as travel. Also, if more than three letters from a vocab-
ulary word or a syllable with the same pronunciation as the vocabulary word oc-
curred in a key word of the patients definition, then that error was considered to be
stimulus bound. Thus, responses like struck for obstruct, eliminate for termi-
nate, and tragedy for travesty were also scored as stimulus-bound errors.

Scoring Procedures
At least two of the investigators, blind to the diagnoses, scored the qualitative mea-
sures separately. Scoring on the numerical qualitative measures was compared for accu-
racy. For those measures requiring judgments, the averages of the raters scores were
used in the analyses.

RESULTS

Quantitative Indexes
Prior to adjusting for age and level of impairment, statistically significant differences
were found for all WAIS subtests except Digit Symbol and Object Assembly. Compari-
son data are presented in Table 1. In the case of the WAIS Verbal Scale, the Scheff
Test comparisons indicated that the MS group outperformed the other two groups.
However, in the case of Digit Span, the MS group significantly outperformed the cortical
 726

TABLE 1
Test Results Comparing Multiple Sclerosis, Huntingtons Disease, and Cortical Dementia Groups

Multiple Sclerosis Huntingtons Disease Cortical Dementia

Measure M SD M SD M SD F p p1

WAIS Verbal IQ 104.53 15.71 86.69 14.78 86.94 19.27 10.07 .001
WAIS Performance IQ 89.11 16.50 79.20 14.15 79.39 16.80 3.15 .05
WAIS Full Scale IQ 97.40 15.78 82.33 14.54 82.61 17.40 7.41 .01
Average Impairment Rating 2.55 0.86 3.29 0.69 3.20 0.86 5.63 .01
WAIS subtests
Information 11.44 2.71 9.06 2.82 8.17 3.81 8.05 .001 .05
Comprehension 11.33 3.99 6.75 2.74 8.00 4.13 9.86 .001 .05
Arithmetic 10.53 3.96 6.69 2.70 6.67 3.79 10.19 .001 .05
Similarities 10.33 3.49 7.44 3.14 6.39 3.88 8.76 .001 .05
Digit Span 8.78 3.17 6.31 2.94 5.94 4.17 5.39 .01 .05
Vocabulary 10.81 2.84 8.13 2.78 8.00 3.97 5.65 .01 .05
Digit Symbol 4.80 2.59 3.53 2.39 3.33 3.24 1.31 .05 .001
Picture Completion 9.06 3.30 6.47 3.04 6.00 3.20 6.72 .01 .05

726
Block Design 7.26 3.35 5.88 3.48 4.33 3.33 4.55 .05 .05
Picture Arrangement 7.14 3.04 5.20 2.76 4.78 2.67 4.90 .05 .05
Object Assembly 6.63 3.26 4.93 2.52 5.00 3.46 2.32 .05 .05
HalsteadReitan
M. A. Butters et al.

Category Test, Errors 88.56 32.29 104.06 26.89 110.56 31.80 3.27 .05 .05
Tactual Performance, Test Time 27.66 5.90 28.27 5.34 27.91 4.34 0.06 .05 .05
Memory, Blocks 5.09 2.19 4.54 1.85 3.27 2.31 3.71 .05 .01
Location, Blocks 1.53 1.91 0.92 1.32 0.93 1.49 0.95 .05 .05
Speech Perception, Errors 14.94 12.78 20.93 10.03 21.75 12.97 2.23 .05 .05
Rhythm Test, Errors 7.68 5.06 12.27 4.27 9.31 5.07 4.61 .05 .05
Aphasia Screening, Score 8.52 8.53 16.50 11.74 17.06 13.37 4.95 .01 .05
Trail Making A (sec) 91.14 80.38 105.56 65.36 108.44 92.45 0.33 .05 .05
Trail Making B (sec) 161.71 79.63 239.63 80.46 211.82 91.82 5.37 .01 .05
Finger Tapping, Right Hand 30.57 14.36 24.94 9.82 39.78 12.84 5.72 .01 .05
Finger Tapping, Left Hand 29.26 11.47 23.13 8.69 32.61 10.85 3.39 .05 .05
Pegboard, Dominant Hand (sec) 171.15 85.40 156.50 67.54 129.95 69.47 1.59 .05 .05
Pegboard, Nondominant Hand (sec) 201.93 144.68 198.38 120.43 144.84 66.21 1.24 .05 .05

Note. p1 was calculated following correction for age and Average Impairment Rating. WAIS Wechsler Adult Intelligence Scale.
 Cortical and Subcortical Disorders 727

FIGURE 1. Comparisons of level-of-performance-adjusted scores among multiple sclerosis, Huntingtons

disease, and cortical dementia groups on the Wechsler Adult Intelligence Scale subtests. MS multiple
sclerosis. HD Huntingtons disease. INF Information. COM Comprehension. ARI Arithmetic.
SIM Similarities. DSP Digit Span. VOC Vocabulary. DSY Digit Symbol. PC Picture
Completion. BD Block Design. PA Picture Arrangement. OA Object Assembly.

dementia group but not the HD group. With regard to the WAIS Performance Scale, the
MS group did significantly better than the other two groups on Picture Completion. On
Block Design and Picture Arrangement, the MS group did better than the cortical de-
mentia group but not the HD group.
With regard to the HRNB, significant differences were found for the Category Test,
the Memory component of the Tactual Performance Test, the Rhythm Test, the Aphasia
Screening Test, Part B of the Trail Making Test, and Finger Tapping. The Scheff Tests
revealed no significant intergroup differences for the Category Test and the Memory
component of the Tactual Performance Test. There was significantly inferior perfor-
mance by the HD group on the Rhythm Test and Part B of the Trail Making Test, with
the MS and cortical dementia groups not differing from each other. The MS group did
significantly better than the cortical dementia group on the Aphasia Screening Test,
whereas the cortical dementia group did better than the MS and the HD groups on Fin-
ger Tapping.
The profiles of scores from the WAIS and HRNB tests adjusted for general level of
impairment are presented in Figures 1 and 2. For the HRNB data (Figure 2), the raw
scores were converted to z scores to allow for intertest comparisons. Adjustment for
level of generalized impairment revealed that the profiles among the three groups were
essentially identical for the WAIS, but there were major differences on the HRNB. In
728 M. A. Butters et al.

FIGURE 2. Comparisons of level-of-performance-adjusted scores among multiple sclerosis, Huntingtons

disease, and cortical dementia groups on the HalsteadReitan Battery subtests. Higher scores reflect better
performance. MS multiple sclerosis. HD Huntingtons disease. HCT Halstead Category Test. FBT
Tactual Performance Test (total time). MEM Memory component of the Tactual Performance Test.
LOC Location component of Tactual Performance Test. SPR Speech Perception Test. SEA
Seashore Rhythm Test. TMA Trail Making Test, Part A. TMB Trail Making Test, Part B. TAPR
Finger Tapping, Right Hand. TAPL Finger Tapping, Left Hand. RAS Reitan Aphasia Screening Test.
PBR Grooved Pegboard, Right Hand. PBL Grooved Pegboard, Left Hand.

the case of the MS participants, there was a pronounced discrepancy between tests of
motor function and the other tests. This discrepancy occurred, but to a lesser extent, in
the case of the HD group in which there was a precipitous drop on Pegboard with Finger
Tapping scores that were more commensurate with the other scores. The cortical de-
mentia patients showed a somewhat different pattern, with poorer pegboard than tap-
ping scores.
Analyses of covariance produced a substantial reduction in number of significant dif-
ferences. The two p values contained in Table 1 provide significance levels before and
after controlling for age and overall level of impairment (p and p1, respectively). On the
WAIS, significant differences were found for Comprehension, Similarities, Picture Com-
pletion, and Block Design, with the MS group performing significantly better than the
HD and cortical dementia groups. On the HRNB, the Memory component of the Tac-
tual Performance Test, Finger Tapping with both the dominant and nondominant hands,
and Grooved Pegboard with both the dominant and nondominant hands were statisti-
cally significant. The significant multiple comparisons were for the Memory component
of the Tactual Performance Test (on which the MS group did better than the other
 Cortical and Subcortical Disorders 729

groups), right- and left-hand Finger Tapping (on which the cortical dementia group did
better than the MS and HD groups), and Grooved Pegboard (on which there was a dis-
crepancy between dominant and nondominant hand scores). In the case of the dominant
hand, the MS group did better than the two other groups. For the nondominant hand,
the HD group did worse than the other two groups, which did not differ from each other.

Qualitative Indexes
Comparison data are presented in Table 2. Significant differences were found for im-
pulsive errors on Part A of the Trail Making Test, loss of set errors on Part B of the Trail
Making Test, percent correct on WAIS Comprehension proverb items, making or not
making a yell fire response on WAIS Comprehension, stimulus-bound responses on
WAIS Vocabulary, loss of set on the Similarities WAIS subtests and, perseverative re-
sponses on WAIS Information and Vocabulary key words. Scheff multiple comparisons
resulted in the following findings. On Trail Making-A impulsive errors, the only signifi-
cant difference was between the cortical dementia and the MS groups, with the cortical
dementia and HD groups making significantly more errors than the MS group. The same
pattern was obtained for loss of set on Trail Making-B. On Comprehension proverbs,
the MS group outperformed the HD group but not the cortical dementia group. The HD
and cortical dementia groups did not differ from each other. On the Comprehension
yell fire item, the HD group produced yell fire responses more frequently than the
MS and cortical dementia groups, which did not differ from each other. Because this er-
ror type was bivariate (yes or no), a chi-square test was also performed. The obtained
2(2) value of 9.66 was also statistically significant (p .01). On stimulus-bound errors
on Vocabulary, the MS and HD groups did not differ significantly from each other, mak-
ing substantially more errors than the cortical dementia group. On loss of set errors on
Similarities, all three groups were significantly different from each other, with the HD
group making the most and the cortical dementia group making the least number of er-
rors. The MS group made significantly more Information perseverative errors than the
cortical dementia group but did not differ from the HD group. The same patten was
found on Vocabulary key word perseverative errors.
Following analysis of covariance, Trail Making-A impulsive errors, Comprehension
yell fire responses, stimulus-bound Vocabulary errors, Similarities loss of set, and In-
formation and Vocabulary key word perseverative errors remained statistically signifi-
cant. With regard to the Scheff tests, on Trail Making-A impulsive errors, the HD and
the cortical dementia groups made significantly more errors than the MS group, but they
did not differ from each other. Because the Comprehension yell fire score was a bi-
variate (yes or no) variable, it did not lend itself to correction using covariates. It is
noted, however, that only two of the cortical dementia participants made a yell fire
type response, whereas over half of the HD participants and about one fourth of the MS
participants did so. On stimulus-bound vocabulary errors, the MS and HD groups did
not differ from each other, but both did significantly worse than the cortical dementia
group. The only significant difference for Similarities loss of set was between the HD
group and the MS group, with the HD group doing worse. The cortical dementia group
did better than the HD and MS groups, which did not differ from each other, on perse-
verations on the Information subtest. On Vocabulary key word perseverative errors, the
MS and HD groups did not differ from each other, both doing more poorly than the cor-
tical dementia group.
To summarize the findings for qualitative errors, we prepared Table 3, which contains
for each group the incidences of occurrence of at least one error on each of the measures
 730

TABLE 2
Qualitative Results Comparing Multiple Sclerosis, Huntingtons Disease, and Cortical Dementia Groups

Huntingtons
Multiple Sclerosis Disease Cortical Dementia

Measure M SD M SD M SD F p p1

Picture Arrangement Sequence Index 0.42 0.22 0.29 0.18 0.33 0.18 2.39 .05 .05
Category Test Difference Score 54.56 5.61 53.33 4.48 52.29 5.55 0.94 .05 .05
Impulsive Errors, Trail Making A 0.06 0.24 0.25 0.45 0.61 0.87 6.50 .01 .01
Impulsive Errors, Trail Making B 0.06 0.24 0.25 0.58 0.38 0.77 2.41 .05 .05
Loss of Set, Trail Making B 0.15 0.44 0.56 0.81 0.77 0.73 5.79 .01 .05

730
Comprehension Proverbs 0.32 0.29 0.08 0.10 0.24 0.29 5.04 .01 .05
Comprehension Yell Firea 1.78 0.42 1.44 0.51 1.88 0.34 4.86 .01 .05
Stimulus Bound Vocabulary Errors 11.06 10.88 12.50 10.49 0.69 0.95 8.17 .001 .01
Stimulus Bound Similarities Errors 2.88 4.42 3.13 4.79 0.56 0.73 2.22 .05 .05
M. A. Butters et al.

Similarities, Loss of Set 10.15 11.02 18.75 12.18 1.60 1.35 11.28 .001 .001
Information-Perseverative Errors 6.25 7.26 4.33 7.04 0.19 0.40 4.85 .01 .01
Vocabulary, Key Word Perseverative Errors 13.02 10.13 16.25 11.03 1.44 2.71 12.10 .001 .001
Vocabulary, General Perseverative Errors 3.64 11.03 3.56 12.51 0.50 1.32 0.58 .05 .05
Similarities, Perseverative Errors 1.50 3.97 2.50 5.16 0.69 1.14 0.88 .05 .05

Note. p1 was calculated following correction for age and Average Impairment Rating.
a1 yes; 2 no.
 Cortical and Subcortical Disorders 731

TABLE 3
Percentages of Incidence of Qualitative Errors Comparing Multiple Sclerosis, (MS),
Huntingtons Disease, (HD), and Cortical Dementia Groups

Measure MS % HD % Cortical %

Impulsive Errors, Trail Making A 6 25 46

Loss of Set, Trail Making B 12 44 62
Comprehension, Yell Fire 22 56 13
Stimulus Bound Vocabulary Errors 71 75 44
Similarities, Loss of Set 76 88 67
Information, Perseverative Errors 50 44 19
Vocabulary, Key Word Perseverative Errors 85 75 38

that produced significant intergroup differences. The 2(12) value for this table was
equal to 131.11 (p .001), indicating a strong Error Type Group interaction. It is par-
ticularly noteworthy that the MS and HD groups made substantially more perseverative
and stimulus-bound errors than the cortical dementia group.

DISCUSSION

Quantitative Indexes
Analyses with unadjusted scores indicated that the MS group had a clearly higher
level of performance. All three groups had their highest scaled score on the Information
subtests and their lowest scaled score on Digit Symbol. This finding is not surprising,
given that Information has long been considered a hold test in that it is among the
least sensitive subtests to the presence of brain damage. In addition, Digit Symbol is a
no-hold test and is very sensitive to essentially any kind of cerebral dysfunction. Thus
all three groups, relative to their own general levels of performance, appear to have
well-preserved verbal cognitive function and severely impaired psychomotor speed and
coordination. All three groups produced their best Performance scale results on Picture
Completion, the only subtest that does not have a motor component. The MS group ob-
tained mean Verbal intelligence subtest scores mainly in the average range, whereas the
HD and cortical dementia groups obtained scores in the low average range.
The unadjusted HRNB profiles are more distinct among the three groups. The MS
profile is characterized by relatively better performance on the cognitive tests and
poorer or equal level performance on the motor tests relative to the other groups. The
cortical dementia group shows about the same level of cognitive deficit as the HD group
but did relatively well on motor tasks, sometimes exceeding the performance level of the
MS group. Putting the WAIS and HRNB profiles together, the MS group is character-
ized by well-preserved verbal intelligence, superior cognitive function to the other two
groups, and a mixed pattern of motor performance, sometimes reflecting better perfor-
mance and sometimes poorer performance than the HD group. In that regard, the MS
group had the lowest performance level on the Grooved Pegboard, a measure of manual
dexterity, but did better than the HD group on measures of psychomotor speed and effi-
ciency. This finding is consistent with the differing nature of the movement disorder in
the two diseases. The HD group profiles reflected relatively generalized impairment,
with no evidence of superior performance to the cortical dementia group on any test.
732 M. A. Butters et al.

The MS group produced mean scores that generally reflected more intact function
than did the other groups, but the reason for the group finding may be that many of the
MS patients in the sample did not meet diagnostic criteria for dementia. Thus, one can-
not really say that the subcortical dementia of MS is milder than that of HD or cortical
dementia, because it is not appropriate to suggest that all individuals with MS have de-
mentia.
The HD and cortical dementia patients were most different from MS patients in the
areas of general level of performance, visual-spatial tasks that do not have a major mo-
tor component, and language. HD and cortical dementia patients are mainly different
from each other in motor abilities, with the HD participants performing more poorly.
Examination of the profiles shown in Figures 1 and 2 that equate for general level of
impairment indicates that, on the WAIS in particular, there is a strong resemblance
among the three groups with regard to pattern. The major effect of adjusting scores for
age and level of impairment either using level-of-performance-adjusted scores or analy-
sis of covariance was that the MS group experienced an attenuated superiority in lan-
guage-related functions to the other groups, although its superior performance on Com-
prehension and Similarities remained statistically significant following analysis of
covariance. The HRNB-adjusted profile provides a clear picture of relative comparabil-
ity of the HD and AD groups and a sharp dissociation in the MS group between cogni-
tive and motor abilities. This dissociation is also seen, but to a lesser extent, in the HD
group. We see the opposite pattern in the cortical dementia group in which motor ability
tests are done better than cognitive tests. Neuropsychological profile differences re-
mained after adjusting scores for age and general level of impairment. Thus, differences
found among the three groups cannot be readily attributed only to general level of per-
formance considerations.

Qualitative Indexes
The results summarized in Table 3 indicate rather distinctively different patterns
among the three groups. Perhaps most interestingly, the MS group, although substan-
tially less cognitively impaired than the two other groups, committed remarkably high
numbers of perseverative and stimulus-bound errors. Correspondingly, the cortical de-
mentia group made relatively few perseverative and stimulus-bound errors relative to
the MS and HD groups. The cortical dementia group appeared to have its major diffi-
culty in maintaining set, as indicated by the high percentages of Trail Making-A impul-
sive errors and losses of set on Trail Making-B and Similarities. All three groups actually
made substantial numbers of loss of set errors on Similarities, but only the cortical de-
mentia group showed a marked dissociation between numerous loss of set errors and
few perseverative errors. In general, the participants with MS and HD demonstrated
high frequencies of both recurrent and stuck-in-set perseveration, using the terminology
of Sandson and Albert (1984), whereas the cortical dementia participants predominantly
demonstrated loss of set perseveration. The HD participants differed from both the MS
and cortical dementia participants in the area of impulsive errors, particularly on the
Comprehension yell fire item. This finding is consistent with the impulsivity suggested
by the mean score of 12.7 errors on the Rhythm test, a score that approaches chance ex-
pectation of 15 errors. Thus, the MS and HD patients demonstrated the cognitive rigid-
ity or stuck-in-set characteristics commonly observed in patients with Parkinsons dis-
ease (Freedman, 1990), whereas the cortical dementia participants were characterized
more by an inability to maintain a set particularly when the task is made complex
through such means as introducing an alternation requirement. The HD participants ap-
 Cortical and Subcortical Disorders 733

pear to share both characteristics, possibly because of the involvement of both subcorti-
cal and frontal lobe structures in HD.

Comparisons With Other Studies

With regard to comparisons between MS and HD in Caine et al. (1986) and the
present study, some similarities and differences are apparent. However, direct compari-
sons between our results and those of Caine et al. (1986) are limited because we used a
significantly different battery of neuropsychological tests, and Caine et al. (1986) did not
control for differences in overall level of cognitive impairment when comparing their
HD and MS groups. With these limitations in mind, it appears that our findings are simi-
lar to Caine et al.s as follows:
1. MS patients performed better than HD patients on most neuropsychological mea-
sures. Caine et al. (1986) reported that HD patients performed worse than MS pa-
tients on 23 of 27 test indexes; we found that HD patients performed worse on 26
of 28 indexes.
2. HD and MS patients exhibited similar patterns of performance across most tests,
particularly the WAIS subtests.
3. Prior to correcting for age and overall level of cognitive impairment, significant
differences were present between groups on tasks requiring mathematical abili-
ties, but no significant differences were present on tasks requiring simple motor
speed and dexterity abilities.
In contrast to Caine et al.s (1986) results, we found significant differences between
MS and HD groups on tests requiring verbal comprehension, even after controlling for
overall level of cognitive impairment. We also found that differences between the
groups on tests requiring mathematical abilities disappeared after overall level of cogni-
tive impairment was controlled. It therefore appears advisable for future investigations
to control for general level of impairment before addressing the matter of differentiating
selective deficits in MS and HD. Following adjustment for age and general level of per-
formance, all three groups showed patterns on the WAIS and HRNB that have been
characterized previously as dementia patterns (Hom, 1992; Russell, 1979; Russell & Po-
lakoff, 1993).
Hodges, Salmon, and Butters (1991) reported that proportions of error types on the
Boston Naming Test distinguished between Alzheimers and HD patients. The Alz-
heimers patients made relatively more semantic errors, whereas the HD patients made
more visual errors. Similarly, Monsch et al. (1994) found that Alzheimers patients had a
different form of verbal fluency defect from what was found in HD patients. The Alz-
heimers disease patients difficulty resulted from a defect in semantic structure, whereas
the HD patients did poorly mainly because of problems with initiation and retrieval.
However, differences of this type may or may not be directly pertinent to the cortical-
subcortical distinction.
The present study was based on the HRNB and the WAIS, which do not include spe-
cific and detailed tests of memory. Memory deficits have been well described in all three
disorders and are known to be cardinal symptoms of both cortical and subcortical de-
mentia. The specific characteristics of memory function differ among the three disorders
studied here, but their consideration goes beyond the limits of the present study, which
focuses on differing cognitive profile characteristics. In that memory is required to per-
form many of the tests in the HRNB (Reitan & Wolfson, 1992), it is likely that its influ-
ence on the findings was present, if not specifically evaluated.
734 M. A. Butters et al.

Summary and Conclusions

Considering the data from the standpoint of the concept of subcortical dementia, two
conclusions are clear. Different subcortical disorders differ markedly in level and, to some
extent, in cognitive pattern. MS looks quite different neuropsychologically from HD, par-
ticularly with regard to general level of performance. This finding may be attributable to
the different rates of progression of the two disorders. Second, HD had a quantitative neu-
ropsychological profile that is highly similar to what is found in cortical dementia, except
for the presence of a prominent movement disorder. However, the qualitative indexes sug-
gest that there are differences between the two subcortical dementias studied and cortical
dementia. In the case of MS and HD, there was a high incidence of both recurrent and loss
of set perseverative behavior, whereas the cortical dementia participants predominantly
demonstrated loss of set behavior, with relatively few recurrent perseverations.
The between-groups differences noted in severity of impairment indicate that subcor-
tical dementia cannot really be characterized in terms of some fixed severity level. We
point this out to dispel the commonly held view that the cognitive deficits produced by
neuropathology of subcortical structures are of mild severity (see Cummings, 1990, for a
review). Some patients with subcortical disease experience significant cognitive impair-
ment, and level of impairment varies among disease processes. Folstein, Brandt, and
Folstein (1990) also pointed out that much of the cortical input to the caudate nucleus
comes from the parietal and prefrontal lobes; therefore, there appears to be a strong
neuropathological basis for significant impairment of numerous cognitive functions.
In summary, not all subcortical dementias are alike from the standpoint of cognitive
function, even though they may all have their primary neuropathologies in the subcor-
tex. MS in particular probably should not be generally characterized as a dementia, be-
cause many patients with that disorder would not meet current diagnostic criteria for de-
mentia. In that quantitative measures of cognitive function in a sample of middle-stage
HD patients was found greatly to resemble what was found in a sample of patients with
cortical dementia, the distinction between cortical and subcortical dementia may be
meaningful from the point of view of pathophysiology but may not always be a clinically
meaningful distinction. These conclusions should not be taken to suggest that there are
not important neuropsychological differences between HD and cortical dementia. We
found differences in patterns of perseveration that might connote neuropathological dif-
ferences involving combined major cortical and subcortical pathology as opposed to
mainly cortical pathology. The strong resemblance between HD and cortical dementia
participants found on quantitative measures of cognitive function suggests that although
the two diseases may be associated with equal levels of impairment at certain points in
their progressions, qualitative differences may reveal possibly important distinctions be-
tween cortical and subcortical disorders.

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