Acta Neurol Scand 2013: 127: 391–398 DOI: 10.1111/ane.

12037 Ó 2012 John Wiley & Sons A/S

ACTA NEUROLOGICA
SCANDINAVICA

Cognitive impairment and magnetic

resonance imaging correlations in Wilson’s
disease
Frota NAF, Barbosa ER, Porto CS, Lucato LT, Ono CR,
Buchpiguel CA, Caramelli P. Cognitive impairment and magnetic
resonance imaging correlations in Wilson’s disease.
Acta Neurol Scand: 2013: 127: 391–398.
© 2012 John Wiley & Sons A/S.
Objectives – To evaluate the cognitive performance of a group of
patients with Wilson’s disease (WD) and to correlate the cognitive
findings with changes in magnetic resonance imaging (MRI).
Methods – All patients with WD consecutively attended in a
Movement Disorders Clinic between September 2006 and October
2007 were invited to participate in the study, together with a group of
matched healthy controls. Patients and controls were submitted to
comprehensive neuropsychological assessment. MRI was performed in
all patients, and abnormalities (high-intensity signal, low-intensity
signal and atrophy) were semi-quantitatively rated. Performance of
patients and controls in each cognitive test was compared, and
correlations between cognitive scores and MRI changes were
investigated within the patients’ group. Results – Twenty patients with
WD (11 men) and 20 controls (nine men) were evaluated. Mean age
in the WD and control groups was 30.05 ± 7.25 and
32.15 ± 5.37 years, respectively. Mean schooling years were
11.15 ± 3.73 among WD cases and 10.08 ± 2.62 among controls.
Patients with WD performed significantly worse than controls in the
Mini-Mental State Examination, Dementia Rating Scale, phonemic
verbal fluency (FAS), verb generation, digit span forward, Stroop test,
Frontal Assessment Battery and in the Brief Cognitive Screening
Battery. A significant correlation emerged between global cognitive
impairment and MRI scale (r = 0.535), being higher for high-intensity
signal plus atrophy (r = 0.718). Conclusion – Patients with WD
presented cognitive impairment, especially in executive functions, with
good correlation between cognitive abnormalities and MRI changes.
N. A. F. Frota1,2, E. R. Barbosa2,
C. S. Porto2, L. T. Lucato3,
C. R. Ono3, C. A. Buchpiguel3,
P. Caramelli4
1
School of Medicine, University of Fortaleza, Fortaleza,
Ceará Brazil; 2Department of Neurology, University of
São Paulo School of Medicine, São Paulo, São Paulo
Brazil; 3Department of Radiology, University of São
Paulo School of Medicine, São Paulo, Brazil;
4
Department of Internal Medicine, Faculty of Medicine,
Federal University of Minas Gerais, Belo Horizonte,
Minas Gerais Brazil
Key words: Wilson’s disease; cognitive impairment;
dementia; neuropsychological tests; magnetic
resonance imaging
P. Caramelli, Departamento de Clínica Médica,
Faculdade de Medicina da Universidade Federal de
Minas Gerais, Av. Prof. Alfredo Balena, 190, Room
246, 30130-100 Belo Horizonte, Minas Gerais, Brazil
Tel.: +55-31-3409.9746
Fax: +55-31-3409.9746
e-mail: caramelp@usp.br
Accepted for publication October 2, 2012

ganglia, thalamus and cerebellum, but it can also

Introduction
Wilson’s disease (WD) (or hepatolenticular
degeneration) is a rare genetic disease that affects
between one in 30,000 and one in 100,000 indi-
viduals (1). Alterations in the gene responsible
for the synthesis of protein ATP7B, related to the
transport of copper, were described for the first
time in 1993 in these patients. Since then, more
than 300 mutations in this gene have been
reported (1).
In the central nervous system, the accumula-
tion of copper occurs preferentially in the basal
affect the subcortical white matter (1). This accu-
mulation is related to the appearance of extrapy-
ramidal symptoms and signs, such as dysarthria,
walking difficulties, sardonic smile, dystonia,
rigidity, bradykinesia and rest tremor in up to
50% of the patients (1, 2).
Despite being present in the first patients
described by Wilson in 1912, cognitive impair-
ment has been little studied and is still a matter
of controversy until today (3–9). Patients with
neurological involvement present impaired perfor-
mance on scales of intelligence evaluation and

391
Frota et al.
global cognitive performance (3, 4), as well as in
memory (3–5, 7) and divided attention tests (3,
9). Cognitive impairment may persist after treat-
ment and also coexists with depressive symptoms
(9). Other authors, however, did not find differ-
ences between patients with WD and healthy con-
trols (6), and patients presenting only with
hepatic manifestations seem to perform similarly
to controls (3, 4).
Magnetic resonance imaging (MRI) of the head
demonstrates excellent sensitivity in patients with
neurological manifestations, being abnormal in
approximately 100% of affected patients (10–12).
The most frequent abnormalities depicted by
MRI in WD are the presence of hyperintense T2
signals in the basal ganglia (10–12) and atrophy
either focal or generalized (12, 13). The presence
of hypointense T2 signals in the basal ganglia has
also been described by some authors (10, 12),
where it can be related to the deposition of cop-
per or iron, with a tendency to increase with time
of treatment (12).
Impaired cognitive performance of patients
with lesions restricted to the basal ganglia has
been previously reported (5), as well as the corre-
lation between the presence of hyperintense T2
signals on MRI and severity of functional impair-
ment (11).
This study was prompted by the few data on
the cognitive profile in patients with WD on
treatment who do not show depressive or anxious
symptoms (9), factors that could lead to decline
in cognitive performance, and also by the paucity
of information about the correlation between
cognitive impairment and the presence and sever-
ity of structural changes found on MRI.
N = 44 Regular follow-up
Included
11 Men 9 Women
Age at symptoms’ onset: 18.85 years
Mean age: 30.05 years
Symptoms’ duration: 18.85 years
Education (mean): 11.15 years
Motor score (mean): 2.8
D-penicillamine: 14 patients
Zinc: 4 patients
Trientine: 2 patients
Figure 1. Patients’ flowchart.
392
Population and methods
Patients
All patients with WD, diagnosed by clinical his-
tory, physical examination, serum ceruloplasmin
(<20 mg/dl), 24-h urinary copper excretion
(>100 mcg/24 h) and ophthalmologic examination
by slit lamp, who were followed in a Movement
Disorders Clinic from September 2006 to October
2007, were invited to participate in the study. All
patients were on stable doses of treatment for at
least 1 year, without neurological worsening dur-
ing this period. Exclusion criteria included the
presence of motor abnormalities that could inter-
fere with performance in the cognitive tests, such
as difficulty in writing and severe dysarthria that
impeded the comprehension of speech by the
examiner, clinical signs of hepatic encephalopa-
thy, like asterixis, presence of depressive/anxious
symptoms according to the Goldberg scale (14)
and contraindications for MRI of the head. A
control group was composed of volunteers with-
out neurological or psychiatric diseases, matched
for age, gender and education with the patients
(Fig. 1). The study was approved by Institution’s
Ethics Committee, and all patients and controls
signed a consent form.
Neurological evaluation
All patients were evaluated by a board-certified
neurologist (NAFF), and the features were
recorded and scored according to a previously
published scale (10, 12), which includes 13 clinical
signs (bradykinesia, rigidity, postural instability,
Excluded
9 Declined to participate
4 With anarthria
9 With depression
2 Declined to participate after first step

tremor, dystonia, chorea, athetosis, cerebellar dis-
turbances, dysarthria, dysphagia, walking difficul-
ties, psychiatric disturbances and other
alterations), each graded from 0 to 3 (absent,
slight, moderate and intense). Hence, the total
score in the scale ranges from 0 to 39.
Cognitive evaluation
All patients and controls were submitted to cog-
nitive evaluation divided into two parts, per-
formed in two different occasions, with a mean
duration of 40 min each.
The first session was applied by the same
examining neurologist (NAFF), who has a spe-
cific training in Behavioral Neurology, and
included the following tests: Mini-Mental State
Examination (15); digit span forward and back-
ward; a memory test of figures (16), clock draw-
ing (17); verbal fluency tests (animals, verbs and
FAS); CERAD naming test (18); Stroop test (19)
and Frontal Assessment Battery (FAB) (20). The
patients’ relatives also answered the Pfeffer Func-
tional Activities Questionnaire (21). The choice of
more simple cognitive tests was adopted to
achieve an easier reproducibility of the results,
even in the clinical practice.
The second evaluation session was performed
by an experienced neuropsychologist (CSP), with
a similar duration to that of the first evaluation,
consisting on the following tests: Mattis Demen-
tia Rating Scale (DRS) (22), Wisconsin Card
Sorting Test (WCST) and Hooper and Cubes
(subscale of Wechsler intelligence scale).
Cognitive alterations
As some of the tests applied have not been previ-
ously validated in Brazil for the specific popula-
tion’s age of the study, we considered that a
patient showed altered performance in the cogni-
tive tests where the result was below -1.5 stan-
dard deviation (SD) of the mean found in the
group of healthy controls. The DSM-IV was used
for the diagnosis of dementia.
Magnetic resonance imaging
Acquisition of images – Magnetic resonance imag-
ing examinations were performed in all patients
who completed the two cognitive evaluations
using a 1.5 Tesla apparatus, GE Signa Horizon
LX 8.2, with a gradient of 23 mT intensity, in a
quadrature coil for the study of the head. The pro-
tocol for the acquisition of images in MRI of the
head consisted of the following sequences: spin
Cognitive impairment in WD and MRI changes
echo (SE) in the sagittal and axial planes, weighted
T1 (repetition time of 500 ms and echo time of
14 ms), fast spin echo (FSE) in the axial plane T2
weighted (repetition time of 4500 ms and echo
time of 101 ms), FLAIR weighted in the axial
plane (repetition time of 11002 ms and echo time
of 161 ms) and spin echo T2 weighted in the coro-
nal plane (repetition time of 2400 ms and echo
time of 80 ms). Sequences were not utilized after
the use of paramagnetic contrast in any patient.
Image analysis – The analyses of the images were
performed by an experienced neuroradiologist
(LTL), who was blind to the clinical and cogni-
tive picture of the patients, by means of a scale
previously used in other studies (23) for quantita-
tive assessment of the MRI structural changes. In
this scale, one point is given in the presence of a
hyperintense T2 signal in each of the following
structures (maximum 7 points): putamen, globus
pallidus, caudate, thalamus, mesencephalus, cere-
bellum and cerebral white matter. An additional
point is given for the presence of a hypointense
T2 signal (SE) in the following structures (maxi-
mum 6 points): globus pallidus, putamen, cau-
date, red nucleus, substantia nigra and dentate
nucleus of the cerebellum. The presence of a
hyperintense T1 signal in the globus pallidus also
received one point. In virtue of the lesions classi-
cally being bilateral and symmetrical, laterality
was not taken into account. The last two points
of the scale are supplied by a semi-quantitative
analysis of global atrophy, determined by the
prominence of the CSF spaces in detriment of the
encephalic parenchyma and classified as follows:
absent (0), slight (1) or severe (2). Hence, the
final score may vary from 0 to 16, with higher
scores indicating greater involvement.
Statistical analysis
Initially, descriptive analysis of the cognitive tests
in patients with WD and controls (means and
SD) was undertaken. The Shapiro-Wilks test was
utilized for the verification of normality of the
tests. The means of the two groups were com-
pared by Student’s t-test and Mann–Whitney test,
depending on the occurrence of normal distribu-
tion or not of the variables. Linear correlation
analysis was carried out by Spearman’s test. The
level of statistical significance was initially set at
5% (P < 0.05). However, we used Bonferroni
correction because of the number of tests
employed (16), and the new level of statistical sig-
nificance was P < 0.0031. All analyses were
performed using the SPSS 13.0 program.
393
Frota et al.

dentate nucleus and 45% in the caudate nucleus.

Results
The demographical and motor impairment char-
acteristics of the patients are depicted in Table 1.
Four patients had a prior history of hepatic
changes (increased liver transaminases or ultraso-
nographic changes) without liver function wors-
ening in the last year.
Patients with WD were impaired, in relation to
controls, in global evaluation tests (DRS) as well
as in tests of executive functions (FAB, phonemic
fluency, fluency for verbs and number of errors
on the third part of the Stroop test) (Table 2).
Cognitive performance on individual level was
altered (below –1.5 SD) in all but one patient in
at least one test. The number of altered tests per
patient ranged from 0 to 14, with a mean of
6 ± 4. All tests showed at least one subject with a
result below –1.5 SD.
Scores in the Pfeffer Functional Activities
Questionnaire varied between 0 and 8 points,
with a mean of 2.10 ± 2.69 points. Half of the
individuals scored zero, and in 20% of cases,
scores were > 5, indicating significant functional
impairment. Dementia was diagnosed in one indi-
vidual, according to DSM-IV criteria.
Magnetic resonance imaging scans were abnor-
mal in all patients. Hypointense T2 signal (SE)
areas were observed in 100% of cases in the glo-
bus pallidus, 90% in the substantia nigra, 60% in
the putamen, 60% in the red nucleus, 60% in the
Hyperintense T2 signal areas occurred in 80% of
patients with decreasing order of frequency: puta-
men (65%), pons (45%), mesencephalon (40%),
subcortical white matter (40%), globus pallidus
(35%), cerebellum/cerebellar peduncle (25%) and
thalamus/subthalamus (15%). These alterations
had a symmetrical distribution, except for focal
lesions, which showed some slight asymmetry.
Atrophy was found in 75% of cases. The score of
the MRI scale varied between 2 and 12 points
(mean = 7.80 ± 2.89).
A good correlation was found between the
number of altered tests per patient and the total
score in MRI (Fig. 2). When scores related to the
hypointense T2 signals were excluded from the
total MRI score, a stronger correlation with cog-
nitive impairment was found, suggesting that hy-
perintense lesions and atrophy were the two MRI
variables more closely related to the cognitive
changes (Fig. 3). A good correlation was found
between cognitive deficits and motor and func-
tional impairment, but no correlation with the
duration of symptoms or with hypointense lesions
on MRI (Table 3).
Discussion
The present study demonstrated that patients
with WD, even those with mild neurological
symptoms, long treatment course and without

Table 1 Main sociodemographical and clinical characteristics of patients

Education Hepatic Numbers of altered

Patient/sex Age (years) changes Duration of symptoms (years) Motor impairment cognitive tests

1–M 20 6 No 4 3-Dystonia*; Dysarthria ** 9

2–F 34 12 No 15 3-Dystonia**; Dysarthria* 3
3–M 25 14 No 3 1-Rigidity* 5
4–M 28 11 No 18 5-Bradykinesia*; Dystonia**; Dysarthria** 9
5–F 34 12 No 12 2-Other alterations** 5
6–F 34 4 No 5 4-Bradykinesia*; Rigidity*;Chorea*; Dysarthria* 14
7–F 21 11 No 7 0 5
8–F 40 20 No 16 2-Tremor*; Dysarthria* 1
9–F 37 15 No 3 3-Bradykinesia**; Rigidity* 7
10 – F 29 16 Yes 7 4-Bradykinesia*; Dystonia**; Dysarthria* 0
11 – M 42 11 No 32 1-Dysarthria* 3
12 – M 29 5 No 16 5-Bradykinesia*; Dystonia*; Dysarthria**;Dysphagia* 11
13 – M 28 8 Yes 9 4-Bradykinesia**; Dysarthria** 12
14 – F 37 11 No 21 1-Dysarthria* 4
15 – M 22 11 No 6 6-Bradykinesia*; Tremor***; Dysarthria*; Cerebellar syndrome* 9
16 – M 40 11 No 14 1-Dysarthria* 4
17 – M 33 11 Yes 23 1-Dysarthria* 7
18 – M 20 11 No 10 0 2
19 – M 19 9 No 2 6-Bradykinesia*, Chorea**, Athetosis*; Dysarthria** 8
20 – F 29 14 Yes 12 1-Tremor* 2

M, Male; F, Female.
Motor impairment is scored by a specific scale, ranging from 0 (no impairment) to 39 (severe impairment; see text for details). *slight, **moderate, ***
intense.

394
 Cognitive impairment in WD and MRI changes

Table 2 Test results of patients with WD and controls

No. of
patients
Test WD Controls P < 1.5 SD

MMSE 26.70 ± 2.452 28.75 ± 1.293 0.0051* 9

DRS 132.45 ± 10.778 140.55 ± 3
720 0.0014** 9
DS-FW 4.95 ± 0.825 6.15 ± 1.424 0.0056* 7
DS-BW 3.50 ± 0.688 4.15 ± 1.348 0.0965 1
AF 17.35 ± 5.770 20.35 ± 3.856 0.0920 7
FAS 22.40 ± 12.403 38.75 ± 9.118 <0.0001** 13
VF 8.50 ± 6.637 15.40 ± 6.227 0.0016** 10
STROOP 4.40 ± 4.871 0.50 ± 0.688 0.0006** 15
FAB 12.95 ± 2.856 16.25 ± 1.251 <0.0001** 13
WCST 2.25 ± 1.372 2.60 ± 1.314 0.3983 1
Encoding Memory 9.20 ± 0.696 9.75 ± 0.444 0.0050* 14
Delayed Memory 8.45 ± 1.356 9.50 ± 0.761 0.0070* 11
CERAD naming 14.20 ± 1.540 14.55 ± 0.759 0.7584 3
Clock design 8.00 ± 2.449 9.20 ± 0.616 0.2354 4 Figure 3. Correlation between number of altered tests per
Hooper 21.10 ± 3.779 21.85 ± 4.069 0.3834 1 patient and hyperintense lesions plus atrophy.
Cubes 23.70 ± 10.648 27.20 ± 10.962 0.3122 2

Table 3 Correlation between number of altered tests and some variables

MMSE, Mini-Mental State Examination; DRS, Dementia Rating Scale; DS-FW,
digit span forward; DS-BW, digit span backward; AF, animal fluency; FAS, phone-
mic fluency; VF, verb fluency; FAB, Frontal Assessment Battery; WCST, Wisconsin Variables Spearman P
Card Sorting Test; WD, Wilson’s disease.
Years of disease 0.366 0.112
*lost significance after Bonferroni correction.
Motor impairment 0.606 0.005
**maintain significance after Bonferroni correction.
MRI hyposignal 0.008 0.970
Pfeffer functional activities questionnaire 0.700 0.001

MRI, magnetic resonance imaging.

was used. Poor performance in the DRS was also

Figure 2. Correlation between number of altered tests per
patient and total magnetic resonance imaging (MRI) score.
significant depressive or anxious symptomatology,
showed global cognitive impairment, as well as of
deficits in executive functions and memory.
Altered performance in tests such as the
MMSE has already been reported by other
authors (24, 25), but education of the patients
was not indicated, nor was there a control group.
These factors limit the comparison of our findings
with these previous studies. In the present work,
45% of patients had cognitive performance below
–1.5 SD in MMSE in relation to controls and
30% could be considered impaired when the cut-
off suggested for the Brazilian elderly population
observed by Medalia (26) (36.8% of her sample),
although slightly less common than observed in
the present study.
In our group of patients, we observed signifi-
cant impairment in tests assessing executive func-
tions, which was found to be the most affected
cognitive domain in our sample. Such deficit was
expected, because executive functioning is subject
to great influence from the fronto-striatal circuits.
Alterations in tests that evaluated these functions,
such as Raven’s progressive matrices (5) and pho-
nemic fluency (27), were already reported in WD.
Another study (6) did not find alterations in this
domain, possibly because patients with and with-
out neurological impairment were combined in
the analysis.
Impairment of phonemic fluency with the pres-
ervation of semantic fluency indicates that this
deficit cannot be explained by dysarthria. The
preferential deficit of phonemic fluency as com-
pared with semantic fluency has already been
described in carriers of Huntington’s disease
mutation, even before the appearance of clinical
symptoms of the disease (28).
The Stroop was the test with the highest number
of patients with performance below –1.5 SD. The
number of errors on the third part of the test was

395
Frota et al.
the only variable considered for excluding the influ-
ence of dysarthria on performance, demonstrating
the difficulty in the inhibitory control of stimuli.
The FAB was proposed as a brief tool to eval-
uate executive functions. Diseases that affect the
basal ganglia, such as Parkinson’s disease, lead to
altered performance in this scale (29). The find-
ings of the present study demonstrated that this
also is true for WD, suggesting that the FAB
may be an interesting instrument to use in the
clinical setting, allowing a rapid, albeit adequate,
assessment of executive functioning in the disease.
Although patients with severe motor impairment
were excluded, a possible negative influence of
motor deficit on the third part of the battery
could not be entirely avoided.
The normal performance in the WCST was
also observed by Medalia et al. (3), although
impairment was recently observed by Hegde et al.
(7). The absence of correlation between perfor-
mance on FAB and the number of categories
formed in the WCST was observed in patients
with PD (29), as well as conflicting results in the
presence of alterations in this test in patients with
frontal lobe lesions (30). Owing to that, the nor-
mal performance in the WCST does not exclude
minor deficits of executive functions or damage
to fronto-striatal circuits.
Taking together all tests that evaluate executive
functions, only 10% of patients did not show any
deficit, while 80% displayed an altered perfor-
mance in two or more tests. This finding confirms
that executive function impairment is a key fea-
ture of the cognitive profile of WD.
Alterations in the memory domain have also
been reported by Medalia et al. (3), but the
authors suggested that impaired performance
could be explained by the motor picture. In our
study, the difference between patients and con-
trols was small, losing statistical significance with
the Bonferroni correction, although many
patients performed worst than controls. This type
of test, by its nature, is not influenced by motor
impairment. Hence, this latter clinical feature
cannot be imputed for the memory deficits dis-
played. Memory deficits without motor influence
were previously reported (4, 5, 7). Furthermore,
the level of information loss did not differ
between the two groups, indicating that deficits
are due to difficulty in encoding information,
which may be explained by dysfunction in the
fronto-striatal circuits observed in these patients
(4). In addition, learning difficulties were recently
observed in patients with WD, probably second-
ary to the involvement of basal ganglia (31), thus
corroborating our findings.
396
Normal performance in naming, visuospatial
and constructive praxis tests was already
observed by other authors (3, 5). Impaired per-
formance found in the execution of the Cubes
subtest of the WAIS may have been influenced
by the motor difficulties (4).
Even excluding patients with severe motor
impairment, 5% of our sample fulfilled diagnos-
tic criteria for dementia, an intermediate rate
between previous studies (2, 31). Moreover,
despite that all subjects evaluated were on drug
treatment for more than 1 year, a considerable
percentage (35%) had a functional impairment
and were unemployed because of the disease.
The presence of hypointense areas on T2 (SE)-
weighted images on MRI is due to the deposition
of copper and iron, without any correlation with
the inflammatory process or neuronal loss, fea-
tures that are related to T2 hyperintense areas
(12). This latter aspect can explain the strong cor-
relation found between cognitive performance
and the presence of both hyperintensities and
brain atrophy, and no correlation with hypoin-
tense areas. Subcortical T2 hyperintense signs in
patients with cardiovascular risk factors have
been related to poorer performance in the sub-
scale Initiation/Perseveration of the DRS (32).
Subcortical involvement can lead to disconnec-
tion between cortical and subcortical structures
and may thus influence the performance of execu-
tive tests. Previous studies reported correspon-
dence between atrophy, mainly in the
mesencephalus, with motor abnormalities (13), as
well as between the burden of hyperintense
lesions on T2-weighted images and motor and
functional impairment (33). A recent study found
a correlation between hyperintensities in putamen
and worse cognitive performance (7). In our
study, the presence and severity of hyperintensi-
ties and brain atrophy on MRI were found to be
significantly correlated with cognitive impairment
related to WD.
The presence of subclinical hepatic encephalop-
athy may lead to executive dysfunction (34), but
only four patients from our sample had a prior
history of liver dysfunction and, of these, two
had normal cognitive performance, thus making
this possibility unlikely. Acquired hepatolenticu-
lar degeneration can lead to motor and cognitive
impairments (35), mimicking the findings of the
present study. However, differently to what was
found in our patients, in this condition, promi-
nent visuospatial impairment, in addition to typi-
cal MRI changes (hypersignal in basal ganglia on
T1), is evident, which was not observed in any of
our cases. These data confirm that the changes

found in the current study are due to neurologi-
cal impairment and not to liver function damage.
The exclusion of patients with more intense
motor impairment may have underestimated our
findings. The small sample size limited some statisti-
cal analyses, which impeded us from identifying
which factors were more related to cognitive
decline, as well as establishing topographical corre-
lations with the tests employed. The exclusion of
patients with depression, although leading to reduc-
tion in the number of patients, prevented bias that
could result from including patients with executive
dysfunction better explained by the mood disorder.
In conclusion, the present study shows that
brief cognitive tests assessing executive functions,
such as FAS, FAB and Stroop, can demonstrate
impairment in these patients, and suggests that
their use shall be encouraged in all individuals
with WD and neurological symptoms, as part of
a cognitive screening. These tests displayed good
correlation with specific structural abnormalities
identified on MRI. Further studies aiming at pro-
spectively evaluating cognitive changes in these
patients before and after the initiation of drug
therapy should be conducted.
Acknowledgement
This research was supported in part by CAPES (Coordina-
tion of Improvement of Higher Education Personnel). Paulo
Caramelli, MD, PhD, is funded by CNPq (Bolsa de Produti-
vidade em Pesquisa) and FAPEMIG (Programa Pesquisador
Mineiro), Brazil. The authors thank all the patients and vol-
unteers who participated in the study.
Conflict of interest
There is lack of conflict of interest of any authors.
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