Cognitive/personality pattern and triplet expansionsize in adult myotonic dystrophy type 1 (DM1): CTGrepeats, cognition and personality in DM1

A. Sistiaga1*, I. Urreta2, M. Jodar3, A. M. Cobo4, J. Emparanza2, D. Otaegui1, J. J. Poza5, J. J. Merino1,

H. Imaz6, J. F. Martı-Masso5 and A. Lopez de Munain5

1 Experimental Unit, Hospital Donostia, San Sebastian, Spain2 Epidemiology Unit, Hospital Donostia, San Sebastian, Spain3 Health and Social Psychology Department, Universidad Autonoma de Barcelona and Hospital de Sabadell, Barcelona, Spain4 Association Francaise contre les Myopathies, Hopital Marin (AP-HP), Hendaye, France5 Neurology Department, Hospital Donostia, San Sebastian, and CIBERNED, Spain6 Psychiatry Department, Hospital Donostia, San Sebastian, Spain

Background. Although central nervous system (CNS) involvement in adult myotonic dystrophy type 1 (DM1) was

described long ago, the large number of variables affecting the cognitive and personality profile have made it difficult

to determine the effect of DM1 on the brain. The aim of this study was to define the cognitive and personality

patterns in adult DM1 patients, and to analyse the relationship between these clinical patterns and their association

with the underlying molecular defect.

Method. We examined 121 adult DM1 patients with confirmed molecular CTG repeat expansion and 54 control

subjects using comprehensive neuropsychological tests and personality assessments with the Millon Clinical

Multiaxial Inventory (MCMI)-II. We used a multiple linear regression model to assess the effect of each variable on

cognition and personality adjusted to the remainders.

Results. Patients performed significantly worse than controls in tests measuring executive function (principally

cognitive inflexibility) and visuoconstructive ability. In the personality profile, some paranoid and aggressive traits

were predominant. Furthermore, there was a significant negative correlation between the CTG expansion size and

many of the neuropsychological and personality measures. The molecular defect also correlated with patients’

daytime somnolence.

Conclusions. Besides muscular symptomatology, there is significant CTG-dependent involvement of the CNS in

adult DM1 patients. Our data indicate that the cognitive impairment predominantly affects the fronto-parietal lobe.

Received 31 October 2007 ; Revised 2 June 2009 ; Accepted 2 June 2009 ; First published online 23 July 2009

Key words : Dysexecutive function, genotype–phenotype correlation, myotonic dystrophy, paranoid traits, personality,

trinucleotide repeat disease.

Introduction

Myotonic dystrophy type 1 (DM1) is a slowly

progressive muscular dystrophy characterized by

multisystemic involvement. It is transmitted in an

autosomal dominant manner and is caused by an

unstable pathological expansion of (CTG)n repeats

(Brook et al. 1992). Four clinical pictures are dis-

tinguished based on the age of onset and the pre-

dominant symptoms: a congenital form; a juvenile

form; a classical or adult form; and a partial syndrome

(Harley et al. 1993). Epidemiologically, DM1 is the

most frequent neuromuscular disorder with a re-

ported prevalence of 69 to 90 cases per million

(Mostacciuolo et al. 1987 ; Emery, 1991). However, the

prevalence is significantly higher in Gipuzkoa (North

of Spain), reaching 300 cases per million inhabitants

(Lopez et al. 1993).

Previous genotype–phenotype correlation studies

described an association between the CTG repeat

size and certain clinical features, such as cognitive

impairment (Perini et al. 1999 ; Winblad et al. 2006b).

Nevertheless, this issue remains controversial (Meola

& Sansone, 2007) and some of these relationships have

been questioned on the basis of somatic mosaicism in

different tissues (Sergeant et al. 2001).

Some neuropathological studies of DM1 have de-

scribed alterations in the central nervous system

* Address for correspondence : A. Sistiaga, Experimental Unit,

Donostia Hospital, Px Dr Begiristain s/n, 20014 San Sebastian, Spain.

(Email : andone.sistiagaberrondo@osakidetza.net)

Psychological Medicine (2010), 40, 487–495. f Cambridge University Press 2009doi:10.1017/S0033291709990602

ORIGINAL ARTICLE

(CNS) associated with cell loss, atrophy and focal

white matter lesions (Ashizawa, 1998). More recently,

anomalies in tau were also described (Sergeant et al.

2001), suggesting that cognitive dysfunction in DM1

could be explained by post-transcriptional alterations

in this protein (Hernandez-Hernandez et al. 2006).

Moreover, functional positron emission tomography

(PET) studies have identified reduced blood flow af-

fecting the frontal, parietal and temporal lobes (Meola

et al. 2003).

Although cognitive impairment in DM1 was re-

ported long ago (Adie & Greenfield, 1923), systematic

studies to characterize the cognitive profile have

only recently been initiated. The available clinical

data suggest that patients’ difficulties are focused on

executive functions (D’Angelo & Bresolin, 2003), on

visuospatial/constructive abilities (Malloy et al. 1990)

and memory (Rubinsztein et al. 1997), and even on

facial emotion recognition (Winblad et al. 2006a).

Although there is still no general consensus about the

existence of emotional and personality disorders as-

sociated with DM1 (Bungener et al. 1998 ; Winblad et al.

2005), depression and anxiety (Antonini et al. 2006),

apathy (Rubinsztein et al. 1998) and avoidance (Meola

et al. 2003) are features and symptoms most frequently

associated with DM1. In addition, more than 50%

of patients with classic DM1 are referred because of

excessive daytime sleepiness (Rubinsztein et al. 1998 ;

Phillips et al. 1999 ; Laberge et al. 2004).

The aim of this study was to define the cognitive

and personality patterns associated with the adult

form of DM1, and to analyse both the relationship be-

tween such patterns and the association of these clini-

cal patterns with the underlying molecular defect.

Method

Participants

A total of 121 adult DM1 patients (from 68 families)

who were consecutively attending the Neuromuscular

Unit of the Neurology Service at Donostia Hospital

agreed to participate in this study (121 of 126), and

they were recruited between October 2005 and March

2007. The inclusion criteria were (1) age between 16

and 70 years and (2) molecular confirmation of the

DM1 diagnosis. The exclusion criteria were (1) a his-

tory of major psychiatric or somatic illness (according

to DSM-IV criteria), acquired brain injury or alcohol or

drug abuse, and (2) suffering from a congenital form of

DM1. Functional muscle impairment in patients was

quantified by the Muscular Impairment Rating Scale

(MIRS; Mathieu et al. 2001) and patients’ daytime

somnolence was assessed with the Epworth Sleepi-

ness Scale (ESS; Johns, 1991).

The data from the patient group were compared

with those from a control group of 54 volunteers aged

16 to 70 years. The control subjects were healthy

relatives of the DM1 patients (46%), healthy subjects

not related to the DM1 patients (30%), and subjects

(24%) with limb-girdle muscular dystrophy type 2A,

a neuromuscular disease in which CNS involvement

has been ruled out (Miladi et al. 1999).

The patients’ educational level was registered ac-

cording to the following classification: primary school

(<14 years old), high school (14–18 years old) and

university studies (>18 years old).

Neuropsychological assessment

An abbreviated form of the Spanish version of

the Wechsler Adult Intelligence Scale-III (WAIS-III ;

Wechsler, 2001), composed of Vocabulary, Similarities,

Arithmetic, Block Design and Object Assembly sub-

tests, was used to estimate the patients’ Intellectual

Quotient (IQ) (Lopez et al. 2003). The neuropsycho-

logical assessment also included: WAIS-III digits to

assess attention and working memory; the Wisconsin

Card Sorting Test (WCST) to assess categorization and

cognitive flexibility (Heaton et al. 2001 ; the Stroop

Color and Word Test to assess automatic response in-

hibition (Golden, 2001) ; Raven’s Progressive Matrices

for visual deduction, semantic and phonetic verbal

fluency (Raven et al. 2001) ; the Benton Judgment

of Line Orientation Test (BJLOT) as a measure of

visuospatial ability (Benton et al. 1983) ; Rey’s Complex

Figure (RCF) for visual-motor organization and plan-

ning strategies (Osterrieth, 1944) ; and the California

Computerized Assessment Package (CalCAP) for

maintained attention and simple and complex reaction

time (RT) (Miller, 1990).

We used Rey’s Auditory Verbal Learning Test

(RAVLT) to assess immediate and delayed memory

(Rey, 1964). An index of learning level was estimated

by the following formula :

Learning level=[(E5xE1)=(15xE1)]r100,

Where E1 is the number of words learnt in the first

RAVLT and E5 the words learnt in the fifth and last

assay.

The neuropsychological assessment took approxi-

mately 2 h to complete, with a short break to avoid the

effects of fatigue. This study was approved by the

Donostia Hospital ethical committee.

Personality assessment

Personality traits and psychopathology in our subjects

were assessed with the Millon Multiaxial Clinical

Inventory II (MCMI-II ; Millon, 2004). In our opinion,

the main advantage of the MCMI is that it has an

488 A. Sistiaga et al.

underlying theory, it is fairly short, and it as valid and

reliable as other well-known questionnaires (Choca,

2004). This self-report questionnaire contains 175 true–

false items that describe 13 defined personality traits

according to Axis II of the DSM-IV, nine scales that

evaluate clinical symptoms and three validation

scales. It has been validated for the Spanish language

by Avila-Espada (1998) (in Millon, 2004) and is used to

detect possible emotional problems in patients. In

clinical practice, the scores are converted directly into

base rate (BR) scores, which take into account the

prevalence of a particular characteristic in the popu-

lation. According to Millon’s criteria, BR punctuations

>75 signify the presence of a trait and BR punctu-

ations >85 are considered very meaningful. All sub-

jects received the questionnaire to complete at home.

All the questionnaires completed by the subjects in

this study that were labelled as not very reliable or

invalid according to the inventory criteria (validity

scale=1 or 2) were excluded from the study.

Genetic analysis

DNA was extracted from peripheral blood lympho-

cytes and the expansion of the CTG repeat in the dys-

trophia myotonica-protein kinase (DMPK) gene was

analysed. The analysis was performed by polymerase

chain reaction (PCR) and Southern blotting using the

pGB2.6 probe (Hunter et al. 1992). The size of the CTG

expansion was assessed visually from exposed X-ray

films. When X-rays from patients with DM1 showed

a smear rather than a distinct band, due to somatic

mosaicism, the approximate midpoint of the smear

was recorded. Each study subject signed an informed

consent.

Statistical analysis

SPSS version 13.0 (SPSS Inc., USA) was used to analyse

the data. The variables were described with the most

appropriate statistical parameter according to their

nature and measurement scale : absolute and relative

(percentage) frequencies for categorical variables, and

mean and standard deviation (S.D.) for continuous

variables. Differences between groups were analysed

by the t test or ANOVA in the case of continuous

variables and the x2 test for categorical variables.

To analyse the contribution of different variables on

personality traits and cognitive performance, we used

multiple linear regression models. This allowed us to

define the effect of each individual variable adjusted

to the remainders. The coefficient of each individual

variable in the model expresses numerically the

relationship that exists between this variable and the

dependent one. This model takes into account

differences in distribution between the patient and the

control group to define the intrinsic value of every

variable included in the model. A simple linear re-

gression method was used to study the association

between two variables.

A significance level was set at 0.05 for all categories.

Results

The sociodemographic data describing the subjects

analysed in this study are shown in Table 1. There

were significant differences between patients and

controls in terms of gender and educational level.

The neuropsychological evaluation identified sig-

nificant differences between patients and controls in :

the abbreviated form of the WAIS-III and all of its

subtests, direct digit spam, WCST, interference level

of the Stroop test, RAVLT’s learning level, Raven,

CalCAP’s first sequential RT, and planning used to

copy RCF (see Table 2). However, the multiple linear

regression analysis indicated that it was the actual

condition of the patient (i.e. as patient rather than

Table 1. Sociodemographic data

Variables

Patients

(n=121)

Controls

(n=54)

Mean age, years (S.D.) 41.8 (11.0) 42.6 (14.0)

Mean Epworth Sleepiness

Scale (S.D.)

6.3 (4.5)a –

Gender (%)

Men 52.9 29.6

Women 47.1 70.4

Educational level (%)

Primary 53.9 29.6

High school 25.2 37.1

University 20.9 33.3

MIRS (%)

1 14.3 –

2 16.0 –

3 42.9 –

4 20.2 –

5 6.7 –

Clinical form (%)

Juvenile 7.9 –

Adult 78.1 –

Partial 14.0 –

Inheritance (%)

Maternal 30.5 –

Paternal 69.5 –

MIRS, Muscular Impairment Rating Scale ; S.D., standard

deviation.a This value corresponds to 85 patients.

CTG repeats, cognition and personality in DM1 489

control) and not the effect of other variables, such as

the educational level or patients’ gender, that was

responsible for the poorer performance of the patients

compared with the control individuals in the abbrevi-

ated WAIS-III and in the Block Design and Object

Assembly subtests. The results obtained by the

patients were also worse in the Wisconsin categ-

orization test (WCST), in Raven’s Progressive Matrices

and in the strategy used to copy the RCF. The rest of

the variables that were significantly different in the

univariate analysis were no longer significant when

the subjects’ educational level was controlled for.

Therefore, it was the fact of having a lower educational

level and not the fact of suffering DM1 that was re-

sponsible for patients showing lower results in those

tests. Including gender as a covariable in the multi-

variate model did not vary the significant association

found between being a DM1 patient and different

neuropsychological variables.

A significant association was found between

planning and results in the Block Design and Object

Assembly visuoconstructive tasks (see Fig. 1). In both

cases, no significant differences were seen in the

performance between normal and middle planning

groups, although they were evident when the normal

and middle groups were compared with the impaired

one.

Regarding the results of the personality test, only

68% (n=119) of the participants in this study returned

the completed questionnaire to the hospital. The

results, after excluding two questionnaires that con-

tained invalid results on the MCMI-II, revealed that

there were more patients than controls with BR scores

>75 in the following scales : Narcissistic, Antisocial,

Aggressive/Sadistic, Paranoid, Thought Psychosis

and Sincerity (p<0.05). However, in a multivariate

model controlling the subjects’ gender and educa-

tional level, significant differences were only main-

tained in the Aggressive/Sadistic and Paranoid scales

(see Fig. 2).

When divided according to the expansion size,

the patients show statistically significant age and

educational-level differences (patients with smaller

CTG expansion sizes are older and with a higher

educational level than those with large expansion

sizes). Moreover, in 85 subjects questioned, a slight

(p<0.05, R2=0.115) but significant correlation was

observed between CTG repeat number and daytime

somnolence (five out of 89 questioned subjects used

nocturnal ventilator assistance and were excluded

from this analysis), such that those patients with larger

expansion sizes have a greater chance of falling asleep

in daily life. In addition, muscular impairment (MIRS)

is significantly associated with patients’ expansion

size, such that patients with larger expansion sizes are

physically more disabled.

In the genotype–cognitive phenotype correlation,

patients with more CTG repeats performed worse

Table 2. Neuropsychological assessment

Variables

Patients

(n=121)

Controls

(n=54)

Univariate

p

Abbreviated IQ 85.0 (16.5) 95.1 (15.3) <0.05a

Similarities 8.8 (2.7) 9.9 (2.8) <0.05

Vocabulary 9.2 (2.9) 10.3 (2.9) <0.05

Arithmetic 8.5 (3.3) 9.6 (3.3) 0.05

Block design 7.3 (3.0) 9.2 (2.7) <0.05a

Object assembly 6.9 (2.8) 9.1 (2.3) <0.05a

Digits 9.2 (3.0) 10.5 (2.5) <0.05

Direct digits 7.4 (2.5) 8.5 (2.3) <0.05

Inverse digits 5.3 (1.9) 6.0 (2.1) N.S.

WCST

Number of

categories

3.4 (2.2) 4.9 (1.6) <0.05a

Stroop test

Interference

level

x2.8 (8.3) 1.3 (7.4) <0.05

RAVLT

Immediate

memory

6.0 (2.1) 6.1 (2.0) N.S.

Learning level 65.2 (25.0) 75.7 (20.3) <0.05

Delayed

memory

10.1 (3.1) 10.3 (2.8) N.S.

Raven 35.0 (13.8) 43.5 (9.2) <0.05a

BJLOT 20.0 (6.4) 22.0 (5.7) N.S.

Verbal fluency

Phonetic 14.2 (6.2) 16.0 (6.4) N.S.

Semantic 22.0 (6.8) 23.3 (6.6) N.S.

CalCAP

Simple RT 359.3 (102.0) 331.2 (72.0) N.S.

Selective RT 496.0 (114.2) 458.9 (104.9) N.S.

Sequential RT 1 629.8 (116.4) 584.1 (121.7) <0.05

Sequential RT 2 699.9 (127.1) 663.7 (108.8) N.S.

RCF

Copy 29.0 (5.7) 30.6 (4.2) N.S.

Memory 16.1 (6.8) 16.6 (5.7) N.S.

Planning (%) 0.015a

Normal 33.7 47.9

Middle 25.7 35.4

Impaired 40.6 16.7

WCST, Wisconsin Card Sorting Test ; RAVLT, Rey’s

Auditory Verbal Learning Test ; BJLOT, Benton Judgment

of Line Orientation Test ; CalCAP, California Computerized

Assessment Package ; RT, reaction time ; RCF, Rey’s Complex

Figure ; N.S., not significant.

Results presented as mean (standard deviation) or

percentage.a Statistically significant in a multivariate model, including

subjects’ educational level.

490 A. Sistiaga et al.

than those with smaller expansions in a large num-

ber of cognitive tests (see Fig. 3) in a multivariate

model that controlled for patients’ age, educational

level, MIRS and daytime somnolence. However, this

was not the case in Digits, WCST, interference level

on the Stroop test, immediate and delayed memory

and learning level on the RAVLT test and Verbal

fluency.

The expansion size was also correlated with half

of the scales of the MCMI-II : Schizoid, Passive–Ag-

gressive, Autodestructive, Schizotypal, Borderline,

Anxiety, Hysteria, Depressive Neurosis, Thought Psy-

chosis and Major Depression.

Discussion

The analysis we have carried out confirms the

existence of a cognitive profile associated with adult

DM1. Accordingly, patients can be considered as a

group with an IQ within the normal range, although

considerably lower than that of the control subjects

(Portwood et al. 1986 ; Turnpenny et al. 1994 ; Winblad

11

9

7

5

4

Blo

ck d

esig

n

Normal Middle Impaired

Planning

11

9

7

5

3

Ob

ject

ass

emb

ly

Normal Middle Impaired

Planning

Fig. 1. Linear regression analysis : association between planning and results in the Block Design and Object Assembly

visuoconstructive tasks (p<0.05).

**

0

10

20

30

40

50

60

70

80

90

100

Desira

bility

Altera

tion

Sincerit

y

Schizo

id

Phobic

Depen

dent

Histrio

nic

Narcis

sistic

Antisocia

l

Aggress

ive/S

adic

Compulsi

ve

Passiv

e/Aggre

ssive

Autodes

tructi

ve

Schizo

typal

Border

line

Paran

oid

Anxiety

Hypom

ania

Depre

ssive

Alcohol a

buse

Hyster

ia

Drug ab

use

Thought psy

chosis

Majo

r dep

ress

ion

Delusio

nal diso

rder

MCMI-II scales

Bas

e ra

te >

75 (%

of s

ub

ject

s)

Validity Personality patterns Clinical syndromes

Fig. 2. Personality assessment using the Millon Clinical Multiaxial Inventory (MCMI)-II. Percentage of subjects with

base rate (BR) >75 : comparison between patients (&, n=84) and controls (%, n=33). * Statistically significant in

a multivariate model, including subjects’ educational level.

CTG repeats, cognition and personality in DM1 491

et al. 2006b), and with a neuropsychological pattern

principally displaying executive function impairment

with difficulties in planning and cognitive flexibility,

and problems in their visuoconstructive capacity,

principally in assembly.

In the cognitive evaluation of genetic disorders it is

difficult to separate the influence that some socio-

demographic factors affected by the disorder exert

over the biological disorder itself. This is particularly

relevant for a disorder such as DM1, where socio-

economic deprivation has long been noted (Adie &

Greenfield, 1923). As in previous studies, the edu-

cational attainment of the DM1 patients reported

here was lower than the controls (Fowler et al. 1997 ;

Laberge et al. 2007). However, the sample size allowed

us to control a series of variables, such as age, gender

or educational level, with sufficient statistical power so

as to be able to detect the real effect of the disease on

cognitive performance.

Our findings suggest the existence of alterations

that evoke an effect in the prefrontal lobe (Meola et al.

2003 ; Gaul et al. 2006), predominantly dorsolateral.

Indeed, the dorsolateral cortex is the most specifically

centred in executive functions. As described pre-

viously, our patients display visuospatial construction

but not spatial orientation impairment (Johnson et al.

1995 ; Winblad et al. 2006), although the origin of this

impairment is not clear. On the one hand, there are

functional neuroimaging and structural studies that

provide evidence of parietal lobe alterations associ-

ated with DM1 (Meola et al. 2003 ; Antonini et al. 2004)

that could explain the observed visuoconstructive

difficulties. On the other hand, prefrontal cortex

impairment gives rise to deficits in strategic planning

(Meola & Sansone, 2007) that could affect a patients’

performance in visuoconstructive tasks. In fact, we

found a significant association between patients’

planning capacity and visuoconstructive ability.

In contrast to other reports (Modoni et al. 2004 ;

Winblad et al. 2005), we find similar attention levels

in control subjects and patients. In relation to mem-

ory, age-related frontal dysfunction and memory

0 1000 2000 3000

500

IQ

0

10

20

30

40

50

60

RA

VE

N

0

5

10

15

20

25

30

35

BJL

OT

50

60

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130

Expansion size (CTG)

0 1000 2000 3000

Expansion size (CTG)

0 1000 2000 3000

Expansion size (CTG)

0 1000 2000 3000

Expansion size (CTG) Expansion size (CTG)

0 1000 2000 3000

Expansion size (CTG)

0 1000 2000 3000

Expansion size (CTG)

0 1000 2000 3000

Expansion size (CTG)

0

10

20

30

40

RC

F co

py

0

10

20

30

300 700 900

RC

F p

lan

nin

g

100

200

300

400

500

600

700

800

100

200

300

400

500

600

700

800

900

Cal

CA

P (

seq

uen

tial

RT

)R

CF

mem

ory

Cal

CA

P (

sim

ple

RT

)

I

M

N

Fig. 3. Genotype–cognitive phenotype correlation. Only variables with a statistically significant correlation (after controlling

for age and educational level) are shown. I, Impaired ; M, middle ; N, normal ; RAVEN, Raven’s Progressive Matrices ;

BJLOT, Benton Judgment of Line Orientation Test ; RCF, Rey’s Complex Figure ; CalCAP, California Computerized

Assessment Package.

492 A. Sistiaga et al.

impairment have been reported, indicating the poss-

ible involvement of the temporal lobe in DM1

(Rubinsztein et al. 1997 ; Modoni et al. 2004). However,

in our study the mnesic capacity of the patients was

no worse than in the controls, in fact age alone was

significantly associated with the variation in memory

performance in adult DM1 patients and control sub-

jects. Moreover, irrespective of peripheral factors that

could affect speech in DM1, it is accepted that language

function is normal. However, although there is evi-

dence of lower phonetic and semantic verbal fluency

in adult DM1 patients (Gaul et al. 2006 ; Modoni et al.

2008), those patients have normal fluency.

Genotype–cognitive phenotype correlation is of

particular interest because of the ongoing controversy.

In contrast to other recent studies (Meola et al. 2003 ;

Modoni et al. 2004), our results confirm a significant

negative correlation between many cognitive func-

tions and the molecular defect (Jaspert et al. 1995 ;

Perini et al. 1999 ; Marchini et al. 2000 ; Winblad et al.

2006b). Hence, we could almost predict the per-

formance of adult DM1 patients’ in some cognitive

functions according to the number of CTG repeats.

However, patients perform worse than controls in

cognitive flexibility, where no such correlation was

observed. Accordingly, this inflexibility seems to be

common to all adult DM1 patients irrespective of the

magnitude of their molecular defect.

Nevertheless, the research on this issue has a great

limitation, on the accessibility of samples. Brain tissue

would be the appropriate source for this analysis

because CTG length varies in the different tissues

(Fortune et al. 2000).

Whether the specific patterns of personality or the

special attitudes observed in DM1 patients are just the

consequence of their motor and cognitive impairment

remains to be determined (Bird et al. 1983 ; Meola &

Sansone, 2007). With respect to personality, adult DM1

patients in our study demonstrated some paranoid

personality traits as described in earlier studies

(Delaporte, 1998), in addition to elevated scores in the

Aggressive/Sadistic scale. Nevertheless, it should be

noted that an elevated score in a scale on the MCMI-II

does not imply a relationship, but rather the clinical

symptoms at the time of the examination (Choca,

2004). Furthermore, MCMI-II relies on limited em-

pirical information when used as part of a neuro-

psychological examination.

A jealous and suspicious attitude and also a sense of

superiority are the most pronounced characteristics

evaluated by the MCMI-II Paranoid scale (Choca,

2004). Patients with paranoid traits are characterized

by the rigidity of their thoughts and it is often difficult

to go against them (Millon, 2004). Rash, dogmatic,

hostile, competitive, pernicious and explosive are

some of the attributes that Millon uses to describe an

Aggressive/Sadistic personality. The Aggressive scale

is a more pathological variant of the antisocial per-

sonality style and it measures a tendency for an indi-

vidual to be at least aggressive, if not hostile, in his or

her interactions with others. An elevation in this scale

describes an individual who tends to emphasize the

ability to remain independent, competitive, distrust-

ing, excitable and irritable (Choca, 2004).

Excessive daytime sleepiness is accepted as one of

the most common complaints of patients with DM1

(Ashizawa, 1998). Although, to our knowledge, no

significant association between daytime sleepiness

and CTG repeats has yet been identified (Rubinsztein

et al. 1998; Phillips et al. 1999; Laberge et al. 2004),

we did identify a mild association between daytime

sleepiness and the CTG repeat number. Daytime

sleepiness does not significantly affect any neuro-

psychological variable, and it does not significantly

alter the association between the CTG repeat number

and the different neuropsychological variables. Hence,

although this sleep disturbance probably represents a

direct effect of the CNS lesions, cognitive impairment

cannot be attributed to this symptom in patients with

adult DM1 (Broughton et al. 1990).

In summary, dysexecutive and visuoconstructive

impairment in adult DM1 suggest a predominantly

fronto-parietal influence. Awareness of these deficits

in adults with DM1 should be considered when

adjusting the scholastic burden and employment to

patients’ capacities. Moreover, the predictive value of

CTG repeats on the cognitive and personality pheno-

type should be taken into account in the clinical man-

agement of adult DM1.

Acknowledgements

A. Sistiaga was supported by a predoctoral grant from

the Spanish Ministry of Education and Science (MEC).

We thank the patients (FENEUME), relatives and vol-

untary subjects who participated in the study. We

also acknowledge the technical skills of L. Loinaz

(Molecular Diagnosis Unit) and we thank M. Sefton

for his help in the preparation of the English version

of this manuscript.

Declaration of Interest

None.

References

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