**3.1 Cognitive functions in adults with DMD**

Ueda et al. [20] conducted a study using a wide range of neuropsychological assessment instruments to investigate whether the cognitive weaknesses remain in adult patients with DMD.

Fifteen inpatients and outpatients with DMD (mean age = 30.4 years, age range = 19–44 years) participated in the study. Twenty-four subscales of the Wechsler Adult Intelligence Scale-III (WAIS-III), the Clinical Assessment for Attention (CAT) [21], and the Wechsler Memory Scale (WMS-R) were used for the assessment. The assessment instruments were:


All assessment instruments were standardized for use in Japan. Therefore, the Z test was used to compare the scores of DMD patients on the 24 subscales with the normal population.

The mean and SD of WAIS-III in DMD adults patients (**Figure 1**), Picture Completion (M = 6.20, SD = 2.86), Arithmetic (M = 5.80, SD = 1.97), Matrix Reasoning (M = 7.47, SD = 3.74), Symbol Search (M = 6.20, SD = 3.84), Letter-Number Sequencing (M = 6.97, SD = 4.64), and Digit Span (M = 7.33, SD = 2.23) were significantly deficient (p < . 01) compared to the normal population (M = 10, SD = 3). However, there were no significant differences in Vocabulary (M = 8.80, SD = 3.28), Similarities (M = 8.80, SD = 4.31), Information (M = 8.93, SD = 3.08), and Comprehension (M = 9.33, SD = 4.61). The mean FIQ of adult patients with DMD was 87.4 (SD = 15.96, range = 61–109), which was estimated by dyadic short forms of WAIS-III [22, 23].

On the CAT, they were significantly deficient in all subscales (**Figure 2**): Symbol Digit Modalities (M = 42.5, SD = 12.5), Auditory Detection (M = 84.2, SD = 18.8), Memory Updating 3 span (M = 79.2, SD = 25.9), Memory Updating (4 span) (M = 51.4, SD = 30.4), PASAT (2 sec.) (M = 37.2, SD = 30.5), PASAT(1 sec.) (M = 17.4, SD = 16.1), and Position Stroop (M = 97.1, SD = 3.3). In addition, the total Response Time for Position Stroop of patients group (M = 163.0, SD = 75.5) was significantly longer than the normal population.

#### **Figure 1.**

*Comparison between DMD sample (N = 15) and normal population for WAIS-III. Means and SDs for standard scores are shown. The mean and SD for the normal population are 10 and 3. \*\*p < .01. Ueda et al. [4].*

#### **Figure 2.**

*Comparison between DMD sample (N = 15) and normal population for CAT. Means and SDs for percentage of correct answers are shown. \*\*p < .01. Ueda et al. [4].*

On the WMS-R, Logical Memory (M = 18.3, SD = 13.1) and Delayed Logical Memory (M = 15.8, SD = 11.7, Z = 2.495, p < .01) were significantly lower. However, there were no significant differences between patient group and normal population in other subscales: Visual Paired Association (M = 14.6, SD = 4.1), Verbal Paired Associates (M = 19.3, SD = 5.4), Figural Memory (M = 7.6, SD = 2.0), Delayed Visual Paired Association (M = 5.7, SD = 0.8), and Delayed Verbal Paired Association (M = 7.5, SD = 1.1) (**Figure 3**).

These results indicate that specific cognitive functions of adults with DMD are deficient compared to the normal population. In particular, the ability to sequentially process auditory information was reduced in attention and memory. On the other hand, cognitive abilities that do not require sequential processing were not impaired, suggesting that adults with DMD remain relatively weak in sequential auditory information processing. Moreover, tests of visual information processing showed impairments. These findings suggest that sequential visual information

**39**

**Figure 3.**

*shown. \*p < .05, \*\*p < .01. Ueda et al. [4].*

*Cognitive Function and Quality of Life of Muscular Dystrophy*

processing involving alterations of attention and processing speeds were weak in adult patients with DMD. The weaknesses of cognitive functions were maintained without improvement in adults with DMD. It suggests that these deficits are not

*Comparison between DMD sample (N = 15) and normal population for WMS-R. Raw means and SDs are* 

Taylor et al. [24] reported differences in neuropsychological profiles of DMD patients and then postulated that these differences are caused by the affected number and type of CNS-expressed isoforms. The site of DMD mutation and the extent of the cognitive deficits are related to each other distinctly. The best model for this phenomenon was that mutations affecting exons 45 to 50 are mainly mutations of coding exons. This effect is restricted to Dp260 and Dp427. In the case of mutations that affected the coding regions of the CNS expressing isoforms Dp140pc and Dp71 are clustered together, there was a significant difference in the degree of cognitive disability. Mutations affecting the Dp140 isoforms affected FIQ less than mutations affecting the Dp140 promoter or protein-coding regions [24]. Nevertheless, the relationship between these isoforms and the ability of sequential information processing has not been clarified. Further research is needed to explore the mecha-

Over the past few decades, the prognosis of DMD patients has shown remarkable improvement; however, the improvement of their quality of life still remains as an important task. Compared with ADHD [25], autistic spectrum disorders, and obsessive–compulsive disorders [25, 26], cognitive problems of DMD patients have been discussed. Particularly, the poor facial recognition of DMD patients [27] might have a negative influence on their QOL. A better evaluation of cognitive deficits in DMD patients could improve their relationship with care staff, thereby contributing

Myotonic dystrophy type 1 (DM1) is a chronic progressive multi-system disorder

thymine-guanine (CTG) repeat expansion in the protein kinase (DMPK) gene [28],

with autosomal dominant inheritance. This disorder is caused by a cytosine-

caused by environmental factors but represent organic impairments.

nisms underlining cognitive deficits associated with DGC.

**4. Cognitive functions of myotonic dystrophy type 1**

to better care and improving the QOL.

*DOI: http://dx.doi.org/10.5772/intechopen.86222*

*Cognitive Function and Quality of Life of Muscular Dystrophy DOI: http://dx.doi.org/10.5772/intechopen.86222*

#### **Figure 3.**

*Muscular Dystrophies*

**Figure 1.**

**Figure 2.**

**38**

(M = 7.5, SD = 1.1) (**Figure 3**).

*of correct answers are shown. \*\*p < .01. Ueda et al. [4].*

On the WMS-R, Logical Memory (M = 18.3, SD = 13.1) and Delayed Logical Memory (M = 15.8, SD = 11.7, Z = 2.495, p < .01) were significantly lower. However, there were no significant differences between patient group and normal population in other subscales: Visual Paired Association (M = 14.6, SD = 4.1), Verbal Paired Associates (M = 19.3, SD = 5.4), Figural Memory (M = 7.6, SD = 2.0), Delayed Visual Paired Association (M = 5.7, SD = 0.8), and Delayed Verbal Paired Association

*Comparison between DMD sample (N = 15) and normal population for CAT. Means and SDs for percentage* 

*Comparison between DMD sample (N = 15) and normal population for WAIS-III. Means and SDs for standard scores are shown. The mean and SD for the normal population are 10 and 3. \*\*p < .01. Ueda et al. [4].*

These results indicate that specific cognitive functions of adults with DMD are deficient compared to the normal population. In particular, the ability to sequentially process auditory information was reduced in attention and memory. On the other hand, cognitive abilities that do not require sequential processing were not impaired, suggesting that adults with DMD remain relatively weak in sequential auditory information processing. Moreover, tests of visual information processing showed impairments. These findings suggest that sequential visual information

*Comparison between DMD sample (N = 15) and normal population for WMS-R. Raw means and SDs are shown. \*p < .05, \*\*p < .01. Ueda et al. [4].*

processing involving alterations of attention and processing speeds were weak in adult patients with DMD. The weaknesses of cognitive functions were maintained without improvement in adults with DMD. It suggests that these deficits are not caused by environmental factors but represent organic impairments.

Taylor et al. [24] reported differences in neuropsychological profiles of DMD patients and then postulated that these differences are caused by the affected number and type of CNS-expressed isoforms. The site of DMD mutation and the extent of the cognitive deficits are related to each other distinctly. The best model for this phenomenon was that mutations affecting exons 45 to 50 are mainly mutations of coding exons. This effect is restricted to Dp260 and Dp427. In the case of mutations that affected the coding regions of the CNS expressing isoforms Dp140pc and Dp71 are clustered together, there was a significant difference in the degree of cognitive disability. Mutations affecting the Dp140 isoforms affected FIQ less than mutations affecting the Dp140 promoter or protein-coding regions [24]. Nevertheless, the relationship between these isoforms and the ability of sequential information processing has not been clarified. Further research is needed to explore the mechanisms underlining cognitive deficits associated with DGC.

Over the past few decades, the prognosis of DMD patients has shown remarkable improvement; however, the improvement of their quality of life still remains as an important task. Compared with ADHD [25], autistic spectrum disorders, and obsessive–compulsive disorders [25, 26], cognitive problems of DMD patients have been discussed. Particularly, the poor facial recognition of DMD patients [27] might have a negative influence on their QOL. A better evaluation of cognitive deficits in DMD patients could improve their relationship with care staff, thereby contributing to better care and improving the QOL.

### **4. Cognitive functions of myotonic dystrophy type 1**

Myotonic dystrophy type 1 (DM1) is a chronic progressive multi-system disorder with autosomal dominant inheritance. This disorder is caused by a cytosinethymine-guanine (CTG) repeat expansion in the protein kinase (DMPK) gene [28],

resulting in cognitive and psychiatric dysfunctions that have a significant impact on the QOL [29, 30].

Okkersen et al. [31], based on a systematic review and meta-analysis, demonstrated that DM1 patients have significant deficits in all cognitive domains compared to controls. Effect sizes were large (−.76–−1.01) for global cognition, intelligence, visual memory, visuospatial perception, visuoconstruction, psychomotor speed, and social cognition. Moreover, small to medium effect sizes (−.33–−.66) were observed for language, executive functioning, overall and verbal memory, as well as attention.

A few studies have examined the relationship between cognitive impairment and the QOL [30, 32, 33]. However, the majority of these studies did not take all the


**41**

**Table 2.**

*Cognitive Function and Quality of Life of Muscular Dystrophy*

domains of cognition into consideration, and they used QOL measures insensitive

Fujino et al. [34] conducted a study of the affected cognitive domains and evaluated the relationship between cognitive functions, psychological factors, and the QOL. Participants (N = 60) were recruited from five hospitals of National Hospital Organization in Japan. The general cognitive functions of the participants were evaluated with the Japanese version of the Mini-Mental State Examination (MMSE), and the estimated IQ was calculated from two subsets (Picture Completion and Information) of WAIS-III. Abstract reasoning was evaluated by using the Similarities subset and the Visual Perceptions Test for Agnosia (VTPA) Story Telling subset [35] in WAIS-III. Attention and working memory were evaluated with CAT subsets (Digit Span [forward, backward], Tapping Span [forward, backward], Auditory Detection task, Memory Updating 3, and PASAT-2. Executive function was evaluated with the Wisconsin Card Sorting Test (WCST), the Frontal Assessment Battery (FAB), the Trail Making Test (TMT)-B, the CAT Position Stroop test, and the semantic and phonemic fluency test. For the assessment of processing speed, TMT-A and 2 CAT subtests (Visual Cancelation task and Symbol Digit Modalities test) were used. For the evaluation of visuoconstructive ability, the WAIS-III Block Design and VPTA subtests (Copying Figures and Flowers, Bisection of Lines) were used. The CAT and VPTA are cognitive functional test batteries, which were developed by the Japan Society for Higher Brain Dysfunction.

As in psychological functioning, the five specific domains were assessed: apathy, depression, excessive daytime sleepiness, fatigue, and social responsiveness. The evaluation tools were Apathy Scale [36], Patients Health Questionnaire-9 (PHQ-9) [37], Epworth Sleepiness Scale (ESS) [38], Multidimensional Fatigue Inventory (MFI) [39], and Social Responsiveness Scale (SRS) [40]. The QOL was estimated with the Muscular Dystrophy Quality of Life Scale (MDQoL) [41] that was developed for Japanese patients with muscular dystrophies including DM1. This scale consists of 10 subscales: Psychological Stability, ADL, Environment, Hope, Activity,

Health Relationships, Family, Sexuality, Breathing, and Defecation.

*Psychological variables and QOL of patients with DM1 (Fujino et al. [34]).*

*DOI: http://dx.doi.org/10.5772/intechopen.86222*

**4.1 Assessment of cognitive function of DM1**

to specific issues related to DM1.

#### **Table 1.**

*Cognitive function of patients with DM1 (Fujino et al. [34]).*

domains of cognition into consideration, and they used QOL measures insensitive to specific issues related to DM1.
