Background

Cognitive dysfunction can be observed early in the disease course of multiple sclerosis (MS) patients and has important consequences for daily activities. International guidelines recommend annual screening with the Symbol Digit Modalities Test (SDMT) and use of electronic administration to increase clinical adoption. The Processing Speed Test (PST) is a self-administered, iPad®-based validated adaptation of the SDMT in MS. The PST is not yet widely used in Japan, and there are few reports of its usage in Japanese subjects.

Objectives

To develop normative data of the PST score on Japanese healthy volunteers (HVs) in order to utilize it as a cognitive function test on Japanese patients with MS, and to characterize the PST score distribution between Japanese HVs and United States (US) HVs.

Methods

A single arm, cross-sectional study was conducted in Japanese HVs. The primary endpoint was the distribution of PST score. The secondary endpoints were distribution of PST scores stratified by age, educational status, and gender. Comparison of the PST scores between Japanese and US HVs collected in a previously reported study was evaluated using an age, gender, and education matched analysis.

Results

Of 254 subjects who participated in this study, 242 subjects with a Mini Mental State Examination score ≥ 27 were analyzed. The mean age was 44.1 years, 51.2% were male and 60.7% were educated over 13 years (vocational school, university, or more educated). Mean PST score (±SD) was 61.8±10.0, median of 62.0 (min 37, max 88). The mean PST score (±SD) significantly decreased with age, with scores of 69.6±8.8 (20-29 years, n=52), 64.9±10.9 (30-39 years, n=45), 63.5±6.1 (40-49 years, n=46), 57.1±8.7 (50-59 years, n=44) and 54.3±6.7 (60-65 years, n=55). The mean score (±SD) with education over 13 years (63.9±9.8) was significantly higher than with education 12 years or less (58.7±9.7) (p<0.0001). There was no significant difference in PST score between males (61.6±10.9) and females (62.0±9.1) (p=0.75). Mean (95% CI) difference between Japanese and US HV PST scores from the matched analysis was 10.2 (8.2, 12.2) (p<.0001), with Japanese > US.

Conclusions

The PST score in healthy Japanese subjects significantly decreased with age and was significantly higher in subjects with higher educational background. The average PST score was higher in Japanese HVs compared to US HVs. Use of country specific normative data may contribute to more accurate cognitive screening in Japanese MS patients.

Study supported by: Biogen

Background

In Japan, nationwide survey for multiple sclerosis (MS) including neuromyelitis optica spectrum disorders (NMOSD) has regularly been conducted since 1972, and the past 4 surveys conducted before the discovery of anti-aquaporin 4 antibodies demonstrated the rapid increase of MS.

Objectives

To investigate the epidemiological characteristics of MS and NMOSD in Japan simultaneously through the 5^th nationwide survey.

Methods

Preliminary survey was conducted to ascertain the approximate number of patients with either MS (pwMS) or NMOSD (pwNMOSD) who had seen at the selected facilities in 2017. Preliminary survey packages were sent to departments of neurology, internal medicine, ophthalmology, and pediatrics, at the facilities randomly selected using pre-determined sampling rates stratified based on the hospital bed counts. Secondary questionnaire was sent to the facilities with the cases to collect the detailed clinical information of each patient.

Results

Out of 3,799 departments where we sent preliminary survey, 2,284 (60.1%) replied and 645 departments reported the presence of the patients with the diseases. Second questionnaire form was sent to the 645 departments for 13,067 cases, and 6,990 (53.5%) forms were returned for further analysis. Estimated number of pwMS and pwNMOSD were 24,118 in total, which is more than 10-fold higher than that (2,280) of the 1^st survey in 1972. The crude prevalence for both MS and NMOSD was 19.6/100,000 (14.3 for MS and 5.3 for NMOSD). Male: female ratios of MS and NMOSD were 1: 2.2 and 1: 4.1, respectively. The onset ages (mean ± standard deviation, year) of MS and NMOSD were 32.3 ± 11.6 and 44.2 ± 16.1, respectively. The Expanded Disability Status Scale scores and disease durations were 2.7 ± 2.4 in 12.9 ± 9.0 years for MS and 3.7 ± 2.4 in 10.9 ± 9.5 years for NMOSD. Disease-modifying therapy had been used for 77.2% in MS. The proportion of pwNMOSD against pwMS was 1: 0.37. Based on the prefectures at birth, the distribution of pwMS demonstrated north-south gradient (ρ = 0.39, p = 0.008), although no significant gradient was observed in pwNMOSD. Based on the registered sites, the proportion of pwMS among both pwMS and pwNMOSD showed north-south gradient (ρ = 0.4, p = 0.004).

Conclusions

As the combined prevalence of MS and NMOSD was 7.7/100,000 in the 4^th survey (4.4 for conventional MS and 3.3 for others including opticospinal form), the prevalence of both MS and NMOSD appears to be still increasing. Disease severity may have become milder in MS and NMOSD compared with the 4^th survey (3.5 ± 2.9 in conventional MS and 4.3 ± 2.7 in opticospinal form), though the disease durations in the two studies were comparable. Higher latitude is a risk for MS but not NMOSD in Japanese.

Background

Cognitive dysfunction in patients with multiple sclerosis (MS) is known to be associated with physical disability and impaired quality of life (QOL) but is often overlooked in clinical practice. Several tests have been designed to assess cognitive function in MS patients. However, performing these tests is challenging in routine clinical settings because of time constraints and unavailability of trained technicians. The Processing Speed Test (PST) is a tablet computer application designed to evaluate cognitive function in patients with MS. It is a modified form of the Symbol Digit Modality Test (SDMT), and its close performance correlation with the original SDMT has been validated. Furthermore, the PST can be performed by patients themselves in a relatively short period and is therefore a reliable and convenient method for assessing cognitive function in MS patients in clinical settings.

Objectives

This study sought to evaluate the usefulness of PST by assessing the relationships between PST performance and physiological disability, brain volume, depression, fatigue, and QOL in patients with MS.

Methods

PST was performed in 43 patients with MS using the iPad^®-based CogEVAL^® application. Brain volume was estimated from three-dimensional T1 brain magnetic resonance imaging data using SIENAX software. Depression, fatigue, and QOL were assessed in a subgroup of 30 patients using Japanese versions of the Beck Depression Inventory (BDI)-II, Fatigue Severity Scale (FSS), and functional assessment of MS (FAMS), respectively.

Results

The mean PST score was 53.2 ± 16.4 (SD). PST score was negatively correlated with expanded disability status score (rs = −0.67, p < 0.0001), and was positively correlated with total brain volume (rs = 0.70, p < 0.0001) and cortical gray matter volume (rs = 0.78, p < 0.001). Additionally, PST score was negatively correlated with BDI-II (rs = −0.52, p = 0.0031) and FSS (rs = −0.37, p=0.045), and was positively correlated with total FAMS score (rs = −0.60, p = 0.0005).

Conclusions

PST score was correlated with physical disability, brain volume, depression, fatigue, and QOL in MS patients. PST is thus a reliable and convenient tool for evaluating cognitive function in MS patients.

Background

Cognitive dysfunction in patients with multiple sclerosis (MS) is known to be associated with physical disability and impaired quality of life (QOL) but is often overlooked in clinical practice. Several tests have been designed to assess cognitive function in MS patients. However, performing these tests is challenging in routine clinical settings because of time constraints and unavailability of trained technicians. The Processing Speed Test (PST) is a tablet computer application designed to evaluate cognitive function in patients with MS. It is a modified form of the Symbol Digit Modality Test (SDMT), and its close performance correlation with the original SDMT has been validated. Furthermore, the PST can be performed by patients themselves in a relatively short period and is therefore a reliable and convenient method for assessing cognitive function in MS patients in clinical settings.

Objectives

This study sought to evaluate the usefulness of PST by assessing the relationships between PST performance and physiological disability, brain volume, depression, fatigue, and QOL in patients with MS.

Methods

PST was performed in 43 patients with MS using the iPad^®-based CogEVAL^® application. Brain volume was estimated from three-dimensional T1 brain magnetic resonance imaging data using SIENAX software. Depression, fatigue, and QOL were assessed in a subgroup of 30 patients using Japanese versions of the Beck Depression Inventory (BDI)-II, Fatigue Severity Scale (FSS), and functional assessment of MS (FAMS), respectively.

Results

The mean PST score was 53.2 ± 16.4 (SD). PST score was negatively correlated with expanded disability status score (rs = −0.67, p < 0.0001), and was positively correlated with total brain volume (rs = 0.70, p < 0.0001) and cortical gray matter volume (rs = 0.78, p < 0.001). Additionally, PST score was negatively correlated with BDI-II (rs = −0.52, p = 0.0031) and FSS (rs = −0.37, p=0.045), and was positively correlated with total FAMS score (rs = −0.60, p = 0.0005).

Conclusions

PST score was correlated with physical disability, brain volume, depression, fatigue, and QOL in MS patients. PST is thus a reliable and convenient tool for evaluating cognitive function in MS patients.