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

Neuro-performance testing has been used extensively in MS clinical trials, resulting in a large literature on processing speed (Symbol Digit Modalities Test [SDMT]), manual dexterity (9-Hole Peg Test [9HPT]), and walking speed (25-foot walk [25FW]). Computer adapted versions were developed and validated, to support widespread use in clinical practice. The Multiple Sclerosis Performance Test (MSPT) includes a self-administered Processing Speed Test (PST), simulating SDMT; Manual Dexterity Test (MDT), simulating 9HPT; and Walking Speed Test (WST), simulating 25FW. MSPT is deployed within the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network. Optimal test thresholds associated with employment status in a real-world population have not been reported.

Objectives

To determine thresholds for standardized test scores of processing speed, manual dexterity, and walking speed as predictors of employment status in a real world MS population.

Methods

Neuroperformance testing was done as part of clinical visits in MS PATHS. Employment status was collected via standardized questionnaire. Patients aged 18 to 60 in the US were divided into a training set (n=3210) and a test set (n=1605). PST, MDT and WST benchmarks predicting unemployment at baseline and employment worsening at 2 years were identified as the test scores with the minimum p-value in logistic regression models adjusting for age, sex and education. Odds ratios representing the risk of unemployment or employment worsening were calculated based on the identified benchmarks.

Results

4815 of 9585 participants (50%) were employed full-time at baseline. In the training set benchmarks for unemployment were: PST ≤44 correct, OR (95% CI) 5.3 (4.7, 6.0); MDT >28.7 seconds, OR 7.2 (6.3, 8.1); and WST >8 seconds, OR 6.7 (5.8, 7.7). For patients employed at baseline, benchmarks for worsening employment status were: PST ≤44 correct, OR 4.3 (3.1, 6.0); MDT >24 seconds, OR 3.3 (2.3, 4.6); and WST >7.6 seconds, OR 6.4 (4.7, 8.8). Benchmarks were confirmed in the validation set.

Conclusions

Clinically relevant neuroperformance test benchmarks for predicting unemployment and employment worsening were identified in a training set and confirmed in a validation set using a large real world MS population. Future research will determine early risk factors for these benchmarks in order to identify potential employment preservation strategies.

Disclosures: MS PATHS is sponsored by Biogen