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Age of onset differentially influences the progression of regional dysfunction in sporadic amyotrophic lateral sclerosis

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Abstract

The clinical courses of sporadic amyotrophic lateral sclerosis (ALS) show extensive variability. Our objective was to elucidate how age of onset influences the progression of regional symptoms and functional losses in sporadic ALS. We included 648 patients with sporadic ALS from a multicenter prospective ALS cohort. We investigated the distribution of initial symptoms and analyzed the time from onset to events affecting activities of daily living (ADL) as well as the longitudinal changes in each regional functional rating score among four groups with different ages of onset. The frequencies of dysarthria and dysphagia as initial symptoms were higher in the older age groups, whereas weakness of upper limbs was the most common initial symptom in the youngest age group. The survival times and the times from onset to loss of speech and swallowing were significantly shorter in the older age group (p < 0.001), although the times from onset to loss of upper limb function were not significantly different among the age groups. According to joint modeling analysis, the bulbar score declined faster in the older age groups (<50 vs. 60–69 years: p = 0.029, <50 vs. ≥70 years: p < 0.001), whereas there was no significant correlation between the age of onset and decline in the upper limb score. Our results showed that age of onset had a significant influence on survival time and the progression of bulbar symptoms, but had no influence on upper limb function in sporadic ALS.

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Acknowledgments

We thank all the patients with ALS who participated in this study. We also thank all of the doctors and staff who participated in the Japanese Consortium for Amyotrophic Lateral Sclerosis research (JaCALS).

Author information

Authors and Affiliations

  1. Department of Neurology, Nagoya University, 65, Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan

    Daichi Yokoi, Naoki Atsuta, Ryoichi Nakamura, Mizuki Ito, Hirohisa Watanabe, Masahisa Katsuno & Gen Sobue

  2. Department of Neurology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Aichi, Japan

    Hazuki Watanabe

  3. Center for Advanced Medicine and Clinical Research, Nagoya University, Nagoya, Aichi, Japan

    Akihiro Hirakawa

  4. Department of Neurology, Tokushima University, Tokushima, Tokushima, Japan

    Yuishin Izumi & Ryuji Kaji

  5. Department of Neurology, Jichi Medical University, Shimono, Tochigi, Japan

    Mitsuya Morita

  6. Department of Neurology, Mie University Graduate School of Medicine, Tsu, Japan

    Akira Taniguchi

  7. Department of Neurology, Vihara Hananosato Hospital, Miyoshi, Hiroshima, Japan

    Masaya Oda

  8. Department of Neurology, Okayama University, Okayama, Okayama, Japan

    Koji Abe

  9. Department of Neurology, Shizuoka Fuji Hospital, Fujinomiya, Shizuoka, Japan

    Kouichi Mizoguchi

  10. Division on Neurology, Department of Internal Medicine, Toho University School of Medicine, Ota-ku, Tokyo, Japan

    Osamu Kano

  11. Department of Neurology, Chiba University, Chiba, Chiba, Japan

    Satoshi Kuwabara

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  1. Daichi Yokoi
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  2. Naoki Atsuta
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  13. Koji Abe
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  18. Gen Sobue
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JaCALS

Corresponding author

Correspondence to Gen Sobue.

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Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Funding source for study

This work was supported by a Grant (15Aek0109071 h0002) from the Japan Agency for Medical Research and Development (AMED), Health and Labour Sciences Research Grants (H26-086) and Grants-in Aid (25,461,277) for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. A section of this study is the result of the “Integrated Research on Neuropsychiatric Disorders” study, which was performed under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Ethical standard

The ethics committees of all participating institutions approved the study. Ethical standards were consistent with the 1964 Declaration of Helsinki and its later amendments.

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Written informed consent was obtained from all participants.

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Yokoi, D., Atsuta, N., Watanabe, H. et al. Age of onset differentially influences the progression of regional dysfunction in sporadic amyotrophic lateral sclerosis. J Neurol 263, 1129–1136 (2016). https://doi.org/10.1007/s00415-016-8109-0

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  • DOI: https://doi.org/10.1007/s00415-016-8109-0

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