title: Age of onset differentially influences the progression of regional dysfunction in sporadic amyotrophic lateral sclerosis.
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.
authors.affiliation: Department of Neurology, Nagoya University, 65, Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Yokoi
authors.affiliation: Department of Neurology, Nagoya University, 65, Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Atsuta
authors.affiliation: Department of Neurology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Aichi, Japan.
authors.forename: Hazuki
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Neurology, Nagoya University, 65, Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University, Nagoya, Aichi, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirakawa
authors.affiliation: Department of Neurology, Nagoya University, 65, Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Neurology, Nagoya University, 65, Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Neurology, Nagoya University, 65, Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.affiliation: Department of Neurology, Tokushima University, Tokushima, Tokushima, Japan.
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Neurology, Jichi Medical University, Shimono, Tochigi, Japan.
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Neurology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Taniguchi
authors.affiliation: Department of Neurology, Vihara Hananosato Hospital, Miyoshi, Hiroshima, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Oda
authors.affiliation: Department of Neurology, Okayama University, Okayama, Okayama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.affiliation: Department of Neurology, Shizuoka Fuji Hospital, Fujinomiya, Shizuoka, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Mizoguchi
authors.affiliation: Division on Neurology, Department of Internal Medicine, Toho University School of Medicine, Ota-ku, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kano
authors.affiliation: Department of Neurology, Chiba University, Chiba, Chiba, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuwabara
authors.affiliation: Department of Neurology, Tokushima University, Tokushima, Tokushima, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
authors.affiliation: Department of Neurology, Nagoya University, 65, Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan. sobueg@med.nagoya-u.ac.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
keywords: Age of onset; Bulbar upper limb function; Sporadic ALS