META-ANALYSIS Age-specific ALS incidence: a dose–response meta-analysis Benoı ˆt Marin 1,2,3,4,5,6 • Andrea Fontana 7 • Simona Arcuti 7,9 • Massimilano Copetti 7 • Farid Boume ´ diene 1,2,3 • Philippe Couratier 1,2,8 • Ettore Beghi 4 • Pierre Marie Preux 1,2,3 • Giancarlo Logroscino 5,6 Received: 8 November 2017 / Accepted: 2 April 2018 Ó Springer Science+Business Media B.V., part of Springer Nature 2018 Abstract To evaluate the association between worldwide ALS incidence rates and age, using a dose–response meta-analysis. We reviewed Medline and Embase up to July 2016 and included all population-based studies of newly-diagnosed cases, using multiple sources for case ascertainment. A dose–response meta-analysis was performed. A meta-regression investigated potential sources of heterogeneity. Of 3254 articles identified in the literature, we included 41 incidence studies covering 42 geographical areas. Overall, the fit between observed and predicted age-specific rates was very good. The expected variation of ALS incidence with age was characterized, in each study, by a progressive increase in the incidence from the 40s leading to a peak in the 60s or 70s, followed by a sharp decrease. Cochran’s Q test suggested a significant heterogeneity between studies. Overall, estimated patterns of ALS age-specific incidence (at which the peak was reached) were similar among subcontinents of Europe and North America: peak of ALS incidence ranged in these areas between 6.98 and 8.17/ 100,000 PYFU, which referred to age in the range 71.6–77.4 years. The relationship between age and ALS incidence appeared different for Eastern Asia which was characterized by a peak of ALS incidence at 2.20/100,000 PYFU around 75 years of age. This study confirms the consistency of the age-specific ALS incidence pattern within different subcon- tinents. Age-specific incidence appears lower in Eastern Asia as compared to Europe and North America. Keywords Amyotrophic lateral sclerosis Á Epidemiology Á Incidence Á Ethnic groups Á Age-specific Abbreviations ALS Amyotrophic lateral sclerosis PDC Parkinson dementia complex PD Parkinson’s disease MOOSE Meta-analysis of observational studies in epidemiology PYFU Person years of follow-up Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10654-018-0392-x) contains supplementary material, which is available to authorized users. & Giancarlo Logroscino giancarlo.logroscino@uniba.it 1 INSERM, U1094, Neuroe ´pide ´miologie Tropicale, 87000 Limoges, France 2 Univ. Limoges, UMR_S 1094, Neuroe ´pide ´miologie Tropicale, Institut d’Epide ´miologie Neurologiqueet de Neurologie Tropicale, CNRS FR 3503 GEIST, 87000 Limoges, France 3 CHU Limoges, Centre d’Epide ´miologie de Biostatistique et de Me ´thodologie de la Recherche, Limoges, France 4 Laboratorio di Malattie Neurologiche, Dipartimento di Neuroscienze, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy 5 Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari ‘‘Aldo Moro’’, Bari, Italy 6 Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari ‘‘Aldo Moro’’, at ‘‘Pia Fondazione Cardinale G. Panico’’, 73039 Tricase, Lecce, Italy 7 Unit of Biostatistics, IRCCS ‘‘Casa Sollievo della Sofferenza’’, San Giovanni Rotondo, Italy 8 CHU Limoges, Service de Neurologie, Centre expert SLA, Limoges, France 9 Neurology Unit, Department of Medicine, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy 123 European Journal of Epidemiology https://doi.org/10.1007/s10654-018-0392-x