title: Association Between Childhood-Onset Epilepsy and Amyloid Burden 5 Decades Later.
abstract: The effect of childhood epilepsy on later-life cognitive and brain health is an unclear and little-explored issue.
  
  
  
  To determine whether adults with a history of childhood-onset epilepsy exhibit increased brain amyloid accumulation, possibly predisposing to accelerated cognitive impairment or even frank cognitive disorders in later life.
  
  
  
  Forty-one adults from a population-based cohort of individuals with childhood-onset epilepsy in southwestern Finland, together with 46 matched population-based controls, underwent amyloid ligand carbon 11-labeled Pittsburgh Compound B (PiB) positron emission tomography after long-term prospective follow-up. The PiB uptake was quantified as a region to cerebellar cortex ratio. Tracer uptake was evaluated visually and analyzed voxel by voxel over the entire brain to investigate the spatial distribution of amyloid deposition. The study was conducted from May 2011 to October 2013; data analysis was performed from January 2014 to October 2016.
  
  
  
  Brain amyloid accumulation.
  
  
  
  The 41 individuals with epilepsy were originally enrolled in the Turku Adult Childhood Onset Epilepsy study at the mean (SD) age of 5.1 (4.5) years (range, 0-14 years). After a mean 52.5 (4.0) years of follow-up, the participants were evaluated (26 [63%] were women; the mean [SD] age was 56.0 [4.3] years). Nine individuals with childhood-onset epilepsy (22%) and 3 control participants (7%) had a visually abnormal PiB scan showing high cortical uptake in at least 1 of the evaluated brain regions (P = .04). In semiquantitative analyses, there was a significant interaction effect indicating higher prefrontal cortex uptake in apolipoprotein E (APOE) ε4 allele carriers than in noncarriers in participants (mean [SD], 1.66 [0.41] vs 1.43 [0.15]) compared with controls (1.40 [0.26) vs 1.41 [0.12]) (group × APOE interaction, F = 6.8; P = .01). In addition, there was a significant group effect showing higher tracer uptake in participants compared with controls (group effect, F = 8.0; P = .006).
  
  
  
  Adults with childhood-onset epilepsy, particularly APOE ε4 carriers, have an increased brain amyloid load at late middle age. Thus, epilepsy is linked with a biomarker that might be related to accelerated brain aging and can be considered a neurobiological predisposition to later-life cognitive disorders.
authors.affiliation: Turku PET Centre, Turku University Hospital, Turku, Finland 2Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland3Department of Clinical Neurophysiology, Turku University Hospital, Turku, Finland4now with the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown.
authors.forename: Juho
authors.initials: J
authors.lastname: Joutsa
authors.affiliation: Turku PET Centre, Turku University Hospital, Turku, Finland 2Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Bruce
authors.initials: B
authors.lastname: Hermann
authors.affiliation: Department of Psychology, Åbo Akademi University, Turku, Finland.
authors.forename: Mira
authors.initials: M
authors.lastname: Karrasch
authors.affiliation: Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Anttinen
authors.affiliation: Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York8Department of Pediatrics, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York9Department of Epidemiology and Population Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Shinnar
authors.affiliation: Department of Public Health, University of Turku, Turku, Finland11Department of Child Neurology, University of Turku, Turku, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Sillanpää
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000378:metabolism*; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D015415:Biomarkers; D013844:Thiazoles