Association between childhood-onset epilepsy and amyloid burden 5 decades later

Juho Joutsa, Juha O. Rinne, Bruce Hermann, Mira Karrasch, Anu Anttinen, Shlomo Shinnar, Matti Sillanpaa

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE The effect of childhood epilepsy on later-life cognitive and brain health is an unclear and little-explored issue. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOMES AND MEASURES Brain amyloid accumulation. RESULTS 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). CONCLUSIONS AND RELEVANCE 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.

Original languageEnglish (US)
Pages (from-to)583-590
Number of pages8
JournalJAMA Neurology
Volume74
Issue number5
DOIs
StatePublished - May 1 2017

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Amyloid
Epilepsy
Brain
Apolipoprotein E4
Cerebellar Cortex
Population Control
Apolipoproteins E
Finland
Prefrontal Cortex
Positron-Emission Tomography
Carbon
Biomarkers
Alleles
Outcome Assessment (Health Care)
Ligands
Control Groups
Health
Population
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Joutsa, J., Rinne, J. O., Hermann, B., Karrasch, M., Anttinen, A., Shinnar, S., & Sillanpaa, M. (2017). Association between childhood-onset epilepsy and amyloid burden 5 decades later. JAMA Neurology, 74(5), 583-590. https://doi.org/10.1001/jamaneurol.2016.6091

Association between childhood-onset epilepsy and amyloid burden 5 decades later. / Joutsa, Juho; Rinne, Juha O.; Hermann, Bruce; Karrasch, Mira; Anttinen, Anu; Shinnar, Shlomo; Sillanpaa, Matti.

In: JAMA Neurology, Vol. 74, No. 5, 01.05.2017, p. 583-590.

Research output: Contribution to journalArticle

Joutsa, J, Rinne, JO, Hermann, B, Karrasch, M, Anttinen, A, Shinnar, S & Sillanpaa, M 2017, 'Association between childhood-onset epilepsy and amyloid burden 5 decades later', JAMA Neurology, vol. 74, no. 5, pp. 583-590. https://doi.org/10.1001/jamaneurol.2016.6091
Joutsa, Juho ; Rinne, Juha O. ; Hermann, Bruce ; Karrasch, Mira ; Anttinen, Anu ; Shinnar, Shlomo ; Sillanpaa, Matti. / Association between childhood-onset epilepsy and amyloid burden 5 decades later. In: JAMA Neurology. 2017 ; Vol. 74, No. 5. pp. 583-590.
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AU - Sillanpaa, Matti

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