title: Determinants of iron accumulation in the normal aging brain.
abstract: In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p ≤ 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution.
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Pirpamer
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
authors.forename: Edith
authors.initials: E
authors.lastname: Hofer
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Benno
authors.initials: B
authors.lastname: Gesierich
authors.affiliation: APHP Lariboisière Hosp, Department of Neurology & University Paris Diderot, Sorbonne Paris Cité, UMR 1161 INSERM, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: De Guio
authors.affiliation: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Freudenberger
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Stephan
authors.initials: S
authors.lastname: Seiler
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Duering
authors.affiliation: APHP Lariboisière Hosp, Department of Neurology & University Paris Diderot, Sorbonne Paris Cité, UMR 1161 INSERM, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Jouvent
authors.affiliation: Neurospin, CEA Saclay, Gif sur Yvette, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Duchesnay
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ropele
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria. Electronic address: reinhold.schmidt@medunigraz.at.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D015992:Body Mass Index; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects
chemical_list: D007501:Iron
keywords: Determinants for iron accumulation; Magnetic resonance imaging; Neocortex; Normal aging brain; R(2)* brain iron mapping