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P1‐121: Influence of iron genes and gender on brain iron and cognition
Author(s) -
Bartzokis George,
Lu Po H.,
Tingus Kathleen,
Tishler Todd A.,
Peters Douglas G.,
Richard Aurore,
Mintz Jim,
Villablanca Pablo,
Finn J. Paul,
Laub Gerhard,
Connor James R.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.126
Subject(s) - ferritin , hippocampus , physiology , hippocampal formation , medicine , transferrin , iron status , psychology , endocrinology , iron deficiency , anemia
Background: Brain iron increases with age and is abnormally elevated early in the disease process in several neurodegenerative disorders including Alzheimer’s disease (AD). Studies have liked higher iron levels in males with younger age at onset and presence of the HFE hemochromatosis and transferrin C2 gene variants (iron genes) with AD. Objective: Examine whether cognitive performance in healthy older individuals is associated with increased brain ferritin iron and highly prevalent iron genes. Methods: Ferritin iron can be measured with specificity in vivo with MRI utilizing the Field Dependent Relaxation Rate Increase (FDRI) method. FDRI was assessed in basal ganglia, hippocampus, and white matter. Results: 48% of the sample carried neither gene (the IRONgroup) and 52% carried one and/or the other (IRONþ group). A robust gender by gene group interaction was observed. IRONþ men had significantly higher FDRI compared to the IRONgroup but in secondary analyses only the caudate nucleus showed a significant FDRI increase in IRONþ compared to IRONmen (t1⁄42.31, p1⁄4.027). This gene effect was not observed in women. Independent of genes, memory performance was significantly associated with hippocampal iron in men but not in women. Conclusions: This is the first evidence that these prevalent mutations can influence brain iron levels in men. Irrespective of gene status, verbal memory is negatively associated with hippocampal iron accumulation in men. Clinical phenomena such as gender-associated risk of developing neurodegenerative diseases and age at onset may be associated with the interactions between iron genes and brain ferritin iron accumulation. Reducing brain iron accumulations in old age may be a worthwhile therapeutic target for age-related neurodegenerative diseases.