Higher Striatal Iron Concentration is Linked to Frontostriatal Underactivation and Poorer Memory in Normal Aging.
In the brain, intracellular iron is essential for cellular metabolism. However, an overload of free iron is toxic, inducing oxidative stress and cell death. Although an increase of striatal iron has been related to atrophy and impaired cognitive performance, the link between elevated iron and altered brain activity in aging remains unexplored. In a sample of 37 younger and older adults, we examined whether higher striatal iron concentration could underlie age-related differences in frontostriatal activity induced by mental imagery of motor and non-motor scenes, and poorer recall of the scenes. Higher striatal iron concentration was linked to underrecruitment of frontostriatal regions regardless of age and striatal volume, the iron-activity association in right putamen being primarily driven by the older adults. In older age, higher striatal iron was related to poorer memory. Altered astrocytic functions could account for the link between brain iron and brain activity, as astrocytes are involved in iron buffering, neurovascular coupling, and synaptic activity. Our preliminary findings, which need to be replicated in a larger sample, suggest a potential frontostriatal target for intervention to counteract negative effects of iron accumulation on brain function and cognition.
Aging Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Grégoria
G
Kalpouzos
Aging Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Benjamín
B
Garzón
MRI Research Center, Karolinska University Hospital, Stockholm, Sweden.
Rouslan
R
Sitnikov
Aging Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Carmel
C
Heiland
Aging Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden.|Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden.|Department of Integrative Medical Biology, Physiology Section, Umeå University, Umeå, Sweden.
Alireza
A
Salami
Aging Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Jonas
J
Persson
Aging Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Lars
L
Bäckman
D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging; D000704:Analysis of Variance; D001931:Brain Mapping; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D011939:Mental Recall / Q000502:physiology; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D014706:Verbal Learning
D007501:Iron; D010100:Oxygen
aging; brain iron; functional MRI; imagery; memory