Relevance of Iron Deposition in Deep Gray Matter Brain Structures to Cognitive and Motor Performance in Healthy Elderly Men and Women: Exploratory Findings (original) (raw)
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In Vivo MRI Mapping of Brain Iron Deposition across the Adult Lifespan
Disruption of iron homeostasis as a consequence of aging is thought to cause iron levels to increase, potentially promoting oxidative cellular damage. Therefore, understanding how this process evolves through the lifespan could offer insights into both the aging process and the development of aging-related neurodegenerative brain diseases. This work aimed to map, in vivo for the first time with an unbiased whole-brain approach, age-related iron changes using quantitative susceptibility mapping (QSM)—a new postprocessed MRI contrast mechanism. To this end, a full QSM standardization routine was devised and a cohort of N 116 healthy adults (20 –79 years of age) was studied. The whole-brain and ROI analyses confirmed that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their exact anatomical location. Whereas only patchy signs of iron scavenging were observed in white matter, strong, bilateral, and confluent QSM–age associations were identified in several deep-brain nuclei— chiefly the striatum and midbrain—and across motor, premotor, posterior insular, superior prefrontal, and cerebellar cortices. The validity of QSM as a suitable in vivo imaging technique with which to monitor iron dysregulation in the human brain was demonstrated by confirming age-related increases in several subcortical nuclei that are known to accumulate iron with age. The study indicated that, in addition to these structures, there is a predilection for iron accumulation in the frontal lobes, which when combined with the subcortical findings, suggests that iron accumulation with age predominantly affects brain regions concerned with motor/output functions.
Brain iron deposits are associated with general cognitive ability and cognitive aging
Neurobiology of Aging, 2010
A novel analysis of magnetic resonance imaging (MRI) scans based on multispectral image fusion was used to quantify iron deposits in basal ganglia and microbleeds in 143 nondemented subjects of the generally healthy Lothian Birth Cohort, who were tested for general cognitive ability (intelligence) at mean ages of 11, 70, and 72 years. Possessing more iron deposits at age 72 was significantly associated with lower general cognitive ability at age 11, 70, and 72, explaining 4% to 9% of the variance. The relationships with old age general cognitive ability remained significant after controlling for childhood cognition, suggesting that iron deposits are related to lifetime cognitive decline. Most iron deposits were in the basal ganglia, with few microbleeds. While iron deposits in the general population have so far been dismissed in the literature, our results show substantial associations with cognitive functioning. The pattern of results suggests that iron deposits are not only a biomarker of general cognitive ability in old age and age-related cognitive decline, but that they are also related to the lifelong-stable trait of intelligence.
Cerebral Cortex
Aging is associated with brain iron accumulation, which has been linked to cognitive decline. However, how brain iron affects the structure and function of cognitive brain networks remains unclear. Here, we explored the possibility that iron load in gray matter is associated with disruption of white matter (WM) microstructure within a network supporting cognitive function, in a cohort of 95 cognitively normal older adults (age range: 60–86). Functional magnetic resonance imaging was used to localize a set of brain regions involved in working memory and diffusion tensor imaging based probabilistic tractography was used to identify a network of WM tracts connecting the functionally defined regions. Brain iron concentration within these regions was evaluated using quantitative susceptibility mapping and microstructural properties were assessed within the identified tracts using neurite orientation dispersion and density imaging. Results indicated that high brain iron concentration was ...
In vivo MR evaluation of age-related increases in brain iron
AJNR. American journal of neuroradiology, 1994
To assess the validity of an MR method of evaluating tissue iron. The difference between the transverse relaxation rate (R2) measured with a high-field MR instrument and the R2 measured with a lower field instrument defines a measure termed the field-dependent R2 increase (FDRI). Previous in vivo and in vitro studies indicated that FDRI is a specific measure of tissue iron stores (ferritin). T2 relaxation times were obtained using two clinical MR instruments operating at 0.5 T and 1.5 T. T2 relaxation times were measured in the frontal white matter, caudate nucleus, putamen, and globus pallidus of 20 healthy adult male volunteers with an age range of 20 to 81 years. R2 was calculated as the reciprocal of T2 relaxation time. These in vivo MR results were correlated with previously published postmortem data on age-related increases of nonheme iron levels. The FDRI was very highly correlated with published brain iron levels for the four regions examined. In the age range examined, robu...
NeuroImage, 2009
Quantifying tissue iron concentration in vivo is instrumental for understanding the role of iron in physiology and in neurological diseases associated with abnormal iron distribution. Herein, we use recently-developed Quantitative Susceptibility Mapping (QSM) methodology to estimate the tissue magnetic susceptibility based on MRI signal phase. To investigate the effect of different regularization choices, we implement and compare ℓ 1 and ℓ 2 norm regularized QSM algorithms. These regularized approaches solve for the underlying magnetic susceptibility distribution, a sensitive measure of the tissue iron concentration, that gives rise to the observed signal phase. Regularized QSM methodology also involves a pre-processing step that removes, by dipole fitting, unwanted background phase effects due to bulk susceptibility variations between air and tissue and requires data acquisition only at a single field strength. For validation, performances of the two QSM methods were measured against published estimates of regional brain iron from postmortem and in vivo data. The in vivo comparison was based on data previously acquired using Field-Dependent Relaxation Rate Increase (FDRI), an estimate of MRI relaxivity enhancement due to increased main magnetic field strength, requiring data acquired at two different field strengths. The QSM analysis was based on susceptibilityweighted images acquired at 1.5 T, whereas FDRI analysis used Multi-Shot Echo-Planar Spin Echo images collected at 1.5 T and 3.0 T. Both datasets were collected in the same healthy young and elderly adults. The in vivo estimates of regional iron concentration comported well with published postmortem measurements; both QSM approaches yielded the same rank ordering of iron concentration by brain structure, with the lowest in white matter and the highest in globus pallidus. Further validation was provided by comparison of the in vivo measurements, ℓ 1 -regularized QSM versus FDRI and ℓ 2 -regularized QSM versus FDRI, which again yielded perfect rank ordering of iron by brain structure. The final means of validation was to assess how well each in vivo method detected known age-related differences in regional iron concentrations measured in the same young and elderly healthy adults. Both QSM methods and FDRI were consistent in identifying higher iron concentrations in striatal and brain stem ROIs (i.e., caudate nucleus, putamen, globus pallidus, red nucleus, and substantia nigra) in the older than in the young group. The two QSM methods appeared more sensitive in detecting age differences in brain stem structures as they revealed differences of much higher statistical significance between the young and elderly groups than did FDRI. However, QSM values are influenced by factors such as the myelin content, whereas FDRI is a more specific indicator of iron content. Hence, FDRI demonstrated higher specificity to iron yet yielded noisier data despite longer scan times and lower spatial resolution than QSM. The robustness, practicality, and demonstrated ability of predicting the change in iron deposition in adult aging suggest that regularized QSM algorithms using single-field-strength data are possible alternatives to tissue iron estimation requiring two field strengths.
Journal of Alzheimer's disease : JAD, 2017
Abnormally high deposition of iron can contribute to neurodegenerative disorders with cognitive impairment. Since previous studies investigating cognition-brain iron accumulation relationships focused on elderly people, our aim was to explore the association between iron concentration in subcortical nuclei and two types of memory performances in a healthy young population. Gender difference was found only in the globus pallidus. Our results showed that iron load characterized by R2* value on the MRI in the caudate and putamen was related to visual memory, while verbal memory was unrelated to iron concentration.
In vivo assessment of age‐related brain iron differences by magnetic field correlation imaging
2012
Purpose: To assess a recently developed magnetic resonance imaging (MRI) technique called magnetic field correlation (MFC) imaging along with a conventional imaging method, the transverse relaxation rate (R2), for estimating age-related brain iron concentration in adolescents and adults. Brain region measures were compared with nonheme iron concentrations (C PM) based on a prior postmortem study. Materials and Methods: Asymmetric spin echo (ASE) images were acquired at 3T from 26 healthy individuals (16 adolescents, 10 adults). Regions of interest (ROIs) were placed in areas in which age-related iron content was estimated postmortem: globus pallidus (GP), putamen (PUT), caudate nucleus (CN), thalamus (THL), and frontal white matter (FWM). Regression and group analyses were conducted on ROI means. Results: MFC and R2 displayed significant linear relationships to C PM when all regions were combined. Whereas MFC was significantly correlated with C PM for every individual region except FWM and detected significantly lower means in adolescents than adults for each region, R2 detected significant correlation and lower means for only PUT and CN. Conclusion: Our results support the hypothesis that MFC is sensitive to brain iron in GM regions and detects agerelated iron increases known to occur from adolescence to adulthood. MFC may be more sensitive than R2 to ironrelated changes occurring within specific brain regions.
Age-Related Differences in Iron Content of Subcortical Nuclei Observed< i> in vivo: A Meta-Analysis
2012
Accumulation of non-heme iron in the brain has been proposed as a biomarker of the progressive neuroanatomical and cognitive declines in healthy adult aging. Postmortem studies indicate that iron content and lifespan differences therein are regionally specific, with a predilection for the basal ganglia. However, the reported in vivo estimates of adult age differences in iron content within subcortical nuclei are highly variable. We present a meta-analysis of 20 in vivo magnetic resonance imaging (MRI) studies that estimated iron content in the caudate nucleus, globus pallidus, putamen, red nucleus, and substantia nigra. The results of the analyses support a robust association between advanced age and high iron content in the substantia nigra and striatum, with a smaller effect noted in the globus pallidus. The magnitude of age differences in estimated iron content of the caudate nucleus and putamen partially depended on the method of estimation, but not on the type of design (continuous age vs. extreme age groups).