R2* mapping for brain iron: associations with cognition in normal aging

Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Éric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean‐François; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

doi:10.1016/j.neurobiolaging.2014.09.013

Cited by 123 publications

(126 citation statements)

References 34 publications

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“…Given the role of excessive unbound iron in induction of mitochondrial dysfunction, energetic decline and oxidative stress, its accumulation is likely to have detrimental cognitive consequences. In extant cross-sectional studies in healthy adults, greater iron content in subcortical structures was associated with poorer memory performance (Bartzokis et al, 2011; Rodrigue et al, 2013; Ghadery et al, 2015), lower general cognitive aptitude (Penke et al, 2012), mental slowing (Pujol et al, 1992; Sullivan et al, 2009), and poorer cognitive and motor control (Adamo, Daugherty, Raz, 2014). Greater iron content and small hippocampal volume conjointly contributed to cross-sectional age differences in memory (Rodrigue et al, 2013).…”

Section: Brain Iron and Cognitive Performancementioning

confidence: 99%

Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

2015

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Age-related increase in frailty is accompanied by a fundamental shift in cellular iron homeostasis. By promoting oxidative stress, the intracellular accumulation of non-heme iron outside of binding complexes contributes to chronic inflammation and interferes with normal brain metabolism. In the absence of direct non-invasive biomarkers of brain oxidative stress, iron accumulation estimated in vivo may serve as its proxy indicator. Hence, developing reliable in vivo measurements of brain iron content via magnetic resonance imaging (MRI) is of significant interest in human neuroscience. To date, by estimating brain iron content through various MRI methods, significant age differences and age-related increases in iron content of the basal ganglia have been revealed across multiple samples. Less consistent are the findings that pertain to the relationship between elevated brain iron content and systemic indices of vascular and metabolic dysfunction. Only a handful of cross-sectional investigations have linked high iron content in various brain regions and poor performance on assorted cognitive tests. The even fewer longitudinal studies indicate that iron accumulation may precede shrinkage of the basal ganglia and thus predict poor maintenance of cognitive functions. This rapidly developing field will benefit from introduction of higher-field MRI scanners, improvement in iron-sensitive and -specific acquisition sequences and post-processing analytic and computational methods, as well as accumulation of data from long-term longitudinal investigations. This review describes the potential advantages and promises of MRI-based assessment of brain iron, summarizes recent findings and highlights the limitations of the current methodology.

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Section: Brain Iron and Cognitive Performancementioning

confidence: 99%

Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

2015

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“…59,60 Whether this accumulation is driven by uptake or redistribution of iron is unclear. The rate of iron deposition differs between brain regions: some areas display dramatic acceleration in iron retention, 61 whereas others show a decline in iron levels with age.…”

Section: Iron In the Ageing Brainmentioning

confidence: 99%

Is early-life iron exposure critical in neurodegeneration?

et al. 2015

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The effects of iron deficiency are well documented, but relatively little is known about the long-term implications of iron overload during development. High levels of redox-active iron in the brain have been associated with neurodegenerative disorders, most notably Parkinson disease, yet a gradual increase in brain iron seems to be a feature of normal ageing. Increased brain iron levels might result from intake of infant formula that is excessively fortified with iron, thereby altering the trajectory of brain iron uptake and amplifying the risk of iron-associated neurodegeneration in later life. In this Perspectives article, we discuss the potential long-term implications of excessive iron intake in early life, propose the analysis of iron deposits in teeth as a method for retrospective determination of iron exposure during critical developmental windows, and call for evidence-based optimization of the chemical composition of infant dietary supplements.

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“…It has also been demonstrated that cerebral iron levels increase with age (Hallgren and Sourander, 1958;Bartzokis et al, 2007), which, in turn, has been linked to cognitive impairment (Penke et al, 2012;Daugherty et al, 2015;Ghadery et al, 2015) and motor system degeneration (Spatz, 1922). Therefore, with age being the strongest risk factor for many neurodegenerative diseases, it has been proposed that iron overload might be a marker or even predictor of neurodegenerative pathology (Ward et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

In VivoMRI Mapping of Brain Iron Deposition across the Adult Lifespan

et al. 2016

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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 ϭ 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.

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R2* mapping for brain iron: associations with cognition in normal aging

Cited by 123 publications

References 34 publications

Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

Is early-life iron exposure critical in neurodegeneration?

In VivoMRI Mapping of Brain Iron Deposition across the Adult Lifespan

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