Investigation on positive correlation of increased brain iron deposition with cognitive impairment in Alzheimer disease by using quantitative MR R2′ mapping

Qin, Yuanyuan; Zhu, Wenzhen; Zhan, Chuanjia; Zhao, Lingyun; Wang, Jian‐Zhi; Tian, Qing; Wang, Wei

doi:10.1007/s11596-011-0493-1

Cited by 51 publications

(33 citation statements)

References 31 publications

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“…Elevated concentrations of brain iron have also been observed in Parkinson’s disease (PD; Antonini et al, 1993; Gorell et al, 1995; Ulla et al, 2013; Kosta et al, 2006; Kienzel et al, 1995), Alzheimer’s disease (AD; Qin et al, 2011; Ding et al, 2009; Wang et al, 2014; Bartzokis et al, 2000; 2004; Quintana et al, 2006; Raven et al, 2013; Langkammer et al, 2014; Acosta-Cabronero et al, 2013), and multiple sclerosis (Brass et al, 2006; Ceccarelli et al, 2009; Rudko et al, 2014; Walsh et al, 2014; Pinter et al, 2015; Khalil et al, 2015). When, however, the totality of published evidence was evaluated by a meta-analysis, no significant differences between AD and normal aging were noted (Schrag et al, 2011).…”

Section: Brain Iron In Neurodegenerative Disordersmentioning

confidence: 99%

“…For instance, in PD, greater iron content in the basal ganglia and substantia nigra correlates with severity of cognitive and motor impairment (Atasoy et al, 2004; Gorell et al, 1995), as well as progressive increase in symptoms’ severity (Ulla et al, 2013). Greater regional iron deposition has also been associated with cognitive impairment in AD (Zhu et al, 2009; Ding et al, 2009; Qin et al, 2011; Luo et al, 2013; van Rooden et al, 2014). Altered iron homeostasis may explain the pathology of iron in Lewy bodies in PD (Berg et al, 2007), as well as tangles (House et al, 2004), plaques (Quintana et al, 2006; Smith and Perry, 1995) and amyloid burden (El Tannir El Tayara et al, 2006; Rival et al, 2009; Becerril-Ortega et al, 2014) in AD.…”

Section: Brain Iron In Neurodegenerative Disordersmentioning

confidence: 99%

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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 In Neurodegenerative Disordersmentioning

confidence: 99%

Section: Brain Iron In Neurodegenerative Disordersmentioning

confidence: 99%

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

2015

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“…Elevated iron is also a feature of AD-effected post-mortem brains (Zhu et al, 2009; Duce et al, 2010; Smith et al, 2010; Qin et al, 2011; Antharam et al, 2012; Loef and Walach, 2012). Iron accumulation occurs in AD cortex and hippocampus, but not cerebellum (Andrasi et al, 1995; Duce et al, 2010; Antharam et al, 2012), consistent with the pathological profile of neurodegeneration in AD.…”

Section: Iron Accumulation In the Brainmentioning

confidence: 99%

A delicate balance: Iron metabolism and diseases of the brain

Hare¹,

Ayton²,

Bush³

et al. 2013

Front. Aging Neurosci.

371

298

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Iron is the most abundant transition metal within the brain, and is vital for a number of cellular processes including neurotransmitter synthesis, myelination of neurons, and mitochondrial function. Redox cycling between ferrous and ferric iron is utilized in biology for various electron transfer reactions essential to life, yet this same chemistry mediates deleterious reactions with oxygen that induce oxidative stress. Consequently, there is a precise and tightly controlled mechanism to regulate iron in the brain. When iron is dysregulated, both conditions of iron overload and iron deficiencies are harmful to the brain. This review focuses on how iron metabolism is maintained in the brain, and how an alteration to iron and iron metabolism adversely affects neurological function.

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“…Excessive deposition of iron in brain may be a risk factor for degenerative disease [1], [2], [3] and knowledge of the normal range of iron accumulation is essential [4]. In particular, the lenticular nucleus may exhibit susceptibility to mineralization as a result of its high metabolic rate [5].…”

Section: Introductionmentioning

confidence: 99%

An Investigation of Age-Related Iron Deposition Using Susceptibility Weighted Imaging

Wang

Wei

et al. 2012

PLoS ONE

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AimTo quantify age-dependent iron deposition changes in healthy subjects using Susceptibility Weighted Imaging (SWI).Materials and MethodsIn total, 143 healthy volunteers were enrolled. All underwent conventional MR and SWI sequences. Subjects were divided into eight groups according to age. Using phase images to quantify iron deposition in the head of the caudate nucleus and the lenticular nucleus, the angle radian value was calculated and compared between groups. ANOVA/Pearson correlation coefficient linear regression analysis and polynomial fitting were performed to analyze the relationship between iron deposition in the head of the caudate nucleus and lenticular nucleus with age.ResultsIron deposition in the lenticular nucleus increased in individuals aged up to 40 years, but did not change in those aged over 40 years once a peak had been reached. In the head of the caudate nucleus, iron deposition peaked at 60 years (p<0.05). The correlation coefficients for iron deposition in the L-head of the caudate nucleus, R-head of the caudate nucleus, L-lenticular nucleus and R-lenticular nucleus with age were 0.67691, 0.48585, 0.5228 and 0.5228 (p<0.001, respectively). Linear regression analyses showed a significant correlation between iron deposition levels in with age groups.ConclusionsIron deposition in the lenticular nucleus was found to increase with age, reaching a plateau at 40 years. Iron deposition in the head of the caudate nucleus also increased with age, reaching a plateau at 60 years.

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Investigation on positive correlation of increased brain iron deposition with cognitive impairment in Alzheimer disease by using quantitative MR R2′ mapping

Cited by 51 publications

References 31 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

A delicate balance: Iron metabolism and diseases of the brain

An Investigation of Age-Related Iron Deposition Using Susceptibility Weighted Imaging

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