Developmental variation in regional brain iron and its relation to cognitive functions in childhood

Hect, Jasmine L; Daugherty, Ana M.; Hermez, Klodia; Thomason, Moriah E.

doi:10.1016/j.dcn.2018.05.004

Cited by 38 publications

(34 citation statements)

References 79 publications

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“…We used a multimodal neuroimaging approach to investigate developmental changes in indices of pre-and post-synaptic DA neurobiology through adolescence and young-adulthood. R2′ measures of tissue iron concentration showed increases throughout adolescence, replicating prior work 23,24,29,31,32 and were specifically associated with PET DTBZ measures of presynaptic vesicular dopamine. Given that DTBZ BP quantifies presynaptic vesicular DA storage 30 , these findings suggest that DA availability, following the observed developmental pattern of R2′, increases through the adolescent period before stabilizing by early-adulthood.…”

Section: Discussionsupporting

confidence: 80%

Maturation of the human striatal dopamine system revealed by PET and quantitative MRI

et al. 2020

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The development of the striatum dopamine (DA) system through human adolescence, a time of increased sensation seeking and vulnerability to the emergence of psychopathology, has been difficult to study due to pediatric restrictions on direct in vivo assessments of DA. Here, we applied neuroimaging in a longitudinal sample of n = 146 participants aged 12-30. R2′, an MR measure of tissue iron which co-localizes with DA vesicles and is necessary for DA synthesis, was assessed across the sample. In the 18-30 year-olds (n = 79) we also performed PET using [11C]dihydrotetrabenazine (DTBZ), a measure of presynaptic vesicular DA storage, and [11C]raclopride (RAC), an indicator of D2/D3 receptor availability. We observed decreases in D2/D3 receptor availability with age, while presynaptic vesicular DA storage (as measured by DTBZ), which was significantly associated with R2′ (standardized coefficient = 0.29, 95% CI = [0.11, 0.48]), was developmentally stable by age 18. Our results provide new evidence for maturational specialization of the striatal DA system through adolescence.

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Section: Discussionsupporting

confidence: 80%

Maturation of the human striatal dopamine system revealed by PET and quantitative MRI

et al. 2020

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“…Model estimated regional R2* values-covarying for sex and visit number-closely matched prior studies (Hallgren and Sourander, 1958;Bartzokis et al, 1997Bartzokis et al, , 2007Aquino et al, 2009;Péran et al, 2009;Haacke et al, 2010 p.201;Langkammer et al, 2010;Sedlacik et al, 2014;Ghadery et al, 2015;Hect et al, 2018 3). All regions significantly differed from each other (Table 2).…”

Section: Regional Differences In Iron Concentrationsupporting

confidence: 52%

Longitudinal Development of Brain Iron Is Linked to Cognition in Youth

Larsen¹,

Bourque²,

Moore³

et al. 2020

J. Neurosci.

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Brain iron is vital to multiple aspects of brain function, including oxidative metabolism, myelination, and neurotransmitter synthesis. Atypical iron concentration in the basal ganglia is associated with neurodegenerative disorders in aging and cognitive deficits. However, the normative development of brain iron concentration in adolescence and its relationship to cognition are less well understood. Here, we address this gap in a longitudinal sample of 922 humans aged 8 -26 years at the first visit (M ϭ 15.1, SD ϭ 3.72; 336 males, 486 females) with up to four multiecho T2* scans each. Using this sample of 1236 imaging sessions, we assessed the longitudinal developmental trajectories of tissue iron in the basal ganglia. We quantified tissue iron concentration using R2* relaxometry within four basal ganglia regions, including the caudate, putamen, nucleus accumbens, and globus pallidus. The longitudinal development of R2* was modeled using generalized additive mixed models (GAMMs) with splines to capture linear and nonlinear developmental processes. We observed significant increases in R2* across all regions, with the greatest and most prolonged increases occurring in the globus pallidus and putamen. Further, we found that the developmental trajectory of R2* in the putamen is significantly related to individual differences in cognitive ability, such that greater cognitive ability is increasingly associated with greater iron concentration through late adolescence and young-adulthood. Together, our results suggest a prolonged period of basal ganglia iron enrichment that extends into the midtwenties, with diminished iron concentration associated with poorer cognitive ability during late adolescence.

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“…All studies included in this review controlled for sex during their analyses. Fifteen of the included studies assessed sex-mediated brain iron differences statistically; 1 study found that while temporal iron levels did not significantly differ between men and women, cerebellar iron was significantly higher in males compared to females [ 27 ]; 1 studies found significantly higher hippocampal iron in men compared to women [ 28 ]; 1 study found that regional brain iron in women plateaus later than in men during development [ 1 ] and the remaining 12 studies observed no significant difference in brain iron in any assessed region between males and females [ 29 , 31 , 34 – 36 , 38 , 42 , 44 , 47 , 51 , 54 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

“…Haller et al, 2010 [43] There was a significantly increased iron concentration in R-PA and R-SN in MCI groups compared to controls (p<0.01); There was significantly decreased iron concentration in the R-RN in MCI groups compared to controls (p<0.05); No difference in iron concentration was found in any regions between stable and progressive MCI Hect et al, 2018 [44] Brain iron in CN (p = 0.03), PU (p<0.01), GP (p = 0.04) and SN (p<0.01) correlated with general intelligence scores; Brain iron in the CN (p<0.001) and PU (p<0.01) correlated processing speed; HP (p>0.69) and RN (p>0.33) iron content were unrelated to cognition; Greater general brain iron content predicted faster processing speed (p = 0.02) and better general intelligence (p = 0.01)…”

Section: Ghadery Et Al 2015 [42]mentioning

confidence: 99%

The impact of brain iron accumulation on cognition: A systematic review

2020

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Iron is involved in many processes in the brain including, myelin generation, mitochondrial function, synthesis of ATP and DNA and the cycling of neurotransmitters. Disruption of normal iron homeostasis can result in iron accumulation in the brain, which in turn can partake in interactions which amplify oxidative damage. The development of MRI techniques for quantifying brain iron has allowed for the characterisation of the impact that brain iron has on cognition and neurodegeneration. This review uses a systematic approach to collate and evaluate the current literature which explores the relationship between brain iron and cognition. The following databases were searched in keeping with a predetermined inclusion criterion: Embase Ovid, PubMed and PsychInfo (from inception to 31 st March 2020). The included studies were assessed for study characteristics and quality and their results were extracted and summarised. This review identified 41 human studies of varying design, which statistically assessed the relationship between brain iron and cognition. The most consistently reported interactions were in the Caudate nuclei, where increasing iron correlated poorer memory and general cognitive performance in adulthood. There were also consistent reports of a correlation between increased Hippocampal and Thalamic iron and poorer memory performance, as well as, between iron in the Putamen and Globus Pallidus and general cognition. We conclude that there is consistent evidence that brain iron is detrimental to cognitive health, however, more longitudinal studies will be required to fully understand this relationship and to determine whether iron occurs as a primary cause or secondary effect of cognitive decline.

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Developmental variation in regional brain iron and its relation to cognitive functions in childhood

Cited by 38 publications

References 79 publications

Maturation of the human striatal dopamine system revealed by PET and quantitative MRI

Maturation of the human striatal dopamine system revealed by PET and quantitative MRI

Longitudinal Development of Brain Iron Is Linked to Cognition in Youth

The impact of brain iron accumulation on cognition: A systematic review

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