Accumulation of iron in the putamen predicts its shrinkage in healthy older adults: A multi-occasion longitudinal study

Daugherty, Ana M.; Raz, Naftali

doi:10.1016/j.neuroimage.2015.12.045

Cited by 76 publications

(56 citation statements)

References 77 publications

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“…Moreover, Khalil et al showed that GM atrophy (combined cortical and deep GM) was the strongest predictor of basal ganglia mean R2*, and Langkammer et al described significant negative associations between mean QSM values in DGM and normalized DGM volumes. A longitudinal study in HCs has shown that mean R2* increases over time actually preceded atrophy in the putamen but not in the caudate nucleus . These results indicate a different behavior of putamen compared with the caudate nucleus with aging, which might be aggravated under conditions of MS. Our findings similarly separate these two regions.…”

Section: Discussionmentioning

confidence: 94%

Increased mean R2* in the deep gray matter of multiple sclerosis patients: Have we been measuring atrophy?

Hernández‐Torres

Wiggermann

Machan

et al. 2018

Magnetic Resonance Imaging

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Background Magnetic resonance relaxometry studies in multiple sclerosis (MS) have suggested that iron accumulates within deep gray matter (DGM) structures early in the disease course. However, the commonly utilized mean R2* and magnetic susceptibility measures reflect regional iron concentration but not a structure's total iron content. Thus, tissue atrophy could impact mean R2* and magnetic susceptibility estimates. Purpose To demonstrate that both average iron concentration and total iron content need to be reported in order to distinguish between atrophy‐related and definite magnetic susceptibility changes. Study Type Observational. Population The study was performed on 30 healthy controls (HCs) and 39 people with definite MS. Field Strength/Sequence 3T Philips Achieva using an 8‐channel SENSE head coil. R2* data were acquired using a multiecho gradient echo sequence and diffusion tensor imaging data were acquired using an echo‐planar sequence. Assessment Total iron content in DGM structures was assessed by calculating the sum of all R2* values within a region (denoted as R2mass*) and compared to the mean R2* as a measure of iron concentration. Statistical Test Significant group differences were investigated in a linear regression model. All DGM structures were assessed individually and the significance threshold was adjusted using the Bonferroni‐Holm correction for multiple comparisons. Results There was an increased mean DGM R2* in MS patients compared to HCs (significant in the pallidus, P = 0.0051). In contrast, R2mass* in patients was found to be lower in the thalamus and the caudate (P = 0.0011) compared to HCs, and similar between the two cohorts in the other DGM regions. Data Conclusion An increase in mean R2* may not necessarily reflect increased iron accumulation. We propose R2mass* as an additional metric to account for the effects of tissue atrophy when assessing tissue content changes, such as iron deposition or loss. Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:201–208.

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Section: Discussionmentioning

confidence: 94%

Increased mean R2* in the deep gray matter of multiple sclerosis patients: Have we been measuring atrophy?

Hernández‐Torres

Wiggermann

Machan

et al. 2018

Magnetic Resonance Imaging

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“…As putamen volume is expected to decrease with age (in contrast to QSM, which increases with age), 39 age effects were also examined. In controls, putamen gray matter volume was significantly negatively correlated with QSM ( r =−0.53, P <0.001) and age ( r =−0.37, P =0.015) but these relationships were not seen in CUD (QSM: r =−0.13, P =0.416; age: r =0.05, P =0.770).…”

Section: Resultsmentioning

confidence: 99%

Disrupted iron regulation in the brain and periphery in cocaine addiction

et al. 2017

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Stimulant drugs acutely increase dopamine neurotransmission in the brain, and chronic use leads to neuroadaptive changes in the mesolimbic dopamine system and morphological changes in basal ganglia structures. Little is known about the mechanisms underlying these changes but preclinical evidence suggests that iron, a coenzyme in dopamine synthesis and storage, may be a candidate mediator. Iron is present in high concentrations in the basal ganglia and stimulant drugs may interfere with iron homeostasis. We hypothesised that morphological brain changes in cocaine addiction relate to abnormal iron regulation in the brain and periphery. We determined iron concentration in the brain, using quantitative susceptibility mapping, and in the periphery, using iron markers in circulating blood, in 44 patients with cocaine addiction and 44 healthy controls. Cocaine-addicted individuals showed excess iron accumulation in the globus pallidus, which strongly correlated with duration of cocaine use, and mild iron deficiency in the periphery, which was associated with low iron levels in the red nucleus. Our findings show that iron dysregulation occurs in cocaine addiction and suggest that it arises consequent to chronic cocaine use. Putamen enlargement in these individuals was unrelated to iron concentrations, suggesting that these are co-occurring morphological changes that may respectively reflect predisposition to, and consequences of cocaine addiction. Understanding the mechanisms by which cocaine affects iron metabolism may reveal novel therapeutic targets, and determine the value of iron levels in the brain and periphery as biomarkers of vulnerability to, as well as progression and response to treatment of cocaine addiction.

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“…For example, decline in serum BDNF levels have been shown to predict hippocampal but not caudate volume decline in older adults [Erickson et al, ]. Likewise, brain iron accumulation has been shown to predict putamen but not caudate volume decline in late life [Daugherty and Raz, ], again suggesting that volume decline in deep gray matter may be influenced by unique physiological mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Evolution of deep gray matter volume across the human lifespan

Narvacan

Treit

Camicioli

et al. 2017

Human Brain Mapping

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Magnetic resonance imaging of subcortical gray matter structures, which mediate behavior, cognition and the pathophysiology of several diseases, is crucial for establishing typical maturation patterns across the human lifespan. This single site study examines T1-weighted MPRAGE images of 3 healthy cohorts: (i) a cross-sectional cohort of 406 subjects aged 5-83 years; (ii) a longitudinal neurodevelopment cohort of 84 subjects scanned twice approximately 4 years apart, aged 5-27 years at first scan; and (iii) a longitudinal aging cohort of 55 subjects scanned twice approximately 3 years apart, aged 46-83 years at first scan. First scans from longitudinal subjects were included in the cross-sectional analysis. Age-dependent changes in thalamus, caudate, putamen, globus pallidus, nucleus accumbens, hippocampus, and amygdala volumes were tested with Poisson, quadratic, and linear models in the cross-sectional cohort, and quadratic and linear models in the longitudinal cohorts. Most deep gray matter structures best fit to Poisson regressions in the cross-sectional cohort and quadratic curves in the young longitudinal cohort, whereas the volume of all structures except the caudate and globus pallidus decreased linearly in the longitudinal aging cohort. Males had larger volumes than females for all subcortical structures, but sex differences in trajectories of change with age were not significant. Within subject analysis showed that 65%-80% of 13-17 year olds underwent a longitudinal decrease in volume between scans (∼4 years apart) for the putamen, globus pallidus, and hippocampus, suggesting unique developmental processes during adolescence. This lifespan study of healthy participants will form a basis for comparison to neurological and psychiatric disorders. Hum Brain Mapp 38:3771-3790, 2017. © 2017 Wiley Periodicals, Inc.

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Accumulation of iron in the putamen predicts its shrinkage in healthy older adults: A multi-occasion longitudinal study

Cited by 76 publications

References 77 publications

Increased mean R2* in the deep gray matter of multiple sclerosis patients: Have we been measuring atrophy?

Increased mean R2* in the deep gray matter of multiple sclerosis patients: Have we been measuring atrophy?

Disrupted iron regulation in the brain and periphery in cocaine addiction

Evolution of deep gray matter volume across the human lifespan

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