Voxel‐based quantitative susceptibility mapping in Parkinson's disease with mild cognitive impairment

Uchida, Yuto; Kan, Hirohito; Sakurai, Keita; Arai, Nobuyuki; Kato, Daisuke; Kawashima, Shoji; Ueki, Yoshino; Matsukawa, Noriyuki

doi:10.1002/mds.27717

Cited by 80 publications

(86 citation statements)

References 49 publications

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“…Previous ROI analyses reported increased QSM in bilateral hippocampus and thalamus in PD dementia 22. A recent ROI analysis found increased QSM in PD-MCI (mild cognitive impairment) relative to PD in regions including precuneus and orbitofrontal cortex, and higher QSM with decreasing MoCA in cuneus and caudate nucleus 35. Here we show for the first time that cognitive scores relate to QSM signal detected in a whole-brain analysis.…”

Section: Discussionsupporting

confidence: 63%

Brain iron deposition is linked with cognitive severity in Parkinson’s disease

Thomas

Leyland

Schrag

et al. 2020

J Neurol Neurosurg Psychiatry

157

127

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BackgroundDementia is common in Parkinson’s disease (PD) but measures that track cognitive change in PD are lacking. Brain tissue iron accumulates with age and co-localises with pathological proteins linked to PD dementia such as amyloid. We used quantitative susceptibility mapping (QSM) to detect changes related to cognitive change in PD.MethodsWe assessed 100 patients with early-stage to mid-stage PD, and 37 age-matched controls using the Montreal Cognitive Assessment (MoCA), a validated clinical algorithm for risk of cognitive decline in PD, measures of visuoperceptual function and the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 (UPDRS-III). We investigated the association between these measures and QSM, an MRI technique sensitive to brain tissue iron content.ResultsWe found QSM increases (consistent with higher brain tissue iron content) in PD compared with controls in prefrontal cortex and putamen (p<0.05 corrected for multiple comparisons). Whole brain regression analyses within the PD group identified QSM increases covarying: (1) with lower MoCA scores in the hippocampus and thalamus, (2) with poorer visual function and with higher dementia risk scores in parietal, frontal and medial occipital cortices, (3) with higher UPDRS-III scores in the putamen (all p<0.05 corrected for multiple comparisons). In contrast, atrophy, measured using voxel-based morphometry, showed no differences between groups, or in association with clinical measures.ConclusionsBrain tissue iron, measured using QSM, can track cognitive involvement in PD. This may be useful to detect signs of early cognitive change to stratify groups for clinical trials and monitor disease progression.

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Section: Discussionsupporting

confidence: 63%

Brain iron deposition is linked with cognitive severity in Parkinson’s disease

Thomas

Leyland

Schrag

et al. 2020

J Neurol Neurosurg Psychiatry

157

127

View full text Add to dashboard Cite

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“…Cortical thinning and higher iron burden in this region were observed in PD (including MCI cases) compared with controls and were associated with worse cognitive performances in patients, suggesting this region as vulnerable for patients' cognitive decline. 36,37 Thus, it is possible that thicker cortex manifests early in the disease before giving way to atrophic processes, following an inverted U-shape function. A similar rationale was provided to explain increased cortical thickness and hippocampal and cerebellar volumes in early PD.…”

Section: Discussionmentioning

confidence: 99%

Tracking Cortical Changes Throughout Cognitive Decline in Parkinson's Disease

et al. 2020

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A BS TRACT: Background: The objectives of this study were to investigate progressive cortical thinning and volume loss in Parkinson's disease (PD) patients with different longitudinal patterns of cognitive decline: with stable normal cognition, with stable mild cognitive impairment, with conversion to mild cognitive impairment, and with conversion to dementia. Methods: We recruited 112 patients (37 Parkinson's disease with stable normal cognition, 20 Parkinson's disease with stable mild cognitive impairment, 36 Parkinson's disease with conversion to mild cognitive impairment, 19 Parkinson's disease with conversion to dementia) and 38 healthy controls. All patients underwent at least 2 visits within 4 years including clinical/cognitive assessments and structural MRI (total visits, 393). Baseline cortical thickness and gray matter volumetry were compared between groups. In PD, gray matter changes over time were investigated and compared between groups. Results: At baseline, compared with Parkinson's disease with stable normal cognition cases, Parkinson's disease with conversion to mild cognitive impairment patients showed cortical atrophy of the parietal and occipital lobes, similar to Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia patients. The latter groups (ie, patients with cognitive impairment from the study entry) showed additional involvement of the frontotemporal cortices. No baseline volumetric differences among groups were detected. The longitudinal analysis (group-by-time interaction) showed that, versus the other patient groups, Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia cases accumulated the least cortical damage, with Parkinson's disease with conversion to dementia showing unique progression of right thalamic and hippocampal volume loss; Parkinson's disease with conversion to mild cognitive impairment patients showing specific cortical thinning accumulation in the medial and superior frontal gyri, inferior temporal, precuneus, posterior cingulum, and supramarginal gyri bilaterally; and Parkinson's disease with stable normal cognition patients showing cortical thinning progression, mainly in the occipital and parietal regions bilaterally. Conclusions: Cortical thinning progression is more prominent in the initial stages of PD cognitive decline. The involvement of frontotemporoparietal regions, the hippocampus, and the thalamus is associated with conversion to a more severe stage of cognitive impairment. In PD, gray matter alterations of critical brain regions may be an MRI signature for the identification of patients at risk of developing dementia.

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“…Recent studies on PD patients with cognitive impairment describe increased iron accumulation in the caudate and cortex. [191][192][193] Arguing in favor of a causative role for iron in PD are the observations that direct infusion of Fe 3þ to the SN in rats results in mitochondrial dysfunction, oxidative stress, neuronal loss, striatal dopamine depletion, and impaired motor function, all characteristic features of PD. [194][195][196][197] Administration of MPTP or 6-OHDA to rodents and monkeys also increases iron content in the SN and this increase is proportional to the loss of neurons.…”

Section: Age-associated Neurodegenerative Diseasesmentioning

confidence: 99%

“…203 Relevant to this point, some human studies have found that the increase of SN iron occurs only in the most severely affected patients. [189][190][191][192][193][194][195] At least one study utilizing monkeys and the MPTP model also found that the increase of iron in the SN occurs only with severe PD pathology and behavioral deficits. 207 Given that the clinical symptoms, neuropathological features, and rate of disease progression display a significant level of variability, it is possible that in a subset of PD cases, iron accumulation may be causally involved in disease progression, whereas it may be associated or result from degeneration in some other cases of PD.…”

Section: Age-associated Neurodegenerative Diseasesmentioning

confidence: 99%

Overdosing on iron: Elevated iron and degenerative brain disorders

D’Mello¹,

Kindy

2020

Exp Biol Med (Maywood)

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All cells in organisms ranging from yeast to humans utilize iron as a cofactor or structural element of proteins that function in diverse and critical cellular functions. However, deregulation of the homeostatic mechanisms regulating iron metabolism resulting in a reduction or excess of iron within the cell or outside of it can have serious effects to the health of cells and the organism. This review provides a brief overview of the molecular and cellular mechanisms regulating iron physiology, including the molecules and processes regulating iron uptake, its storage and utilization, its recycling, and its release from the cell, such that the cellular iron levels are sufficient to meet metabolic demand but below those that cause permanent damage. The major focus of review is on the pathological consequences of dysregulation of these homeostatic mechanisms, focusing on the brain. Current advances on the role of iron accumulation to the pathogenesis of rare neurological disorders caused by genetic mutations as well as to the more prevalent and age-associated neurodegenerative diseases are described. Impact statement Brain degenerative disorders, which include some neurodevelopmental disorders and age-associated diseases, cause debilitating neurological deficits and are generally fatal. A large body of emerging evidence indicates that iron accumulation in neurons within specific regions of the brain plays an important role in the pathogenesis of many of these disorders. Iron homeostasis is a highly complex and incompletely understood process involving a large number of regulatory molecules. Our review provides a description of what is known about how iron is obtained by the body and brain and how defects in the homeostatic processes could contribute to the development of brain diseases, focusing on Alzheimer’s disease and Parkinson’s disease as well as four other disorders belonging to a class of inherited conditions referred to as neurodegeneration based on iron accumulation (NBIA) disorders. A description of potential therapeutic approaches being tested for each of these different disorders is provided.

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Voxel‐based quantitative susceptibility mapping in Parkinson's disease with mild cognitive impairment

Cited by 80 publications

References 49 publications

Brain iron deposition is linked with cognitive severity in Parkinson’s disease

Brain iron deposition is linked with cognitive severity in Parkinson’s disease

Tracking Cortical Changes Throughout Cognitive Decline in Parkinson's Disease

Overdosing on iron: Elevated iron and degenerative brain disorders

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