Iron Accumulation Is Not Homogenous among Patients with Parkinson’s Disease

Abstract

Background. Iron is considered to lead to neurodegeneration and has been hypothesized as a possible cause of Parkinson's disease (PD). Susceptibility-weighted imaging (SWI) is a powerful tool to measure phase related iron content of brain. Methods. Twelve de novo patients with PD were recruited from the Movement Disorders Clinic, Department of Neurology, Loma Linda University. Twelve age- and sex-matched non-PD subjects were recruited from neurology clinic as controls. Using SWI, the phase related iron content was estimated from different brain regions of interest (ROIs). Results. There was a trend between increasing age and iron accumulation in the globus pallidus and putamen in all subjects. Iron accumulation was not significant in different ROIs in PD patients compared to controls after adjustment for age. Our data revealed heterogeneity of phase values in different brain ROIs among all subjects with an exaggerated trend at SN in PD patients. Conclusions. Our data suggest a nonhomogeneous pattern of iron accumulation in different brain regions among PD patients. Further studies are needed to explore whether this may correlate to the progression of PD. To our knowledge, this is the first study demonstrating the heterogeneity of iron accumulation in the brain, among patients with PD.

Imaging synucleinopathies

“…17,18 A heterogeneous iron content was noted across PD patients, despite the homogeneity of their unilateral bradykinesia, and rigidity. 19 The combination of SWI and R2* has shown enhanced relaxation and susceptibility in the SNc and anterior GP in PD with R2*, but not SWI, values correlating with tremor and disease duration. 20 Nigrosomes are small clusters of dopaminergic cells within the SN exhibiting calbindin D28K negativity on immunohistochemical staining.…”

“…Lower levels of phase radians in the SNc as well as in the caudate nuclei and RN, with higher phase shift in SNc and basal ganglia (BG), were found in PD patients, implying an increased iron content correlating with UPDRS scores . A heterogeneous iron content was noted across PD patients, despite the homogeneity of their unilateral bradykinesia, and rigidity . The combination of SWI and R2* has shown enhanced relaxation and susceptibility in the SNc and anterior GP in PD with R2*, but not SWI, values correlating with tremor and disease duration …”

The role of high‐field magnetic resonance imaging in parkinsonian disorders: Pushing the boundaries forward

“…A possible explanation of this finding may be that consecutive gliosis with neuronal degeneration in late‐stage PD might lengthen T2 relaxation times within the tissue and thus counteract the increase of relaxation rates . This could also explain that some authors found no difference in iron content between PD patients and HCs, whereas most studies did . Although relaxometry might track disease progression early in the disease process, available evidence suggests that relaxometry may not be a sufficient staging biomarker by itself .…”

“…Nigral changes reflecting increases have been consistently reported in PD at 1.5T and 3T . However, PD values overlapped with those of HCs, and a few studies found no changes in PD, limiting its clinical use as disease marker today . Increased iron content was also reported in symptomatic and asymptomatic leucine‐rich repeat kinase 2 ( LRRK2 ) and Parkin mutation carriers .…”

“…[2][3][4][5][6][7] However, PD values overlapped with those of HCs, and a few studies found no changes in PD, limiting its clinical use as disease marker today. [8][9][10] Increased iron content was also reported in symptomatic and asymptomatic leucine-rich repeat kinase 2 (LRRK2) and Parkin mutation carriers. 3 Asymptomatic carriers had R2* values in the range of PD values, suggesting that iron deposition may occur early during the preclinical phase of the disease.…”