Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease

Abstract

BackgroundIn Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population.MethodsHere, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals.ResultsWe found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus.ConclusionsOur findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease.

Tissue microstructural changes in dementia with Lewy bodies revealed by quantitative MRI

“…During healthy aging, qT2* (a quantitative MRI parameter related to qT2) has also been found to be negatively correlated with age in a wide range of brain areas, in particular in bilateral putamen, reflecting an increased level of iron [32]. In parkinson's disease, lower qT2* in putamen is also associated with more severe motor symptoms [33]. In addition, we have shown that qT1 parameters were decreased in the left caudate nucleus by 68 % with DLB.…”

High-resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7 T

“…Since aging is the major risk factor for many neurodegenerative diseases, agerelated accumulation of iron may be an important factor that contributes to neurodegenerative pathology (Ward et al, 2014). This notion has been supported by post mortem and in vivo human studies identifying abnormal iron deposition in neurodegenerative diseases such as Alzheimer's disease (AD) (Cornett et al, 1998;Bartzokis et al, 2000) and Parkinson's disease (PD) (Bartzokis et al, 1999;Bunzeck et al, 2013;Sofic et al, 1991).…”

Imaging in Parkinson's Disease

“…Over a 3-year follow-up, increased R2* in the substantia nigra correlated with the worsening of motor symptoms of PD, suggesting that R2* may be a biomarker of disease progression in PD (Ulla et al, 2013). Association between high R2* signal and LIDs has yielded inconsistent results either showing a positive (Bunzeck et al, 2013) or no correlations (Wieler, Gee, & Martin, 2015) between iron deposition and motor complications. Early-onset PD patients showed a higher field-dependent R2 increases in the substantia nigra, putamen, and pallidum, which decreases as the disease progresses, suggesting that dysregulation of iron metabolism occurs in PD (Bartzokis et al, 1999).…”