Putative brain iron content indicates changes related to Parkinson’s

Changes related to Parkinson’s disease (PD) were found in putative iron content over two years, according to a study published in the January 2014 issue of Academic Radiology. Rather than correlating with disease duration, the rate of the changes were mildly affected by individual factors like age at disease onset and eventual cognitive decline.

Accurate diagnosis of PD is key to beginning early initiation of treatment for patients with the disease, yet it is challenging to achieve. PD patients have most successfully been imaged with imaging dopamine transporters that use PET and techniques of MRI. Brain iron content, which has been shown to increase in the substantia nigra pars compacta (SSNc) of PD patients, can be investigated by diffusion tensor imaging (DTI) and functional imaging.

“Although the iron content in SNc is increased in comparison with healthy volunteers, this has not correlated with the duration of PD symptoms. However, in substantia nigra pars reticulata (SNr), the hypointense part of substantia nigra, the iron content may increase over time during disease progression, while with later-onset PD, the iron content may, in contrast to early onset, decrease,” wrote the study’s lead author, Maija Elina Rossi, PhD, of the Tampere University Hospital in Finland, and colleagues.

The researchers decided to investigate changes of brain iron content and diffusion patterns longitudinally in early-stage PD using T2- and T2*- based MRI over a two year follow-up period. The rate of brain iron accumulation was compared with clinical and neuropsychological data from the patients.

Thirty-two PD patients with tremor were included in the study. Of the 32 participants, 25 were included in the two year follow-up. Evaluation with the Unified Parkinson’s Disease Rating Scale (UPDRS) and Mini-Mental State Examination (MMSE) was also done in the investigation. Besides the 32 PD patients, 19 healthy volunteers also partook in the study. All participants underwent clinical, neuropsychological, and MRI exams on the same day. T2-weighted imaging, susceptibility-weighted imaging, and T2* mapping were all used and their results were then compared. Diffusion tensor data between groups was also evaluated with tract-based spatial statistics (TBSS).

The study’s results showed that over the two year follow-up, the iron-related relaxation increased in the globus pallidus anterior, the caudate nucleus, and slightly in the SNc. The change was associated with mild cognitive impairment in the globus pallidus anterior and medial SNc. In the caudate nucleus, the increase was evident in patients with disease onset at 67 years or older. In the SNc, medial transverse relaxation was increased. However, medial transverse relaxation decreased in the thalamus in the patients with PD. TBSS data did not vary between groups based on sex or the Unified Parkinson's Disease Rating Scale. Decreasing fractional anisotropy in the genu of corpus callosum and bilaterally in corona radiata occurred slightly over the two years.

Though slight consistency in putative iron content changes were found in patients with PD, four problems could have affected the study’s results. According to the study’s authors, these include possible external factors that could have deteriorated the measurement of iron content, the challenge of ROI localization in T2* maps because of unavoidable image distortion, lack of correction for the increase of nonhemin iron deposits with age, and the overlook of the effect of crossing fibers in TBSS analysis.

“As the main focus of our study was to analyze iron content changes, the fractional anisotropy should be analyzed in more detail in future studies,” the authors concluded.