1. Laura Behler,University of Wisconsin-Stout
The effects of abnormal iron metabolism on Parkinson’s disease patients with Probable Rapid Eye Movement Sleep Behavior Disorder
Laura Behler,University of Wisconsin-Stout
Abstract
Abnormal iron metabolism is linked with Probable Rapid Eye Movement Sleep Behavior Disorder(PRBD) which is a common disorder among patients who have Parkinson’s Disease (PD). The aim of this poster is to investigate the link between increased and decreased iron levels in the brain and periphery tissues and the development of PRBD in PD patients. 210 PD patients and 31 control group patients were examined in this study. Of the 210 PD patients 67 had PRBD so the PD patients were divided into two groups: PRBD and NPRBD. With the control that is three groups total. The three groups underwent questionnaires as well as cerebral spinal fluid (CSF) tests. The results indicate that there are abnormalities in iron metabolism because there are excessive amounts of iron deposits in the brain of a PRBD patient.
Methods
Participants: The subjects were divided into two groups: PD patients and Normal Control patients. 210 PD patients that were used were diagnosed with PD based on United Kingdom’s Parkinson’s disease brain bank criteria. Patients demographics were recorded like: gender, age, age of disease onset, disease duration and disease severity were recorded. None of the PD subjects had histories of blood donations, systemic diseases, RLS, PLMD, EDS and were not premenopausal women. The 31 normal control subjects were age matched and recruited based on the criteria of: no neurological signs or symptoms, no history of sleep disorders, no epilepsy history, no obvious cognitive impartment and no drug and alcohol abuse. The excluded subjects were based on the same criteria as those excluded in PD subjects.
Time Frame: The CSF serum samples were taken from each person over a 3 hour period. The subjects were in a fasting state and had to withhold all anti-Parkinson’s medication for hours.
Measurements: All PD patients were given a RBD questionnaire and then were divided into two groups based on their answers. PRDB and NPRBD. Symptoms were evaluated by a clinical scale. They took CSF from the brain and periphery tissues and looked at iron levels as well as inflammatory factors. They then compared the levels of iron in the CSF of the PRBD and NRBD to each other and the questionnaire score. The control group also did these tests and the results were compared to the PD patients.
Iron Metabolism
Heme Iron
Must be hydrolyzed before absorption. Heme contains iron bound to porphyrin ring. It is absorbed across brush border by heme carrier protein 1. Iron is absorbed throughout the entire small intestine but it is most efficient in the duodenum. Inside the cell the heme porphyrin ring is hydrolyzed by heme oxygenase into ferrous iron and protoporphyrin. These are released and can be used by cells, stored as ferritin, excreted or it can be used by other body tissues.
NonHeme Iron
Is bound to components in foods. It needs to be hydrolyzed or freed in GI tract to be absorbed. Hydrochloric acid and proteases in stomach release nonheme iron as Fe3+ or ferric iron. Ferric iron is reduced to ferrous iron (Fe2+) in the stomach to match the alkaline state of the small intestine. In the small intestine ferrous iron undergoes different compound and redox reactions to perform different functions. The first picture illustrates this process.
Transferrin
-glycoprotein that transports and store iron.
-it has two binding sites that both have very high affinity for ferric iron.
- serves as a protective mechanisms against iron’s strong redox activity which can result in the formation of harmful free radicals.
Ferritin
-storage form of iron within the cells.
-not a stable compound because it’s constantly being degraded and resynthesized creating an iron pool within the cell.
-Normal concentrations for adults typically rage from ng/mL
It is not considered a reliable source for iron stores during and for several weeks after an illness.
-An overview of iron’s uptake and storage is demonstrated in the first picture
Parkinson’s Disease
PD is when one’s brain gradually stops producing the neurotransmitter dopamine which results in one losing the ability to regulate body movements and emotions. This lack of dopamine results in motor and nonmotor symptoms. Motor symptoms involve body movements like slow movement, tremors and stiffness. Nonmotor symptoms are other health related problems like: mood disorders, cognitive changes, hallucinations, vision problem and RBD.
RBD- Rapid Eye Movement Sleep Disorder which is a nonmotor symptom. This involves vivid dreams that one physically acts out while sleeping. This is very dangerous to the patient and to their sleeping partners.
Results and Outcomes
Of the total 210 PD participants 67 had PRBD.
Relationship between PRBD and iron levels in CSF: The levels of iron and transferrin are much higher in the CSF in the PRBD patients compared to the NPRBD and control group. Ferritin level in the CSF was significantly decreased in all PD patients compared to the control but there were no significant differences in ferritin levels between the PRBD group and the NPRBD group. This is shown in Table 4.
Influencing factors of abnormal iron metabolism in PD group: Based on a Multiple Linear Regression Model, the only influencing factor of abnormal iron metabolism in the PD group is the RBDQ score. The linear regressions showed that for iron and transferrin levels in the CSF the only component that had an impact on the levels was the RBDQ score. Disease duration and other factors were looked at but appeared to have no influence on the iron or Transferrin levels.
Relationship between PRBD in iron levels in periphery system serum: In the periphery system the levels of transferrin in the CSF are significantly decreased in all PD patients compared to the control group. The PRBD group have even greater decreased levels compared to NPRBD and the control. This is shown in Table 6.
Relationship among levels of iron and transferrin and in CSF and age, age of disease onset and disease duration in PD group: The PRBD group has earlier disease onset, longer disease duration, more advanced disease states, more nonmotor symptoms and higher medication dosing than NPRBD PD patients. This is shown on Table 1.
Overall Results Suggest: Overall this information suggests that increased levels of iron in the brain and decreased levels of iron in the periphery system causes PD patients to exhibit symptoms of PRBD. Based on what is known about normal iron metabolism this suggests that for PD patients who have PRBD that there is a flaw in their iron metabolism that has had a impact on their sleep disorder. This supports the hypothesis that there is a correlation between excessive iron deposits in the brain and PRBD.
Discussion
This study demonstrates that in patients with PD there is a relationship between excessive iron in the brain and RBD. Based on the results of this study the enhanced transferrin level in the CSF of PRBD patients suggests that there is damage to the blood-brain barrier and that transferrin, which transports iron to periphery tissues, is able to transport large amounts of iron to the brain. The result of this is dysregulation of iron metabolism proteins which may contribute to the development of PRBD. Ferritin does not appear to be a contributor in PRBD because all PD patients had decreased Ferritin compared to the control but no significant changes between PRBD and NRBD. - Another study (3) evaluated lipid pathway alterations and their effect on the visual cortex of Parkinson’s disease patient. The results showed that there were alterations in the DAG and glycerophospholipid metabolism that resulted in dysfunctional primary visual cortexes in Parkinson’s disease patients which affects their visual perception.
- Another study (4) evaluated the relationship between trace element concentrations in plasma and the progression of PD. When looking at iron specifically, it was found that iron levels in the plasma were increased 9.5% compared to the control group. However, in this study they found that there was only the elevated plasma iron levels in the younger PD patients. The older PD patients actually had decreased plasma iron levels. It was explain that the possible reasoning for this is as the disease progresses there tends to be more iron present in the brain then anywhere else.
Introduction
What is known about this topic is that in some cases of Parkinson’s disease the patient can have severe PRBD which can be very dangerous and other PD patients do not show any symptoms of PRBD. This study looks at the abnormality within iron metabolism that plays a role in developing PRBD. What is not known about this topic is how to go about correcting and preventing abnormalities in iron metabolism to improve the likelihood of a PD patient developing PRBD. This study shows specifically that there is a correlation between abnormal iron metabolism and PRBD but now there needs to be more research and experiments done to determine what can be done to improve or fix this problem and possibly prevent it for future patients.
Hypothesis
There is a correlation between excessive iron deposits in regions of the brain, as a result of abnormal iron metabolism, and the development of Probable Rapid Eye Movement Sleep Behavior Disorder in people with Parkinson’s Disease.
Summary
Abnormal iron metabolism appears to be correlated with Parkinson’s Disease patients developing Probable Rapid Eye Movement Sleep Behavior Disorder. It appears as though when the transferrin is transporting the iron throughout the body it is not delivering sufficient quantities of iron to the proper periphery tissues. Instead the iron is being transported into the brain in excessive amounts, most likely due to damage in the blood brain barrier causing dysregulation in metabolism. Because of this flaw in iron metabolism people with Parkinson’s Disease are more likely to develop PRBD which is very dangerous to their own safety as well the safety to those around them. In conclusion this study found evidence that supported an abnormality in iron metabolism now this study can be used as a base for more research to be done in order to determine what can be done to possibly correct the problem or prevent it from happening ultimately to improve life quality
References
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Cheng D, Jenner AM, Shui G, Cheong WF, Mitchell TW, et al. (2011) Lipid Pathway Alterations in Parkinson’s Disease Primary Visual Cortex. PLoS ONE 6(2): e doi: /journal.pone
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