[Stitcher]

Higher occurrence of Parkinson's linked to low LDL cholesterol

Public release date: 19-Dec-2006
University of North Carolina School of Medicine
http://www.eurekalert.org/pub_releas...hoo121906.php#

CHAPEL HILL -- People with low levels of LDL cholesterol are more likely to have Parkinson's disease than people with high LDL levels, according to University of North Carolina at Chapel Hill researchers.

LDL stands for low-density lipoprotein cholesterol; low levels of LDL cholesterol are considered an indicator of good cardiovascular health. Earlier studies have found intriguing correlations between Parkinson's disease, heart attacks, stroke and smoking.

"People with Parkinson's disease have a lower occurrence of heart attack and stroke than people who do not have the disease," said Dr. Xuemei Huang, medical director of the Movement Disorder Clinic at UNC Hospitals and an assistant professor of neurology in the UNC School of Medicine. "Parkinson's patients are also more likely to carry the gene APOE-2, which is linked with lower LDL cholesterol." And for more than a decade, researchers have known that smoking, which increases a person's risk for cardiovascular disease, is also associated with a decreased risk of Parkinson's disease.

These findings led Huang to examine whether higher LDL cholesterol might be associated with a decreased occurrence for Parkinson's disease, and vice versa. "If my hypothesis was correct," she said, "lower LDL-C, something that is linked to healthy hearts, would be associated with a higher occurrence of Parkinson's." The results of Huang's study, published online Dec. 18 by the journal Movement Disorders, confirmed her hypothesis. "We found that lower LDL concentrations were indeed associated with a higher occurrence of Parkinson's disease," Huang said. Participants with lower LDL levels (less than 114 milligrams per deciliter) had a 3.5-fold higher occurrence of Parkinson's than the participants with higher LDL levels (more than 138 milligrams per deciliter).

Huang cautioned that people should not change their eating habits, nor their use of statins and other cholesterol-lowering drugs, because of the results. The study was based on relatively small numbers of cases and controls, and the results are too preliminary, she said. Further large prospective studies are needed, Huang added.

"Parkinson's is a disease full of paradoxes," Huang said. "We've known for years that smoking reduces the risk of developing Parkinson's. More than 40 studies have documented that fact. But we don't advise people to smoke because of the other more serious health risks," she said.

Huang and her colleagues recruited 124 Parkinson's patients who were treated at the UNC Movement Disorder Clinic between July 2002 and November 2004 to take part in the study. Another 112 people, all spouses of patients treated in the clinic, were recruited as the control group. Fasting cholesterol profiles were obtained from each participant. The researchers also recorded information on each participant's gender, age, smoking habits and use of cholesterol-lowering drugs.

Huang notes that the study also found participants with Parkinson's were much less likely to take cholesterol-lowering drugs than participants in the control group. This, combined with the findings about LDL cholesterol, suggests two questions for additional study, Huang said.

"One is whether lower cholesterol predates the onset of Parkinson's. Number two, what is the role of statins in that? In other words, does taking cholesterol-lowering drugs somehow protect against Parkinson's? We need to address these questions," she said.

###
Research funding was provided by the National Institute on Aging, the Intramural Research Program of the National Institute of Environmental Health Sciences and the General Clinical Research Center at UNC Hospitals.

Huang's co-authors include Dr. Richard B. Mailman, Jennifer L. Woodard, Peter C. Chen, and Drs. Dong Xiang, Richard W. Murrow and Yi-Zhe Wang, all of the UNC School of Medicine. Additional co-authors include Dr. Honglei Chen of the National Institute of Environmental Health Sciences and Drs. William C. Miller and Charles Poole, both from the department of epidemiology in the UNC School of Public Health.

Note: School of Medicine contact: Tom Hughes, (919) 966-6047 or tahughes@unch.unc.edu

News Services contact: Clinton Colmenares, (919) 843-1991(office), (919) 218-7833 (cell) or clinton_colmenares@unc.edu

[olsen]

Carolyn, thanks for posting this study. Interesting finding in light of a notation in a small study by Abraham Lieberman reported in 2005 in which he compared 2 groups--one with PD and on statins and one group with PD and not on statins. though his findings were reported that the groups were "similar" in progression of their disease, there was a very interesting notation concerning 5 patients who were originally in the non statin group who were started on a statin during the trial. He noted that ALL 5 of these patients developed "worsening" of their PD symptoms after beginning a statin--which I assume means worsening of the disease or progression of the disease, though he did not make that distinction. the statins were stopped for 2 weeks in all these patients and because their symptoms did not regress to pre statin levels, they assumed the worsening of symptoms was not caused by statins--even though it is factual that the tissue half life of statins is unknown (vs plasma half life) and it is unknown the time required to re-establish normal levels of products blocked by statins other than cholesterol--ie dolichol, isoprenoid adenosine, selenoprotein N, coQ10. there was no further mention of this curious finding in the 5 patients started on statins in the study...

Parkinsonism Relat Disord. 2005 Mar;11(2):81-4.

Statins, cholesterol, Co-enzyme Q10, and Parkinson's disease.


Lieberman A, Lyons K, Levine J, Myerburg R.


Department of Neurology, University of Miami School of Medicine, Miami, FL
33136, USA. a...@parkinson.org

[ZucchiniFlower]

Olsen, in response to:

because their symptoms did not regress to pre statin levels, they assumed the worsening of symptoms was not caused by statins

That doesn't make sense to me. The levels of CoQ10 could have been decreased by the statins and that could have worsened symptoms.

If a CoQ10 supplement wasn't ingested to address the shortfall caused by the statins, then the patients would still have a problem with low CoQ10, even tho the statins were discontinued.

They would still need to take CoQ10 to get their levels up to normal, because low CoQ10 can worsen PD symptoms, even tho the statins had been stopped.

[RLSmi]

Madelyn, I agree with ZF. Apparently the people doing the study, the authors, were ignorant of the requirement of CoQ10 biosynthesis on "HMGCoA synthase" the enzyme that is inhibited by statins. Either that, or they did not know the connection between PD and possible CoQ10 deficiency.
Robert

[olsen]

I wonder how well known it is that both serum and platelet coQ10 levels are found to be decreased in PD patients whether on statins or not--that low coq10 is thought to be a part of the disease process or at least a result of Parkinson's?
I cannot find a western medical recommendation for supplemental coq10 for patients taking statins--the drug companies maintain that it is unnecesary--since muscle tissue levels of coq10 have not consistently been depressed in patients on statins--actually depressed serum and platelet coq10 is not found in all patients on statins, just a large number of them (coq10 was depressed in 13 of 15 studies reported). since the tissue levels have not consistently been depressed, the issue is dismissed. Most of these studies have been conducted in reference to myalgias and myopathies patients can encounter on statins, thus the emphasis on muscle tissue levels.
compounding the problem for patients with PD is the fact that statins interrupt the pathway to selenoprotein N (through its effect of blocking the isoprenylated protein pathway) --a precursor to glutathione reductase--one of the compounds responsible for re-cyclling glutathione (probably THE major antioxidant in the brain), another compound found to be deficient in most patients with PD.
statins also block the pathway to production of dolichol, a big, fat lipid (is that redundant?) thought to have a function in the production of neuropeptides, and is also found to be the primary lipid component of the substantia nigra!
the turnover for brain cholesterol is projected to be 4 1/2 to 5 yrs.--cholesterol is made de novo in the brain (since cholesterol does not readily cross the blood brain barrier)via the same HMG-CO A pathway as in the liver. (The lipid soluble statins are found to be able to cross the blood brain barrier--some mroe than others. But all of them do to a degree--thus these can have a direct effect upon the brain pathway for cholesterol)--Many of the studies on statins do not run for that long a period of time--and if someone develops Parkinson's or any other disease while taking a statin in the trials, the disease state is not recorded as related to the drug--which it may not be--but would be great to have those statistics just to determine if there appears to be a causal relationship..
Why the researcher noted that statins may be protective for patients with PD is beyond my ability to comprehend--because more control patients were taking statin than PD patients??? I would guess they were also taking low dose aspirin, too, and given the anti inflammatory effects of aspirin, could at least be as effective as statins in this regard. statins are touted to be the answer for almost every disease entity today. for individuals who need the statins (ie for "seconday prevention in middle aged men who have suffered a cardiac event), it is felt they are the answer--with that I do not quibble. but for "primary prevention" for individuals with mild to moderate hypercholesterolemia, they have not proven to be of benefit (nor for women nor elderly men)--it is for those people I feel these drugs are questionable. and everyone taking a statin should take supplemental coq10.
I will step down from my soap box--i am obviously over involved in this issue....madelyn

[olsen]

from carolyn's original posting:
" 'People with Parkinson's disease have a lower occurrence of heart attack and stroke than people who do not have the disease,' said Dr. Xuemei Huang, medical director of the Movement Disorder Clinic at UNC Hospitals and an assistant professor of neurology in the UNC School of Medicine"


Stroke. 2006 May;37(5):1184-8. Epub 2006 Mar 30. Links
Comment in:
Stroke. 2006 Sep;37(9):2217.
Reduced risk factors for vascular disorders in Parkinson disease
patients: a case-control study.Scigliano G, Musicco M, Soliveri P,
Piccolo I, Ronchetti G, Girotti F.
Istituto Nazionale Neurologico C. Besta, Via Celoria 11, 20131 Milan,
Italy. giulioscigli...@tiscalinet.it


BACKGROUND AND PURPOSE: Sympathetic hyperactivity is a contributing
cause of vascular disorders because it increases blood pressure, blood
sugar, and blood lipids. Pervasive compromise of the central and
peripheral autonomic nervous systems is common in idiopathic Parkinson
disease (IPD) resulting in reduced sympathetic and parasympathetic
function. We hypothesized that IPD was associated with reduced
prevalence of cardiovascular disease risk factors as a result of
reduced sympathetic activity. METHODS: We performed a retrospective
case-control study on 178 newly diagnosed consecutive IPD patients, and
533 age- (+/-3 years) and sex-matched controls with other neurological
diseases seen over the same period at the same hospital. For each case
and control the following were noted on admission: smoking, diabetes,
hypertension, body mass index, serum glucose, plasma cholesterol,
triglycerides and total lipid levels, and blood pressure. RESULTS:
Diabetes, history of smoking, high blood pressure, high blood glucose,
high blood cholesterol, and triglycerides were significantly less
frequent in IPD than controls. CONCLUSIONS: IDP is a natural model of
impaired hypothalamic-pituitary-adrenal axis activity and generalized
sympathetic denervation. We interpret the association of untreated IPD
with reduced vascular diseases risk factors as attributable to reduced
autonomic activity, suggesting that autonomic hyperactivity may be
involved in the pathogenesis of vascular disorders.


PMID: 16574924 [PubMed - indexed for MEDLINE]