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Our first publication in Movement Disorders1 reporting an “association” between lower cholesterol and Parkinson's disease (PD) noted the limitations of case-control analysis. It cautioned the readers that “we could not make a causal inference between LDL-C and/or statin use and risk of PD.1” To reduce the possibility of reserve causality, we subsequently studied a prospective cohort2 and found a similar association. Similar findings were also reported in two other prospective cohorts.3, 4 Interestingly, Scigliano and colleagues themselves found “the association of untreated IPD with reduced vascular diseases risk(s)” including higher cholesterol.5 There has been one inconsistent report6 in which the cases were identified from a National Insurance Register that entitles patients to medication free of charge.

Therefore, the overall evidence to date favors an association between higher cholesterol and lower PD occurrence. The three prospective cohorts cited earlier2–4 have generated some useful insight on PD etiology. Rigorous diagnostic criteria7 were applied in the Honolulu Asia Aging Study, and of 25 cases that had autopsy, PD was confirmed pathologically in 21. Further, the age of onset in any study population is bounded by its age distribution. The average age at cholesterol assay in the Honolulu cohort was 77 years old,2 thus, it is not surprising that the onset of incident cases was also higher in this cohort. Given the consistency of this association across prospective studies, it seems to us that more, not less, research should be conducted to understand the nature of this finding and its medical ramifications, if any. Thus, we disagree with Scigliano et al.'s notion that future studies should simply be abandoned. It is both inconsistent with the weight of available evidence, and contrary to the scientific method.

References

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  • 1
    Huang X,Chen H,Miller WC, et al. Lower LDL cholesterol levels are associated with Parkinson's disease: a case control study. Mov Disord 2007; 22: 377381.
  • 2
    Huang X,Abbott RD,Petrovitch H,Mailman RB,Ross GW. Low LDL cholesterol and increased risk of Parkinson's disease: Prospective results from Honolulu-Asia aging study. Mov Disord 2008; 23: 10131018.
  • 3
    de Lau LM,Koudstaal PJ,Hofman A,Breteler MM. Serum cholesterol levels and the risk of Parkinson's disease. Am J Epidemiol 2006; 164: 9981002.
  • 4
    Simon KC,Chen H,Schwarzschild M,Ascherio A. Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease. Neurology 2007; 69: 16881695.
  • 5
    Scigliano G,Musicco M,Soliveri P,Piccolo I,Ronchetti G,Girotti F. Reduced risk factors for vascular disorders in Parkinson disease patients: a case-control study. Stroke 2006; 37: 11841188.
  • 6
    Hu G,Antikainen R,Jousilahti P,Kivipelto M,Tuomilehto J. Total cholesterol and the risk of Parkinson disease. Neurology 2008; 70: 19721979.
  • 7
    Ward CD,Gibb WR. Research diagnostic criteria for Parkinson's disease. Adv Neurol 1990; 53: 245249.

Xuemei Huang*, Honglei Chen†, Helen Petrovitch‡, Richard Mailman§, Webster Ross‡, * Department of Neurology, Penn State University College of Medicine, Happy Valley, Pennsylvania, USA, † Department of Epidemiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA, ‡ The Pacific Health Research, Institute and Kuakini Medical Center, Honolulu, Hawaii, USA, § Department of Pharmacology, Penn State University College of Medicine, Happy Valley, Pennsylvania, USA.