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Page 4 PSG Request for Datamining Abstract Parkinson’s disease (PD) has many paradoxes. For example, although smoking is highly associated with cancer and cardiovascular disease, smoking is associated with a much lower risk of PD (which itself is associated with a lower occurrence of cardiovascular disease). Whereas the apolipoprotein E ε4 allele is associated with higher risk of Alzheimer’s disease, the ε2 allele, rather than ε4, is associated with greater risk of PD (1). Because the ε2 allele also is associated with lower low density lipoprotein-cholesterol (LDL-C), we recently tested the hypothesis that lower LDL-C concentration was positively associated with PD, first in a clinic based case-control study (2; 3) and then in the prospective Honolulu-Asia Aging Study (4). The results from both studies supported this hypothesis. Concurrently, two independent prospective studies reported a similar association, one in the Rotterdam cohort (5) and the other in the Nurses' Health Study and the Health Professionals Follow-up Study (6). A third report whose case identification was based on national insurance data, however, offered a contradictory finding (7). There is yet no study examining the relationship between serum cholesterol and PD progression, although hyperlipidemia was found to be a significant prognostic factor for survival of patients with ALS (8). Cholesterol has a host of critical biological functions that range from roles in affecting cellular repair or degeneration (9-14) to being a neurosteroid precursor (15-18). Thus, it is possible that lower LDL-C is etiologically linked to PD and influences PD progression, and this hypothesis may have critical clinical and public health impact. We propose to test the hypothesis that lower plasma cholesterol may be associated with faster progression of PD. For this purpose, we plan to study the relationship between serum cholesterol values obtained at baseline visit and outcome data from the DATATOP and PRECEPT studies. Our aims are to: Aim 1: Explore the association prospectively of baseline serum cholesterol and the time to require levodopa therapy of PD subjects in both the DATATOP and PRECEPT studies. Aim 2: Explore the association prospectively between baseline serum cholesterol and other important clinical landmark(s) of PD progression [i.e. time to freezing of gait, time to death] in the DATATOP Study. Aim 3: Explore the association between baseline serum cholesterol and both clinical (reflected as UPDRS scores) and radiographic progression [reflected as striatal uptake of [I]-2--carbomethoxy-3--(4iodophenyl)tropanes] in PD in the PRECEPT study.