Apolipoprotein E gene polymorphism, total plasma cholesterol level, and Parkinson disease dementia

BACKGROUND: Apolipoprotein E gene (APOE) polymorphism is an important determinant for the development of various cardiovascular and neurodegenerative disorders. There have been conflicting reports of association of APOE polymorphism with dementia in Parkinson disease (PD). OBJECTIVE: To determine the relationship between APOE polymorphisms and plasma cholesterol concentration, and PD with dementia (PDD). DESIGN: Four-year (1999-2002) case-control study. SETTING: Academic medical center with inpatient and outpatient movement disorders services. Patients Consecutive white patients of the same ethnic background with PD. INTERVENTIONS: Strict clinical, neuropsychological, and neuroimaging criteria were used to exclude dementia with Lewy bodies, Alzheimer disease, and vascular dementia. Findings were compared in 2 clinical groups, including 98 patients (47 men and 51 women; mean age, 71 years) with PDD and 100 patients (52 men and 48 women; mean age, 62 years) with PD without dementia. MAIN OUTCOME MEASURES: Analysis of APOE genotypes and allelic frequency (polymerase chain reaction) and plasma cholesterol concentration (enzymatic assay) were evaluated by a clinician blinded to the clinical diagnosis, and findings were compared between the groups with PDD or PD without dementia. Multiple stepwise regression analysis and the Spearman rank correlation coefficient were used to evaluate relationships between dementia and both APOE polymorphism and cholesterol concentration. Statistical significance was set at P<.05. RESULTS: Epsilon4 allele frequencies were similar in PDD and PD without dementia (16.8% vs 19%, respectively). Cholesterol concentration, APOE genotypes, and allelic frequencies did not relate to PDD. CONCLUSIONS: In contrast to Alzheimer disease, when PDD is carefully defined, it is clearly not associated with APOE polymorphisms or with a distinctive plasma cholesterol profile. Ongoing longitudinal follow-up with emphasis on autopsy recruitment will enable further analyses of biochemical alterations underlying PDD.