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Neurology 2000 Mar 28;54(6):1272-6 APOE and the risk of PD with or without dementia in a population-based study. Harhangi BS, de Rijk MC, van Duijn CM, Van Broeckhoven C, Hofman A, Breteler MM Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, The Netherlands. OBJECTIVE: To study the association between APOE genotype and PD with or without dementia. METHODS: The study formed part of the Rotterdam Study, a prospective, population-based cohort study on the frequency, etiology, and prognosis of chronic diseases. The cohort examined for PD consisted of 6,969 independently living or institutionalized inhabitants from a suburb of Rotterdam, the Netherlands, aged 55 years or older. All participants were screened at baseline (1990 to 1993) and at follow-up (1993 to 1994) for symptoms of parkinsonism by study physicians; screen positives received a diagnostic workup by a neurologist. RESULTS: APOE genotyping was available for 107 PD patients (26 with and 81 without dementia) and 4,805 non-PD control subjects. The presence of at least one epsilon2 allele significantly increased the risk of PD (OR = 1.7; 95% CI, 1.0 to 2.8). When we looked separately for demented and nondemented PD patients as compared with nonparkinsonian controls, APOE did not appear to be associated with PD without dementia, but both the epsilon2 and the epsilon4 allele increased the risk of PD with dementia (OR = 5.6; 95% CI, 2.0 to 15.2 and OR = 3.6; 95% CI, 1.3 to 9.9). The risk of dementia for epsilon4 allele carriers was not significantly different for persons with or without PD. However, the epsilon2 allele strongly increased the risk of dementia in patients with PD (interaction p < 0.007). CONCLUSIONS: In the elderly the APOE-epsilon2 allele increases the risk of PD and, in particular, the risk of PD with dementia.