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Epidemiology:
The Sixteenth Conference of the International Society for Environmental Epidemiology (ISEE): Abstracts

RELATIONSHIP BETWEEN PD PHENOTYPES AND GENETIC AND ENVIRONMENTAL RISKS

Marder, Karen

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Columbia University, New York, NY

ISEE-340

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Abstract:

The cardinal features of Parkinson's disease (PD) include rest tremor, bradykinesia, and rigidity. Accuracy of diagnosis of PD based on clinicopathological correlation is about 80%. The heterogeneity in signs and symptoms and the difficulties in distinguishing PD from parkinsonism during life suggest that more refined phenotypes would be valuable in assessing genotype phenotype correlations and the influence of environmental factors on onset and progression. In July 1998, we initiated a four year study to compare the risk of PD in relatives of 221 PD cases with age at onset (AAO) >50 (early-onset), 266<50 (late-onset), and 409 control probands. We also assessed risk in relatives of tremor dominant PD cases vs. postural instability gait disorder (PIGD) PD. The magnitude of increased risk in relatives of PD cases vs. controls was similar in early-onset patients (RR: 2.9, 95% CI: 1.6-5.0, p=0.0002) and late-onset patients (RR: 2.7, 95% CI: 1.6-4.4, p=0.0002). However in the families of early-onset patients, risk was significantly elevated in siblings (RR: 7.9, 95% CI: 2.5-25.5, p=0.0005), but not parents (RR: 1.7, 95% CI: 0.9-3.3, p=0.2). This pattern of familial aggregation is consistent with an autosomal recessive contribution to inheritance. In the families of late-onset cases, risks of PD were significantly elevated in both parents and siblings, which is inconsistent with a recessive model. We found no difference in risk of PD among first degree relatives of tremor dominant PD compared to PIGD PD, however relatives of tremor dominant PD were more likely to have first-degree relatives with an action tremor than were relatives of PIGD PD cases. Whether the tremor in these relatives represents essential tremor requires further investigation.

In a separate cohort of non-demented PD patients followed annually for up to 8.2 years (mean 3.6 years) we examined several risk factors for incident dementia in PD including age, disease severity and specific motor characteristics defined based on levodopa responsiveness. An increased risk of dementia (9.7 95% CI 3.9-24.4) among older, motorically impaired PD cases compared to younger, less impaired cases was due to their combined rather than individual contributions. Dementia in the setting of PD may be due to Alzheimer's disease (AD), dementia with Lewy bodies or PD alone. We examined environmental risk factors for Alzheimer's disease (AD) including estrogen use, smoking, hypertension, head injury and family history of AD. tOnly smoking was associated with incident dementia in PD. Refining phenotypes may help focus further research into the etiopathogenesis of PD.

© 2004 Lippincott Williams & Wilkins, Inc.

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