Familial associations of Alzheimer disease and essential tremor with Parkinson disease

Background: We constructed a cohort of first-degree relatives of participants in a population-based case-control study of Parkinson disease (PD) and compared the occurrence of Alzheimer disease (AD) and essential tremor (ET) in relatives of PD cases and controls. Methods: We relied on proband interviews to assess family history in 372 probands with incident PD confirmed by a movement disorder specialist and 404 controls from three rural California counties. Results: Overall, for the 2980 first-degree relatives of PD cases, the risk of AD was not increased compared with the 2981 relatives of controls. But relatives of younger onset PD cases (< 60 years of age) were three times more likely to have received an AD diagnosis [hazard ratios (HR): 2.86; 95%CI: 1.44, 5.71]. Our data also suggest that some relatives of PD probands might be at a slightly increased risk of receiving an ET diagnosis, especially relatives of tremor dominant cases (HR: 1.69; 95%CI 0.99, 2.88), younger onset cases (HR: 2.03; 95%CI 0.93, 4.44), and male relatives (HR: 2.31; 95%CI 1.13, 4.73). In addition, fathers of cases were almost 15 years younger than fathers of controls when diagnosed with ET. Results were stable in sensitivity analyses. Conclusion: Our study suggests a familial susceptibility to AD amongst first-degree relatives of younger onset PD cases.