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Lack of Familial Aggregation of Parkinson Disease and Alzheimer Disease
Gilberto Levy, MD;
Elan D. Louis, MD, MS;
Helen Mejia-Santana, MS;
Lucien Côté, MD;
Howard Andrews, PhD;
Juliette Harris, PhD, MS;
Cheryl Waters, MD, FRCP;
Blair Ford, MD, FRCP;
Steven Frucht, MD;
Stanley Fahn, MD;
Ruth Ottman, PhD;
Karen Marder, MD, MPH
Arch Neurol. 2004;61:1033-1039.
Objective To investigate the risk of Alzheimer disease (AD) in first-degree relatives of patients with Parkinson disease (PD) compared with first-degree relatives of controls.
Design Case-control study, family history method, and reconstructed cohort approach.
Methods Probands with PD without dementia and control probands, matched by age strata, sex, and ethnicity, were examined in person and enrolled without knowledge of family history of PD and other neurological disorders. Disease status in first-degree relatives of probands with PD and control probands was ascertained through a structured family history interview administered to the proband and a second informant (self-report or another informant). Cox proportional hazards models with double-censoring techniques for missing information on age of onset of AD were used to analyze the risk of AD in first-degree relatives of patients with PD compared with first-degree relatives of controls.
Results Four hundred eighty-seven probands with PD and 409 control probands provided family history information on 4819 first-degree relatives older than 30 years (2534 relatives of probands with PD and 2285 relatives of control probands). One hundred thirteen first-degree relatives (2.3%; 61 relatives [2.4%] of patients with PD and 52 relatives [2.3%] of controls) were diagnosed with AD. The risk of AD was not increased in relatives of patients with PD compared with relatives of controls (hazard ratio, 1.1; 95% confidence interval, 0.7-1.6; P = .65). Similarly, no significantly increased risk of AD was observed when comparing relatives of patients with early-onset ( 50 years) and late-onset (>50 years) PD with relatives of controls.
Conclusion The lack of familial aggregation of PD and AD does not support the hypothesis of major shared genetic contributions to the etiology of the 2 most common neurodegenerative disorders.
From the Statistical Analysis Center, Department of Biostatistics (Dr Levy), the Departments of Neurology (Drs Louis, Côté, Harris, Waters, Ford, Frucht, Fahn, and Marder and Ms Mejia-Santana), Psychiatry (Drs Andrews and Marder), and Epidemiology (Dr Ottman), the G. H. Sergievsky Center (Drs Louis, Andrews, Ottman, and Marder and Ms Mejia-Santana), and the Taub Institute for Alzheimer's Disease and the Aging Brain (Drs Louis and Marder), Columbia University, and the Epidemiology of Brain Disorders Department, New York State Psychiatric Institute, (Dr Ottman), New York, NY.
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