Risk of Alzheimer's disease in relatives of Parkinson's disease patients with and without dementia

Objective: To determine whether first-degree relatives of PD patients with dementia were at increased risk for the development of AD compared with first-degree relatives of nondemented PD patients and nondemented normal subjects from the community. Methods: A structured family history interview was administered to 146 nondemented PD patients, 120 patients with PD and dementia, and 903 normal subjects from the community to ascertain the presence of AID among parents and siblings of these subjects. Cox proportional hazards models with double censoring techniques for missing information were used to model the risk of AD among relatives. Results: No increase in risk of AD was found among parents of patients with PD and dementia or parents of nondemented PD patients compared with parents of normal subjects. However, siblings of demented PD patients were three times as likely (relative risk [RR] = 3.2, 95% confidence interval [CI] = 1.1 to 9.4, p < 0.04) as siblings of normal subjects to develop AD. When only siblings >65 years of age were considered, there was a fivefold increase in risk of AD among siblings of demented PD patients compared with siblings of normal subjects (RR = 4.9, 95% CI - 1.1 to 21.4, p < 0.03). The risk of AD was also increased for female relatives, regardless of whether the woman was a relative of a demented PD patient, a nondemented PD patient, or a normal subject. Ethnicity and APOE genotype did not affect dementia status among relatives. Conclusions: The increased risk of AD in siblings of demented PD patients compared with siblings of normal subjects supports the possibility of familial aggregation of AD and PD with dementia.