Evidence for modest familial co-aggregation between dementia and parkinsonism.

To investigate the contribution of shared familial risk to the co-occurrence of dementia and parkinsonism by studying familial co-aggregation of Alzheimer's disease (AD) and Parkinson's disease (PD). Using Swedish population-based registers we constructed two cohorts; a first-degree relative cohort of persons born 1932-1960 (n = 2,775,332) and a spouse cohort of persons born 1890-1960 (n = 4,736,006). Study persons were followed up between 1969 and 2009 in the National Patient and Cause of Death Registers. We modeled the association between incidence of disease and having at least one affected relative using Cox proportional hazard regression that estimated hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex and number of relatives. Within each disorder; dementia, AD, parkinsonian disorders and PD, there was a strong association between risk of disease and having at least one affected sibling or parent. There was also a modest shared familial risk between the diseases; risk of parkinsonian disorders was associated with having a sibling with AD (HR 1.35, 95% CI 1.11-1.65) and risk of dementia was associated with having a sibling with PD (HR 1.20, 95% CI 1.02-1.41). There were no meaningful familial risks among spouses. The risk of co-occurring dementia in PD was considerably increased (HR 2.83, 95% CI 2.76-2.89). There is strong familial aggregation within dementia, AD, parkinsonian disorders and PD, and modest familial co-aggregation between dementia and parkinsonism. Thus, co-occurrence of dementia and parkinsonism is not primarily caused by shared familial risk between AD and PD.