Alzheimer's disease in Finnish twins

Abstract

Background: The genetics of Alzheimer's disease (AD) are obscure. Although most cases are sporadic half the patients with sporadic AD have a positive family history. The mode of genetic transmission and the role of environmental factors are unknown. The purpose of this study was to examine the contribution of genetic factors to the pathogenesis of AD in a twin cohort.

Methods: The Finnish Twin Cohort consists of all Finnish same-sexed twin pairs born before 1958 with both co-twins alive in 1975. The total number of twin pairs is 13 888, of whom 4307 are monozygotic (MZ) and 9581 ar dizygotic (DZ). These data were linked with the Hospital Discharge Register from 1972 to 1991 to identify twins who had dementia or related disease as a discharge diagnosis. The linkage of the registries yielded a total of 285 twin individuals. The medical records of these twins and their co-twins were reviewed to confirm and classify dementia (AD, vascular dementia, mixed dementia, and other dementia). The incidence, concordance, and age at onset of AD were examined.

Findings: The incidence of AD was significantly higher in MZ than in DZ twin individuals, with and adjusted MZ/DZ incidence ratio of 1.8 (95% confidence intervals 1.2 to 2.7). In contrast, the incidence of vascular or mixed dementia did not differ between MZ and DZ individuals (MZ/DZ ratio 0.6 [0.3 to 1.2]) for vascular and 1.0 [0.5 to 2.1] for mixed dementia). The pairwise concordance for AD was 18.6% in MZ pairs and 4.7% in DZ pairs and the corresponding probandwise concordance rates were 31.3% and 9.3%. The pairwise concordance for vascular dementia was 18.2% in MZ pairs and 6.7% in DZ pairs with corresponding probandwise rates of 30.8% and 12.5%. The onset age of AD concordant MZ pairs was identical in two pairs and diverged by up to 15 years.

Interpretation: The higher incidence of AD in MZ individuals than in DZ individuals may provide a clue to the aetiology of AD. The higher concordance rate of MZ pairs confirms the contribution of the major genetic component while indicating the need to identify environmental triggers.