Complete ascertainment of dementia in the Swedish Twin Registry: the HARMONY study

Abstract

The purpose of this report is to describe the Study of Dementia in Swedish Twins (known as HARMONY), including procedures for complete ascertainment of all cases of Alzheimer’s disease (AD) and other dementias in 14,435 individuals aged 65 and older from the national Swedish twin registry. Telephone cognitive screening identified 11.5% as positive for cognitive dysfunction. Clinical diagnoses were completed for 1557 individuals, including individuals who screened positive, their twin partners, and a sample of normal controls. Estimated prevalence of dementia ranged from 1.4% for age 65–69 to 29.2% for age 90 and older. Concordance rates for Alzheimer’s disease were 59% for monozygotic twins, 32% for like-sexed, and 24% for unlike-sexed dizygotic twins. Among monozygotic twins where both twins had Alzheimer’s disease, the within pair difference in age of onset ranged from both becoming demented in the same year to 7 years difference in onset.

Introduction

Twin studies offer a valuable context in which to study complex disorders such as Alzheimer’s disease (AD) [34]. Similarity between twins for disease gives evidence of extent to which a disorder is influenced by genetic or environmental factors. For this purpose, concordance rates and quantitative genetic methods are used to compare twins in monozygotic (MZ) pairs to twins in dizygotic (DZ) pairs. Conversely, the co-twin control method, focused on pairs that are discordant for a disorder, provides a unique approach to identify risk factors that differentiate the twin with the disease or protective factors that set apart the twin with no disorder.

Twin studies are most informative if, first and foremost, they are based on a representative sample or an entire population, in order to avoid, for example, biases that might result from soliciting volunteers. A second requirement is a comprehensive and unbiased method of identifying individuals with the disease [4]. For these reasons, in 1998 we initiated the HARMONY study by using the national Swedish twin registry and including as the study population all 20,269 twins who were aged 65 years old and alive at baseline. HARMONY is taken from the Swedish words for “health” (Hälsa), “genes” (ARv), “environment” (Miljö), “and” (Och), and “new” (NY).

The purposes of HARMONY include: quantifying relative environmental and genetic influences on the etiology of AD and other dementing disorders; finding genes that increase the risk of AD; and identifying specific environmental risk or protective factors for dementia and AD. In this paper, we describe the study design, the process of ascertaining dementia cases from the entire population of older Swedish twins, the rate of occurrence of dementia and AD, and initial concordance rates for MZ and DZ twins.