FIGURE 1. Flow chart of 684 ACE genotyped twins from the Longitudinal Study of Aging Danish Twins - the 1997 and 1999 surveys.

ferred to the ability on the day of the interview. Research has shown that physical abilities can be reliably and val- idly assessed through self-report (23). The self-reported physical abilities were determined from 26 items including items from Katz’ index of activities of daily living (ADL) (24) as well as questions about demanding activities like running. This instrument has been validated in Denmark and shown to discriminate different levels of functional abilities among community dwelling elderly (25). All items were rated on a 4 to 1 scale with the response op- tions ranging from “can do without fatigue” (4) to “cannot do” (1). To identify a quantitative subscale the items were factor analyzed in the total twin sample from the 1995 sur- vey (14). This identified two factors where the first factor loaded highest on items dealing with ability to walk, run, climb stairs and carry weights and was interpreted to re- flect a dimension of strength. The second factor loaded highest on items dealing with ability to wash, dress, and get in and out of bed and was interpreted to reflect a di- mension of agility. Only the strength factor was used in this analysis due to little variability on the agility scale.

The strength scores from the 1997 and 1999 surveys were calculated by taking the average response of the 11 items identified to be relevant for this score. The factor has pre- viously been found highly reliable for functional abilities (26). In the 1999 survey three additional items dealing with endurance performance (self-reported walking, run- ning and cycling distance) were included. A composite score was calculated taking the average response from these items.

In the 1999 survey the participants were also invited to perform two tests of physical abilities—maximum handgrip pressure and the repeated chair stand test. The grip strength was measured by a hand dynamometer (Smedley’s dyna- mometer TTM, Tokyo). The maximum value of three mea- sures with each hand was used in the analyses. In the repeated chair stand test the participants were asked to rise and sit five times from a chair as quickly as possible with their arms folded over their chest. The pulse was recorded immediately before and after the test. The test, which was timed, was stopped if five attempts were not successfully performed within 60 seconds.

age was 78.2 with a standard deviation (SD) of 4.4 (females: 78.4 (4.6), males: 77.8 (4.0)). Sixteen (2.3 percent) partici- pated in the interview through a proxy responder.

The cognitive functioning of the participants was as- sessed using the mini mental state examination (MMSE), which was integrated in the interview.

Data Analyses

ACE Genotype

In all, 169 (24.7 percent) twins had the II genotype, 344 (50.3 percent) the DI, and 171 (25.0 percent) the DD gen- otype. The genotype frequencies in men and women, and in the age groups shown in Table 1, were in Hardy-Wein- berg equilibrium (p > | 0.3), and were highly comparable to proportions found in Danish populations in two previous studies (10, 28). The distribution of the ACE genotype in the MZ twins who were assigned to their co-twin’s geno- type did not differ from that of the other study subjects (re- sults not shown).

Allele frequencies were computed from the genotype frequen- cies and Hardy-Weinberg equilibrium was tested by a (cid:4)2 test with one degree of freedom. We compared the three ACE- genotypes with regard to physical and cognitive abilities and other characteristics at baseline (1997 interview wave) and in 1999 at the second interview wave. Longitudinal changes in cognitive skills and physical abilities were examined for twins participating in both interview waves. Finally, we examined the influence of ACE-genotype on survival through linkage with mortality data for the entire cohort.

Continuous variables were compared using multivariate linear regression models and categorical data were com- pared using logistic regression models controlling for the age of the participants. To account for the non-indepen- dence of the observations on twins, twins from pairs where both participated (intact pairs) were analyzed as clusters of two in the multivariate models (27). Data were sex-strati- fied due to a tendency to a larger proportion of women among the DI and DD genotypes.

Baseline Characteristics

Characteristics of the study population, which could poten- tially confound the association between ACE genotype and measures of physical and cognitive abilities and survival, are listed in Table 1. The distribution of most of these po- tential confounders between the ACE genotypes was highly comparable and the differences showed no stepwise trends across genotypes. However, the number with more than eight years of education was significantly higher in DD  than in DI and II males, p 0.02 (Table 1). In addition, the proportion with poor or very poor self-rated health was me)  lower in ID than DD males, p 0.02 (Table 1).