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To the Editor: Dr Kadotani and colleagues1 reported an association between apolipoprotein E ∊4 (which is coded by the ApoE ∊4 allele) and sleep-disordered breathing (SDB) in a study of 791 adults, aged 32 to 68 years, in Wisconsin. We examined this association among 718 Japanese-American men, aged 79 to 97 years, who were evaluated for SDB as part of a recent follow-up examination of participants in the Honolulu-Asia Aging Study of dementia that began in 1991 (previously unpublished data).
Only 18% of our sample had the ApoE ∊4 allele (compared with 28% in the study by Kadotani et al1 ) and consistent with other studies, these men were at increased risk for Alzheimer disease (AD).2 - 3 In contrast, moderate to severe SDB (apnea-hypopnea index of >15) was common in our sample (42%) compared with the 8% prevalence in the younger cohort of Kadotani et al. After adjusting for age, body mass index, smoking, and use of antihypertensive medications, we found no association between ApoE ∊4 and an apnea-hypopnea index greater than 15 (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.52-1.14). Comparing those having severe SDB (apnea-hypopnea index >30; 18%) with those having less severe or no SDB (apnea-hypopnea index <30), we again found no association with ApoE ∊4 status (OR, 1.06; 95% CI, 0.64-1.74).
The differences between our findings and those of Kadotani et al may be explained by several factors. Either finding could have been spurious, because genetic association studies tend to have a high false-positive rate. However, real population differences may have explained these findings because the 2 samples differed significantly in age, ethnicity, body mass index (mean body mass index, 24 kg/m2 in Honolulu vs 30 kg/m2 in Wisconsin), and in the prevalence of SDB and ApoE ∊4 positivity.
In addition, studies of risk factors for chronic diseases often show weaker relationships in older persons than in younger ones. For example, in the Sleep Heart Health Study, a large cohort study of adults older than 40 years, correlations between SDB and cardiovascular disease risk factors and hypertension were less pronounced and sometimes not statistically significant in older persons.4 - 5 The reasons for these weakened relationships may stem from bias due to selective survival, or possibly to greater misclassifications in older persons who typically have multiple chronic conditions that may affect measurements, or from real changes in the biological relationships associated with increased age.
We agree with the authors that their "finding is a simple statistical association that does not indicate a causal relationship between ApoE ∊4 and sleep apnea" and that "further studies will be needed to confirm and extend these findings." Consistent with other observational studies of risk factors, our findings point to a weaker relationship observed in elderly adults compared with middle-aged adults. These comparisons also point to the need to address genetic associations across populations that vary by ethnicity and underlying risk factors, and the challenges in interpreting such differences.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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