Among all participants, those in the highest tertile of plasma Aβ42 level at baseline were at more than twice the risk of dying during the study period compared with those in the lowest tertile, whereas those in the middle tertile of Aβ42 level did not have increased risk of death. The increased risk of death for those in the highest tertile may be related, at least in part, to increased mortality in demented participants. Cognitive impairment has been shown to be strongly associated with mortality in nondemented and demented elderly individuals,27- 30 and dementia is also associated with increased risk of death among adults with DS.31- 33 Among elderly individuals without DS, baseline plasma Aβ42 levels were higher in participants with recent onset of AD who died compared with those who survived or those without AD.5 The investigators suggested that higher levels of Aβ42 may reflect a more advanced disease or a more aggressive form of AD.5 However, in this study, the increased risk of death appeared to be unrelated to the presence of frank dementia. An alternative hypothesis is that high Aβ42 levels are related to poorer overall health status. Therefore, we examined the frequency of seizures, stroke, cancer, hypothyroidism, diabetes, hypertension, osteoporosis, heart disease (all heart disease and, separately, myocardial infarction, coronary artery disease, atrial fibrillation, and congestive heart failure [CHF]) by tertile of Aβ42 level among all participants. Only the frequency of CHF was significantly higher among those in the highest tertile of Aβ42 level (lowest tertile, 1.5%; middle tertile, 2.9%; and highest tertile, 10.3% [P = .04]). Also, the highest frequency of CHF was found in those with prevalent dementia (nondemented, 3.1%; incident dementia, 2.3%; and prevalent dementia, 16.7%). However, when we repeated the Cox models for mortality, including the presence or absence of CHF as a covariate, we found that this had no substantive effect on results (HR without CHF, 2.4 [95% CI, 1.1-5.1]; HR with CHF as a covariate, 2.2 [95% CI, 1,02-4.7]) (data not shown). Thus, the relation of Aβ42 levels to the declines associated with dementia and death is unlikely to be due to differences among our groups in health status.