We are grateful to Drs Qiu and Fratiglioni for pointing out that the recently published Cache County findings are in accord with their earlier work.1 This kind of agreement adds confidence to the findings of the cited studies.1- 3 It is difficult, but appears to be essential, to distinguish any influence of the APOE ε4 allele on cognitive trajectory from its known risk relationship with Alzheimer dementia. Emerging evidence points to early (midlife) effects of the APOE ε4 allele and family history of dementia on cognitive function.4 It remains to be seen, however, if these very early changes are associated with later onset of AD, as our findings may suggest.
Hayden KM, Breitner JCS, Welsh-Bohmer KA. Apolipoprotein E ϵ4 Status and Cognitive Decline With and Without Dementia—Reply. Arch Neurol. 2010;67(8):1036-1037. doi:10.1001/archneurol.2010.164