Apolipoprotein E ε4 genotype as a risk factor for cognitive decline and dementia:: data from the Canadian Study of Health and Aging

Background: Apolipoprotein E (ApoE) epsilon4 genotype is a well-established risk factor for Alzheimer's disease (AD). However, its effect on predicting conversion from normal to "cognitive impairment, no dementia" (CIND) and from CIND to AD is less clear. Methods: We used a nested case-control design from the population-based Canadian Study of Health and Aging (CSHA) to examine the effect of ApoE epsilon4 genotype on the conversion of subjects from normal to CIND and from CIND to AD. We also contrasted these findings with incident cases of AD and vascular dementia (VaD) in the CSHA cohort. Results: The ApoE epsilon4 genotype was a significant risk factor for conversion from CIND to AD and from normal to AD and VaD. However, it was not a significant risk factor for conversion from normal to CIND. This effect is robust to adjustment for age, sex and education level. There is significant interaction between the ApoE epsilon4 genotype and age for AD and for conversion from CIND to AD. No interaction between ApoE epsilon4 genotype, sex, age, ethnicity and education level was found in other subgroup analyses. The positive predictive value of ApoE epsilon4 for predicting CIND conversion to AD was 0.48, and the negative predictive value was 0.65. Interpretation: Possession of an ApoE epsilon4 allele increases the risk of AD developing from CIND. It is also associated with a decrease in the age at onset of AD. Its predictive values do not support its utility as a diagnostic test for predicting progression from CIND to AD, but it may be useful in research studies to enrich study samples that have a higher rate of progression to AD.