Apolipoprotein E allele 4 is not a sufficient or a necessary predictor of the development of Mild Cognitive Impairment

The presence of Mild Cognitive Impairment (MCI) and of an apolipoprotein E (apoE) varepsilon4 allele both predict the development of Alzheimer's disease. However, the extent to which this allele also predicts the development of MCI is unclear even though MCI is an early transitional stage in the development of Alzheimer's disease. The present study investigates the prevalence of the apoE varepsilon4 allele in incipient MCI. Participants were recruited from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). All subjects who were initially cognitively healthy, i.e. did not meet MCI criteria described by Petersen [Petersen RC. Mild cognitive impairment. J Intern Med 2004; 256(3): 183-94], and whose apoE status could be determined were followed-up. After 4.5 years, 15.5% of the cognitively healthy target population had developed MCI. The frequencies of the apoE varepsilon4 genotype did not differ between individuals with incipient MCI (12.9%) and individuals who remained cognitively healthy during the study (18.4%, p>0.5). Consequently, the apoE varepsilon4 genotype is not a necessary or sufficient risk factor for MCI. Further studies need to investigate the influence of the whole range of genetic and environmental risk factors on the course of Alzheimer's disease including the initial development of MCI and the later conversion to Alzheimer's disease.