Original article Apolipoprotein E allele 4 is not a sufficient or a necessary predictor of the development of Mild Cognitive Impairment R. Heun a, * , U. Gühne b , T. Luck b , M.C. Angermeyer b , U. Ueberham c , R. Potluri d , A. Natalwala e , T. Arendt c , S.G. Riedel-Heller b a Department of Psychiatry, Derby City General Hospital, Uttoxeter Road, Derby 22, UK b Department of Psychiatry, Public Mental Health Research Unit, University of Leipzig, Liepzig, Germany c Paul-Flechsig Institute of Brain Research, Leipzig, Germany d Faculty of Medicine, Imperial College, London, UK e The Medical School, University of Birmingham, Birmingham, UK Received 28 October 2008; received in revised form 16 February 2009; accepted 20 February 2009 Available online 26 June 2009 Abstract The presence of Mild Cognitive Impairment (MCI) and of an apolipoprotein E (apoE) e4 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 e4 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 e4 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 e4 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. # 2009 Elsevier Masson SAS. All rights reserved. Keywords: Mild cognitive impairment; Incidence; Apolipoprotein E; Epidemiology; Conversion; Alzheimer’s disease 1. Introduction Epidemiological evidence suggests that individuals suffer- ing from Mild Cognitive Impairment (MCI) are at an increased risk of developing Alzheimer’s disease [15]. The e4 allele of apolipoprotein E (apoE) is another well-established risk factor for the development of Alzheimer’s disease [6,11]. Studies investigating the association between the apoE e4 allele and MCI (according to Petersen [15] and other criteria) have shown inconsistent results with some finding an association [7,21,26] and others finding none [1,4,5]. Most of the work has been based on cross-sectional data from selected samples, and there are very few prospective population-based studies in this area [10,13,20]. Our population-based Leipzig Longitudinal Study of the Aged (LEILA 75+) provided the opportunity to investigate the frequency of apoE e4 carriers in individuals with incipient MCI prospectively. We expect the frequency of apoE e4 to be higher in patients with incipient MCI. 2. Materials and methods 2.1. Sample LEILA75+ is a population-based study on the epidemiology of dementia, which was initiated in January 1997, and its details have been described elsewhere [17]. All participants had been investigated in four visits over 1.5 year intervals and the total individual study period was 4.5 years. The study was approved by the Local Ethics Committee and all subjects gave informed written consent. Participants for the current study were European Psychiatry 25 (2010) 15–18 * Auteur correspondant. Tel.: +44 7595 635638. E-mail address: heun@gmx.com (R. Heun). 0924-9338/$ – see front matter # 2009 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.eurpsy.2009.02.009