AUTHOR COPY Journal of Alzheimer’s Disease 84 (2021) 1005–1014 DOI 10.3233/JAD-210622 IOS Press 1005 Effect of Apolipoprotein E4 on the Driving Behavior of Patients with Amnestic Mild Cognitive Impairment or Mild Alzheimer’s Disease Dementia Evangelia Stanitsa a , Alexandra Economou b,∗ , Ion Beratis a , Dionysia Kontaxopoulou a , Stella Fragkiadaki a , Vicky Papastefanopoulou c , Dimosthenis Pavlou d , Panagiotis Papantoniou d , Christos Kroupis c , John Papatriantafyllou a , Leonidas Stefanis e , George Yannis d and Sokratis G. Papageorgiou a a 1st Department of Neurology, Memory, Cognitive Disorders and Rare Dementias Outpatient Unit, Eginition University Hospital, Athens, Greece b Department of Psychology, National and Kapodistrian University of Athens, Athens, Greece c Department of Clinical Biochemistry, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece d Department of Transportation Planning and Engineering, School of Civil Engineering, National Technical University of Athens, Athens, Greece e 1st Department of Neurology, Aiginiteio University Hospital, National and Kapodistrian University of Athens, Athens, Greece Accepted 2 September 2021 Pre-press 29 September 2021 Abstract. Background: The driving behavior of patients with mild Alzheimer’s disease dementia (ADD) and patients with mild cognitive impairment (MCI) is frequently characterized by errors. A genetic factor affecting cognition is apolipoprotein E4 (APOE4), with carriers of APOE4 showing greater episodic memory impairment than non-carriers. However, differences in the driving performance of the two groups have not been investigated. Objective: To compare driving performance in APOE4 carriers and matched non-carriers. Methods: Fourteen APOE4 carriers and 14 non-carriers with amnestic MCI or mild ADD underwent detailed medical and neuropsychological assessment and participated in a driving simulation experiment, involving driving in moderate and high traffic volume in a rural environment. Driving measures were speed, lateral position, headway distance and their SDs, and reaction time. APOE was genotyped through plasma samples. Results: Mixed two-way ANOVAs examining traffic volume and APOE4 status showed a significant effect of traffic volume on all driving variables, but a significant effect of APOE4 on speed variability only. APOE4 carriers were less variable in their speed than non-carriers; this remained significant after a Bonferroni correction. To further examine variability in the driving performance, coefficients of variation (COV) were computed. Larger headway distance COV and smaller lateral position COV were observed in high compared to moderate traffic. APOE4 carriers had smaller speed COV compared to non-carriers. ∗ Correspondence to: Alexandra Economou, PhD, Associate Professor of Neuropsychology, Department of Psychology, School of Philosophy, National and Kapodistrian University of Athens, Panepistimiopolis, Ilissia 157 84, Athens, Greece. Tel.: +30 210 6524569; E-mail: aoikono@psych.uoa.gr. ISSN 1387-2877/$35.00 © 2021 – IOS Press. All rights reserved.