Journal of Alzheimer’s Disease 53 (2016) 661–676 DOI 10.3233/JAD-150939 IOS Press 661 A Potential VEP Biomarker for Mild Cognitive Impairment: Evidence from Selective Visual Deficit of Higher-Level Dorsal Pathway Takao Yamasaki a,b,∗ , Shizuka Horie a , Yasumasa Ohyagi c , Eri Tanaka d , Norimichi Nakamura d , Yoshinobu Goto e , Shigenobu Kanba f , Jun-ichi Kira d and Shozo Tobimatsu a a Department of Clinical Neurophysiology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan b Department of Neurology, Minkodo Minohara Hospital, Fukuoka, Japan c Department of Neurology and Geriatric Medicine, Graduate School of Medicine, Ehime University, Ehime, Japan d Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan e Department of Occupational Therapy, Faculty of Rehabilitation, International University of Health and Welfare, Fukuoka, Japan f Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Handling Associate Editor: Pravat Mandal Accepted 11 April 2016 Abstract. Visual dysfunctions are common in Alzheimer’s disease (AD). Our aim was to establish a neurophysiological biomarker for amnestic mild cognitive impairment (aMCI). Visual evoked potentials (VEPs) were recorded in aMCI patients who later developed AD (n = 15) and in healthy older (n = 15) and younger controls (n = 15). Visual stimuli were optimized to separately activate lower and higher levels of the ventral and dorsal streams. We compared VEP parameters across the three groups of participants and conducted a linear correlation analysis between VEPs and data from neuropsychological tests. We then used a receiver operating characteristic (ROC) analysis to discriminate those with aMCI from those who were healthy older adults. The latency and phase of VEPs to lower-level stimuli (chromatic and achromatic gratings) were significantly affected by age but not by cognitive decline. Conversely, VEP latencies for higher-ventral (faces and kanji-words) and dorsal (kana-words and optic flow motion) stimuli were not affected by age, but they were significantly prolonged in aMCI patients. Interestingly, VEPs for higher-dorsal stimuli were related to outcomes of neuropsychological tests. Furthermore, the ROC analysis showed that the highest areas under the curve were obtained for VEP latencies in response to higher-dorsal stimuli. These results suggest aMCI-related functional impairment specific to higher-level visual processing. Further, dysfunction in the higher-level of the dorsal stream could be an early indicator of cognitive decline. Therefore, we conclude that VEPs associated with higher-level dorsal stream activity can be a sensitive biomarker for early detection of aMCI. Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, parallel visual pathways, visual evoked potentials, visual perception ∗ Correspondence to: Takao Yamasaki, MD, PhD, Department of Clinical Neurophysiology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Tel.: +81 92 642 5542; Fax: +81 92 642 5545; E-mail: yamasa@neurophy.med.kyushu- u.ac.jp. ISSN 1387-2877/16/$35.00 © 2016 – IOS Press and the authors. All rights reserved