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APOE ε4 Is Associated With Exacerbation of Cognitive Decline in Patients With Multiple Sclerosis

Shi, Jiong MD, PhD*,†; Tu, Jiang-long MD*; Gale, Shawn D. PhD; Baxter, Leslie PhD; Vollmer, Timothy L. MD§; Campagnolo, Denise I. MD*; Tyry, Tuula M. PhD*; Zhuang, Yi MD; Kuniyoshi, Sandra M. MD, PhD

Cognitive and Behavioral Neurology: September 2011 - Volume 24 - Issue 3 - p 128–133
doi: 10.1097/WNN.0b013e31823380b5
Original Studies

Background: In previous studies we and others have demonstrated an association with apolipoprotein (APOE) ε4 genotype and the presence of cognitive deficits in multiple sclerosis (MS). In this follow-up study, we have assessed whether APOE ε4 status exacerbates progression of cognitive deficits in MS.

Methods: A total of 197 patients with MS were assessed for APOE genotype, and baseline cognitive performance was measured using a standardized battery of tests. One hundred seventy patients (86.3%) were clinically followed up for 1 year and were assessed for progression of cognitive deficits.

Results: The APOE ε4 allele was present in 24.7% of patients. During 1-year follow-up, significant progression of cognitive deficits was found in APOE ε4 carriers (P=0.001) after logistic regression analysis controlling for sex, ethnicity, age, education, disease duration, severity, and subtype.

Conclusions: APOE ε4 carriers with MS have worsening progression of cognitive deficits than noncarriers. APOE ε4 carrier status predicts cognitive decline in verbal learning and memory.

*Division of Neurology

Division of Neuropsychology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ

Department of Biostatistics, Arizona State University

§Department of Neurology, University of Colorado Health Sciences, Denver, CO

Supported by a Pilot Research Award from the National Multiple Sclerosis Society and Barrow Neurological Foundation. The authors declare no conflicts of interest.

Reprints: Jiong Shi, MD, PhD, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 500 W. Thomas Road, Suite 720, Phoenix, AZ 85013 (e-mail:

Received April 12, 2010

Accepted July 19, 2011

© 2011 Lippincott Williams & Wilkins, Inc.