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ARTICLES: J. Shi, C. B. Zhao, T. L. Vollmer, T. M. Tyry, and S. M. Kuniyoshi APOE 4 allele is associated with cognitive impairment in patients with multiple sclerosis Neurology 2008; 70: 185-190 [Abstract] [Full text] [PDF]

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APOE 4 allele is associated with cognitive impairment in patients with multiple sclerosis

Alan A. Mazurek   (13 March 2008)

Reply from the authors

Jiong Shi   (13 March 2008)

APOE 4 allele is associated with cognitive impairment in patients with multiple sclerosis 13 March 2008
Alan A. Mazurek, Mt. Sinai Medical Center 371 Merrick Road Suite 401 Rockville Centre,NY 11570 Send Correspondence to journal: Re: APOE 4 allele is associated with cognitive impairment in patients with multiple sclerosis DRAAM{at}aol.com Alan A. Mazurek	I read with interest the article by Shi et al. describing the association of cognitive decline in multiple sclerosis (MS) patients with APOE e4 allele. [1] A 2003 study by Enzinger et al reported the reduction in N-acetylaspartate (NAA) levels in MS patients with the APOE e4 allele. [2] At that time, I questioned whether or not data correlating cognitive decline and reduced NAA levels in MS were available, given the well-known association between the two in a variety of neurologic disorders. [3] Unfortunately, data was not available. [4] Now that there is a correlation in MS between APOE e4 and cognitive decline and between reduced NAA and cognitive decline, do we now have data correlating all three in one cohort, namely APOE e4, NAA and cognitive decline? References 1. Shi J, Zhao CB, Vollmer TL et al. APOE e4 allelle is associated with cognitive impairment in patients with multiple sclerosis. Neurology 2008;70:185-190. 2. Enzinger C, Ropele S, Strasser-Fuchs S, et al. Lower levels of N- acetylaspartate in multiple sclerosis patients with the apolipoprotein E e4 allele. Arch Neurol. 2003;60:65-70. 3. Mazurek AA. Reduced N-acetylaspartate levels and cognitive decline. Arch Neurol. 2004; 61:296. 4. Enzinger C, Fazekas F. response- Reduced N-acetylaspartate levels and cognitive decline. Arch Neurol. 2004; 61:296. Disclosure: The author reports no conflicts of interest.
Reply from the authors 13 March 2008
Jiong Shi, Barrow Neurological Institute 500 W. Thomas Road, Suite 720, Phoenix, AZ 85013 Send Correspondence to journal: Re: Reply from the authors jiong.shi{at}chw.edu Jiong Shi	We appreciate the insightful comments of Dr. Mazurek regarding the need for studies determining the correlation of biomarkers with each other. Cognitive tests are much more sensitive and are more likely than motor and sensory exam (EDSS) to reflect early changes in NAA as well as the effect of APOE 4. While studies indicate that APOE 4 in MS is associated with cognitive deficits [1] and deficits in NAA [2], studies directly addressing the relationship between cognitive deficits and NAA must be accomplished to determine whether they directly correlate as it is not proven in these studies. In Alzheimer disease (AD), decreasing NAA levels have been associated with cognitive deficits. [5] However, we would caution against extrapolation as MS appears to be unique in that the association with APOE 4 and cognitive decline does not have as strong a link to increasing age as the deficits in NAA and cognitive decline in AD and aging do. [6] References 5. Ramirez-Rozzi F. Les hominidés du plio-pléistocène de la vallée de l'Omo, Ethiopie : microanatomie de l'émail et développement dentaire. Paris: CNRS Éditions, 1997. 6. Modrego PJ, Fayed N, Pina MA. Conversion from mild cognitive impairment to probable Alzheimer's disease predicted by brain magnetic resonance spectroscopy. Am J Psychiatry 2005;162:667-675. Disclosure: The authors report no conflicts of interest.