HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Caselli, R. J. Articles by Alexander, G. G. Search for Related Content PubMed PubMed Citation Articles by Caselli, R. J. Articles by Alexander, G. G. Related Collections All Neuropsychology/Behavior All Cognitive Disorders/Dementia Alzheimer's disease All Genetics

Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele

From the Departments of Neurology (Dr. Caselli), Psychiatry (Dr. Reiman), Psychology (Drs. Osborne, Baxter, and Alexander), and Biostatistics (J.G. Hentz and J.L. Hernandez), Mayo Clinic Scottsdale (Drs. Caselli and Osborne, J.G. Hentz, and J.L. Hernandez); University of Arizona (Dr. Reiman); Barrow Neurological Institute (Dr. Baxter); and Arizona State University (Dr. Alexander), Scottsdale, AZ.

Address correspondence and reprint requests to Dr. Richard J. Caselli, Department of Neurology, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259; e-mail: Caselli.Richard{at}Mayo.edu

Objective: To determine whether memory loss is detectable before the symptomatic presentation of mild cognitive impairment (MCI) in those at greater genetic risk for Alzheimer disease (AD) based upon presence or absence of the e4 allele of APOE.

Methods: Participants were age 50 years or older who responded to newspaper advertisements. A total of 212 cognitively normal individuals of known APOE genotype were initially enrolled in a match paradigm that included e4 homozygotes, e3/4 heterozygotes, and e4 noncarriers in a 1:1:2 ratio (53 sets). Of the original 212 individually matched participants, 180 completed at least two epochs of testing including 45 APOE e4/4 homozygotes, 42 APOE e3/4 heterozygotes, and 93 APOE e4 noncarriers, mean age 60 (±6.2) years. Of these, four developed MCI or AD during the follow-up period and were excluded from analysis. Longitudinal neuropsychological study included two verbal (Auditory Verbal Learning Test [AVLT], Selective Reminding Test [SRT]) and two visual (Complex Figure Test [CFT], Visual Retention Test) memory tests.

Results: Multiple measures on both verbal memory tests showed poorer performance over a mean interval of 33 months in e4 carriers than noncarriers: AVLT total learning, long term delayed recall; SRT free and cued recall. Among those age 50 to 59 years, AVLT long term delayed recall, SRT free and cued recall, and CFT recall declined more in APOE e4 carriers. No differences were found in the domains of language, spatial skills, or executive function.

Conclusions: Memory declined in APOE e4 carriers before the symptomatic presentation of MCI in a cohort whose mean age was 60 years over a median period of 33 months. The decline began prior to age 60.

Received June 17, 2003. Accepted in final form February 11, 2004.

This article has been cited by other articles:

				R. J. Caselli, K. Chen, W. Lee, G. E. Alexander, and E. M. Reiman Correlating Cerebral Hypometabolism With Future Memory Decline in Subsequent Converters to Amnestic Pre-Mild Cognitive Impairment Arch Neurol, September 1, 2008; 65(9): 1231 - 1236. [Abstract] [Full Text] [PDF]

				R. J. Caselli, E. M. Reiman, D. E. C. Locke, M. L. Hutton, J. G. Hentz, C. Hoffman-Snyder, B. K. Woodruff, G. E. Alexander, and D. Osborne Cognitive Domain Decline in Healthy Apolipoprotein E {varepsilon}4 Homozygotes Before the Diagnosis of Mild Cognitive Impairment Arch Neurol, September 1, 2007; 64(9): 1306 - 1311. [Abstract] [Full Text] [PDF]

				R. M. Busch, T. T. Lineweaver, R. I. Naugle, K. H. Kim, Y. Gong, C. Q. Tilelli, R. A. Prayson, W. Bingaman, I. M. Najm, and R. Diaz-Arrastia ApoE-{varepsilon}4 is associated with reduced memory in long-standing intractable temporal lobe epilepsy Neurology, February 6, 2007; 68(6): 409 - 414. [Abstract] [Full Text] [PDF]

				A. Papassotiropoulos, D. A. Stephan, M. J. Huentelman, F. J. Hoerndli, D. W. Craig, J. V. Pearson, K.-D. Huynh, F. Brunner, J. Corneveaux, D. Osborne, et al. Common kibra alleles are associated with human memory performance. Science, October 20, 2006; 314(5798): 475 - 478. [Abstract] [Full Text] [PDF]

				H. A. Wishart, A. J. Saykin, L. A. Rabin, R. B. Santulli, L. A. Flashman, S. J. Guerin, A. C. Mamourian, D. R. Belloni, C. H. Rhodes, and T. W. McAllister Increased Brain Activation During Working Memory in Cognitively Intact Adults With the APOE {epsilon}4 Allele Am J Psychiatry, September 1, 2006; 163(9): 1603 - 1610. [Abstract] [Full Text] [PDF]

				V Jelic, M Kivipelto, and B Winblad Clinical trials in mild cognitive impairment: lessons for the future J. Neurol. Neurosurg. Psychiatry, April 1, 2006; 77(4): 429 - 438. [Abstract] [Full Text] [PDF]

				G. Bartzokis, P. H. Lu, D. H. Geschwind, N. Edwards, J. Mintz, and J. L. Cummings Apolipoprotein E Genotype and Age-Related Myelin Breakdown in Healthy Individuals: Implications for Cognitive Decline and Dementia Arch Gen Psychiatry, January 1, 2006; 63(1): 63 - 72. [Abstract] [Full Text] [PDF]

				G. E. Swan, C. N. Lessov-Schlaggar, D. Carmelli, G. D. Schellenberg, and A. La Rue Apolipoprotein E {epsilon}4 and Change in Cognitive Functioning in Community-Dwelling Older Adults J Geriatr Psychiatry Neurol, December 1, 2005; 18(4): 196 - 201. [Abstract] [PDF]

				M. A. Sager, B. Hermann, and A. La Rue Middle-Aged Children of Persons With Alzheimer's Disease: APOE Genotypes and Cognitive Function in the Wisconsin Registry for Alzheimer's Prevention J Geriatr Psychiatry Neurol, December 1, 2005; 18(4): 245 - 249. [Abstract] [PDF]