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) Data Supplement 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 Related articles in Neurology 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 Martins, C.A.R. Articles by Williams, J. H. Search for Related Content PubMed PubMed Citation Articles by Martins, C.A.R. Articles by Williams, J. H. Related Collections All Neuropsychology/Behavior Alzheimer's disease

APOE alleles predict the rate of cognitive decline in Alzheimer disease

A nonlinear model

From the Oxford Project to Investigate Memory and Ageing, Department of Pharmacology, Oxford University, UK.

Address correspondence and reprint requests to Dr. J. Williams, OPTIMA, Radcliffe Infirmary, Woodstock Road, Oxford, OX2 6HE, UK; e-mail: Jonathan.Williams{at}pharm.ox.ac.uk

Background: The APOE genotype predicts the age at onset of Alzheimer disease (AD) and neuropathologic progression. However, studies relating APOE alleles to the rate of cognitive decline have been inconclusive. This may stem from their use of linear statistical analyses.

Objective: To model relations of APOE alleles to the rate of cognitive decline in AD, nonlinearly.

Methods: Serial measures of cognitive ability were obtained using the cognitive scale of the Cambridge Examination for Mental Disorders of the Elderly in 218 patients with AD. The relations of these serial scores to APOE alleles were tested using nonlinear and linear mixed-effects models.

Results: In the non-linear model, possession of an APOE 4 allele related to earlier and faster cognitive decline, but possession of an APOE 2 related to slower decline. Patients homozygous for APOE 4 showed faster cognitive decline than heterozygotes. The linear model was less sensitive and did not detect differences between APOE 4 homo- and heterozygotes.

Conclusions: APOE genotype strongly predicts the rate of cognitive decline in Alzheimer disease. The decline shows a dose–response relation with the APOE 4 allele, but the APOE 2 allele is protective. The nonlinear model yielded larger estimates of the maximal rate of decline than the linear.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the December 27 issue to find the title link for this article.

Editorial, see page 1855

Supported by Phytopharm plc., the Takayama Foundation and the Health Foundation.

Disclosure: The authors report no conflicts of interest.

Received October 12, 2004. Accepted in final form August 22, 2005.

Related articles in Neurology:

Nature throws curveballs: APOE and nonlinear decline in Alzheimer disease

Richard Camicioli and Richard Kryscio
Neurology 2005 65: 1855-1856. [Full Text]  

This article has been cited by other articles:

				J. J. Locascio, H. Fukumoto, L. Yap, T. Bottiglieri, J. H. Growdon, B. T. Hyman, and M. C. Irizarry Plasma Amyloid {beta}-Protein and C-reactive Protein in Relation to the Rate of Progression of Alzheimer Disease Arch Neurol, June 1, 2008; 65(6): 776 - 785. [Abstract] [Full Text] [PDF]

				S. Cosentino, N. Scarmeas, E. Helzner, M. M. Glymour, J. Brandt, M. Albert, D. Blacker, and Y. Stern APOE {varepsilon}4 allele predicts faster cognitive decline in mild Alzheimer disease Neurology, May 6, 2008; 70(19_Part_2): 1842 - 1849. [Abstract] [Full Text] [PDF]

				J. Shi, C. B. Zhao, T. L. Vollmer, T. M. Tyry, and S. M. Kuniyoshi APOE {varepsilon}4 allele is associated with cognitive impairment in patients with multiple sclerosis Neurology, January 15, 2008; 70(3): 185 - 190. [Abstract] [Full Text] [PDF]

				O. Belbin, J. L. Dunn, Y. Ling, L. Morgan, S. Chappell, H. Beaumont, D. Warden, D. A. Smith, N. Kalsheker, and K. Morgan Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene and the rate of cognitive decline in Alzheimer's disease Hum. Mol. Genet., September 15, 2007; 16(18): 2199 - 2208. [Abstract] [Full Text] [PDF]

				M. M. Glymour Invited Commentary: When Bad Genes Look Good--APOE*E4, Cognitive Decline, and Diagnostic Thresholds Am. J. Epidemiol., June 1, 2007; 165(11): 1239 - 1246. [Abstract] [Full Text] [PDF]

				B. Borroni, S. Archetti, M. Ferrari, B. M. Cesana, A. Padovani, C. E. Regan, C. Katona, Z. Walker, and G . Livingston Relationship of vascular risk to the progression of Alzheimer disease Neurology, March 27, 2007; 68(13): 1083 - 1084. [Full Text] [PDF]

				M. S. Beeri, M. Rapp, J. M. Silverman, J. Schmeidler, H. T. Grossman, J. T. Fallon, D. P. Purohit, D. P. Perl, A. Siddiqui, G. Lesser, et al. Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers Neurology, May 9, 2006; 66(9): 1399 - 1404. [Abstract] [Full Text] [PDF]

				R. Camicioli and R. Kryscio Nature throws curveballs: APOE and nonlinear decline in Alzheimer disease Neurology, December 27, 2005; 65(12): 1855 - 1856. [Full Text] [PDF]