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APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model.
Neurology 2005; 65(12):1888-93Neur

Abstract

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 epsilon4 allele related to earlier and faster cognitive decline, but possession of an APOE epsilon2 related to slower decline. Patients homozygous for APOE epsilon4 showed faster cognitive decline than heterozygotes. The linear model was less sensitive and did not detect differences between APOE epsilon4 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 epsilon4 allele, but the APOE epsilon2 allele is protective. The nonlinear model yielded larger estimates of the maximal rate of decline than the linear.

Authors+Show Affiliations

The Oxford Project to Investigate Memory and Ageing, Department of Pharmacology, Oxford University, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16380608

Citation

Martins, C A R., et al. "APOE Alleles Predict the Rate of Cognitive Decline in Alzheimer Disease: a Nonlinear Model." Neurology, vol. 65, no. 12, 2005, pp. 1888-93.
Martins CA, Oulhaj A, de Jager CA, et al. APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model. Neurology. 2005;65(12):1888-93.
Martins, C. A., Oulhaj, A., de Jager, C. A., & Williams, J. H. (2005). APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model. Neurology, 65(12), pp. 1888-93.
Martins CA, et al. APOE Alleles Predict the Rate of Cognitive Decline in Alzheimer Disease: a Nonlinear Model. Neurology. 2005 Dec 27;65(12):1888-93. PubMed PMID: 16380608.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model. AU - Martins,C A R, AU - Oulhaj,A, AU - de Jager,C A, AU - Williams,J H, PY - 2005/12/29/pubmed PY - 2006/4/15/medline PY - 2005/12/29/entrez SP - 1888 EP - 93 JF - Neurology JO - Neurology VL - 65 IS - 12 N2 - 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 epsilon4 allele related to earlier and faster cognitive decline, but possession of an APOE epsilon2 related to slower decline. Patients homozygous for APOE epsilon4 showed faster cognitive decline than heterozygotes. The linear model was less sensitive and did not detect differences between APOE epsilon4 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 epsilon4 allele, but the APOE epsilon2 allele is protective. The nonlinear model yielded larger estimates of the maximal rate of decline than the linear. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/16380608/APOE_alleles_predict_the_rate_of_cognitive_decline_in_Alzheimer_disease:_a_nonlinear_model_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=16380608 DB - PRIME DP - Unbound Medicine ER -