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Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment.

Abstract

BACKGROUND

In cognitively impaired patients without dementia, the utility of apolipoprotein E (APOE) genotyping is unclear.

OBJECTIVE

To evaluate the predictive utility of the APOE epsilon4 genotype for conversion to probable Alzheimer disease (AD).

DESIGN

Naturalistic, longitudinal study.

SETTING

Memory disorders outpatient clinic.

PATIENTS

A total of 136 patients with memory complaints were determined to have mild cognitive impairment and were evaluated every 6 months. Fifty-seven age- and sex-matched healthy controls were evaluated annually.

MAIN OUTCOME MEASURES

Primary outcome measures included conversion to AD. Secondary outcome measures included change over time in Mini-Mental State Examination (MMSE) score and Selective Reminding Test (SRT) delayed recall score.

RESULTS

The APOE epsilon4 allele was present in 25% of patients and 21% of healthy controls. During a mean +/- SD follow-up of 35.2 +/- 24.3 months, 35 of 136 patients converted to AD. APOE epsilon4 carrier status did not differ between converters (31%) and nonconverters to AD (23%, P = .3) and did not affect the time trend in MMSE or SRT scores in the entire sample. Four of 5 APOE epsilon4 homozygotes converted to AD compared with 7 of 29 heterozygotes (P = .02). In a Cox proportional hazards model stratified by age quartiles, after controlling for sex, education, MMSE score, and SRT delayed recall score, APOE epsilon4 increased the risk of AD in patients 70 to 85 years old (n = 57; risk ratio, 2.77; 95% confidence interval, 1.1-7.3; P = .03) but not in patients 55 to 69 years old (n = 79; P = .7).

CONCLUSIONS

APOE epsilon4 carrier status was associated with conversion to AD in older outpatients after controlling for known demographic and clinical risk factors, and APOE epsilon4 homozygosity was associated with increased risk of conversion to AD. However, APOE epsilon4 carrier status by itself did not predict cognitive decline or conversion to AD, indicating that APOE genotyping in patients with mild cognitive impairment may have limited clinical applicability for prediction of outcome.

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  • Authors+Show Affiliations

    ,

    Department of Biological Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. dpd3@columbia.edu

    , , , , , , , ,

    Source

    Archives of neurology 62:6 2005 Jun pg 975-80

    MeSH

    Aged
    Alzheimer Disease
    Ambulatory Care
    Apolipoprotein E4
    Apolipoproteins E
    Cognition Disorders
    Female
    Follow-Up Studies
    Genotype
    Humans
    Longitudinal Studies
    Male
    Middle Aged
    Predictive Value of Tests

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    15956169

    Citation

    Devanand, D P., et al. "Predictive Utility of Apolipoprotein E Genotype for Alzheimer Disease in Outpatients With Mild Cognitive Impairment." Archives of Neurology, vol. 62, no. 6, 2005, pp. 975-80.
    Devanand DP, Pelton GH, Zamora D, et al. Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment. Arch Neurol. 2005;62(6):975-80.
    Devanand, D. P., Pelton, G. H., Zamora, D., Liu, X., Tabert, M. H., Goodkind, M., ... Mayeux, R. (2005). Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment. Archives of Neurology, 62(6), pp. 975-80.
    Devanand DP, et al. Predictive Utility of Apolipoprotein E Genotype for Alzheimer Disease in Outpatients With Mild Cognitive Impairment. Arch Neurol. 2005;62(6):975-80. PubMed PMID: 15956169.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment. AU - Devanand,D P, AU - Pelton,Gregory H, AU - Zamora,Diana, AU - Liu,Xinhua, AU - Tabert,Matthias H, AU - Goodkind,Madeleine, AU - Scarmeas,Nikolaos, AU - Braun,Ilana, AU - Stern,Yaakov, AU - Mayeux,Richard, PY - 2005/6/16/pubmed PY - 2005/7/1/medline PY - 2005/6/16/entrez SP - 975 EP - 80 JF - Archives of neurology JO - Arch. Neurol. VL - 62 IS - 6 N2 - BACKGROUND: In cognitively impaired patients without dementia, the utility of apolipoprotein E (APOE) genotyping is unclear. OBJECTIVE: To evaluate the predictive utility of the APOE epsilon4 genotype for conversion to probable Alzheimer disease (AD). DESIGN: Naturalistic, longitudinal study. SETTING: Memory disorders outpatient clinic. PATIENTS: A total of 136 patients with memory complaints were determined to have mild cognitive impairment and were evaluated every 6 months. Fifty-seven age- and sex-matched healthy controls were evaluated annually. MAIN OUTCOME MEASURES: Primary outcome measures included conversion to AD. Secondary outcome measures included change over time in Mini-Mental State Examination (MMSE) score and Selective Reminding Test (SRT) delayed recall score. RESULTS: The APOE epsilon4 allele was present in 25% of patients and 21% of healthy controls. During a mean +/- SD follow-up of 35.2 +/- 24.3 months, 35 of 136 patients converted to AD. APOE epsilon4 carrier status did not differ between converters (31%) and nonconverters to AD (23%, P = .3) and did not affect the time trend in MMSE or SRT scores in the entire sample. Four of 5 APOE epsilon4 homozygotes converted to AD compared with 7 of 29 heterozygotes (P = .02). In a Cox proportional hazards model stratified by age quartiles, after controlling for sex, education, MMSE score, and SRT delayed recall score, APOE epsilon4 increased the risk of AD in patients 70 to 85 years old (n = 57; risk ratio, 2.77; 95% confidence interval, 1.1-7.3; P = .03) but not in patients 55 to 69 years old (n = 79; P = .7). CONCLUSIONS: APOE epsilon4 carrier status was associated with conversion to AD in older outpatients after controlling for known demographic and clinical risk factors, and APOE epsilon4 homozygosity was associated with increased risk of conversion to AD. However, APOE epsilon4 carrier status by itself did not predict cognitive decline or conversion to AD, indicating that APOE genotyping in patients with mild cognitive impairment may have limited clinical applicability for prediction of outcome. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/15956169/Predictive_utility_of_apolipoprotein_E_genotype_for_Alzheimer_disease_in_outpatients_with_mild_cognitive_impairment_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.62.6.975 DB - PRIME DP - Unbound Medicine ER -