Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Context: Polymorphisms in the cholesteryl ester transfer protein (CETP) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. Objective: To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD). Design, Setting, and Participants: Prospective cohort study comprising 608 community-dwelling adults without dementia aged 70 years or older from the Einstein Aging Study with CETP genotype available. Fifteen participants with prevalent dementia were excluded, and 70 without follow-up-63 lost to follow-up and 7 new to the study-were excluded from the Cox proportional hazards model, which included 523 participants in the analysis. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein (APOE) ε4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory (Free and Cued Selective Reminding Test [FCSRT], possible scores of 0-48), attention (Digit Span), and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or AD in similarly adjusted Cox proportional hazards models with age as the time scale. Main Outcome Measures: Memory decline and incident dementia. Results: Valine allele frequency was 43.5%. A total of 40 cases of incident dementia occurred during follow-up (mean [(SD], 4.3 [3.1] years). Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95% confidence interval [CI], -0.58 to -0.29 vs 0.21 points per year of age for valine; 95% CI, -0.39 to -0.04; difference in linear age slope, 0.22; 95% CI, 0.02 to 0.41; P=.03) and no significant differences on the Digit Span or Digit Symbol Substitution tests. Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; P=.02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; P=.04). Conclusion: This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.

Original languageEnglish (US)
Pages (from-to)150-158
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume303
Issue number2
DOIs
StatePublished - Jan 13 2010

Fingerprint

Cholesterol Ester Transfer Proteins
Dementia
Valine
Incidence
Genes
Confidence Intervals
Isoleucine
Alzheimer Disease
Homozygote
Genotype
Proportional Hazards Models
Single Nucleotide Polymorphism
Independent Living
Sex Education
Episodic Memory
Apolipoproteins
Lost to Follow-Up
Gene Frequency
Codon
Comorbidity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{ca07ffd6bd434dcba5ed6398c3710b7b,
title = "Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia",
abstract = "Context: Polymorphisms in the cholesteryl ester transfer protein (CETP) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. Objective: To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD). Design, Setting, and Participants: Prospective cohort study comprising 608 community-dwelling adults without dementia aged 70 years or older from the Einstein Aging Study with CETP genotype available. Fifteen participants with prevalent dementia were excluded, and 70 without follow-up-63 lost to follow-up and 7 new to the study-were excluded from the Cox proportional hazards model, which included 523 participants in the analysis. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein (APOE) ε4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory (Free and Cued Selective Reminding Test [FCSRT], possible scores of 0-48), attention (Digit Span), and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or AD in similarly adjusted Cox proportional hazards models with age as the time scale. Main Outcome Measures: Memory decline and incident dementia. Results: Valine allele frequency was 43.5{\%}. A total of 40 cases of incident dementia occurred during follow-up (mean [(SD], 4.3 [3.1] years). Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95{\%} confidence interval [CI], -0.58 to -0.29 vs 0.21 points per year of age for valine; 95{\%} CI, -0.39 to -0.04; difference in linear age slope, 0.22; 95{\%} CI, 0.02 to 0.41; P=.03) and no significant differences on the Digit Span or Digit Symbol Substitution tests. Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95{\%} CI, 0.10-0.85; P=.02) and AD (hazard ratio, 0.31; 95{\%} CI, 0.10-0.95; P=.04). Conclusion: This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.",
author = "Sanders, {Amy E.} and Cuiling Wang and Katz, {Mindy Joy} and Derby, {Carol A.} and Nir Barzilai and Laurie Ozelius and Lipton, {Richard B.}",
year = "2010",
month = "1",
day = "13",
doi = "10.1001/jama.2009.1988",
language = "English (US)",
volume = "303",
pages = "150--158",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "2",

}

TY - JOUR

T1 - Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia

AU - Sanders, Amy E.

AU - Wang, Cuiling

AU - Katz, Mindy Joy

AU - Derby, Carol A.

AU - Barzilai, Nir

AU - Ozelius, Laurie

AU - Lipton, Richard B.

PY - 2010/1/13

Y1 - 2010/1/13

N2 - Context: Polymorphisms in the cholesteryl ester transfer protein (CETP) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. Objective: To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD). Design, Setting, and Participants: Prospective cohort study comprising 608 community-dwelling adults without dementia aged 70 years or older from the Einstein Aging Study with CETP genotype available. Fifteen participants with prevalent dementia were excluded, and 70 without follow-up-63 lost to follow-up and 7 new to the study-were excluded from the Cox proportional hazards model, which included 523 participants in the analysis. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein (APOE) ε4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory (Free and Cued Selective Reminding Test [FCSRT], possible scores of 0-48), attention (Digit Span), and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or AD in similarly adjusted Cox proportional hazards models with age as the time scale. Main Outcome Measures: Memory decline and incident dementia. Results: Valine allele frequency was 43.5%. A total of 40 cases of incident dementia occurred during follow-up (mean [(SD], 4.3 [3.1] years). Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95% confidence interval [CI], -0.58 to -0.29 vs 0.21 points per year of age for valine; 95% CI, -0.39 to -0.04; difference in linear age slope, 0.22; 95% CI, 0.02 to 0.41; P=.03) and no significant differences on the Digit Span or Digit Symbol Substitution tests. Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; P=.02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; P=.04). Conclusion: This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.

AB - Context: Polymorphisms in the cholesteryl ester transfer protein (CETP) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. Objective: To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD). Design, Setting, and Participants: Prospective cohort study comprising 608 community-dwelling adults without dementia aged 70 years or older from the Einstein Aging Study with CETP genotype available. Fifteen participants with prevalent dementia were excluded, and 70 without follow-up-63 lost to follow-up and 7 new to the study-were excluded from the Cox proportional hazards model, which included 523 participants in the analysis. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein (APOE) ε4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory (Free and Cued Selective Reminding Test [FCSRT], possible scores of 0-48), attention (Digit Span), and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or AD in similarly adjusted Cox proportional hazards models with age as the time scale. Main Outcome Measures: Memory decline and incident dementia. Results: Valine allele frequency was 43.5%. A total of 40 cases of incident dementia occurred during follow-up (mean [(SD], 4.3 [3.1] years). Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95% confidence interval [CI], -0.58 to -0.29 vs 0.21 points per year of age for valine; 95% CI, -0.39 to -0.04; difference in linear age slope, 0.22; 95% CI, 0.02 to 0.41; P=.03) and no significant differences on the Digit Span or Digit Symbol Substitution tests. Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; P=.02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; P=.04). Conclusion: This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.

UR - http://www.scopus.com/inward/record.url?scp=73949136166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73949136166&partnerID=8YFLogxK

U2 - 10.1001/jama.2009.1988

DO - 10.1001/jama.2009.1988

M3 - Article

VL - 303

SP - 150

EP - 158

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 2

ER -