Apolipoprotein genotype for prediction of Alzheimer's disease in older Japanese

The hisayama study

Tomoyuki Ohara, Toshiharu Ninomiya, Michiaki Kubo, Yoichiro Hirakawa, Yasufumi Doi, Jun Hata, Toru Iwaki, Shigenobu Kanba, Yutaka Kiyohara

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

OBJECTIVES: To estimate the effects of the apolipoprotein E (APOE)-É4 allele on the development of dementia and to elucidate its usefulness in the risk prediction of dementia in Japanese. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: Five hundred twenty-three participants with deoxyribonucleic acid samples from a population of 1,073 community-dwelling participants without dementia aged 60 to 79. MEASUREMENTS: The risk estimates of the APOE-É4 allele on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: During 17 years of follow-up, 136 participants developed dementia, 81 of whom had AD and 39 VaD. After adjusting for age, sex, education, smoking, alcohol intake, systolic blood pressure, use of antihypertensive agents, glycosylated hemoglobin, serum total cholesterol, body mass index, and regular exercise, the risks of all-cause dementia and AD were significantly higher in APOE-É4 carriers than in noncarriers, but no such association was observed for VaD (all-cause dementia: hazard ratio (HR)=1.81, P=.004; AD: HR=3.42, P<.001; VaD: HR=1.08, P=.86). The area under the receiver operating characteristic curve was significantly greater when the APOE genotype was incorporated into a model with potential risk factors for AD (0.74 vs 0.68, P=.02). Other measures of model discrimination (net reclassification improvement: 0.18, P=.01; integrated discrimination improvement: 6.25, P<.001) also confirmed this improvement in AD risk assessment. CONCLUSION: The APOE-É4 allele is a risk factor for AD in the Japanese population. Information on APOE genotype improves AD risk assessment substantially beyond a model based on potential risk factors.

Original languageEnglish
Pages (from-to)1074-1079
Number of pages6
JournalJournal of the American Geriatrics Society
Volume59
Issue number6
DOIs
Publication statusPublished - 01-06-2011
Externally publishedYes

Fingerprint

Apolipoproteins
Alzheimer Disease
Genotype
Dementia
Apolipoprotein E4
Vascular Dementia
Alleles
Apolipoproteins E
Blood Pressure
Independent Living
Sex Education
Glycosylated Hemoglobin A
ROC Curve
Antihypertensive Agents
Population
Japan
Body Mass Index
Cohort Studies
Smoking
Cholesterol

All Science Journal Classification (ASJC) codes

  • Geriatrics and Gerontology

Cite this

Ohara, Tomoyuki ; Ninomiya, Toshiharu ; Kubo, Michiaki ; Hirakawa, Yoichiro ; Doi, Yasufumi ; Hata, Jun ; Iwaki, Toru ; Kanba, Shigenobu ; Kiyohara, Yutaka. / Apolipoprotein genotype for prediction of Alzheimer's disease in older Japanese : The hisayama study. In: Journal of the American Geriatrics Society. 2011 ; Vol. 59, No. 6. pp. 1074-1079.
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abstract = "OBJECTIVES: To estimate the effects of the apolipoprotein E (APOE)-{\'E}4 allele on the development of dementia and to elucidate its usefulness in the risk prediction of dementia in Japanese. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: Five hundred twenty-three participants with deoxyribonucleic acid samples from a population of 1,073 community-dwelling participants without dementia aged 60 to 79. MEASUREMENTS: The risk estimates of the APOE-{\'E}4 allele on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: During 17 years of follow-up, 136 participants developed dementia, 81 of whom had AD and 39 VaD. After adjusting for age, sex, education, smoking, alcohol intake, systolic blood pressure, use of antihypertensive agents, glycosylated hemoglobin, serum total cholesterol, body mass index, and regular exercise, the risks of all-cause dementia and AD were significantly higher in APOE-{\'E}4 carriers than in noncarriers, but no such association was observed for VaD (all-cause dementia: hazard ratio (HR)=1.81, P=.004; AD: HR=3.42, P<.001; VaD: HR=1.08, P=.86). The area under the receiver operating characteristic curve was significantly greater when the APOE genotype was incorporated into a model with potential risk factors for AD (0.74 vs 0.68, P=.02). Other measures of model discrimination (net reclassification improvement: 0.18, P=.01; integrated discrimination improvement: 6.25, P<.001) also confirmed this improvement in AD risk assessment. CONCLUSION: The APOE-{\'E}4 allele is a risk factor for AD in the Japanese population. Information on APOE genotype improves AD risk assessment substantially beyond a model based on potential risk factors.",
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Apolipoprotein genotype for prediction of Alzheimer's disease in older Japanese : The hisayama study. / Ohara, Tomoyuki; Ninomiya, Toshiharu; Kubo, Michiaki; Hirakawa, Yoichiro; Doi, Yasufumi; Hata, Jun; Iwaki, Toru; Kanba, Shigenobu; Kiyohara, Yutaka.

In: Journal of the American Geriatrics Society, Vol. 59, No. 6, 01.06.2011, p. 1074-1079.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apolipoprotein genotype for prediction of Alzheimer's disease in older Japanese

T2 - The hisayama study

AU - Ohara, Tomoyuki

AU - Ninomiya, Toshiharu

AU - Kubo, Michiaki

AU - Hirakawa, Yoichiro

AU - Doi, Yasufumi

AU - Hata, Jun

AU - Iwaki, Toru

AU - Kanba, Shigenobu

AU - Kiyohara, Yutaka

PY - 2011/6/1

Y1 - 2011/6/1

N2 - OBJECTIVES: To estimate the effects of the apolipoprotein E (APOE)-É4 allele on the development of dementia and to elucidate its usefulness in the risk prediction of dementia in Japanese. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: Five hundred twenty-three participants with deoxyribonucleic acid samples from a population of 1,073 community-dwelling participants without dementia aged 60 to 79. MEASUREMENTS: The risk estimates of the APOE-É4 allele on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: During 17 years of follow-up, 136 participants developed dementia, 81 of whom had AD and 39 VaD. After adjusting for age, sex, education, smoking, alcohol intake, systolic blood pressure, use of antihypertensive agents, glycosylated hemoglobin, serum total cholesterol, body mass index, and regular exercise, the risks of all-cause dementia and AD were significantly higher in APOE-É4 carriers than in noncarriers, but no such association was observed for VaD (all-cause dementia: hazard ratio (HR)=1.81, P=.004; AD: HR=3.42, P<.001; VaD: HR=1.08, P=.86). The area under the receiver operating characteristic curve was significantly greater when the APOE genotype was incorporated into a model with potential risk factors for AD (0.74 vs 0.68, P=.02). Other measures of model discrimination (net reclassification improvement: 0.18, P=.01; integrated discrimination improvement: 6.25, P<.001) also confirmed this improvement in AD risk assessment. CONCLUSION: The APOE-É4 allele is a risk factor for AD in the Japanese population. Information on APOE genotype improves AD risk assessment substantially beyond a model based on potential risk factors.

AB - OBJECTIVES: To estimate the effects of the apolipoprotein E (APOE)-É4 allele on the development of dementia and to elucidate its usefulness in the risk prediction of dementia in Japanese. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, in Japan. PARTICIPANTS: Five hundred twenty-three participants with deoxyribonucleic acid samples from a population of 1,073 community-dwelling participants without dementia aged 60 to 79. MEASUREMENTS: The risk estimates of the APOE-É4 allele on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). RESULTS: During 17 years of follow-up, 136 participants developed dementia, 81 of whom had AD and 39 VaD. After adjusting for age, sex, education, smoking, alcohol intake, systolic blood pressure, use of antihypertensive agents, glycosylated hemoglobin, serum total cholesterol, body mass index, and regular exercise, the risks of all-cause dementia and AD were significantly higher in APOE-É4 carriers than in noncarriers, but no such association was observed for VaD (all-cause dementia: hazard ratio (HR)=1.81, P=.004; AD: HR=3.42, P<.001; VaD: HR=1.08, P=.86). The area under the receiver operating characteristic curve was significantly greater when the APOE genotype was incorporated into a model with potential risk factors for AD (0.74 vs 0.68, P=.02). Other measures of model discrimination (net reclassification improvement: 0.18, P=.01; integrated discrimination improvement: 6.25, P<.001) also confirmed this improvement in AD risk assessment. CONCLUSION: The APOE-É4 allele is a risk factor for AD in the Japanese population. Information on APOE genotype improves AD risk assessment substantially beyond a model based on potential risk factors.

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