The impact of apolipoprotein E4 on cause of death in Alzheimer's disease

John M Olichney, M. N. Sabbagh, C. R. Hofstetter, D. Galasko, M. Grundman, R. Katzman, L. J. Thal

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective: We tested the hypothesis that the apolipoprotein E ε4 (apoE4) allele is associated with an increased proportion of vascular- related mortality in Alzheimer's disease (AD). Background: ApoE4 is associated with an increased risk of developing AD, with an earlier onset, and may predispose to vascular dementia as well. In the general population, apoE4 has been associated with increased coronary artery disease and shorter lifespan. There is a paucity of data regarding the effect of the apolipoprotein E (apoE) genotype upon the contributing causes of death in AD. Methods: Death certificates of 114 AD cases were reviewed blind to apoE genotype. Deaths due to ischemic heart disease (IHD), cerebrovascular disease (CVD), vascular disease (either IHD or CVD), pneumonia, and other causes were analyzed as a function of apoE genotype. Logistic regression analyses were employed to control for age and gender effects. Results: The likelihood of vascular disease contributing to death increased in association with the ε4 allele (29% in cases without an ε4 allele, 43% in cases with one ε4 allele, 53% in ε4/4 homozygous cases; p = 0.035 after corrections for age and gender). This increase appeared largely due to an increase in ischemic heart disease, which was reported more frequently on death certificates of cases with one or more ε4 allele (adjusted odds ratio [OR] = 1.85 per ε4 allele; p < 0.05). There were nonsignificant trends for apoE4 to be associated with increased mortality related to cerebrovascular disease (OR = 1.45) and decreased mortality related to pneumonia (OR = 0.77) and AD itself (OR = 0.72). The ε4/4 cases had significantly earlier age of onset (mean = 64.5 yr), earlier death, and longer duration of disease (mean = 10.1 yr). Cases with one or more ε4 allele tended to have lower mean MMSE scores prior to death (6.6 versus 9.5) and were more often female (54% versus 45%). Conclusions: The apoE4 allele appears to increase the risk of vascular and ischemic heart disease-related death in patients with AD.

Original languageEnglish (US)
Pages (from-to)76-81
Number of pages6
JournalNeurology
Volume49
Issue number1
StatePublished - Jul 1997

Fingerprint

Apolipoprotein E4
Cause of Death
Alzheimer Disease
Alleles
Cerebrovascular Disorders
Myocardial Ischemia
Apolipoproteins E
Odds Ratio
Death Certificates
Genotype
Vascular Diseases
Blood Vessels
Mortality
Pneumonia
Vascular Dementia
Age of Onset
Coronary Artery Disease
Logistic Models
Regression Analysis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Olichney, J. M., Sabbagh, M. N., Hofstetter, C. R., Galasko, D., Grundman, M., Katzman, R., & Thal, L. J. (1997). The impact of apolipoprotein E4 on cause of death in Alzheimer's disease. Neurology, 49(1), 76-81.

The impact of apolipoprotein E4 on cause of death in Alzheimer's disease. / Olichney, John M; Sabbagh, M. N.; Hofstetter, C. R.; Galasko, D.; Grundman, M.; Katzman, R.; Thal, L. J.

In: Neurology, Vol. 49, No. 1, 07.1997, p. 76-81.

Research output: Contribution to journalArticle

Olichney, JM, Sabbagh, MN, Hofstetter, CR, Galasko, D, Grundman, M, Katzman, R & Thal, LJ 1997, 'The impact of apolipoprotein E4 on cause of death in Alzheimer's disease', Neurology, vol. 49, no. 1, pp. 76-81.
Olichney JM, Sabbagh MN, Hofstetter CR, Galasko D, Grundman M, Katzman R et al. The impact of apolipoprotein E4 on cause of death in Alzheimer's disease. Neurology. 1997 Jul;49(1):76-81.
Olichney, John M ; Sabbagh, M. N. ; Hofstetter, C. R. ; Galasko, D. ; Grundman, M. ; Katzman, R. ; Thal, L. J. / The impact of apolipoprotein E4 on cause of death in Alzheimer's disease. In: Neurology. 1997 ; Vol. 49, No. 1. pp. 76-81.
@article{8d36817cf750403eae1b30e8c84931a6,
title = "The impact of apolipoprotein E4 on cause of death in Alzheimer's disease",
abstract = "Objective: We tested the hypothesis that the apolipoprotein E ε4 (apoE4) allele is associated with an increased proportion of vascular- related mortality in Alzheimer's disease (AD). Background: ApoE4 is associated with an increased risk of developing AD, with an earlier onset, and may predispose to vascular dementia as well. In the general population, apoE4 has been associated with increased coronary artery disease and shorter lifespan. There is a paucity of data regarding the effect of the apolipoprotein E (apoE) genotype upon the contributing causes of death in AD. Methods: Death certificates of 114 AD cases were reviewed blind to apoE genotype. Deaths due to ischemic heart disease (IHD), cerebrovascular disease (CVD), vascular disease (either IHD or CVD), pneumonia, and other causes were analyzed as a function of apoE genotype. Logistic regression analyses were employed to control for age and gender effects. Results: The likelihood of vascular disease contributing to death increased in association with the ε4 allele (29{\%} in cases without an ε4 allele, 43{\%} in cases with one ε4 allele, 53{\%} in ε4/4 homozygous cases; p = 0.035 after corrections for age and gender). This increase appeared largely due to an increase in ischemic heart disease, which was reported more frequently on death certificates of cases with one or more ε4 allele (adjusted odds ratio [OR] = 1.85 per ε4 allele; p < 0.05). There were nonsignificant trends for apoE4 to be associated with increased mortality related to cerebrovascular disease (OR = 1.45) and decreased mortality related to pneumonia (OR = 0.77) and AD itself (OR = 0.72). The ε4/4 cases had significantly earlier age of onset (mean = 64.5 yr), earlier death, and longer duration of disease (mean = 10.1 yr). Cases with one or more ε4 allele tended to have lower mean MMSE scores prior to death (6.6 versus 9.5) and were more often female (54{\%} versus 45{\%}). Conclusions: The apoE4 allele appears to increase the risk of vascular and ischemic heart disease-related death in patients with AD.",
author = "Olichney, {John M} and Sabbagh, {M. N.} and Hofstetter, {C. R.} and D. Galasko and M. Grundman and R. Katzman and Thal, {L. J.}",
year = "1997",
month = "7",
language = "English (US)",
volume = "49",
pages = "76--81",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - The impact of apolipoprotein E4 on cause of death in Alzheimer's disease

AU - Olichney, John M

AU - Sabbagh, M. N.

AU - Hofstetter, C. R.

AU - Galasko, D.

AU - Grundman, M.

AU - Katzman, R.

AU - Thal, L. J.

PY - 1997/7

Y1 - 1997/7

N2 - Objective: We tested the hypothesis that the apolipoprotein E ε4 (apoE4) allele is associated with an increased proportion of vascular- related mortality in Alzheimer's disease (AD). Background: ApoE4 is associated with an increased risk of developing AD, with an earlier onset, and may predispose to vascular dementia as well. In the general population, apoE4 has been associated with increased coronary artery disease and shorter lifespan. There is a paucity of data regarding the effect of the apolipoprotein E (apoE) genotype upon the contributing causes of death in AD. Methods: Death certificates of 114 AD cases were reviewed blind to apoE genotype. Deaths due to ischemic heart disease (IHD), cerebrovascular disease (CVD), vascular disease (either IHD or CVD), pneumonia, and other causes were analyzed as a function of apoE genotype. Logistic regression analyses were employed to control for age and gender effects. Results: The likelihood of vascular disease contributing to death increased in association with the ε4 allele (29% in cases without an ε4 allele, 43% in cases with one ε4 allele, 53% in ε4/4 homozygous cases; p = 0.035 after corrections for age and gender). This increase appeared largely due to an increase in ischemic heart disease, which was reported more frequently on death certificates of cases with one or more ε4 allele (adjusted odds ratio [OR] = 1.85 per ε4 allele; p < 0.05). There were nonsignificant trends for apoE4 to be associated with increased mortality related to cerebrovascular disease (OR = 1.45) and decreased mortality related to pneumonia (OR = 0.77) and AD itself (OR = 0.72). The ε4/4 cases had significantly earlier age of onset (mean = 64.5 yr), earlier death, and longer duration of disease (mean = 10.1 yr). Cases with one or more ε4 allele tended to have lower mean MMSE scores prior to death (6.6 versus 9.5) and were more often female (54% versus 45%). Conclusions: The apoE4 allele appears to increase the risk of vascular and ischemic heart disease-related death in patients with AD.

AB - Objective: We tested the hypothesis that the apolipoprotein E ε4 (apoE4) allele is associated with an increased proportion of vascular- related mortality in Alzheimer's disease (AD). Background: ApoE4 is associated with an increased risk of developing AD, with an earlier onset, and may predispose to vascular dementia as well. In the general population, apoE4 has been associated with increased coronary artery disease and shorter lifespan. There is a paucity of data regarding the effect of the apolipoprotein E (apoE) genotype upon the contributing causes of death in AD. Methods: Death certificates of 114 AD cases were reviewed blind to apoE genotype. Deaths due to ischemic heart disease (IHD), cerebrovascular disease (CVD), vascular disease (either IHD or CVD), pneumonia, and other causes were analyzed as a function of apoE genotype. Logistic regression analyses were employed to control for age and gender effects. Results: The likelihood of vascular disease contributing to death increased in association with the ε4 allele (29% in cases without an ε4 allele, 43% in cases with one ε4 allele, 53% in ε4/4 homozygous cases; p = 0.035 after corrections for age and gender). This increase appeared largely due to an increase in ischemic heart disease, which was reported more frequently on death certificates of cases with one or more ε4 allele (adjusted odds ratio [OR] = 1.85 per ε4 allele; p < 0.05). There were nonsignificant trends for apoE4 to be associated with increased mortality related to cerebrovascular disease (OR = 1.45) and decreased mortality related to pneumonia (OR = 0.77) and AD itself (OR = 0.72). The ε4/4 cases had significantly earlier age of onset (mean = 64.5 yr), earlier death, and longer duration of disease (mean = 10.1 yr). Cases with one or more ε4 allele tended to have lower mean MMSE scores prior to death (6.6 versus 9.5) and were more often female (54% versus 45%). Conclusions: The apoE4 allele appears to increase the risk of vascular and ischemic heart disease-related death in patients with AD.

UR - http://www.scopus.com/inward/record.url?scp=0030853883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030853883&partnerID=8YFLogxK

M3 - Article

C2 - 9222173

AN - SCOPUS:0030853883

VL - 49

SP - 76

EP - 81

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 1

ER -