Role of APOE genotype in gait decline and disability in aging

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Abstract

Objectives. Although apolipoprotein E (APOE) genetic variation may influence risk of gait decline and disability in aging through multiple mechanisms, a systematic examination of this relationship has been lacking. Our objective was to quantify the risk of gait decline and disability associated with the APOE ε4 allele in aging. Methods. We evaluated 627 community-dwelling adults aged 70 and older (white 67.8%) with APOE genotype and quantitative gait measurements participating in the Einstein Aging Study over a median follow-up of 3.0 years. Main outcomes were gait speed decline (cm/s/year) and incident disability. Results. APOE ε4 allele frequency was 24.1%. Presence of APOE ε4 was not significantly associated with gait speed decline overall (p =. 37) but was associated with faster gait speed decline in older men (estimate: -1.16, 95% CI: -2.31 to -0.01, p =. 04). The interaction between the ε4 allele and male sex predicted gait speed decline (estimate: -1.70, 95% CI: -3.33 to -0.07, p =. 04). Presence of the APOE ε4 allele was associated with increased risk of disability in older men (HR 3.72, 95% CI: 1.44-9.59, p =. 007). Associations of the ε4 allele with study outcomes remained significant even after accounting for several potential confounders including vascular and cognitive status. The strength of the associations was stronger in the white subgroup. Conclusion. This preliminary report suggests that the APOE ε4 allele is associated with increased risk of gait speed decline and disability in older men.

Original languageEnglish (US)
Pages (from-to)1395-1401
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume68
Issue number11
DOIs
StatePublished - Nov 2013

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Apolipoprotein E4
Apolipoproteins E
Gait
Alleles
Genotype
Independent Living
Gene Frequency
Blood Vessels
Outcome Assessment (Health Care)
Walking Speed

Keywords

  • Disability
  • Epidemiology
  • Gait
  • Genetics

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

@article{7ed706ee41244a72a779b04ecd080d87,
title = "Role of APOE genotype in gait decline and disability in aging",
abstract = "Objectives. Although apolipoprotein E (APOE) genetic variation may influence risk of gait decline and disability in aging through multiple mechanisms, a systematic examination of this relationship has been lacking. Our objective was to quantify the risk of gait decline and disability associated with the APOE ε4 allele in aging. Methods. We evaluated 627 community-dwelling adults aged 70 and older (white 67.8{\%}) with APOE genotype and quantitative gait measurements participating in the Einstein Aging Study over a median follow-up of 3.0 years. Main outcomes were gait speed decline (cm/s/year) and incident disability. Results. APOE ε4 allele frequency was 24.1{\%}. Presence of APOE ε4 was not significantly associated with gait speed decline overall (p =. 37) but was associated with faster gait speed decline in older men (estimate: -1.16, 95{\%} CI: -2.31 to -0.01, p =. 04). The interaction between the ε4 allele and male sex predicted gait speed decline (estimate: -1.70, 95{\%} CI: -3.33 to -0.07, p =. 04). Presence of the APOE ε4 allele was associated with increased risk of disability in older men (HR 3.72, 95{\%} CI: 1.44-9.59, p =. 007). Associations of the ε4 allele with study outcomes remained significant even after accounting for several potential confounders including vascular and cognitive status. The strength of the associations was stronger in the white subgroup. Conclusion. This preliminary report suggests that the APOE ε4 allele is associated with increased risk of gait speed decline and disability in older men.",
keywords = "Disability, Epidemiology, Gait, Genetics",
author = "Joe Verghese and Roee Holtzer and Cuiling Wang and Katz, {Mindy Joy} and Nir Barzilai and Lipton, {Richard B.}",
year = "2013",
month = "11",
doi = "10.1093/gerona/glt115",
language = "English (US)",
volume = "68",
pages = "1395--1401",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",
number = "11",

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TY - JOUR

T1 - Role of APOE genotype in gait decline and disability in aging

AU - Verghese, Joe

AU - Holtzer, Roee

AU - Wang, Cuiling

AU - Katz, Mindy Joy

AU - Barzilai, Nir

AU - Lipton, Richard B.

PY - 2013/11

Y1 - 2013/11

N2 - Objectives. Although apolipoprotein E (APOE) genetic variation may influence risk of gait decline and disability in aging through multiple mechanisms, a systematic examination of this relationship has been lacking. Our objective was to quantify the risk of gait decline and disability associated with the APOE ε4 allele in aging. Methods. We evaluated 627 community-dwelling adults aged 70 and older (white 67.8%) with APOE genotype and quantitative gait measurements participating in the Einstein Aging Study over a median follow-up of 3.0 years. Main outcomes were gait speed decline (cm/s/year) and incident disability. Results. APOE ε4 allele frequency was 24.1%. Presence of APOE ε4 was not significantly associated with gait speed decline overall (p =. 37) but was associated with faster gait speed decline in older men (estimate: -1.16, 95% CI: -2.31 to -0.01, p =. 04). The interaction between the ε4 allele and male sex predicted gait speed decline (estimate: -1.70, 95% CI: -3.33 to -0.07, p =. 04). Presence of the APOE ε4 allele was associated with increased risk of disability in older men (HR 3.72, 95% CI: 1.44-9.59, p =. 007). Associations of the ε4 allele with study outcomes remained significant even after accounting for several potential confounders including vascular and cognitive status. The strength of the associations was stronger in the white subgroup. Conclusion. This preliminary report suggests that the APOE ε4 allele is associated with increased risk of gait speed decline and disability in older men.

AB - Objectives. Although apolipoprotein E (APOE) genetic variation may influence risk of gait decline and disability in aging through multiple mechanisms, a systematic examination of this relationship has been lacking. Our objective was to quantify the risk of gait decline and disability associated with the APOE ε4 allele in aging. Methods. We evaluated 627 community-dwelling adults aged 70 and older (white 67.8%) with APOE genotype and quantitative gait measurements participating in the Einstein Aging Study over a median follow-up of 3.0 years. Main outcomes were gait speed decline (cm/s/year) and incident disability. Results. APOE ε4 allele frequency was 24.1%. Presence of APOE ε4 was not significantly associated with gait speed decline overall (p =. 37) but was associated with faster gait speed decline in older men (estimate: -1.16, 95% CI: -2.31 to -0.01, p =. 04). The interaction between the ε4 allele and male sex predicted gait speed decline (estimate: -1.70, 95% CI: -3.33 to -0.07, p =. 04). Presence of the APOE ε4 allele was associated with increased risk of disability in older men (HR 3.72, 95% CI: 1.44-9.59, p =. 007). Associations of the ε4 allele with study outcomes remained significant even after accounting for several potential confounders including vascular and cognitive status. The strength of the associations was stronger in the white subgroup. Conclusion. This preliminary report suggests that the APOE ε4 allele is associated with increased risk of gait speed decline and disability in older men.

KW - Disability

KW - Epidemiology

KW - Gait

KW - Genetics

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U2 - 10.1093/gerona/glt115

DO - 10.1093/gerona/glt115

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JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

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