A genotype of exceptional longevity is associated with preservation of cognitive function

Nir Barzilai, G. Atzmon, Carol A. Derby, J. M. Bauman, Richard B. Lipton

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. METHODS: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 ± 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. RESULTS: Subjects with MMSE > 25 were twice as likely to have the CETP VV genotype (29% vs 14%, p = 0.02), and those with the VV genotype were more likely (61% vs 30%, p = 0.02) to have MMSE > 25. Subjects with the VV genotype had lower levels of CETP (1.73 ± 0.11 vs 2.12 ± 0.10 μg/mL, p = 0.01), higher high-density lipoprotein (HDL) levels (p = 0.02), and larger lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21% vs 4%, p = 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory. CONCLUSIONS: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age-related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age-related decline or AD.

Original languageEnglish (US)
Pages (from-to)2170-2175
Number of pages6
JournalNeurology
Volume67
Issue number12
DOIs
StatePublished - Dec 2006

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Cholesterol Ester Transfer Proteins
Cognition
Genotype
Lipoproteins
HDL Lipoproteins
Jews
Particle Size
Genes
Dementia
Cohort Studies
Phenotype

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A genotype of exceptional longevity is associated with preservation of cognitive function. / Barzilai, Nir; Atzmon, G.; Derby, Carol A.; Bauman, J. M.; Lipton, Richard B.

In: Neurology, Vol. 67, No. 12, 12.2006, p. 2170-2175.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVE: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. METHODS: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 ± 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. RESULTS: Subjects with MMSE > 25 were twice as likely to have the CETP VV genotype (29{\%} vs 14{\%}, p = 0.02), and those with the VV genotype were more likely (61{\%} vs 30{\%}, p = 0.02) to have MMSE > 25. Subjects with the VV genotype had lower levels of CETP (1.73 ± 0.11 vs 2.12 ± 0.10 μg/mL, p = 0.01), higher high-density lipoprotein (HDL) levels (p = 0.02), and larger lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21{\%} vs 4{\%}, p = 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory. CONCLUSIONS: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age-related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age-related decline or AD.",
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AU - Barzilai, Nir

AU - Atzmon, G.

AU - Derby, Carol A.

AU - Bauman, J. M.

AU - Lipton, Richard B.

PY - 2006/12

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N2 - OBJECTIVE: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. METHODS: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 ± 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. RESULTS: Subjects with MMSE > 25 were twice as likely to have the CETP VV genotype (29% vs 14%, p = 0.02), and those with the VV genotype were more likely (61% vs 30%, p = 0.02) to have MMSE > 25. Subjects with the VV genotype had lower levels of CETP (1.73 ± 0.11 vs 2.12 ± 0.10 μg/mL, p = 0.01), higher high-density lipoprotein (HDL) levels (p = 0.02), and larger lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21% vs 4%, p = 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory. CONCLUSIONS: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age-related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age-related decline or AD.

AB - OBJECTIVE: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. METHODS: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 ± 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. RESULTS: Subjects with MMSE > 25 were twice as likely to have the CETP VV genotype (29% vs 14%, p = 0.02), and those with the VV genotype were more likely (61% vs 30%, p = 0.02) to have MMSE > 25. Subjects with the VV genotype had lower levels of CETP (1.73 ± 0.11 vs 2.12 ± 0.10 μg/mL, p = 0.01), higher high-density lipoprotein (HDL) levels (p = 0.02), and larger lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21% vs 4%, p = 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory. CONCLUSIONS: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age-related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age-related decline or AD.

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