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

Authors: Barzilai N; Atzmon G; Derby CA; Bauman JM; Lipton RB

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 mug/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.

Keywords: Age Distribution; Age Factors; Aged, 80 and over; Cholesterol Ester Transfer Proteins/*genetics; *Cognition; Cognition Disorders/*epidemiology/*genetics; Female; Genetic Predisposition to Disease/epidemiology/genetics; Genotype; Humans; Jews/*genetics/statistics & numerical data; Longevity/*genetics; Male; New York/epidemiology; Polymorphism, Single Nucleotide/genetics; Prevalence; Risk Assessment/*methods; Risk Factors
Journal: Neurology
Volume: 67
Issue: 12
Pages: 2170-5
Date: Dec. 28, 2006
PMID: 17190939
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Citation:

Barzilai N, Atzmon G, Derby CA, Bauman JM, Lipton RB (2006) A genotype of exceptional longevity is associated with preservation of cognitive function. Neurology 67: 2170-5.


Lifespan Factors:
  • CETP cholesteryl ester transfer protein, plasma


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