A genotype of exceptional longevity is associated with preservation of cognitive function.
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.
Barzilai
N
N
Institute for Aging Research, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. barzilai@aecom.yu.edu
Atzmon
G
G
Derby
C A
CA
Bauman
J M
JM
Lipton
R B
RB
D017677:Age Distribution; D000367:Age Factors; D000369:Aged, 80 and over; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D003071:Cognition; D003072:Cognition Disorders / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D007585:Jews / Q000235:genetics* / Q000706:statistics & numerical data; D008136:Longevity / Q000235:genetics*; D008297:Male; D009518:New York / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
D053480:Cholesterol Ester Transfer Proteins