Genetics
A longevity-associated CETP genotype preserves cognitive function in two independent cohorts (Neurology 2006)
Original title: A genotype of exceptional longevity is associated with preservation of cognitive function
Researchers tested whether CETP VV homozygosity for I405V, already linked to exceptional longevity, is also associated with preserved cognitive function, first in 158 Ashkenazi Jews with exceptional longevity (age 99.2 plus or minus 0.3 years) using the Mini-Mental State Examination (MMSE), then in a younger cohort from the Einstein Aging Study. Among the centenarians, those with MMSE above 25 were twice as likely to carry the CETP VV genotype (29% versus 14%, P equals 0.02), and VV carriers had lower CETP levels (1.73 plus or minus 0.11 versus 2.12 plus or minus 0.10 microgram per mL, P equals 0.01), higher HDL levels (P equals 0.02) and larger lipoprotein particles (P equals 0.03). In the Einstein Aging Study cohort, an approximately fivefold increase in VV genotype frequency (21% versus 4%, P equals 0.02), along with higher HDL and larger lipoprotein particles, was associated with less dementia and better memory, implicating the longevity-associated CETP genotype as a modulator of age-related cognitive function across two independent cohorts.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.