Gene Variation Associated With Lower Risk of Dementia, Alzheimer Disease

Newswise — Preliminary research suggests that variation of a gene for a plasma protein is associated with slower age-related memory decline and a lower risk of dementia and Alzheimer disease (AD), according to a study in the January 13 issue of JAMA.

“As the population ages, the public health and economic burdens of age-associated cognitive decline and dementia will continue to increase,” the authors write. The cholesteryl ester transfer protein (CETP) gene helps regulate the size of cholesterol particles, with research indicating that a variation of this gene is associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk have not been clear, according to background information in the article. This study specifically evaluated the substitution of valine for isoleucine in CETP which is associated with lower CETP protein serum concentration and activity and increases in high density lipoprotein.

Amy E. Sanders, M.D., of the Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, and colleagues examined the associations between variations of the CETP gene and memory performance and risk for new dementia or AD in a community-based sample of healthy adults age 70 years or older without dementia at the beginning of the study. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. There were also various tests of memory, attention and psychomotor speed (assessed by the time it takes to process and react to a signal).

In the study sample of 523 individuals, 40 new cases of dementia occurred during an average follow-up time of 4.3 years. An analysis of the data indicated that compared with the reference group, individuals who have both gene alleles substituting valine for isoleucine (valine homozygotes) had significantly slower (by a relative 51 percent) memory decline on the test of episodic memory and no significant differences on measures of attention and psychomotor speed. In the fully adjusted models, valine homozygosity was associated with lower risk of developing both dementia and AD.

“Despite the small number of incident dementia cases and small decline in memory, this preliminary report suggests that CETP valine homozygosity is associated with slower memory decline and lower risk for incident dementia or AD. This potentially protective association is supported by several observations. First, some (but not all) prior work has shown that at cross-section valine homozygosity was associated with better mental status. Second, valine homozygosity is associated with a slower rate of memory decline in our entire sample, not just those who developed dementia,” the researchers write.

“Third, the hazard ratios in this analysis suggested a possible gene-dose relationship for the CETP gene. Finally, an association between CETP status and cognition and dementia is biologically plausible because other genes involved in lipid metabolism, including APOE, are associated with dementia risk. Future studies should further evaluate the potential protective association of the CETP gene with dementia risk,” the authors conclude.

(JAMA. 2010;303[2]:150-158. Available pre-embargo to the media at www.jamamedia.org)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.