"Everybody ages differently. By looking at genetic variationsand individual differences in markers of vascular health, we beginto understand that preventable factors may affect our chances forsuccessful aging," said Wayne State University psychologydoctoral student Andrew Bender, lead author of a study supported bythe National Institute on Aging of the National Institutes ofHealth and now in press in the journal Neuropsychologia . The report, "Age-related Differences in Memory and ExecutiveFunctions in Healthy APOE ε4 Carriers: The Contribution ofIndividual Differences in Prefrontal Volumes and Systolic BloodPressure," focuses on carriers of the ε4 variant ofthe apolipoprotein (APOE) gene, present in roughly 25 percent ofthe population. Compared to those who possess other forms of theAPOE gene, carriers of the ε4 allele are at significantlygreater risk for Alzheimer's, dementia and cardiovascular disease. |
Many studies also have shown that nondemented carriers of the APOEε4 variant have smaller brain volumes and perform less wellon cognitive tests than carriers of other gene variants. Thosefindings, however, are not consistent, and a possible explanationmay come from examining interactions between the risky genes andother factors, such as markers of cardiovascular health. Priorresearch in typical samples of older adults has shown that indeedother vascular risk factors -- such as elevated cholesterol,hypertension or diabetes -- can exacerbate the impact of the APOEε4 variant on brain and cognition, but it is unclear ifsuch synergy of risks is present in healthy adults. Thus, Wayne State researchers evaluated a group of volunteers from19 to 77 years of age who self-reported as exceptionally healthy ona questionnaire that screened for a number of conditions,representing a "best case scenario" of healthy aging.
Theresearch project, led by Naftali Raz, Ph.D., professor ofpsychology and director of the Lifespan Cognitive NeuroscienceResearch Program at WSU's Institute of Gerontology, testeddifferent cognitive abilities known for their sensitivity to agingand the effects of the APOE ε4 variant. Those abilitiesinclude speed of information processing, working memory (holdingand manipulating information in one's mind) and episodic memory(memory for events). Researchers also measured participants' blood pressure, performedgenetic testing to determine which APOE variant participantscarried, and measured the volumes of several critical brain regionsusing a high-resolution structural magnetic resonance imaging brainscan. Bender and Raz showed that for older APOE ε4carriers, even minor increases in systolic blood pressure (thehigher of the two numbers that are reported in blood pressuremeasures) were linked with smaller volumes of the prefrontal cortexand prefrontal white matter, slower speed of informationprocessing, reduced working memory capacity and worse verbalmemory. Notably, they said, that pattern was not evident in thosewho lacked the ε4 gene variant.
The study concludes that the APOE ε4 gene may make itscarriers sensitive to negative effects of relatively subtleelevations in systolic blood pressure, and that the interplaybetween two risk factors, genetic and physiological, is detrimentalto the key brain structures and associated cognitive functions. "Although genes play a significant role in shaping the effectsof age and vascular risk on the brain and cognition, the impact ofsingle genetic variants is relatively small, and there are quite afew of them. Thus, one's aging should not be seen through the lensof one's genetic profile," cautioned the study's authors. Theycontinued, "The negative impact of many genetic variationsneeds help from other risk factors, and while there isn't much onecan do about genes, a lot can be done about vascular risk factorssuch as blood pressure or cholesterol." "Everybody should try to keep those in check, although peoplewith certain genetic variants more so than others." Raz said."Practically speaking, even with the best deck of geneticcards dealt to you, it still makes sense to reduce risk throughwhatever works: exercise, diet or, if those fail, medication." Because the study is part of a longitudinal project, he and Bendersaid the immediate future task now is to determine how theinteraction between risky genes and vascular risk factors affectthe trajectory of age-related changes -- not differences, as inthis cross-sectional study -- in brain and cognition.
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