Genetic and Vascular Modifiers of Age-Sensitive Cognitive Skills: Effects of COMT BDNF ApoE and Hypertension

摘要

Cognitive phenotypes emerge from multiple genetic and environmental influences. Several single nucleotide polymorphisms have been linked to neural and cognitive variation in healthy adults. We examined contribution of three polymorphisms frequently associated with individual differences in cognition (Catechol-O-Methyl-Transferase Val158Met, Brain-Derived-Neurotrophic-Factor Val66Met, and Apolipoprotein E ɛ4) and a vascular risk factor (hypertension) as well as their interactions in a sample of 189 volunteers (age 18–82). Genotypes were determined from buccal culture samples, and cognitive performance was assessed in four age-sensitive domains – fluid intelligence, executive function (inhibition), associative memory, and processing speed. We found that younger age and COMT Met/Met genotype, associated with low COMT activity and higher prefrontal dopamine content, were independently linked to better performance in most of the tested domains. Homozygotes for Val allele of BDNF polymorphism exhibited better associative memory and faster speed of processing than the Met allele carriers, with greater effect for women and persons with hypertension. Carriers of ApoE ɛ4 allele evidenced steeper age-related increase in costs of Stroop color interference, but showed no negative effects on memory. The findings indicate that age-related cognitive differences in multiple domains are differentially affected by distinct genetic factors and their interactions with vascular health status.