Abstract
The PICALMrs541458 T allele has been recognized as a risk factor for late-onset Alzheimer's disease. And age might modulate the effects of genetic factors on cognitive functions and brain. Thus, the current study intended to examine whether the effects of rs541458 polymorphism on cognitive functions, resting state functional connectivity and gray matter volume would be modulated by age in Chinese non-demented elderly. We enrolled 657 non-demented old subjects to evaluate their cognitions through a series of neuropsychological tests and to detect rs541458 and APOE genotype through their blood samples using Taqman allele-specific assays. Among them, 78 participants received T1-weighted structural imaging and resting state functional magnetic resonance imaging. The results from neuropsychological tests showed that interactive effects of rs541458×age exhibited on executive function and processing speed after controlling for gender, years of education and APOEε4 status. The effects of rs541458 on resting state functional connectivity of the left superior parietal gyrus within left frontal-parietal network and gray matter volume of left middle temporal gyrus were modulated by age as well. Furthermore, the reduction of functional connectivity of superior parietal gyrus was closely related with better executive function in the T allele carriers-<65 years old group. And the increased volume of left middle temporal gyrus was significantly related with better executive function in the two CC genotype groups.
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