The Interactive Effects of Age and PICALM rs541458 Polymorphism on Cognitive Performance, Brain Structure, and Function in Non-demented Elderly

Zhen Liu, Xiangwei Dai, Junying Zhang, Xin Li, Yaojing Chen, Chao Ma, Kewei Chen, Dantao Peng, Zhanjun Zhang

The PICALM rs541458 T allele has been recognized as a risk factor for late-onset Alzheimer's disease, and age might modulate the effects that genetic factors have on cognitive functions and brain. Thus, the current study intended to examine whether the effects of rs541458 on cognitive functions, brain structure, and function were modulated by age in non-demented Chinese elderly. We enrolled 638 subjects aged 50 to 82 years and evaluated their cognitive functions through a series of neuropsychological tests. Seventy-eight of these participants also received T1-weighted structural and resting state functional magnetic resonance imaging. Dividing subjects into groups <65 and ≥65 years old, results of neuropsychological tests showed that interactive effects of rs541458 × age existed with regard to executive function and processing speed after controlling for gender, years of education and APOE ε4 status. In addition, the effects of rs541458 on resting state functional connectivity of left superior parietal gyrus within left frontal-parietal network and on gray matter volume of left middle temporal gyrus were modulated by age. Furthermore, reduction of functional connectivity of left superior parietal gyrus was closely related with better executive function in the T allele carriers <65 years old. Further, greater volume of left middle temporal gyrus was significantly related to better executive function in both CC genotype <65 years old and CC genotype ≥65 years old groups, separately. Pending further confirmation from additional studies, our results support the hypothesis that the modulation of age, with respect to the rs541458, has interactional effects on cognitive performance, brain function, and structural measurements.