Abstract
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.
Highlights
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Beijing 100029, People’s Republic of ChinaAlzheimer’s disease (AD) is the most common type of dementia
We found similar results in the imaging sub-sample, as the interactions of rs541458 × age were significant for executive function (SCWT C-B, P = 0.034, SCWT-C, P = 0.024, TMTb, P = 0.003, and TMTb-a, P = 0.011), processing speed (SDMT, P = 0.011), and general mental status (MMSE, P = 0.013)
The findings from the present study showed that age modulated the effects of PICALM on cognitive performance, which were mainly manifested in the executive function and processing speed, that is, the risk allele T was associated with better cognitive performance in the
Summary
Electronic supplementary material The online version of this article (doi:10.1007/s12035-016-0358-5) contains supplementary material, which is available to authorized users.Beijing 100029, People’s Republic of ChinaAlzheimer’s disease (AD) is the most common type of dementia. Among many risk factors, increased age has always been a pivotal risk factor for late-onset AD (LOAD) [3]. The prevalence of AD increases with age [4], almost doubling every 5 years after the age of 60 [5]. Several well-recognized genetic factors augment the complexity of LOAD [6]. The apolipoprotein E (APOE) ε4 allele is the best known genetic LOAD risk factor, which is associated with increased incidence and a decreased age of onset of LOAD [7]. It has been suggested that the ε4 allele would likely account for approximately 50% or more of the LOAD cases in the USA [8, 9]. Large-scale genome-wide association studies (GWAS) have been carried out to locate additional susceptible loci to more
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