Interaction of physical fitness and resting state functional connectivity on global cognitive function in older adults with mild cognitive impairment

Abstract

Background Mild cognitive impairment (MCI) represents a prodromal stage of Alzheimer's disease. Physical fitness, including cardiorespiratory fitness and muscular strength, is associated with cognitive function in older adults. Resting-state functional connectivity (rsFC) is also linked to cognitive function; however, whether physical fitness modifies the association between rsFC and cognitive function remains unclear. Objective To examine associations of cardiorespiratory fitness and muscular strength with rsFC and their interaction on global cognitive function in older adults with MCI. Methods A cross-sectional study of 95 older adults with MCI. Cardiorespiratory fitness was estimated by the 400-m walk; muscular strength was indexed using grip strength measured by hand dynamometer. Global cognitive function was indexed by the 13-item Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog-13). Using the Yeo 7-network atlas, we computed rsFC within and between seven canonical networks. Significant rsFC-fitness associations were entered into moderation analyses (X = rsFC, Y = ADAS-Cog-13) with cardiorespiratory fitness or grip strength as moderator, adjusted for covariates. Simple slopes were examined at ±1 SD from the mean of moderator. Results Participants had a mean age of 73.49 years, and 53.7% were female. Cardiorespiratory fitness interacted with rsFC in relation to ADAS-Cog-13, whereas grip strength did not. Specifically, greater limbic-visual (standardized b = −0.22, p = 0.009), limbic-somatomotor ( b = −0.20, p = 0.049), and limbic-ventral attention ( b = −0.19, p = 0.020) rsFC were associated with better global cognitive function among individuals with higher cardiorespiratory fitness. Conclusions Higher between-network rsFC is generally associated with worse cognitive function. Thus, higher cardiorespiratory fitness may attenuate the negative association between higher between-network rsFC and global cognitive function in MCI.