The structural-functional-connectivity coupling of the aging brain

Abstract

Aging primarily affects memory and executive functions, a relationship that may be underpinned by the fact that almost all adults over 60 years old develop small vessel disease (SVD). The fact that a wide range of neuropathologies could only explain up to 43% of the variation in age-related cognitive impairment suggests that other factors, such as cognitive reserve, may play a role in the brain's resilience against aging-related cognitive decline. This study aims to examine the relationship between structural-functional-connectivity coupling (SFC), and aging, cognitive abilities and reserve, and SVD-related neuropathologies using a cohort of n = 176 healthy elders from the Harvard Aging Brain Study. The SFC is a recently proposed biomarker that reflects the extent to which anatomical brain connections can predict coordinated neural activity. After controlling for the effect of age, sex, and years of education, global SFC, as well as the intra-network SFC of the dorsolateral somatomotor and dorsal attention networks, and the inter-network SFC between dorsolateral somatomotor and frontoparietal networks decreased with age. The global SFC decreased with total cognitive score. There were significant interaction effects between years of education versus white matter hyperintensities and between years of education versus cerebral microbleeds on inter-network SFC. Enlarged perivascular space in basal ganglia was associated with higher inter-network SFC. Our results suggest that cognitive ability is associated with brain coupling at the global level and cognitive reserve with brain coupling at the inter-functional-brain-cluster level with interaction effect from white matter hyperintensities and cerebral microbleed in a cohort of healthy elderlies.

Keywords: Aging; Cognitive reserve; Harvard Aging Brain Study; Small vessel disease; Structural–functional-connectivity coupling.

Fig. 1

Spatial distribution of network modules. The 333 brain regions from the Gordon atlas were aligned to twelve different functional brain clusters [30], namely, A visual (VIS), B dorsal somatomotor (SMhand), C ventral somatomotor (SMmouth), D auditory network (AN), E cingulo-opercular network (CON), F cingulo-parietal network (CPN), G DMN, H dorsal attentional network (DAN), I frontoparietal network (FPN), J retrosplenial temporal network (RTN), K ventral attentional network (VAN), and L salience network (SN)

Fig. 2

Illustration on the estimation of SFC at intra and inter-functional-brain-cluster levels. Intra-network SFC was computed from correlation between the structural and functional connections of brain regions within a single functional brain cluster, whereas inter-network SFC from correlation between the structural and functional connections of brain regions from a pair of different functional brain clusters

Fig. 3

The F-statistics for the comparison in the intra and inter-network modularity of the structural (A) and functional (B) brain network of healthy elderly between the first and second visit. Significant increase in modularity was indicated using + and decrease using − . VIS, visual; SMhand, dorsal somatomotor; SMmouth, ventral somatomotor; AN, auditory network; CON, cingulo-opercular network; CPN, cingulo-parietal network; DMN, default mode network; DAN, dorsal attentional network; FPN, frontoparietal network; RTN, retrosplenial temporal cortex; VAN, ventral attentional network; SN, salience network

Fig. 4

Group-averaged intra and inter-network coupling A at the first visit (N = 176) and B at the second visit (3 years apart) (N = 176) C shows the F-statistics for the comparison in the intra and inter-network coupling. Significant decrease in SFC was indicated using − . D, E The brain regions of the functional brain clusters with significant difference in SFC from baseline. All p values were FDR-adjusted