Functional Connectivity and White Matter integrity of intercommunity hub nodes in Subjective Cognitive Decline

Abstract

AbstractBackgroundSubjective Cognitive Decline (SCD) is considered an early preclinical stage of Alzheimer’s Disease and related dementias (ADRD) which may show promise for targeted preventative treatments. Subtle changes in functional connectivity and white matter integrity (WMI) may occur in SCD. Few studies have applied both functional graph theory (GT) and diffusional kurtosis imaging (DKI) techniques in tandem to identify differences in vulnerable network hubs. We addressed these issues by applying GT and DKI to study differences in intercommunity brain hubs. The hypothesis was that in hubs identified in healthy controls, SCD subjects’ hubs would show decreased GT diversity coefficient (DC) and DKI mean kurtosis (MK).MethodImages were acquired on a Siemens PRISMA scanner. Matlab was used to calculate DC and identify 5 hubs in 107 healthy controls (HC) and DC in 30 SCD (93 females, mean age = 67.51). SCD classification was determined by a comprehensive clinician evaluation or Everyday Cognition average item score>1.6, with objectively healthy cognitive performance (Montreal Cognitive Assessment score>22). Hub DC was the target in GLMM analysis, with diagnosis as predictor. Mean Kurtosis (MK) was analyzed in DSI Studio’s cross‐sectional connectometry using the hubs as seeds. Only the covariate of gray matter volume approached significance (p = .059), and was included in analysis. Mean age, education, head motion, and sex balance did not significantly differ between groups.ResultAll hubs had lower DC in SCD compared to HC (p ≤ .006). Connectometry identified positive correlation between MK and diagnosis in Left hemisphere tracts associated with two hubs: Inferior Fronto‐Occipital, Extreme capsule, and Uncinate tracts from Insular cortex, and Superior Longitudinal, Superior Corticalstriatal, Arcuate, Frontal Aslant, and Corticalspinal tracts from Middle Frontal gyrus.Conclusion Conclusion Rs‐fMRI findings show that intercommunity functional hubs are weaker in SCD compared to healthy individuals. Furthermore, the study identified a relationship of higher MK values in SCD for hubs located in insular cortex and middle frontal gyrus, all left hemisphere biased. Higher MK in SCD also runs counter to our hypothesis but is supported by recent paradoxical increase theories of decline. WMI differences between groups may be subtler than functional changes, warranting examination of the 2 modalities’ relationship.