A more randomly organized grey matter network is associated with deteriorating language and global cognition in individuals with subjective cognitive decline

Objectives: Grey matter network disruptions in Alzheimer's disease (AD) are associated with worse cognitive impairment cross-sectionally. Our aim was to investigate whether indications of a more random network organization are associated with longitudinal decline in specific cognitive functions in individuals with subjective cognitive decline (SCD). Experimental design: We included 231 individuals with SCD who had annually repeated neuropsychological assessment (3±1 years; n=646 neuropsychological investigations) available from the Amsterdam Dementia Cohort (54% male, age: 63±9, MMSE: 28±2). Single-subject grey matter networks were extracted from baseline 3D-T1 MRI scans and we computed basic network (size, degree, connectivity density) and higher-order (path length, clustering, betweenness centrality, normalized path length [lambda] and normalized clustering [gamma]) parameters at whole brain and/or regional levels. We tested associations of network parameters with baseline and annual cognition (memory, attention, executive functioning, language composite scores, and global cognition [all domains with MMSE]) using linear mixed models, adjusted for age, sex, education, scanner and total gray matter volume. Principal observations: Lower network size was associated with steeper decline in language (β±SE=0.12±0.05, p<0.05FDR). Higher-order network parameters showed no cross-sectional associations. Lower gamma and lambda values were associated with steeper decline in global cognition (gamma: β±SE=0.06±0.02); lambda: β±SE=0.06±0.02), language (gamma: β±SE=0.11±0.04; lambda: β±SE=0.12±0.05; all p<0.05FDR). Lower path length values in precuneus and fronto-temporo-occipital cortices were associated with a steeper decline in global cognition. Conclusions: A more randomly organized grey matter network was associated with a steeper decline of cognitive functioning, possibly indicating the start of cognitive impairment.