GREY MATTER CONNECTIVITY IS RELATED TO A STEEPER LOSS OF MEMORY AND LANGUAGE FUNCTIONING OVER TIME IN PATIENTS WITH SUBJECTIVE COGNITIVE DECLINE

Abstract

Grey matter connectivity is related to cognitive functioning, and disrupted in early stages of Alzheimer's disease (AD). We aimed to investigate the association between single-subject grey matter connectivity and changes in cognitive functioning over time in patients with subjective cognitive decline (SCD). We included 235 patients with SCD, with baseline 3D-T1 MRI and repeated neuropsychological testing (on average 3±1 years) from the Amsterdam Dementia Cohort (54% male, age: 63±9, MMSE: 28±2). We assessed baseline and annual change in cognitive functioning of four domains: memory, attention, executive function and language (n=654 neuropsychological investigations). Single-subject grey matter networks were extracted from T1-weighted structural MRI and the following parameters were computed at whole brain level and in 90 anatomical AAL areas: degree, connectivity density, path length, clustering, betweenness centrality, lambda and gamma. Effects of grey matter baseline connectivity measures (predictors) on changes in annual cognitive performance (dependent variables) were assessed with linear mixed models. Analyses were adjusted for age, sex, education, scanner and total intracranial volume. At baseline, there were no associations between structural connectivity and cognitive functioning. Lower lambda values were associated with a steeper decline in memory (β=0.09, SE=0.02; p<.05). Lower values of network size (β=0.11, SE=0.05), degree (β=0.10, SE=0.05) and betweenness centrality (β=0.13, SE=0.05) were associated with a steeper decline in language (all p<0.05). Additional adjustment for hippocampal volumes did not change these results. Regional analyses showed that lower path length values were associated with faster memory decline specifically in the bilateral parahippocampal gyri and the superior and middle temporal poles. Associations between lower betweenness centrality and faster language decline were specific for the bilateral orbitofrontal, medial frontal, middle temporal, inferior parietal, and right insula and parahippocampal gyrus (all p<0.05). SCD patients with lower values of grey matter network parameters showed faster decline in memory and language. Lower values of lambda are indicative of a loss of connectivity and a more random network organisation, which is often observed in AD-dementia patients. These findings suggest that less efficient grey matter network organisation may precede objective cognitive impairment and the clinical manifestation of AD.