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

Hum Brain Mapp. 2018 Aug;39(8):3143-3151. doi: 10.1002/hbm.24065. Epub 2018 Mar 30.


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.

Keywords: Alzheimer's disease; MRI; cognition; connectivity; graph theory; grey matter network; longitudinal; mild cognitive impairment; subjective cognitive decline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Brain Mapping
  • Cognition*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / physiopathology*
  • Diagnostic Self Evaluation
  • Female
  • Gray Matter / diagnostic imaging
  • Gray Matter / physiopathology*
  • Humans
  • Imaging, Three-Dimensional
  • Language*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Perception