Abstract
ObjectivesGrey 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.ConclusionsA more randomly organized grey matter network was associated with a steeper decline of cognitive functioning, possibly indicating the start of cognitive impairment.
Highlights
The pathogenesis of Alzheimer’s Disease (AD) takes years, eventually causing progressive neurodegeneration and cognitive decline (Jack et al, 2013; Scheltens et al, 2016)
A more randomly organized grey matter network was associated with a steeper decline of cognitive functioning, possibly indicating the start of cognitive impairment
A group-based network study suggested that grey matter networks that more resemble randomly organized networks are associated with future progression to dementia in individuals with mild cognitive impairment (Pereira et al, 2016)
Summary
The pathogenesis of Alzheimer’s Disease (AD) takes years, eventually causing progressive neurodegeneration and cognitive decline (Jack et al, 2013; Scheltens et al, 2016). About 25–50% of people older than 60 years perceive cognitive decline (Jonker, Geerlings, & Schmand, 2000), but longitudinal studies show that only a minority (11–16%) of SCD subjects shows clinical progression over time (Jessen et al, 2010; Van Harten et al, 2013). At this point it remains difficult to understand which individuals with SCD will show future cognitive decline. It can be hypothesized that lower clustering coefficients values in grey matter networks might provide a biological explanation for cognitive decline
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