Coevolution of brain structures in amnestic mild cognitive impairment.

Network accounts of the progression of Alzheimer's disease (AD), based on cross-sectional brain imaging observations, postulate that the biological course of the disease is characterized by coordinated spatial patterns of brain change to distributed cognitive networks. This study tests this conjecture by quantifying inter-regional covariance in cortical gray matter atrophy rates in 317 Alzheimer's Disease Neuroimaging Initiative participants who were clinically diagnosed with amnestic mild cognitive impairment at baseline and underwent serial MRI at 6-month intervals over the course of 2years. A factor analysis model identified five factors (i.e. groupings of regions) that exhibited highly correlated rates of atrophy. Four groupings approximately corresponded to coordinated change within the posterior default mode network, prefrontal cortex, medial temporal lobe, and regions largely spared by the early pathological course of AD (i.e., sensorimotor and occipital cortex), while the fifth grouping represented diffuse, global atrophy. The data-driven observation of "frontal aging" superimposed upon medial temporal atrophy typical of early AD and default mode network changes supports the view that in individuals at high risk of eventual clinical AD, multiple patterns of distributed neuronal death corresponding to multiple biological substrates may be active.