Abstract
Local brain signal variability [SD of the BOLD signal (SD(BOLD)]] correlates with age and cognitive performance, and recently differentiated Alzheimer's disease (AD) patients from healthy controls. However, it is unknown whether changes to SD(BOLD) precede diagnosis of AD or mild cognitive impairment. We compared ostensibly healthy older adult humans who scored below the recommended threshold on the Montreal cognitive assessment (MoCA) and who showed reduced medial temporal lobe (MTL) volume in a previous study ("at-risk" group, n = 20), with healthy older adults who scored within the normal range on the MoCA ("control" group, n = 20). Using multivariate partial least-squares analysis we assessed the correlations between SD(BOLD) and age, MoCA score, global fractional anisotropy, global mean diffusivity, and four cognitive factors. Greater SD(BOLD) in the MTL and occipital cortex positively correlated with performance on cognitive control/speed tasks but negatively correlated with memory scores in the control group. These relations were weaker in the at-risk group. A post hoc analysis assessed associations between MTL volumes and SD(BOLD) in both groups. This revealed a negative correlation, most robust in the at-risk group, between MTL SD(BOLD) and MTL subregion volumetry, particularly the entorhinal and parahippocampal regions. Together, these results suggest that the association between SD(BOLD) and cognition differs between the at-risk and control groups, which may be because of lower MTL volumes in the at-risk group. Our data indicate relations between MTL SD(BOLD) and cognition may be helpful in understanding brain differences in individuals who may be at risk for further cognitive decline.