No abstract

Local brain signal variability (standard deviation of the BOLD signal [SDBOLD]) correlates with age and cognitive performance, and recently differentiated Alzheimer's disease (AD) patients from healthy controls. However, it is unknown if changes to SDBOLD precede diagnosis of AD or mild cognitive impairment (MCI). 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 SDBOLD and age, MoCA score, global fractional anisotropy, global mean diffusivity, and four cognitive factors. Greater SDBOLD 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 SDBOLD in both groups. This revealed a negative correlation, most robust in the at-risk group, between MTL SDBOLD and MTL subregion volumetry, particularly the entorhinal and parahippocampal regions. Taken together, these results suggest that the association between SDBOLD and cognition differs between the at-risk and control groups, which may be due to lower MTL volumes in the at-risk group. Our data indicate relations between MTL SDBOLD and cognition may be helpful in understanding brain differences in individuals who may be at risk for further cognitive decline. 3 Significance StatementMoment-to-moment variability in the BOLD signal, once dismissed as nuisance noise, is now understood to be an information-bearing signal. BOLD variability correlates with age and cognitive performance and was recently used to differentiate Alzheimer's disease (AD) patients from controls. As AD is a progressive disease, AD patients may benefit from its early detection. We found that older adults at-risk for cognitive decline showed differences in the relationships between BOLD variability and cognitive performance, relative to healthy controls. Notably, the differences were strongest in medial temporal lobe (MTL), areas where AD is known to begin. Our data suggest correlations between MTL BOLD variability and cognition may be useful for understanding brain differences in individuals at risk for further cognitive decline.