Higher intraindividual variability in neuropsychological test performance is associated with reduced cerebral blood flow in older adults

Abstract

AbstractBackgroundIntraindividual variability (IIV) across neuropsychological measures within a single testing session has become a promising sensitive marker predictive of cognitive decline and development of Alzheimer’s disease (AD). We have previously shown that higher IIV is associated with medial temporal lobe atrophy. However, to our knowledge, IIV has yet to be examined in relation to cerebral blood flow (CBF). Therefore, we examined associations between IIV and regional CBF among older adults free of dementia.Method141 Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent neuropsychological testing, magnetic resonance imaging (MRI), and florbetapir positron emission tomography (PET) imaging. The IIV index was calculated as the intraindividual standard deviation across 6 demographically‐corrected neuropsychological measures. Mean neuropsychological performance was computed as the mean of the 6 z‐scores. Pulsed arterial spin labeling MRI was used to quantify CBF. Six free‐surfer derived a priori CBF regions of interest were examined: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. PET amyloid‐β (Aβ) positivity was determined using the recommended threshold for cross‐sectional florbetapir of 1.11 using whole cerebellum as the reference region.ResultIn the entire sample, linear regression models showed that after adjusting for age, sex, mean neuropsychological performance, and regional cortical thickness, greater IIV was significantly associated with lower inferior parietal CBF (β=‐2.712, p=.004), inferior temporal CBF (β=‐3.259, p=.001), and reduced entorhinal CBF at trend level (β=‐.407, p=.073). Sensitivity analyses showed that among Aβ+ individuals, greater IIV was significantly associated with lower CBF in inferior parietal (β=‐2.729, p=.018) and inferior temporal regions (β=‐2.704, p=.043). In Aβ‐ individuals, there were no significant associations between IIV and CBF (all ps>.05).ConclusionIIV may be sensitive to early cerebrovascular changes in AD‐vulnerable regions above and beyond demographics, mean neuropsychological performance, and cortical thickness. These relationships were seen among Aβ+ individuals, suggesting that IIV may be a marker of early brain changes among those individuals on the AD continuum. Future studies should examine how IIV may predict future brain and cognitive changes in more diverse samples and among those with greater vascular risk burden.