BETA-AMYLOID ACCUMULATION HURTS AND CRYSTALLIZED KNOWLEDGE HELPS BRAIN MODULATORY CAPACITY: AN FMRI STUDY

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We have previously demonstrated that crystallized knowledge, as a typical neural enrichment factor, confers protection of brain modulation to task difficulty across the adult lifespan (Jingting et al., in preparation), although modulatory capacity declines with age (Kennedy et al., 2015). Here we investigated (1) whether beta-amyloid, as a typical risk factor for Alzheimer's disease, might affect modulatory capacity; and (2) whether the protective effects of crystallized knowledge on modulation remain with the accumulation of beta-amyloid. We studied 274 cognitively normal participants (40–89 years) who completed an F-18 Florbetapir PET scan and an fMRI scan, where participants judged ambiguous (“Hard”) and unambiguous (“Easy”) words for animacy. Modulatory capacity was measured by contrasting hard vs. easy in functional activation. Age, amyloid and crystallized ability were entered in a multiple regression model for each of the 8 brain regions in the frontoparietal cognitive control network to assess whether amyloid and crystallized knowledge accounted for variance in modulation beyond age. We first replicated our previous findings that older adults had decreased modulatory capacity in the frontoparietal network. After controlling for age, amyloid accumulation was related to declined modulatory capacity in parietal and right prefrontal but not left prefrontal cortex, and such depletive effects were found in middle-aged (40–60 years) but not older (60–69 years) adults. After controlling for age and continuous accumulation of amyloid, better crystallized knowledge predicted higher modulation in the frontoparietal network. Because we were particularly interested in whether the facilitating role of crystallized knowledge in modulatory capacity was related to amyloid positivity status, in a second analysis, we conducted multiple regressions with age and crystallized knowledge predicting brain modulation for amyloid negative and positive individuals, respectively. We found that better crystallized knowledge predicted higher modulatory capacity in prefrontal regions and left angular gyrus for amyloid negative individuals but only mildly (p = 0.057) in medial superior frontal gyrus for amyloid positive individuals. Our findings suggested that brain modulatory capability is impaired with age and amyloid. Crystallized knowledge protects modulatory capacity, which seems to have stronger effects for amyloid negative individuals, compared to amyloid positive individuals.