Effects of beta-amyloid accumulation on neural function during encoding across the adult lifespan

Abstract

Limited functional imaging evidence suggests that increased beta-amyloid deposition is associated with alterations in brain function, even in healthy older adults. However, the majority of these findings report on resting-state activity or functional connectivity in adults over age 60. Much less is known about the impact of beta-amyloid on neural activations during cognitive task performance, or the impact of amyloid in young and middle-aged adults. The current study measured beta-amyloid burden from PET imaging using (18)Florbetapir, in a large continuous age sample of highly-screened, healthy adults (N=137; aged 30-89 years). The same participants also underwent fMRI scanning, performing a memory encoding task. Using both beta-amyloid burden and age as continuous predictors of encoding activity, we report a dose-response relationship of beta-amyloid load to neural function, beyond the effects of age. Specifically, individuals with greater amyloid burden evidence less neural activation in bilateral dorsolateral prefrontal cortex, a region important for memory encoding, as well as reduced neural modulation in areas associated with default network activity: bilateral superior/medial frontal and lateral temporal cortex. Importantly, this reduction of both activation and suppression as a function of amyloid load was found across the lifespan, even in young- and middle-aged individuals. Moreover, this frontal and temporal amyloid-reduced activation/suppression was associated with poorer processing speed, verbal fluency, and fluid reasoning in a subgroup of individuals with elevated amyloid, suggesting that it is detrimental, rather than compensatory in nature.

Figure 1

Dose-response effect of Aβ burden: increasing precuneus Aβ is associated with reduced activation and suppression during scene encoding in task positive (red labels) and task negative regions (blue labels).

Figure 2

Scatterplots illustrating dose-response effect of increasing amyloid and decreasing activation/suppression in the whole sample for representative frontal and temporal regions. Contrast estimates controlled for age.

Figure 3

Beta-Amyloid-altered neural function predicts poorer cognitive performance. Panel A indicates the effect of Aβ-associated reduced suppression in superior frontal region on verbal fluency and fluid reasoning. Panel B indicates the effect of Aβ-associated reduced activation in temporal and frontal regions on processing speed and fluid reasoning.