title: 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.
authors.affiliation: Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, 1600 Viceroy Dr., Ste 800, Dallas, TX 75235, USA. Kristen.kennedy1@utdallas.edu
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Kennedy
authors.forename: Karen M
authors.initials: KM
authors.lastname: Rodrigue
authors.forename: Michael D
authors.initials: MD
authors.lastname: Devous
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hebrank
authors.forename: Gérard N
authors.initials: GN
authors.lastname: Bischof
authors.forename: Denise C
authors.initials: DC
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D005026:Ethylene Glycols / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008136:Longevity; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009415:Nerve Net / Q000502:physiology*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; C545186:florbetapir