TY - JOUR
T1 - Effects of beta-amyloid accumulation on neural function during encoding across the adult lifespan
AU - Kennedy, Kristen M.
AU - Rodrigue, Karen M.
AU - Devous, Michael D.
AU - Hebrank, Andrew C.
AU - Bischof, Gérard N.
AU - Park, Denise C.
N1 - Funding Information:
This study was supported in part by NIH grants 5R37AG-006265-25 , 3R37AG-006265-25S1 , and Alzheimer's Association grant IIRG-09-135087 . KMK was supported in part by NIA grant 1K99-AG-0368180-2 . The radiotracer was provided by Avid Radiopharmaceuticals. We thank Dr. Dana Mathews and Michael Viguet for assistance with PET scanning and Jenny Rieck and Prasanna Tamil for participant recruitment, scheduling and testing.
PY - 2012/8/1
Y1 - 2012/8/1
N2 - 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 18Florbetapir, in a large continuous age sample of highly-screened, healthy adults (N=137; aged 30-89years). 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.
AB - 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 18Florbetapir, in a large continuous age sample of highly-screened, healthy adults (N=137; aged 30-89years). 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.
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U2 - 10.1016/j.neuroimage.2012.03.077
DO - 10.1016/j.neuroimage.2012.03.077
M3 - Article
C2 - 22569063
AN - SCOPUS:84861606292
SN - 1053-8119
VL - 62
SP - 1
EP - 8
JO - NeuroImage
JF - NeuroImage
IS - 1
ER -