title: β-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly.
abstract: The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease (AD), has been associated with functional alterations, often in an episodic memory system with a particular emphasis on medial temporal lobe function. The topography of Aβ deposition, however, largely overlaps with frontoparietal control (FPC) regions implicated in cognitive control that has been shown to be impaired in early mild AD. To understand the neural mechanism underlying early changes in cognitive control with AD, we examined the impact of Aβ deposition on task-evoked FPC activation using functional magnetic resonance imaging (fMRI) in humans. Forty-three young and 62 cognitively normal older adults underwent an fMRI session during an executive contextual task in which task difficulty varied: single (either letter case or vowel/consonant judgment task) vs dual (switching between letter case and vowel/consonant decisions) task. Older subjects additionally completed (18)F-florbetaben positron emission tomography scans and were classified as either amyloid positive (Aβ+) or negative (Aβ-). Consistent with previous reports, age-related increases in brain activity were found in FPC regions commonly identified across groups. For both task conditions, Aβ-related increases in brain activity were found compared with baseline activity. For higher cognitive control load, however, Aβ+ elderly showed reduced task-switching activation in the right inferior frontal cortex. Our findings suggest that with Aβ deposition, brain activation in the cognitive control region reaches a maximum with lower control demand and decreases with higher control demand, which may underlie early impairment in cognitive control with AD progression.
  
  
  CONCLUSIONS
  The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease, spatially overlaps with frontoparietal control (FPC) regions implicated in cognitive control, but the impact of Aβ deposition on FPC regions is largely unknown. Using functional magnetic resonance imaging with a task-switching task, we found Aβ-related increases in FPC regions compared with baseline activity. For higher cognitive control load, however, Aβ-related hypoactivity was found in the right inferior frontal cortex, a region highly implicated in cognitive control. The findings suggest that with Aβ deposition, task-related brain activity may reach a plateau early and undergo downstream pathways of neural dysfunction, which may relate to the early impairment of cognitive control seen in the progression of Aβ pathology.
authors: Cognitive Neuroscience Division, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032-3784 hwamee.oh@columbia.edu.
authors: Hwamee
authors: H
authors: Oh
authors: Cognitive Neuroscience Division, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032-3784.
authors: Jason
authors: J
authors: Steffener
authors: Cognitive Neuroscience Division, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032-3784.
authors: Qolamreza R
authors: QR
authors: Razlighi
authors: Cognitive Neuroscience Division, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032-3784.
authors: Christian
authors: C
authors: Habeck
authors: Cognitive Neuroscience Division, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032-3784.
authors: Yaakov
authors: Y
authors: Stern
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000814:Aniline Compounds; D003071:Cognition / Q000502:physiology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology*; D019275:Radiopharmaceuticals; D011930:Reaction Time / Q000502:physiology; D013267:Stilbenes; D055815:Young Adult
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D013267:Stilbenes; C527756:4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene
keywords: amyloid PET; cognitive control; cognitively normal older adults; fMRI; frontoparietal cortex; β-amyloid