title: Neural mechanisms of age-related slowing: the ΔCBF/ΔCMRO2 ratio mediates age-differences in BOLD signal and human performance.
abstract: The precise mechanisms that give rise to the blood-oxygen-level-dependent (BOLD) activation differences that accompany age-related cognitive slowing remain fundamentally unknown. We sought to isolate the origin of age-related BOLD changes by comparing blood-flow and oxygen-metabolic constituents of the BOLD response using dual-echo arterial spin labeling during visual stimulation and CO2 ingestion. We hypothesized, and our results confirmed, that age-related changes in the ratio of fractional cerebral blood flow to fractional cerebral metabolic rate of oxygen consumption (ΔCBF/ΔCMRO2) lead to the BOLD changes that are observed in older adults. ΔCBF/ΔCMRO2 was also significantly related to performance, suggesting that age-related cognitive slowing results from neural cell assemblies that operate less efficiently, requiring greater oxygen metabolism that is not matched by blood-flow changes relative to younger adults. Age-related changes in ΔCBF/ΔCMRO2 are sufficient to explain variations in BOLD responding and performance cited throughout the literature, assuming no bias based on physiological baseline CMRO2.
authors.affiliation: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75080, USA.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Hutchison
authors.forename: Hanzhang
authors.initials: H
authors.lastname: Lu
authors.forename: Bart
authors.initials: B
authors.lastname: Rypma
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D004192:Discrimination, Psychological / Q000502:physiology*; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D010775:Photic Stimulation; D011930:Reaction Time / Q000502:physiology*; D012039:Regional Blood Flow; D055815:Young Adult