Neural mechanisms of age-related slowing: The ΔCBF/ΔCMRO ₂ ratio mediates age-differences in BOLD signal and human performance

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/ΔCMRO ₂) 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.