# Cerebral oxygen extraction and blood flow in community-based older adults: associations with white matter hyperintensity and neurocognitive function

## TL;DR

In older adults, high oxygen use with low blood flow in the brain is linked to worse brain health and cognitive decline, while better balance between blood flow and oxygen use is associated with better outcomes.

## Contribution

The study identifies a 'misery perfusion' pattern (high OEF, low CBF) as a novel marker for cognitive vulnerability and brain disease in community-based seniors.

## Key findings

- High OEF and low CBF (misery perfusion) is associated with higher white matter hyperintensity volume and worse cognitive performance.
- Low OEF and high CBF is linked to lower white matter hyperintensity and better cognition.
- A U-shaped relationship between OEF and cognition suggests optimal cognitive function at moderate OEF levels.

## Abstract

Cerebral oxygen extraction fraction (OEF) and cerebral blood flow (CBF) are key haemodynamic markers. Emerging evidence suggests that they may exert compensatory effects on small vessel disease and cognitive outcomes, with potentially nonlinear relationships, particularly in community-dwelling seniors. Therefore, we conducted a cross-sectional study of 296 participants from the Heritage Study in China. OEF was assessed using T2-relaxation-under-spin-tagging (TRUST) MRI, while CBF was measured using phase contrast MRI. White matter hyperintensity (WMH) volumes were segmented through T2 fluid-attenuated inversion recovery (FLAIR) imaging and log-transformed. Neurocognitive function was evaluated across multiple domains and summarized as a global composite Z-score. Based on the median values of CBF and OEF, participants were categorized into four quadrants and generalized linear models were used to examine associations between OEF CBF patterns and WMH and cognition. Participants with high OEF and low CBF had highest WMH volume (4.48 ± 8.02 cm3) and worse cognitive performance (−0.13 ± 1.04). Overall, higher OEF was significantly related to lower global cognition (P = 0.012), whereas lower CBF was significantly associated with greater WMH burden (P = 0.001). Compared with those in high OEF and low CBF, individuals in low OEF and high CBF exhibited significantly lower WMH volume (β = −0.55, 95% confidence interval (CI) = [−1.05, −0.05]) and better cognition (β = 0.28, 95% CI = [0.02, 0.54]). In contrast, low OEF and low CBF were associated with relative cognitive reserve (β = 0.32, 95% CI = [0.02, 0.61]) but higher WMH volume. Domain-based analyses for attention, visuospatial and memory functions showed similar results. To further explore potential nonlinear effects, response surface analysis was performed to investigate relationships among OEF, CBF, WMH, and global cognition, revealing a significant association between CBF and WMH (β = −1.42, 95% CI = [−2.85, −0.01]). For global cognitive performance, OEF was negatively associated with cognitive outcomes (OEF: β = −0.49, 95% CI = [−0.87, −0.11], OEF²: β = 0.01, 95% CI = [0.00, 0.01]), indicating a U-shaped association between OEF and cognition. Notably, when CBF was high, cognition was relatively preserved even under higher OEF. In summary, OEF emerged as a sensitive marker of cognitive vulnerability in community-based seniors, particularly in attention, executive function, visuospatial ability, and memory, while CBF was the primary determinant of WMH burden. Combined OEF CBF patterns enabled classification of at-risk community-dwelling individuals, with the ‘misery perfusion’ pattern (high OEF, low CBF) showing the most adverse profile and representing a promising target for early risk stratification.

Yan et al. report that in community-dwelling older adults, higher cerebral oxygen extraction with lower cerebral blood flow (‘misery perfusion’) is associated with greater white matter hyperintensity burden and poorer cognitive performance, whereas better matching of blood supply to oxygen use relates to healthier brain structure and neurocognitive function.

Graphical AbstractFor image description, please refer to the figure legend and surrounding text.