Brain oxygen extraction and neural tissue susceptibility are associated with cognitive impairment in older individuals

Abstract

Background and Purpose:We investigated the effects of aging, white matter hyperintensities (WMH), and cognitive impairment on brain iron levels and cerebral oxygen metabolism, known to be altered in Alzheimer's disease (AD), using quantitative susceptibility mapping and MR-based cerebral oxygen extraction fraction (OEF). Methods:In 100 individuals over the age of 50 (68/32 cognitively impaired/intact), OEF and neural tissue susceptibility (χ n ) were computed retrospectively from MRI multi-echo gradient echo data, obtained on a 3 Tesla MRI scanner. The effects of age and WMH on OEF and χ n were assessed within groups, and OEF and χ n were assessed between groups, using multivariate regression analyses.Results: Cognitively impaired subjects were found to have 19% higher OEF and 34% higher χ n than cognitively intact subjects in the cortical gray matter and several frontal, temporal, and parietal regions (p < .05). Increased WMH burden was significantly associated with decreased OEF in the cognitively impaired, but not in the cognitively intact.Older age had a stronger association with decreased OEF in the cognitively intact group.Both older age and increased WMH burden were significantly associated with increased χ n in temporoparietal regions in the cognitively impaired.Conclusions: Higher brain OEF and χ n in cognitively impaired older individuals may reflect altered oxygen metabolism and iron in areas with underlying AD pathology. Both age and WMH have associations with OEF and χ n but are modified by the presence of cognitive impairment.

Research Progress on MRI for White Matter Hyperintensity of Presumed Vascular Origin and Cognitive Impairment

“…The OEF of cognitively impaired subjects was higher than that of those with cognitive integrity. The increase of WMH load in cognitive impairment subjects was significantly correlated with the decrease of OEF, but not in the cognitively intact ( 68 ).…”

“…In addition, in concentric contours close to WMH, OEF gradually increased, and CBF decreased ( 66 ). WMH is related to OEF, but it will change due to the existence of cognitive impairment ( 68 ). The lower the OEF, the more severe the cognitive impairment, possibly due to reduced oxygen consumption resulting from reduced neural activity ( 67 ).…”

“…The lower the OEF, the more severe the cognitive impairment, possibly due to reduced oxygen consumption resulting from reduced neural activity ( 67 ). The recent studies have shown that WMH is related to OEF, but it will change due to the existence of cognitive impairment ( 68 ). The OEF of cognitively impaired subjects was higher than that of those with cognitive integrity.…”

Cerebral oxygen metabolism from MRI susceptibility

“…QQ-based OEF further showed higher OEF in the QSM hyperintense rim within choric active MS lesions than the rest of the lesions, which agrees with active inflammation in the rim. In dementia ( Chiang et al, 2022 ), QQ-based OEF showed positive associations with white matter hyperintensity, an important predictor of dementia. Also, QQ showed OEF abnormalities in brain tumor ( Shen et al, 2021 ) and preeclampsia ( Yang et al, 2022 ).…”

“…One study ( Chiang et al, 2022 ) combined QSM with qBOLD to assess OEF in clinical cohorts of cognitively impaired and healthy elderly subjects. Based on the hypothesis that cognitive impairment and dementia are predicted by age and white matter hyperintensities, this study investigated the effect of these two factors on OEF.…”