Biomarkers

Background: Cerebral metabolic rate of oxygen (CMRO₂) denotes the amount of O₂ that the brain consumes. Changes in CMRO₂ during aging and neurodegeneration have not been fully characterized. Using a non-invasive, non-contrast MRI CMRO₂ technique, the present study reports CMRO₂ changes in older adults from a total of 526 measurements, the largest CMRO₂ dataset to date.

Method: Experimental procedure: Analyses included 227 participants from the Biomarkers-for-Older-Controls-at-Risk-for-Dementia (BIOCARD) cohort. Figure 1 shows the demographic information. Participants were categorized into 3 diagnostic categories: cognitively normal individuals who remained cognitively normal (n=187), individuals who progressed from normal cognition to Mild Cognitive Impairment (MCI) or dementia during follow-up (n=13), and individuals with MCI/dementia at baseline (n=27). Participants were scanned on a 3T MRI (Philips) in a longitudinal study design. On average, participants had 2 scans (range = 1-4) collected over 3.1 years of follow-up. CMRO₂ was estimated from the arterio-venous difference in oxygen content, using a non-invasive MRI technique.

Data analysis: Linear mixed effect models were used to examine longitudinal changes in CMRO₂ over time, as well as the effect of impairment (MCI/dementia) on CMRO₂.

Result: In individuals who remained cognitively normal during follow-up (Figure 2), there was an increase in CMRO₂ over time (p<0.001), suggesting that the brain is "working harder" to compensate for its lower efficiency. However, the rate of increase in CMRO₂ was attenuated among individuals with higher baseline ages (p=0.039). There were also main effects of baseline age (p=0.001) and sex (p=0.014), indicating lower CMRO₂ levels among older than younger adults and among men than women. Next, we included participants who were cognitively impaired and those who progressed from normal cognition to cognitive impairment (Figure 3A). CMRO₂ was lower among progressors and impaired participants than those who remained normal (p=0.001). There was an interaction effect between time and diagnosis category (p=0.044), indicating that participants who were impaired at baseline or progressed to impairment showed a different pattern of CMRO₂ change over time compared to those who remained normal (Figure 3B).

Conclusion: CMRO₂ revealed a non-monotonic change in aging and cognitive impairment, suggesting a multi-factorial and/or multi-phase alteration of brain metabolism.