Longitudinal changes in cerebral metabolic rate of oxygen in older adults without and with cognitive impairment

Abstract Background Cerebral metabolic rate of oxygen (CMRO 2 ) denotes the amount of O 2 that the brain consumes. Changes in CMRO 2 during aging and neurodegeneration have not been fully characterized. Using a non‐invasive, non‐contrast MRI CMRO 2 technique, the present study reports CMRO 2 changes in older adults from a total of 526 measurements, the largest CMRO 2 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. CMRO 2 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 CMRO 2 over time, as well as the effect of impairment (MCI/dementia) on CMRO 2 . Result In individuals who remained cognitively normal during follow‐up (Figure 2), there was an increase in CMRO 2 over time (p<0.001), suggesting that the brain is “working harder” to compensate for its lower efficiency. However, the rate of increase in CMRO 2 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 CMRO 2 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). CMRO 2 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 CMRO 2 change over time compared to those who remained normal (Figure 3B). Conclusion CMRO 2 revealed a non‐monotonic change in aging and cognitive impairment, suggesting a multi‐factorial and/or multi‐phase alteration of brain metabolism.