Peak substrate oxidation and peak oxygen consumption are diminished in individuals with mild cognitive impairment
Authors: Rizzi Nicholas , Kramer Mary , DeConne Theodore , Ellison James , Lanzi Alyssa , Overstreet Matthew , Edwards David , Cohen Matthew , Johnson Curtis , Martens Christopher 
Published: May 2023

The number of persons with Alzheimer’s Disease (AD) is projected to double within the coming decades, placing great emphasis on identifying accessible risk factors. Prior to AD, there is an important transitional phase, called mild cognitive impairment (MCI), where individuals first display objective declines in cognitive functioning. Growing evidence suggests that the risk factors of AD and MCI adversely affect mitochondrial function, presenting a potential measure that may be useful in risk stratification. Metabolic flexibility represents the capacity of the mitochondria to oxidize a variety of fuel substrates (i.e., carbohydrates and fatty acids), and can be assessed using a graded exercise test. Thus, metabolic flexibility may be a useful index of mitochondrial health that can be evaluated prior to the development of clinical AD. OBJECTIVE: To determine whether cardiorespiratory fitness and metabolic flexibility are attenuated in older adults with MCI in response to a graded exercise test. HYPOTHESIS: We hypothesized that individuals with MCI would have similar baseline, but reduced peak oxygen consumption (VO2peak), fat oxidation (FatOx), and carbohydrate oxidation (CHOOx) compared to healthy controls. METHODS: 22 older adults with MCI and 21 sedentary healthy controls (HCs) matched for both age and sex underwent a modified Bruce Protocol treadmill test to assess VO2peak. FatOx and CHOOx were calculated based on ventilatory equivalents using the equations: FatOx = 1.67VO2 - 1.70VCO2 [L/min] and CHOOx = 4.585VO2 - 3.2255VCO2 [L/min], respectively. Unpaired t-tests were conducted to determine whether baseline or peak oxygen consumption, FatOx, and CHOOx were different between groups. RESULTS: The MCI and the HC groups were similar in age (73.5 + 8.81 vs. 71.2 + 6.33, p=0.33) and BMI (26.2 + 4.92 vs. 26.8 + 5.16, p=0.70). Baseline FatOx (0.09 + 0.03 vs. 0.10 + 0.05 g/min, p=0.47) and CHOOx (0.51 + 0.17 vs. 0.59 + 0.21 g/min, p=0.23) were not different between the MCI and HC groups. Peak FatOx (0.31 + 0.13 vs. 0.39 + 0.10 g/min, p=0.018*), and peak CHOOx (1.89 + 0.41 vs. 2.18 + 0.49 g/min, p=0.047*) were lower in the MCI group relative to HCs. Additionally, the MCI group had a lower absolute (1.32 + 0.33 vs. 1.61 + 0.47 L/min, p=0.027*), and relative (22.0 + 5.0 vs. 19.1 + 5.30 mL/kg/min, p=0.070) VO2peak, although the latter was not statistically significant. CONCLUSION: Peak FatOx, CHOOx, and absolute VO2peak are diminished in older adults with MCI, which may suggest impaired whole body mitochondrial capacity and metabolic flexibility. However, future studies are necessary to determine the exact physiological and behavioral components to these observed reductions. Supported by NIH Grants R01 AG058853 and K01 AG054731 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.