Relationships among cardiorespiratory fitness, brain age, and neurodegeneration in older adults with amnestic mild cognitive impairment

Background There is growing evidence that cardiorespiratory fitness (CRF) mitigates the likelihood of dementia caused by Alzheimer's disease and may underlie the cognitive benefits observed from aerobic exercise. Previous evidence further demonstrates neurodegeneration is the biological substrate for cognitive deterioration and younger brain age may protect the brain from the deleterious effects of neurodegeneration. However, little is known about the relationships between CRF, brain age, and neurodegeneration in older adults with amnestic mild cognitive impairment (aMCI). Objective The aim of this cross-sectional study was to examine associations between CRF, brain age, and neurodegeneration among individuals with aMCI, using baseline data from the Aerobic exercise and Cognitive Training (ACT) trial, which examined the cognitive effects and underlying mechanisms of a 6-month ACT in older adults with aMCI. Methods CRF was measured with peak oxygen uptake (VO 2peak ), from a symptom-limited peak cycle-ergometer test. Brain age and hippocampal volume were obtained from structural magnetic resonance imaging. Brain age was estimated using brainageR. Descriptive statistics and bivariate correlations were assessed. Linear regression models were used to analyze the relationships between CRF, brain age, and hippocampal volume, while adjusting for covariates. All analyses were conducted using R (version 4.3.2). Results The sample ( N = 141) averaged 73.66 ± 5.78 years of age, 16.91 ± 2.89 years of education, 27.46 ± 5.15 in BMI, and 23.49 ± 2.16 on Montreal Cognitive Assessment, with 53% male and 92.2% White. The mean brain age was 72.37 ± 7.89 years with 3157.31 ± 449.35 mm 3 hippocampal volume. No association was found between CRF, brain age, and hippocampal volume. Conclusions Future studies need to explore other brain indicators related to CRF. Trial Registry ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT03313895 , NCT03313895, October 18, 2017