Background: Performing aerobic exercise and maintaining high levels of aerobic fitness may have positive effects on both brain structure and function in older adults. Despite decades of research however, there is still a rather poor understanding of the neurocognitive mechanisms explaining the positive effects of aerobic exercise on cognition. Changes in prefrontal gray matter as well as dopaminergic neurotransmission in striatum are both candidate neurocognitive mechanisms. The main aims of this thesis are: 1. To investigate the effects of aerobic exercise and fitness on cognition and magnetic resonance imaging (MRI) derived gray matter volumes using data from a 6 month physical exercise intervention in older adults (Study I). 2. To simulate the effect of atrophy in longitudinal positron emission tomography (PET) which could pose a challenge to interpreting changes in longitudinal PET imaging (Study II). 3. To study the influence of aerobic exercise and fitness on the dopamine D2-receptor (D2R) system in striatum using [11C]raclopride PET as a potential mechanism for improved cognition (Study III). Results: In Study I, aerobic exercise was found to improve cognitive performance in a broad, rather than domain-specific sense. Moreover, aerobic fitness was related to prefrontal cortical thickness, and improved aerobic fitness over 6 months was related to increased hippocampal volume. In Study II, we identified areas in the striatum vulnerable to the effect of shrinkage, which should be considered in longitudinal PET imaging. Finally, in Study III, the effect of being aerobically fit, and improving fitness levels was found to impact dopaminergic neurotransmission in the striatum, which in turn mediated fitness-induced improvements in working memory updating performance. Conclusion: The findings in this thesis provide novel evidence regarding the neurocognitive mechanisms of aerobic exercise-induced improvements in cognition, and impacts the interpretation of longitudinal PET imaging. Performing aerobic exercise and staying aerobically fit at an older age have positive effects on cognition and brain systems important for memory and cognition. Specifically, fitness-induced changes to the dopaminergic system stands out as one novel neurocognitive mechanism explaining the positive effects of aerobic fitness on working-memory performance in healthy older adults.

Multi-site MRI studies collect large amounts of data in a short time frame. Large sample sizes are desirable to address power and replicability issues that have been problematic for scientists in the past. Although multi-site MRI solves the sample size problem, it brings with it a new set of challenges. Scanning the same person at different sites might result in differences in MRI derived measurements. In this thesis we compared three approaches to facilitate the analysis of multi-site MRI data: quantitative R1 mapping, adding site as a covariate in a linear model, and using the ComBat method. We also investigated the relationship between two common MRI measurements: signal and volume. We collected data from 64 healthy participants across 3 GE scanners and 1 Siemens scanner at 3T. We found that signal intensity was different between vendors whereas volume was not. Our R1 method resulted in values that were different across vendor and significantly lower than those reported in the literature. B1+ maps used to calculate R1 were different across sites. Using a scale factor, we were able to compensate for mistakes in R1 mapping. We also found that adding site as a covariate corrected mean differences in signal intensity across sites, but not differences in variance. The ComBat method gave best similarity between sites. However, since different people were scanned at each site, we couldn’t evaluate the effectiveness of each method as variation in the data could have been due to site effects or heterogeneity in participants. White matter volume and signal intensity in the white matter were correlated in males but not in females. We found that this low correlation was caused by outliers in our female sample. The correlation between white matter volume and signal in males suggests that both metrics are measuring myelin and can be used as converging evidence to detect changes in brain myelination. / Thesis / Master of Science (MSc)