Exercise engagement drives changes in cognition and cardiorespiratory fitness after 8 weeks of aerobic training in sedentary aging adults at risk of cognitive decline.

Background: With our aging population, many individuals are at risk of developing age-related cognitive decline. Physical exercise has been demonstrated to enhance cognitive performance in aging adults. This study examined the effects of 8 weeks of aerobic exercise on cognitive performance and cardiorespiratory fitness in sedentary aging adults at risk for cognitive decline. Methods: Fifty-two participants (age 62.9 ± 6.8, 76.9% female) engaged in eight weeks of moderate-to high-intensity exercise (19 in-person, 33 remotely). Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status, the Delis-Kaplan Executive Function System, and the Digit Span subtest of the Wechsler Adult Intelligence Scale (WAIS) Fourth Edition. Cardiorespiratory fitness was measured via heart rate recovery at minute 1 (HRR1) and 2 (HRR2), and exercise engagement (defined as percent of total exercise time spent in the prescribed heart rate zone). We measured pre and post changes using paired t-tests and mixed effects models, and investigated the association between cardiorespiratory and cognitive performance using multiple regression models. Cohen's d were calculated to estimate effect sizes. Results: Overall, 63.4 % of participants demonstrated high engagement (≥ 70% total exercise time spent in the prescribed heart rate zone). There were significant pre-post improvements in verbal fluency and verbal memory, and a significant decrement in working memory, but these were associated with small effect sizes (Cohen's d <0.5). Concerning cardiorespiratory fitness, there was a pre-to-post significant improvement in HRR1 (p = 0.01, d = 0.30) and HRR2 (p < 0.001, d = 0.50). Multiple regressions revealed significant associations between cardiorespiratory and cognitive performance, but all were associated with small effect sizes (Cohen's d < 0.5). Interestingly, there were significant between-group differences in exercise engagement (all p < 0.001), with remote participants demonstrating greater exercise engagement than in-person participants. Conclusion: Improvements in cognition and cardiorespiratory fitness were observed after 8 weeks of moderate to high-intensity exercise in aging adults. These results suggest that committing to a regular exercise regimen, even for a brief two-month period, can promote improvements in both cardiorespiratory fitness and cognitive performance, and that improvements are driven by exercise engagement.

Corticomotor plasticity as a predictor of response to high frequency transcranial magnetic stimulation treatment for major depressive disorder.

BACKGROUND: Many patients with treatment-resistant depression (TRD) respond to repetitive transcranial magnetic stimulation (rTMS) treatment. This study aimed to investigate whether modulation of corticomotor excitability by rTMS predicts response to rTMS treatment for TRD in 10 Hz and intermittent theta-burst stimulation (iTBS) protocols. METHODS: Thirteen TRD patients underwent two evaluations of corticomotor plasticity-assessed as the post-rTMS (10 Hz, iTBS) percent change (%∆) in motor evoked potential (MEP) amplitude elicited by single-pulse TMS. Following corticomotor plasticity evaluations, patients subsequently underwent a standard 6-week course of 10 Hz rTMS (4 s train, 26 s inter-train interval, 3000 total pulses, 120% of motor threshold) to the left dorsolateral prefrontal cortex. Treatment efficacy was assessed by the Beck Depression Inventory II (BDI-II) and Hamilton Depression Rating Scale (HAM-D). The change in MEPs was compared between 10 Hz and iTBS conditions and related to the change in BDI-II and HAM-D scores. RESULTS: Analyses of variance revealed that across all time-points, higher post-10 Hz MEP change was a significant predictor of greater improvement on the BDI-II (p < 0.001) and HAM-D (p = 0.022). This relationship was not observed with iTBS (p-values≥0.100). Post-hoc tests revealed the MEP change 20 min post-10 Hz was the strongest predictor of BDI-II improvement. LIMITATIONS: Cortical excitability was measured from the motor cortex, rather than the dorsolateral prefrontal cortex, where treatment is applied. The 10 Hz and iTBS protocols were performed at different intensities consistent with common practice. CONCLUSIONS: Modulation of corticomotor excitability by 10 Hz can predict response to rTMS treatment with 10 Hz rTMS.

Harnessing Neuroplasticity to Promote Brain Health in Aging Adults: Protocol for the MOVE-Cog Intervention Study.

BACKGROUND: Extensive evidence supports a link between aerobic exercise and cognitive improvements in aging adults. A major limitation with existing research is the high variability in cognitive response to exercise. Our incomplete understanding of the mechanisms that influence this variability and the low adherence to exercise are critical knowledge gaps and major barriers for the systematic implementation of exercise for promoting cognitive health in aging. OBJECTIVE: We aimed to provide an in-person and remotely delivered intervention study protocol with the main goal of informing the knowledge gap on the mechanistic action of exercise on the brain by characterizing important mechanisms of neuroplasticity, cardiorespiratory fitness response, and genetics proposed to underlie cognitive response to exercise. METHODS: This is an open-label, 2-month, interventional study protocol in neurologically healthy sedentary adults. This study was delivered fully in-person and in remote options. Participants underwent a total of 30 sessions, including the screening session, 3 pretest (baseline) assessments, 24 moderate-to-vigorous aerobic exercise sessions, and 3 posttest assessments. We recruited participants aged 55 years and above, sedentary, and cognitively healthy. Primary outcomes were neuroplasticity, cognitive function, and cardiorespiratory fitness. Secondary outcomes included genetic factors, endothelium function, functional mobility and postural control, exercise questionnaires, depression, and sleep. We also explored study feasibility, exercise adherence, technology adaptability, and compliance of both in-person and remote protocols. RESULTS: The recruitment phase and data collection of this study have concluded. Results are expected to be published by the end of 2021 or in early 2022. CONCLUSIONS: The data generated in these studies will introduce tangible parameters to guide the development of personalized exercise prescription models for maximal cognitive benefit in aging adults. Successful completion of the specific aims will enable researchers to acquire the appropriate expertise to design and conduct studies by testing personalized exercise interventions in person and remotely delivered, likely to be more effective at promoting cognitive health in aging adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT03804528; http://clinicaltrials.gov/ct2/show/NCT03804528. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/33589.