Introduction: Anxiety and depression are amongst the most common forms of mental illness, of whom 20-30% experience concomitant cardiovascular disease (CVD). Cardiorespiratory fitness (CRF) improves brain-derived neurotrophic factor (BDNF) potentially improving mental health and resilience. Unique barriers to increasing PA engagement exist in those with mental distress, contributing to CVD risk. Research strategies using guideline-based PA programming and motivation may enhance mental well-being, thereby mitigating CVD risk. Objective: To examine the effects of meeting weekly PA recommendations on levels of depression, anxiety, resilience, and associations with CVD risk factors in sedentary middle-aged adults. Methods: Sedentary adults (n=29, 40-60 years) completed a tailored 4-week MVPA regimen after establishing baseline CRF (VO 2 max) using an Astrand-Rhyming cycle ergometer test. Activity trackers (Mi Smart Band 6; Xiaomi) recorded heart rate (HR), and daily steps, along with motivational messaging. Mental health status was measured by pre- and post - brain-derived neurotrophic factor (BDNF) levels, and depression (BDI-II), and anxiety (BAI) scores. CVD risk factors included resting HR, systolic blood pressure (SBP), HbA1c, waist circumference (WC), body mass index (BMI), percent body fat, and lean body mass. Logistical regression determined if factors related to mental health affected achieving MVPA goal. Nonparametric analysis compared pre- and post-response to MVPA. Results: Percentage change of meeting the PA goal decreased by 29% (p=0.048) when the depression score increased by one point. When anxiety scores increased by one point, the likelihood of meeting PA goals increased by 41% (p=0.057). As the resilience score increased by one point, the percentage change of meeting PA goals increased by 17% (p=0.58). Of 29 participants, 19 (65.5%) exhibited no change depression level, two (6.9%) exhibited increased depression, and eight (27.6%) exhibited a decrease in depression. The BDNF decreased in those meeting PA goals, although platelets harbor significant BDNF content posing a profound confounding variable in measured plasma. Following MVPA average weight, BMI and fat mass decreased by 0.5 pounds, 0.11 kg/m 2 and 0.42 lbs., respectively. HbA1c decreased by 0.05% nearing significance (p=0.056). Significant improvements were observed in SBP by 5.44 mmHg (p=0.026) and resting HR (p=0.001). On average WC, fat free mass and VO 2 max increased by 0.61 cm, 9.44 kg/m 2 and 1.22 ml/kg/min respectively. Conclusions: MVPA consistent with the guidelines in middle-aged adults predicts improved anxiety and depression compared to sedentary behavior, likely improving cardiovascular health. A longer-term study to evaluate body composition and metabolic response to PA, in addition to further investigation of BDNF to assess its value in response to MVPA is currently warranted.
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