Hippocampal volume is established as biomarker for neurodegeneration in ageing-associated disorders. One of the remaining open questions in neuroscience is the link between hippocampus neurogenesis and its role in memory. The investigation of lifetime modifiable factors such as physical activity could enhance our understanding of age-related cognitive impairment, particularly in the context of exercise-induced increased rate of neurogenesis. Given that cardiovascular risk factors, education level and current depression influence the slope of cognitive decline, there is cumulating evidence of their complex interactions with impact on hippocampal volume. The aim of our study was to investigate the main effects of physical activity on hippocampus volume taking into account individuals cardio-vascular risk factors and mood. We studied a large-scale cohort from the general population (n=858) aged 45-85 years old alongside actimetry-based characteristics of gait and objectively measured cardiovascular risk factors. We describe a complex pattern of relationships between these variables with impact on hippocampus volume. We conclude with an interpretation of the obtained results in view of the role of physical activity in the adult hippocampal neurogenesis.