Risk factors for long-term non-motor symptoms and quality of life following subthalamic nucleus deep brain stimulation (STN DBS) have not yet been fully identified. In the present study, we investigated the impact of motor symptom asymmetry in Parkinson’s disease. Data were extracted for 52 patients with Parkinson’s disease (half with predominantly left-sided motor symptoms and half with predominantly right-sided ones) who underwent bilateral STN and a matched healthy control group. Performances for cognitive tests, apathy and depression symptoms, as well as quality-of-life questionnaires at 12 months post-DBS were compared with a pre-DBS baseline. Results indicated a deterioration in cognitive performance post-DBS in patients with predominantly left-sided motor symptoms. Performances of patients with predominantly right-sided motor symptoms were maintained, except for a verbal executive task. These differential effects had an impact on patients’ quality of life. The results highlight the existence of two distinct cognitive profiles of Parkinson’s disease, depending on motor symptom asymmetry. This asymmetry is a potential risk factor for non-motor adverse effects following STN DBS.