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Abstract Motor symptom asymmetry, a key feature of Parkinson’s disease, has been associated with differences in non-motor symptoms, such as cognitive and neuropsychiatric impairments, and in biomarker profiles. However, the longitudinal relationship between biomarkers and non-motor symptoms as a function of motor symptom asymmetry remains to be fully explored in early-stage patients. Clinical data from the Parkinson’s Progression Marker Initiative was extracted from 179 patients showing predominantly left-sided motor symptoms and 234 patients showing predominantly right-sided motor symptoms during a 3-year follow-up. General estimating equations revealed differential relationships over time between biospecimen and cognitive-neuropsychiatric scores based on motor symptom asymmetry. A more important implication of uric acid and beta-amyloid was noted in patients with predominantly left-sided motor symptoms, whereas patients with predominantly right-sided motor symptoms showed associations with alpha-synuclein and phosphorylated-tau levels. In summary, asymmetry of motor symptoms influences clinical trajectories in early-stage patients, holding important implications for symptom management in this clinical population.
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