The <scp>O</scp>nset of <scp>N</scp>onmotor <scp>S</scp>ymptoms in <scp>P</scp>arkinson's disease (<scp>T</scp>he <scp>ONSET PD</scp><scp>S</scp>tudy)

Nonmotor symptoms (NMS) in Parkinson's disease (PD) can precede onset of motor symptoms. Relationship between premotor symptoms onset and motor features is limited. Our aim is to describe the presence and perceived onset of NMS in PD as well as their possible association with motor phenotype. Presence and onset of NMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls from 11 Spanish and Austrian centers. Seventeen of thirty-one NMS were more common in patients than controls (P < 0.05). They were usually mild and frequently reported to occur at different time-spans before motor symptoms. Anhedonia, apathy, memory complaints, and inattention occurred more frequently during the 2-year premotor period. Those reported more frequently in the 2- to 10-year premotor period were smell loss, mood disturbances, taste loss, excessive sweating, fatigue, and pain. Constipation, dream-enacting behavior, excessive daytime sleepiness, and postprandial fullness were frequently perceived more than 10 years before motor symptoms. No correlation between NMS burden and motor severity, age, or gender was observed. NMS associated in four clusters: rapid eye movement sleep behavior disorder symptoms-constipation, cognition-related, mood-related, and sensory clusters. No cluster was associated with a specific motor phenotype or severity. NMS are common in early unmedicated PD and frequently reported to occur in the premotor period. They are generally mild, but a patient subgroup showed high NMS burden mainly resulting from cognition-related symptoms. Certain NMS when present at the time of assessment or in the premotor stage, either alone or in combination, allowed discriminating PD from controls.