Nonmotor symptoms cluster in Parkinson’s disease patients

By Eleanor McDermid, Senior medwireNews Reporter

Nonmotor symptoms (NMS) tend to appear in specific clusters in patients with Parkinson’s disease (PD) and often predate the onset of motor symptoms, research shows.

The ONSET PD study involved 109 unmedicated patients with early PD recruited from Spanish and Austrian centres. At the time of study entry, which occurred a median of 11 months after the onset of motor symptoms and 1 month after PD diagnosis, 17 of 31 NMS were significantly more frequent in the patients than in 107 controls matched for age and gender.

The most common significant NMS in patients were smell loss, in 46%, mood disturbances in 43%, constipation in 38.5%, fatigue in 36%, heat/cold intolerance in 35% and anhedonia and memory complaints, both in 32%.

Patients had a median of eight NMS, whereas controls had just four. However, the overall burden of NMS was fairly low in most patients, except for a subgroup of about a quarter of the patients, who were mostly male and had prominent smell loss, constipation and mood-related symptoms.

Eduardo Tolosa (Hospital Clínic de Barcelona, Spain) and colleagues found that the NMS clustered in the PD patients, with the exception of smell loss, which did not associate with any other NMS. Mood symptoms (anhedonia, apathy and mood disturbances) clustered together, as did cognitive symptoms (memory complaints, inattention, fatigue and excessive daytime sleepiness) and sensory symptoms apart from smell (pain and taste loss).

However, symptoms indicative of REM sleep behaviour disorder (RBD; frequent nightmares and dream-enacting behaviour) clustered with constipation.

“An association between RBD symptoms and dysautonomia has been previously noticed and might reflect involvement of closely related brain regions by the pathological process”, note the researchers in Movement Disorders.

The PD patients reported that many of the NMS had preceded the onset of motor symptoms, with some, including constipation, heat/cold intolerance, postprandial fullness and frequent nightmares, having affected the patients for more than 10 years before the PD diagnosis. NMS clusters were also observed prior to motor symptom onset, with the RBD–constipation cluster, for example, being present less than 2 years, 2 to 10 years and more than 10 years before motor symptoms began.

The presence of various combinations of current NMS reached a specificity of 98% for discriminating between patients and controls, although they were not very sensitive. Likewise, premotor NMS distinguished between the two groups, with smell loss, constipation and dream-enacting behaviour achieving the best specificity.

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