Worse Early Non-motor Symptoms Predict Faster Function Decline

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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The number and severity of non-motor symptoms increase during the early stages of Parkinson’s disease, and are significantly associated with age and motor symptoms, according to a study in China.

The findings showed that a higher non-motor symptom burden in early Parkinson’s was significantly associated with a faster progression of motor symptoms.

That suggests that non-motor symptoms could be used to predict motor function decline in early disease stages, according to researchers, who said these results provide additional insight into the progression of non-motor symptoms in early Parkinson’s.

Notably, one study finding showed that sexual dysfunction symptoms in these patients were reduced over time.

The study, “Longitudinal evolution of non-motor symptoms in early Parkinson’s disease: a 3-year prospective cohort study,” was published in the journal Npj Parkinson’s Disease.

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Nonmotor Symptoms of Parkinson’s Disease

Besides its well-known motor symptoms, Parkinson’s disease is characterized by non-motor symptoms, such as cognitive impairment, sleep disturbances, depression, and pain. People with the neurodegenerative disease also experience gastrointestinal, urinary, and sexual problems.

These non-motor problems may occur years before the onset of motor symptoms and “can greatly contribute to significant disability and reduced health-related quality of life,” the researchers wrote.

Previous studies on the progression of non-motor symptoms in Parkinson’s patients have provided inconsistent results. While some reported a significant increase in these symptoms over time in early Parkinson’s, another study found no major changes in the initial stages of the disease.

“Differences in genetic background, assessment tools, and study designs might have contributed to such discrepancies,” the researchers wrote, adding that “current evidence suggests that there are ethnic differences in the [non-motor symptom] burden.”

Now, a team of researchers in China evaluated, reportedly for the first time, the progression of non-motor symptoms in Chinese patients with Parkinson’s disease.

The analysis used the demographic and clinical data of 224 adults — 121 men and 103 women — with early Parkinson’s. The patients, living in West China, had been diagnosed in the previous three years and had undergone annual evaluations of motor and non-motor symptoms for up to three years.

The included patients had no signs of cognitive impairment, motor fluctuations, or involuntary muscle movements. Their mean age at enrollment was 57.6, and they had lived with the disease for a mean of 1.5 years. More than half (56.3%) had received no previous treatment.

The severity of their motor symptoms was evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) part III — with fast progression classified as an annual score increase of at least three points — and the Hoehn and Yahr Grade.

Non-motor symptoms were assessed with the Non-motor Symptoms Scale for Parkinson’s (NMSS), which covers nine areas: cardiovascular, sleep/fatigue, mood/apathy, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, sexual dysfunction (impairment), and miscellaneous.

A total of 195 patients (87.1%) completed the three annual visits.

The results showed that the number of non-motor symptoms increased over time in most areas, or domains, with patients having significantly higher scores in the sleep/fatigue, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, and miscellaneous domains after three years.

In turn, the number and score of sexual dysfunction symptoms in these patients were reduced over time. Notably, the number of patients reporting sexual problems dropped from the study’s start to three years (87 to 49 patients), and only six patients had persistent sexual dysfunction over the three years.

Also, the presence of sexual dysfunction was significantly associated with short disease duration, male sex, and higher levels of depression. There was no link between treatment changes and sexual dysfunction.

The team hypothesized that this reduction in sexual problems in early stage Parkinson’s may be related to the observed lower depression scores during follow-up and to potential underreporting. Specifically, patients may see these problems as normal with increasing age.

They also noted that further studies with longer follow-up, using validated, objective scales of sexual function, and considering additional influencing factors are needed to clarify changes in this non-motor symptom in all disease stages of Parkinson’s.

Given that not all non-motor symptom domains were worsened over time, their underlying biological mechanisms are likely different, the researchers noted.

Still, further analysis showed that changes in all NMSS domains had a small effect size from the study start to three years.

In addition, a higher number of non-motor symptoms was significantly linked to older age and higher UPDRS Part III score (worse motor symptoms).

A greater non-motor symptom burden was significantly associated with a faster motor symptom progression at one, two, and three years (up to a nine-point annual increase in UPDRS Part III score), after adjusting for potential influencing factors.

These findings highlighted that the progression of non-motor symptoms “is mild and multidimensional in the early phase of PD [Parkinson’s disease], and a high burden of [these symptoms] in the early phase accelerates the motor progression of [Parkinson’s],” the researchers wrote.

This information may help understand the longitudinal evolution of non-motor symptoms in Parkinson’s and inform future therapy studies and clinical trials targeting these symptoms, the team noted.