3.1 Patients
Demographic information was available for only 2,895 of the 15,119 dialogues analyzed. In that data, most patients were over the age of 50 (86%), with patients between 60 and 70 years old forming the largest group (33.1%). The mean age (±standard deviation) of patients was 63 years (±13.4). Demographic data is represented in Table 2.
Table 2. Demographics
Age Group (years)
|
Participants (n, %)
|
<50
|
405 (14.0%)
|
50–60
|
586 (20.2%)
|
60–70
|
957 (33.1%)
|
>70
|
947 (32.7%)
|
Total:
|
2895 (100%)
|
3.2 Share of Voice and Change of Overall Symptoms
Symptom SOV representing the proportion of dialogues mentioning a given symptom, is depicted in Figure 1. In line with their role as cardinal symptoms, motor symptoms had the highest SOV. Non-motor symptoms also had a significant SOV. The SOV for occurrence of motor symptoms was 79% in 2018, with no growth from 2016 (p = 0.5). The SOV for non-motor symptoms was high at 62% in 2016, reaching 69% in 2018, a statistically significant 7% increase from 2016 (p < 0.01). The SOV for occurrence of motor complications was 9% in 2018, with 6% growth from 2016 (p < 0.01). Motor symptoms maintained a significantly larger SOV than non-motor symptoms and motor complications in every year, (p < 0.01), as did the SOV of non-motor symptoms compared to motor complication SOV (p < 0.01). See Table 3, Table 4 and Table 5 for comparison.
For the details of major motor and non-motor symptoms, see Table 6 and Table 7, respectively. Canonical motor symptoms, like tremors (52.7%), stiffness (29.5%), difficulty walking/slow movement (24.5%), and problems turning over (13.9%) were the most commonly mentioned motor symptoms. Gait postural instabilities (79.3%), falling (16.6%), problems turning over (15%), difficulty walking/slow movement (8.9%) and stiffness (8.0%) all showed increases across the sample period (p < 0.01) with reduced facial expression decreasing by 18.2% (p < 0.01). Changes in tremor, unclear enunciation and speech disorder were all non-significant.
Table 3. Motor Symptoms vs. Non-motor Symptoms Across a Three-Year Period
Year
|
Motor symptom
|
Non-motor symptom
|
p-value
|
2018 (N=2397)
|
79%
|
69%
|
< 0.01
|
2017 (N=5198)
|
76%
|
66%
|
< 0.01
|
2016 (N=7524)
|
79%
|
62%
|
< 0.01
|
Table 4. Non-motor Symptoms vs. Motor Complications Across a Three-Year Period
Year
|
Non-motor symptom
|
Motor complications
|
p-value
|
2018 (N=2397)
|
69%
|
3%
|
< 0.01
|
2017 (N=5198)
|
66%
|
6%
|
< 0.01
|
2016 (N=7524)
|
62%
|
9%
|
< 0.01
|
Table 5. Motor Symptoms vs. Motor Complications Across a Three-Year Period
Year
|
Motor symptom
|
Motor complications
|
p-value
|
2018 (N=2397)
|
79%
|
3%
|
< 0.01
|
2017 (N=5198)
|
76%
|
6%
|
< 0.01
|
2016 (N=7524)
|
79%
|
9%
|
< 0.01
|
Table 6. Overall Motor Symptoms Composition Across a Three-Year Period
Type
|
Symptom
|
2016
|
2017
|
2018
|
2016-2018 CAGR*
|
p-value
|
Tremor
|
Tremor
|
55.6%
|
51.9%
|
52.7%
|
-2.6%
|
0.03
|
Rigidity
|
Stiffness
|
25.3%
|
24.6%
|
29.5%
|
+8.0%
|
<0.01
|
Problems turning over
|
10.5%
|
11.6%
|
13.9%
|
+15.0%
|
<0.01
|
Bradykinesia
|
Difficulty walking/slow movement
|
20.7%
|
19.2%
|
24.5%
|
+8.9%
|
<0.01
|
Reduced facial expression
|
4.5%
|
3.0%
|
3.0%
|
-18.2%
|
<0.01
|
Unclear enunciation
|
3.0%
|
2.2%
|
2.8%
|
-2.0%
|
0.35
|
Speech disorder
|
0.8%
|
0.7%
|
1.0%
|
+14.4%
|
0.25
|
Postural Instability
|
Falling
|
7.3%
|
7.8%
|
9.9%
|
+16.6%
|
<0.01
|
Gait postural instabilities
|
1.6%
|
2.7%
|
5.1%
|
+79.3%
|
<0.01
|
*CAGR, compounded annual growth rate
For non-motor symptoms, pain (25.8%), constipation (12.1%), frequent urination (11.8%), and depression (11.4%) had the largest SOV. The largest increases in symptom mentions were in anxiety (70.6%, p < 0.01) and olfactory disorders (64.5%, p < 0.01), followed by RBD (37.3%, p < 0.01). In general, there was a larger increase in the mention of non-motor symptoms over the reported period compared to the change of SOV for motor symptoms.
Table 7. Overall Non-motor Symptoms Composition Across a Three-Year Period
|
Symptom
|
2016
|
2017
|
2018
|
2016–2018
CAGR*
|
p-value
|
Sleep and Sensory Disorders
|
Pain
|
24.4%
|
25.2%
|
25.8%
|
+2.9%
|
0.15
|
Frequent urination
|
7.5%
|
8.6%
|
11.8%
|
+25.8%
|
<0.01
|
Insomnia
|
6.2%
|
6.3%
|
8.9%
|
+20.0%
|
<0.01
|
RBD
|
3.9%
|
5.1%
|
7.4%
|
+37.3%
|
<0.01
|
Poor sleep quality
|
5.4%
|
5.6%
|
5.7%
|
+2.4%
|
0.34
|
Excessive Daytime Sleepiness
|
3.8%
|
4.1%
|
5.6%
|
+20.9%
|
<0.01
|
Numbness
|
4.9%
|
4.2%
|
5.0%
|
+1.4%
|
0.44
|
Spasm
|
3.7%
|
3.8%
|
3.6%
|
-1.6%
|
0.43
|
Olfactory disorder
|
0.9%
|
1.0%
|
2.5%
|
+64.5%
|
<0.01
|
Cognitive and Psychiatric Disorders
|
Depression
|
6.1%
|
7.0%
|
11.4%
|
+36.2%
|
<0.01
|
Hallucinations
|
7.2%
|
9.1%
|
10.0%
|
+18.1%
|
<0.01
|
Dementia
|
5.7%
|
6.3%
|
9.1%
|
+26.6%
|
<0.01
|
Anxiety
|
2.4%
|
3.3%
|
6.9%
|
+70.6%
|
<0.01
|
Slow reaction
|
2.0%
|
2.0%
|
3.4%
|
+31.4%
|
<0.01
|
Other psychiatric issues
|
1.2%
|
1.1%
|
1.3%
|
+4.7%
|
0.39
|
Autonomic Disorders
|
Constipation
|
7.9%
|
8.4%
|
12.1%
|
+23.9%
|
<0.01
|
Other gastrointestinal dysfunctions
|
6.8%
|
8.3%
|
8.1%
|
+9.5%
|
0.06
|
Drooling
|
4.9%
|
4.8%
|
5.9%
|
+9.6%
|
0.08
|
*CAGR, compounded annual growth rate
3.3 Share of Voice and Change of Nocturnal Symptoms
Nocturnal symptoms, which included all motor and non-motor symptoms and motor complications that occurred at night, can be seen in Table 8. Overall, they had a SOV of 45% in 2018, growing by a compounded annual growth rate (CAGR) of 6% from 2016 (p < 0.01). In 2018, the SOV for individual nocturnal symptoms ranged from 0.8% to 16%. Rigidity, specifically difficulty turning over (16%), insomnia (8.9%) and night tremors (8.7%), had the highest SOV of all nocturnal symptoms in 2018. Difficulty breathing (52.2%) and morning pain (51.0%) had the highest increases in SOV over the 3-year period but remained low in overall SOV. Of interest was the substantial SOV held by sleep-related disturbances (insomnia, RBD, poor sleep quality and frequent nocturia), which corresponded to the fact that symptoms with high SOV tend to result in disruptions of normal sleep. Overall, nocturnal symptoms had a strong tendency to increase over the reported period. Only poor sleep quality and nocturnal spasm did not significantly increase over time (p = 0.34 and p = 0.38, respectively).
Table 8. Nocturnal Motor and Non-motor Symptoms Composition Across a Three-Year Period
Symptom
|
2016
|
2017
|
2018
|
2016–2018
CAGR*
|
p-value
|
Overall Nocturnal Symptoms
|
39%
|
41%
|
45%
|
+6.0%
|
<0.01
|
Rigidity/difficulty turning over
|
11.9%
|
12.8%
|
16.0%
|
+16.0%
|
<0.01
|
Insomnia
|
6.2%
|
6.3%
|
8.9%
|
+20.0%
|
<0.01
|
Night tremor
|
7.0%
|
6.8%
|
8.7%
|
+11.2%
|
0.02
|
RBD
|
3.9%
|
5.1%
|
7.4%
|
+37.3%
|
<0.01
|
Nocturnal pain
|
5.3%
|
5.9%
|
7.3%
|
+17.3%
|
<0.01
|
Poor sleep quality
|
5.4%
|
5.6%
|
5.7%
|
+2.4%
|
0.34
|
Excessive Daytime Sleepiness
|
3.8%
|
4.1%
|
5.6%
|
+20.9%
|
<0.01
|
Frequent nocturia
|
2.9%
|
3.6%
|
5.3%
|
+35.6%
|
<0.01
|
Hallucinations
|
1.6%
|
2.1%
|
2.5%
|
+26.9%
|
0.03
|
Morning pain
|
0.6%
|
1.0%
|
1.4%
|
+ 51.0%
|
<0.01
|
Nocturnal spasm
|
1.1%
|
1.0%
|
1.2%
|
+ 8.2%
|
0.38
|
Difficulty breathing
|
0.3%
|
0.5%
|
0.8%
|
+ 52.2%
|
0.02
|
*CAGR, compounded annual growth rate
3.4 Negative Sentiment of Overall Symptoms and Nocturnal Symptoms
Figure 2 shows a graph of symptoms and their corresponding negative sentiment. In Panel A, all PD symptoms that featured as keywords are shown with their associated negative sentiment score. The symptom group with the highest SOV (motor symptoms) had the lowest average negative sentiment. Non-motor symptoms had higher scores of negative sentiment on average, and a greater range of ratings. Psychiatric symptoms like depression (8.5) and anxiety (7.4) scored highest. See Table 9 for sentiment scores for selected overall motor and non-motor symptoms with higher SOV or sentiment scores for their category. Panel B, and Table 10, show the nocturnal symptom scores, some of which have no corresponding daytime equivalent (e.g. insomnia). Morning pain (5.3), fragmented sleep (4.8), and nocturnal pain (4.4) were particularly high scoring. For symptoms that can occur at either night or day, each nocturnal symptom was rated with a higher negative sentiment score than the same symptom across night and day combined, regardless of the type of symptom (motor, non-motor, or motor complication). Figure 3 shows the comparison of negative sentiment for the symptoms that can occur at either day or night. For the complete list of symptoms and their respective sentiment scores, see Supplementary Table 4.
Table 9. Overall sentiment scores for selected motor and non-motor (*) symptoms
PD Symptom
|
Score
|
Depression*
|
8.5
|
Anxiety*
|
7.4
|
Apathy*
|
5.0
|
Olfactory disorder*
|
3.9
|
Restless Legs Syndrome*
|
3.6
|
Pain*
|
3.5
|
Difficulty breathing*
|
3.4
|
Immobility
|
2.8
|
Hallucinations*
|
2.7
|
Excessive Daytime Sleepiness*
|
2.7
|
Difficulty turning over
|
2.6
|
Frequent urination*
|
2.6
|
Spasm *
|
2.6
|
Falling
|
2.3
|
Stiffness/rigidity
|
2.2
|
Tremors
|
1.6
|
Table 10. Sentiment scores for nocturnal motor and non-motor (*) symptoms
Nocturnal Symptom
|
Score
|
Morning pain*
|
5.3
|
Fragmented sleep*
|
4.8
|
Restless Legs Syndrome*
|
4.4
|
Nocturnal pain*
|
4.4
|
Difficulty breathing*
|
4.4
|
Insomnia*
|
3.5
|
Poor sleep quality*
|
3.5
|
Hallucinations*
|
3.5
|
Nocturnal spasm *
|
3.4
|
Frequent nocturia*
|
3.2
|
RBD*
|
3.1
|
Night tremor
|
2.8
|
Nocturnal Immobility/stiffness/rigidity
|
2.8
|
Excessive Daytime Sleepiness*
|
2.7
|