Journal of Alzheimers Disease & Parkinsonism
Open Access

Parkinson’s disease is a progressive neurological condition characterized by motor impairment. Predisposing to these motor symptoms is the degeneration of dopaminergic neurons within the basal ganglia [1]. Over the last 15 years, there has been a growing consensus within the scientific community that an inherent link involving the brain and the gut exists. First proposed by Braak, et al. a change in the healthy synergistic microbial composition of the gut to a more pathogenic profile may lead to aggregation of α-synuclein enriched Lewy bodies. These Lewy bodies then transcend up the nervous system and deposit within the dopaminergic neurones of the brain, leading to neocortical changes [2].

It is clear patients suffer from a variety of GIT symptoms [3,4]. However, few studies have estimated the prevalence and severity of GIT symptoms in early-stage disease. As per Braak’s hypothesis, if GIT symptoms are present in the early stages, it may firstly be used to identify patients in the prodromal stages and secondly perhaps provide a clearer indication of the disease progression.

This study aims to provide evidence to the body of information supporting the development of PD from within the GIT and further add to the limited studies aimed at investigating the prevalence of these symptoms in the early stages of the disease. Building and researching this topic further could be imperative as it may lead to earlier diagnosis with new and improved treatments for patients.

Patients were recruited from the Neurology Clinics in a tertiary care centre in Norfolk, United Kingdom. Potential participants were screened during their clinic appointment with suitability based on the clinical history, disease staging and eligibility for the study. Participants aged between 50 and 90 years old who fit the inclusion and exclusion criteria (Table 1) were included in this study. All participants in the patient group had a clinical diagnosis of PD and all patients selected were on some form of medication treatment for their PD. The study was approved by the national ethics committee and all subjects involved provided informed consent.

Table 1: Inclusion and Exclusion Criteria.

Clinical assessments firstly involved the Hoehn and Yahr scale [5] to recruit patients in the early-stages of their disease. A common validated scale used to measure the progression of Parkinson’s symptoms and the level of disability, early-stage was defined as any patient diagnosed with PD and a Hoehn and Yahr Stage of I or II. Stage I was defined as symptoms on one side only (unilateral) and Stage II was defined as symptoms on both sides (bilateral) but with no impairment of balance.

The Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) [6] is a common validated scale used to follow the longitudinal progression of PD. It consists of 5 different scales which together provide a comprehensive evaluation of the condition. For this study, we used Part III of the UPDRS, the evaluation of motor function. An 18-point examination was completed by a consultant neurologist in an outpatient clinic setting, each item was rated from 0 to 4 where 0=normal, 1=slight, 2=mild, 3=moderate, and finally 4=severe.

In order to assess the prevalence of gastrointestinal symptoms, the gastrointestinal symptom rating scale was used [7]. Normally used for IBS and dyspepsia, this questionnaire was modified from 15 to 8 symptoms to make it more PD relevant. The symptoms removed were: Nausea and Vomiting, Abdominal Rumbling, Abdominal Sucking Sensations, Eructation or Belching, Flatus, Diarrhoea, Acid Regurgitation and Increased Passage of Stools. Dysphagia, a common PD symptom, was added to our list of symptoms which included Constipation, Tenesmus, Gastro-Oesophageal Reflux, Abdominal Pain, Abdominal Bloating, Early Satiety and Stool Consistency. Each symptom was scored from either the severity or the frequency of the symptom, with each scale ranked from 0 to 3. The total score was calculated by adding all the scores together, therefore the maximum score for any one participant was 24.

Statistical analysis

The software programme G*Power 3.1 was utilised to calculate our sample size. Based on a similar study which investigated the prevalence of GIT symptoms in PD [8], we required at least 8 participants per group to detect a significant effect. This was under the assumption of 95% power for a one-sided α-level of .05, a mean gastrointestinal rating score of 25.43 and a standard deviation of 18.62. Demographic and biological data were analysed using the Statistical Package for the Social Sciences (SPSS; v25.0), applying standard statistical thresholds (p<0.05), corrected for multiple comparisons where appropriate. Correlational, multi-variate and multi-level regression analyses were used to examine relationships between GIT symptoms and clinical information.

Cohort description

For this study, we recruited a total of 21 participants, 12 early-stage PD patients and 9 controls (Table 2). The mean age for PD and controls was 70.7 ± 4.8 and 70.7 ± 6.6 years, respectively. PD group consisted of 8 males and 4 females with every participant in each group of White British ethnicity. For PD patients, the mean Hoehn and Yahr stage was 1.6 ± 0.5, mean motor UPDRS score was 25.3 ± 12.2 and mean duration since diagnosis was 31.7 ± 27.3 months. Finally, PD and control BMI (kg/m2) were 26.1 ± 5.8 and 29.8 ± 5.7. However, one participant from each group declined to provide information for height and weight and therefore we were unable to calculate BMI.

Table 2: Patient Baseline Characteristics (n=21).

All participants completed the PD-specific gastrointestinal tract questionnaire. For the PD group, the most common symptoms experienced by patients were the following: tenesmus (83.3%), constipation (58.3%), bloating (58.3%), reflux (50%), abdominal pain (41.7%), and hard stools (50%). Early satiety (16.7%) and dysphagia (8.33%) were experienced by the fewest number of patients. Tenesmus (p=0.006) and constipation (p=0.03) were the only symptoms to show statistically significant differences between PD and control groups. Binary logistic regression tests were used to determine the odds ratios for the prevalence of gastrointestinal symptoms between the two groups (Table 3). Tenesmus was the only GIT symptoms in PD did not correlate with age or gender. Amongst symptoms, a strong positive correlation was only observed between constipation and hard stools (r=0.708, p<0.001). PD duration correlated with early satiety (r=-0.588, p=0.04), but with no other GIT symptom.

Table 3: Prevalence and Odds Ratios for Gastrointestinal Symptoms between PD and Control groups.

Each gastrointestinal tract symptom was ranked by participants on a scale from 0 to 3 concerning either the frequency or the severity. The total GSRS mean scores for the Parkinson’s disease and control groups was 5.75 ± 3.36 and 2.22 ± 3.38, respectively. The total median GIT symptoms score for PD and Control was 7.0 (IQR 2.25 to 8.75) and 1.0 (IQR 0.0 to 4.50). These median results between the two groups were statistically significant too (p=0.02).

The mean scores for each gastrointestinal symptom are listed in Table 4. For PD patients, constipation, hard stools and tenesmus each had the highest mean frequency and severity score with 1.25. The highest mean scores for controls were reflux (0.67) and bloating (0.44).

Table 4: Mean Gastrointestinal Tract Symptoms frequency and severity in PD and Control Groups.

Pearson’s Correlation test was used to determine the association between the total gastrointestinal symptoms questionnaire score and the UPDRS motor score. A weakly positive correlation was present (r=0.278), however, the result was not statistically significant (p=0.38).

Of the PD participants recruited for this study, 5 had Stage I and 7 had Stage II disease. The mean Hoehn and Yahr scale for participants was 1.58 ± 0.52. Patients with Stage I reported symptoms as follows: tenesmus (80%), constipation (80%), hard stools (80%), bloating (60%), early satiety (40%), reflux (40%) abdominal pain (20%) and dysphagia (0%). Stage II participants reported all symptoms, but most common were tenesmus (85.7%), reflux (57.1%), abdominal pain (57.1%) and bloating (57.1%).

Despite these promising findings, the study has several limitations. Firstly, despite meeting our power calculation, ideally we would have recruited a high volume of patients and therefore recommend a study with a larger sample from both PD and control populations. Secondly, the cross-sectional nature of the study could be considered a limiting factor. We collected data at one moment of time and therefore unable to establish a cause and effect relationship. Ideally, a prospective cohort study over a lengthened period would be suitable to calculate risk and identify any factors which predispose to PD. Thirdly, bias could arise from the unequal distribution of confounding factors and participant self-reporting. Finally, all participants for our study were of White British ethnicity which is expected due to the ethnic composition of Norfolk, as a result, this may reduce the generalisability of the findings.

To summarise, patients with early-stage PD suffered from a variety of gastrointestinal tract symptoms with reported increased prevalence of lower gastrointestinal tract compared with the upper gastrointestinal tract. These results could suggest a possible pathophysiological link seen within the gut and in particular with Braak’s hypothesis. We recommend further assessment of GIT symptoms involving the timing of symptoms in relation to the onset of diagnosis. We also propose all patients in the early-stages should be appropriately screened with a GIT questionnaire to allow prompt recognition of symptoms and thus provide effective treatments in the overall management of Parkinson’s disease.