Journal of Parkinson’s Disease

α-synuclein is a lead Parkinson’s disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating α-synuclein in multiple tissues and biofluids in PD and healthy controls (HC).

To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study.

Participants underwent motor and non-motor clinical assessments, dopamine transporter SPECT, biofluid collection (cerebrospinal fluid, saliva, and blood), and tissue biopsies (skin, sigmoid colon, and submandibular gland). Biopsy adequacy was determined based on presence of adequate target tissue. Tissue sections were stained with the 5C12 monoclonal antibody against unmodified α-synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded.

The final cohort consists of 82 participants (61 PD, 21 HC). In 68 subjects (83%), all types of specimens were obtained but only 50 (61%) of subjects had all specimens both collected and evaluable for α-synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred.

Multicenter tissue and biofluid sampling for α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.

Parkinson’s disease (PD) shares pathological and clinical features with progressive supranuclear palsy (PSP) patients making the diagnosis challenging. Distinguishing PD from PSP is crucial given differences in disease course, treatment and clinical management.

Although some progress has been made in the discovery of biomarkers for PD and PSP, there is an urgent need to identify additional biomarkers capable of distinguishing between these diseases.

In this study, we tested the phosphatases DUSP8 and PTPRC for their diagnostic potential using quantitative PCR assays, in blood of 138 samples from participants nested in the Parkinson’s Disease Biomarkers Program.

Relative abundance of PTPRC mRNA was downregulated in PSP patients compared to PD and healthy controls, whereas there was no significant difference in the expression of DUSP8. Interestingly, PTPRC mRNA correlated with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score and MDS-UPDRS- part III, thus indicating it might be useful as part of a biosignature to stratify patients according to disease severity and progression.

Collectively, these results suggest that PTPRC expression may be useful for distinguishing PD from PSP patients as part of a biosignature. Evaluation of PTPRC along with additional biomarkers in a larger and well-characterized longitudinal study is warranted.

In Parkinson’s disease (PD), postural instability-gait disorder (PIGD) has been associated with more rapid cognitive decline, dementia, and greater non-motor symptom (NMS) burden.

To assess the importance of balance-gait disorder, relative to and in combination with other clinical measures, as a risk factor for cognitive impairment, dementia and NMS burden in PD.

164 PD subjects were evaluated in a retrospective cross-sectional study using the MDS-UPDRS scale, MMSE and Clinical Dementia Rating Scale. Using univariate comparisons followed by multiple stepwise regression, we identified factors most closely associated with NMS burden and concurrent dementia. Nominal logistic regression and linear discriminant analysis was used to compute receiver operating characteristic curves and to measure sensitivity and specificity of predictors of dementia.

Dementia was more frequent in those with the PIGD phenotype (χ² = 11.49, p = 0.003). The MDS-UPDRS balance-gait measure, excluding freezing of gait, was the single best predictor not only of concurrent cognitive impairment and dementia (F = 37.16, p < 0.001) but also of NMS burden, predicting 29% of the MDS-UPDRS total non-motor experiences of daily living score (F = 67.14, p < 0.0001). This measure, together with combined severity of hallucinations/psychosis, daytime sleepiness and urinary problems, a closely correlated symptom cluster (r = 0.63 p < 0.0001), accurately classified 84% of patients with dementia.

In PD, balance-gait impairment is closely associated with dementia and NMS burden, particularly the linked symptoms of cognitive impairment, psychosis, daytime sleepiness and urinary dysfunction. This phenotype characterizes patients likely to require closer surveillance and more comprehensive care. Confirmation of these findings in prospective longitudinal studies might help refine predictive algorithms designed to identify PD patients more likely to progress from mild cognitive impairment to dementia.

Whether dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are distinct disorders or two subtypes of the same entity, is not yet fully understood. There is a dearth of knowledge on differences in longitudinal clinical outcomes between DLB and PDD.

We aimed to compare longitudinal trend of cognitive decline, mortality, and their determinant factors between patients with DLB and PDD.

At baseline, we recruited 1110 DLB, and 764 PDD patients registered in the Swedish dementia registry (SveDem) during 2007–2015. Cognitive status was assessed at baseline and each follow-up visit by mini-mental state examination (MMSE). At least one follow-up MMSE was available for 411 (37.0%) DLB and 229 (30.0%) PDD patients. Rate of cognitive decline and mortality risk were compared between the two groups.

After an average of 2-years, the rate of cognitive decline did not differ between DLB (1.1 MMSE unit/year) and PDD (1.2 MMSE unit/year) groups (p = 0.970). There was no significant difference in the median survival time between DLB (4.0 years) and PDD (4.1 years) groups (Log rank p = 0.614). Antipsychotic drug use in DLB and larger number of medications in PDD were the most important determinants of faster annual cognitive decline.

Our findings from real-world clinical practice demonstrated that the rate of cognitive decline and mortality do not differ significantly between DLB and PDD at least over 2 years, yet, various factors might determine clinical outcome in these two groups. It seems that DLB and PDD are probably similar synucleinopathies, with phenotypical variations in the order of manifestations rather than course of progression and clinical outcome.

Arm swing changes are common even in the early stages of Parkinson’s disease (PD). We hypothesized that arm swing changes decrease with age and can be detected using a low-cost, RGB-D depth-sensing camera.

This study aimed to assess the differences in arm swing between PD patients and healthy participants and to investigate the possible effects of aging on these differences.

Twenty-five PD patients (aged 45–87 years) and 25 age-matched, healthy subjects (aged 46–88 years) were included. Clinical variables were evaluated using a descriptive analysis. No spatiotemporal variables were normally distributed; therefore, we used a Mann–Whitney U test to compare the continuous variables between groups and to perform age-stratified analysis. A receiver operating characteristic analysis was generated to evaluate the discrimination activity of arm swing asymmetry (ASA).

The PD group showed significant reductions in arm swing magnitude (left, p = 0.002; right, p = 0.006) and arm swing speed (left, p = 0.002; right, p = 0.004) and significantly greater ASA (p < 0.001). The age-stratified analysis showed significant differences in ASA in the 40–59-year group (p = 0.001) and bilateral arm swing magnitude in the 60–66-year group. No differences were found in those aged >67 years.

The camera detected differences in ASA, arm swing speed, and arm swing magnitude between PD patients and healthy individuals. Analysis of arm swing variables should be stratified by age, and the validity of the analysis may be questionable in patients aged >67 years.

Weight loss and small intestinal bacterial overgrowth (SIBO) are common in Parkinson’s disease (PD). We aimed to study the relationship between weight loss and SIBO in PD.

This was a cross-sectional study with a prospective, interventional component. Consecutive patients seen in the PD clinic who agreed to participate underwent extensive history, movement exam, SIBO breath testing and answered questionnaires. A subset of those in the weight loss group were treated with rifaximin for 14 days and returned 3 months later for an assessment of their weight, GI symptoms, quality of life and SIBO status. All analyses were adjusted for age and disease duration.

Fifty-one patients participated in the study; 37 without weight loss and 14 with weight loss. Total energy intake including the distribution of macronutrient intake was similar between groups while physical activity was less in those with weight loss. PD severity scores did not differ between groups; however, PD-specific quality of life scores were significantly worse for the summary index and the subscales of emotional well-being, social support and communication. The prevalence of constipation, dyspepsia and abdominal pain/discomfort was higher in those with weight loss. The prevalence of SIBO was 14% in the weight loss group and was not different between groups. Eight PD patients with weight loss were treated with rifaximin; no significant change in GI symptoms, quality of life or weight was seen 3 months later.

Although a number of differences were identified in quality of life and gastrointestinal symptoms between groups with and without weight loss, SIBO was not associated with weight loss in patients with PD. Given the exploratory nature and small number of patients with weight loss, however, further study is suggested.