Abstract - Gut check: Probiotics significantly improve gastrointestinal symptoms in Parkinson’s disease

Title: Gut check: Probiotics significantly improve gastrointestinal symptoms in Parkinson’s disease

Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara

Conference: 7th WPC, Phoenyx, AZ

 

Objective

To evaluate the efficacy of probiotics in alleviating gastrointestinal symptoms and motor outcomes in patients with Parkinson’s disease (PD).

Background

Constipation and gut dysbiosis are prevalent non-motor symptoms in PD, contributing to reduced quality of life and possibly influencing disease progression. Probiotics have been proposed as a therapeutic strategy to restore gut microbiota balance and improve bowel function, yet evidence remains fragmented.

Design/Methods

We conducted a systematic review and meta-analysis of placebo-controlled randomized trials indexed in PubMed. Eligible studies compared probiotics to placebo in PD patients. Outcomes included complete bowel movements (CBM) per week, Bristol Stool Scale (BSS), Patient Assessment of Constipation Quality of Life (PAC-QOL), and Unified Parkinson’s Disease Rating Scale part III (UPDRS-III). Random-effects models were applied to calculate pooled mean differences (MD) with 95% confidence intervals (CI).

Results

Five trials met inclusion criteria. Probiotics significantly increased CBM/week (MD = 1.34, 95% CI [1.04, 1.64], p < 0.001) and improved stool consistency (BSS score: MD = 0.59, 95% CI [0.36, 0.81], p < 0.001). Quality of life related to constipation improved markedly (PAC-QOL: MD = –13.94, 95% CI [–17.93, –9.95], p < 0.001). No significant effect was observed on motor function (UPDRS-III: MD = –1.50, 95% CI [–4.27, 1.27], p = 0.29). Heterogeneity was low across analyses, and publication bias was minimal.

Conclusions

Probiotics are effective in improving gastrointestinal symptoms and constipation-related quality of life in PD, with no clear impact on motor outcomes. These findings support probiotics as a safe adjunctive therapy for non-motor symptoms in PD.

Citation

Rissardo JP, Caprara ALF. Gut check: Probiotics significantly improve gastrointestinal symptoms in Parkinson’s disease. J Parkinsons Dis 2026;16(1_suppl):344-345. doi: 10.1177/1877718X261451755.

Figure 1. Forest plots show probiotics effects on CBM frequency, stool consistency, quality of life, and motor symptoms, with pooled mean differences, confidence intervals, and heterogeneity estimates.

Abstract - Parkinson’s disease risk in patients using metformin versus other antidiabetic agents: A meta-analysis of observational studies

Title: Parkinson’s disease risk in patients using metformin versus other antidiabetic agents: A meta-analysis of observational studies

Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara

Conference: 7th WPC, Phoenyx, AZ

 

Objective

To evaluate whether metformin use is associated with altered risk of Parkinson’s disease compared to other antidiabetic treatments.

Background

Emerging evidence suggests that type 2 diabetes mellitus may influence neurodegenerative processes, including Parkinson’s disease (PD). Metformin, a widely used antidiabetic drug, has been hypothesized to exert neuroprotective effects. However, comparative risk estimates across different glucose-lowering agents remain unclear.

Design/Methods

A systematic review and meta-analysis was conducted using PubMed-indexed observational studies comparing PD incidence among patients treated with metformin versus alternative antidiabetic therapies. Six studies (2012–2025) were included, encompassing over 500,000 participants. Risk ratios (RR) were pooled using a random-effects model (DerSimonian-Laird) with Mantel-Haenszel weighting. Subgroup analyses were performed by comparator drug class. Heterogeneity was assessed using I² and Cochran’s Q. Publication bias was evaluated via Egger’s test and trim-and-fill method.

Results

The overall pooled random-effects estimate showed no significant association between metformin use and PD risk (RR = 0.30; 95% CI: 0.47 to 1.08; p = 0.44), with substantial heterogeneity (Q = 284.07, p < 0.001). Subgroup analyses revealed reduced PD risk for metformin versus insulin (RR = 0.32; 95% CI: 0.05 to 0.95) and versus no-metformin (RR = 0.11; 95% CI: 0.59 to 0.92), but increased risk compared to SGLT2 inhibitors (RR = 1.17; 95% CI: 1.02 to 1.31). Trim-and-fill analysis suggested potential publication bias, with three missing studies and an adjusted effect estimate shifting toward null.

Conclusions

Metformin may confer differential PD risk depending on comparator therapy, with possible protective effects versus insulin and no-metformin, but higher risk compared to SGLT2 inhibitors. High heterogeneity and evidence of publication bias warrant cautious interpretation. Further prospective studies are needed to clarify metformin’s neuroprotective potential.

Citation

Rissardo JP, Caprara ALF. Parkinson’s disease risk in patients using metformin versus other antidiabetic agents: A meta-analysis of observational studies. J Parkinsons Dis 2026;16(1_suppl):71-72. doi: 10.1177/1877718X261451755.

Figure 1. Forest plot with subgroup analyses, L’Abbé and Galbraith plots assessing heterogeneity, effect size distribution, and comparative risks across metformin versus alternative therapies.

Abstract - Autoimmunity meets neurodegeneration: Is systemic lupus erythematosus protective against Parkinson’s disease?

Title: Autoimmunity meets neurodegeneration: Is systemic lupus erythematosus protective against Parkinson’s disease?

Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara

Conference: 7th WPC, Phoenyx, AZ

 

Objective

To evaluate whether systemic lupus erythematosus (SLE) is associated with an altered risk of Parkinson’s disease (PD) using evidence from population-based studies.

Background

Autoimmune mechanisms have been implicated in neurodegenerative disorders, but the relationship between SLE and PD remains unclear. Previous studies report conflicting results, warranting a systematic synthesis of available data.

Design/Methods

A meta-analysis was conducted following PRISMA guidelines. PubMed was searched for observational studies assessing the bidirectional association between SLE and PD. Data extracted included events and sample sizes for exposed (SLE) and control groups. Odds ratios (ORs) were pooled using Mantel–Haenszel methods under fixed and random-effects models. Heterogeneity was assessed with I² and Cochran’s Q. Publication bias was evaluated using Egger’s test and trim-and-fill analysis.

Results

Five studies met inclusion criteria. For SLE→PD, the fixed-effect model showed a significant association (OR = 0.78; 95% CI: 0.64–0.94; p = 0.01), suggesting a lower risk of PD among SLE patients. The random-effects model yielded a non-significant estimate (OR = 2.24; 95% CI: 0.71–6.99; p = 0.17) with high heterogeneity (I² = 95%). For PD→SLE, the fixed-effect model did not show association (OR = 1.24; 95% CI: 0.79–1.93). Trim-and-fill analysis indicated potential publication bias, with two missing studies and a substantial change in effect size (>150%). Fail-safe N calculations suggested susceptibility to bias.

Conclusions

Current evidence does not support a robust association between SLE and PD. While fixed-effect analysis suggests a protective trend, random-effects and bias assessments highlight uncertainty. Larger, well-controlled studies are needed to clarify this relationship.

Citation

Rissardo JP, Caprara ALF. Autoimmunity meets neurodegeneration: Is systemic lupus erythematosus protective against Parkinson’s disease?. J Parkinsons Dis 2026;16(1_suppl):68-69. doi: 10.1177/1877718X261451755.

Figure 1. Forest plots show bidirectional SLE–PD associations; Baujat and Galbraith plots identify heterogeneity contributors and outliers across studies.

Abstract - Association between Graves’ disease and Parkinson’s disease: A systematic review and meta-analysis

Title: Association between Graves’ disease and Parkinson’s disease: A systematic review and meta-analysis

Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara

Conference: 7th WPC, Phoenyx, AZ

 

Objective

To evaluate the bidirectional association between Graves’ disease (GD) and Parkinson’s disease (PD) using data from population-based studies.

Background

Emerging evidence suggests autoimmune thyroid disorders may influence neurodegenerative processes. Graves’ disease, characterized by hyperthyroidism and autoimmunity, could share pathogenic mechanisms with PD, including immune dysregulation and oxidative stress. However, the strength and direction of this association remain unclear.

Design/Methods

A systematic review was conducted using PubMed to identify observational studies assessing the relationship between GD and PD. Studies reporting incidence or prevalence of GD in PD patients or PD in GD patients were included. Data were pooled using Mantel–Haenszel odds ratios (OR) under fixed and random-effects models. Heterogeneity was assessed with I2 and Cochran’s Q. Publication bias was evaluated using fail-safe N methods.

Results

Three studies met inclusion criteria (Rugbjerg et al., 2009; Li et al., 2012; Cho et al., 2022), encompassing 392,280 participants and 1,398 events. For PD→GD (two studies), the fixed-effect pooled OR was 12.36 (95% CI: 9.79–15.61; p < 0.0001), indicating a significantly increased risk of GD among PD patients. Random-effects analysis showed OR 3.38 (95% CI: 0.30 to 10.49; p = 0.35) with high heterogeneity (I2 = 99.2%). For GD→PD (one study), the OR was 1.37 (95% CI: 1.21–1.56; p < 0.0001). Fail-safe N analyses suggested robustness against publication bias.

Conclusions

Our findings support a bidirectional association between GD and PD, with PD patients exhibiting a higher risk of GD and GD patients showing a modestly increased risk of PD. Shared autoimmune and neuroinflammatory pathways may underlie this link. Further longitudinal studies are warranted to clarify causality and mechanisms.

Citation

Rissardo JP, Caprara ALF. Association between Graves’ disease and Parkinson’s disease: A systematic review and meta-analysis. J Parkinsons Dis 2026;16(1_suppl):68. doi: 10.1177/1877718X261451755.

Figure 1. Forest plots show bidirectional PD–GD risk with pooled ORs; Baujat plot identifies study contributions to heterogeneity and overall effect.

Abstract - Quantitative Landscape Analysis of Disease-Modifying Parkinson’s Therapies in Preclinical Development

Title: Quantitative Landscape Analysis of Disease-Modifying Parkinson’s Therapies in Preclinical Development

Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara

Conference: Planning for prevention of Parkinson's and related synucleinopathies: A trial design forum 2026, Phoenyx, AZ

 

Objective

To quantitatively describe therapeutic modalities, biological targets, and development stages within the preclinical Parkinson’s disease (PD) therapeutic pipeline using structured data mining of the Parkinson’s Hope List.

Background

Parkinson’s disease remains without an approved disease-modifying therapy despite increasing mechanistic understanding. The expanding number of investigational programs underscores the need for quantitative synthesis to identify dominant translational priorities and emerging therapeutic strategies.

Design/Methods

The November 2025 Parkinson’s Hope List was systematically reviewed. All research-stage entries were extracted and standardized. Programs were categorized by development stage, therapeutic modality, and mechanistic target using structured fields and keyword-based annotation of mechanism descriptions. Descriptive analyses were performed to quantify distributions and cross-relationships among categories.

Results

A total of 114 unique Parkinson’s disease research-stage therapeutic programs were identified, all designated as disease-modifying. Eighty programs (70.2%) were classified as preclinical, while thirty-four (29.8%) were in discovery. Therapeutic modalities were redominantly new chemical entities, accounting for 83 programs (72.8%). Additional modalities included 13 gene therapy programs (11.4%), 9 cell-based therapies (7.9%), 6 repurposed agents (5.3%), and 3 reformulated compounds (2.6%).Mechanistic analysis identified 13 programs targeting alpha-synuclein aggregation, propagation, or clearance, 10 targeting lysosomal or GBA-related pathways, 7 targeting inflammatory signaling including inflammasome or toll-like receptor pathways, 5 targeting LRRK2, 5 addressing mitochondrial dysfunction or mitophagy, 6 targeting microbiome-related mechanisms, and 7 employing immunotherapeutic strategies such as antibodies, vaccines, or immune cell modulation. Of the 13 gene therapy programs, 3 focused specifically on GBA-related approaches, while others targeted PARKIN, Klotho signaling, or RNA-based mechanisms.

Conclusions

This quantitative analysis demonstrates that the current Parkinson’s disease therapeutic pipeline is heavily weighted toward early-stage, disease-modifying strategies, with substantial convergence on proteostasis, lysosomal biology, immune signaling, mitochondrial integrity, and gut-brain axis mechanisms. The dominance of preclinical programs and small-molecule approaches highlights both the breadth of innovation and the substantial translational distance remaining before clinical validation.

Citation

Rissardo JP, Caprara ALF. Quantitative Landscape Analysis of Disease-Modifying Parkinson’s Therapies in Preclinical Development. J Parkinsons Dis 2026:14-15. doi: 10.1177/1877718X261441451.

Figure 1. Sankey diagram illustrating flow of PD programs from discovery/preclinical stages to therapeutic modalities and mechanistic targets.

Retinal migraine

Retinal migraine

Ocular migraine

-Does not exist

Retinal migraine

Definition: rare form of migraine that causes temporary vision loss in 1 eye

Standing on the shoulders of giants

Standing on the shoulders of giants

Ruth H. Walker

-Reference in genetic chorea

-Intrigued by a family with chorea and normal HTT replication, led to identification of JPH3 gene, later nominated HDL2 chorea

Sarosh R. Irani

-Referenfce in LGI1

-Reviewed uncountable number of video EEG of patients that end-up dying until noticing the specific FBDS pattern

Lumbar puncture

Lumbar Puncture

Anatomy

“Some Spanish Students Ingest Lime-Flavored Drinks And Sip”

S: Skin

S: Subcutaneous tissue (superficial&deep fascia)

S: Supraspinous ligament

I: Interspinous ligament

L: Ligamentum flavum

F: (Epi)Fural space → remember this is the epidural space

D: Dura mater

A: Arachnoid mater

S: Subarachnoid space

Landmarks

-“Pop” = ligamentum flavum

-CSF after dura + arachnoid

Before LP

- Do neuroimaging (CT/MRI) before LP

>Neuroimaging/LP should not delay therapy

Needle types

-Atraumatic (pencil-point): Whitacre, Autocan, Eldor, Greene→ Lower PDPH

-Cutting needle: Quincke→ Higher PDPH risk

-Epidural needles: Tuohy, Crawford→ Do NOT enter subarachnoid space intentionally

Contraindications

Absolute

-⬆️ICP 2/2 mass

-VZV at lumbar site

-Coagulopathy (Plat < 50K, INR > 1.5, PTT > 45s)

-Suspect epidural abscess

Relative

-IC mass without inc ICP

-Coagulopathy that can be reversed (give Plat)

Regarding anti-thrombotics/ thromboprophylaxis

-Non-urgent vs urgent LPs

Interesting

- Clopidogrel→ no correlation P2Y12 & LP safety, still time should be used

Meningitis

Meningitis

Epidemiology

Mortality

-Highest mortality→ Listeria

-Highest number (overall)→ Strep pneumoniae

LGS

LGS

Management ASM

1st VPA + CLB

2nd add LMT

3rd everything (Rufinamide, TPM)

4th Fenfluramine, Cannabidiol, felbamate