Effects of Modafinil on Motor and Non‑Motor Outcomes in Parkinson’s Disease: A Meta‑Analysis of Randomized, Placebo‑Controlled Trials

Title: Effects of Modafinil on Motor and Non‑Motor Outcomes in Parkinson’s Disease: A Meta‑Analysis of Randomized, Placebo‑Controlled Trials

Authors: Amanda Lin, Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, and Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To determine the efficacy and safety of modafinil on motor and non-motor outcomes in Parkinson’s disease (PD) using evidence exclusively from randomized placebo‑controlled clinical trials (RCTs).

Background

Modafinil, a wakefulness-promoting agent with dopaminergic and non-dopaminergic mechanisms, is used to treat excessive daytime sleepiness (EDS) and fatigue in PD. However, clinical trial results have yielded inconsistent results, and its effects on motor and non‑motor outcomes remains unclear.

Design/Methods

A systematic review and meta-analysis of PubMed‑indexed RCTs evaluating modafinil in idiopathic PD were performed. Extracted outcomes included EDS (Epworth Sleepiness Scale – ESS), fatigue (Fatigue Severity Scale – FSS), motor function (MDS-UPDRS III and total scores), and depressive symptoms (Beck & Hamilton depression scales). Effect estimates were pooled using fixed and random‑effects models with REML, as appropriate. Standardized mean differences (SMD) and mean differences (MD) were applied. Adverse events were analyzed using relative risks (RR).

Results

Eight trials including 216 participants (modafinil = 113, placebo = 103) met inclusion criteria. Modafinil significantly improved EDS compared with placebo (MD −2.12 points; 95% CI −3.64 to −0.60; I² = 65%), though meta‑regression showed no association between treatment duration and response. No significant differences were observed in motor outcomes (SMD = 0.20; 95% CI −0.23 to 0.63). Modafinil did not significantly improve fatigue (MD = −0.17; 95% CI −1.12 to 0.79) or depressive symptoms (MD = 1.51; 95% CI −0.10 to 3.11) [Figure 3]. Adverse events, including insomnia (RR 0.72; 0.17–3.10), headache (RR 0.73; 0.21–2.50), dizziness (RR 1.69; 0.36–7.96), and gastrointestinal symptoms (RR 2.57; 0.53–12.48), were infrequent and did not differ significantly from placebo.

Conclusions

In RCTs involving PD patients, modafinil is associated with a modest improvement in EDS without significant effects on motor function, fatigue, or mood. The absence of motor worsening or significant adverse events supports short-term tolerability. However, heterogeneity across studies and limited sample sizes limit confidence in effect estimates. Larger, adequately powered trials are needed to clarify the clinical role of modafinil in PD.

Citation

Lin A, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Effects of Modafinil on Motor and Non‑Motor Outcomes in Parkinson’s Disease: A Meta‑Analysis of Randomized, Placebo‑Controlled Trials. Mov Disord 2026;41(Suppl_1):S1247-S1249.

Figure 1. Forest plot of pooled MD of EDS.

Figure 2. Forest plot of pooled SMD of motor outcomes.

Figure 3. Forest plot of pooled MD of depressive outcomes.

Comparative Motor Response to Bilateral STN‑DBS in LRRK2‑Related and Idiopathic Parkinson’s Disease

Title: Comparative Motor Response to Bilateral STN‑DBS in LRRK2‑Related and Idiopathic Parkinson’s Disease

Authors: Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, and Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To compare motor improvement after subthalamic nucleus deep brain stimulation (STN‑DBS) in patients with LRRK2‑associated Parkinson’s disease (PD) versus idiopathic PD (iPD).

Background

LRRK2 mutations (G2019S, R1441G, G2385R) represent the most common genetic cause of autosomal dominant PD. STN‑DBS generally improves motor symptoms in iPD, yet whether genetic status modifies treatment response remains unclear.

Design/Methods

A meta‑analysis was performed using PubMed studies reporting MDS UPDRS‑III outcomes in LRRK2‑PD versus iPD following bilateral STN‑DBS. Mean differences (MD) in MDS UPDRS‑III improvement (OFF-medication) were pooled using inverse‑variance methods under arandom‑effects model. Heterogeneity and subgroup analyses (G2019S, R1441G, G2385R) were conducted. Mixed‑effects REML meta‑regression examined whether age, DBS duration, or study quality moderated DBS outcomes.

Results

Seven studies (n=392; 73 LRRK2 carriers, 319 iPD) were included. There was no significant difference in MDS UPDRS‑III improvement between LRRK2‑PD and iPD using a random‑effects model (MD −3.26; 95% CI −8.81 to 2.29; I²=58%) [Figure 1][Figure 2]. Mutation subgroup analysis revealed no significant differences between G2019S, R1441G, or G2385R carriers (QM p=0.45). Meta‑regression identified DBS duration as the only significant moderator: duration categories explained most between‑study variability (R²=97.2%), reducing I² to 4% with no residual heterogeneity. Compared with 12 months, the 6–12 months group showed greater improvement (β=10.55±3.57, p=0.003), while the ≤6-months group showed a positive but nonsignificant trend (β=14.86±9.29, p=0.11). Age (p=0.84) and study quality (p=0.29) did not moderate outcomes.

Conclusions

Motor outcomes after STN‑DBS in LRRK2‑associated PD are comparable to those of iPD. No specific LRRK2 mutation subtype showed a differential response. DBS duration, rather than genotype, emerged as the only significant moderator of DBS motor benefit. This may reflect early optimization needs and later disability accrual, underscoring need for longer follow‑up. These findings support comparable DBS candidacy considerations for LRRK2‑PD and iPD.

Citation

Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Comparative Motor Response to Bilateral STN‑DBS in LRRK2‑Related and Idiopathic Parkinson’s Disease. Mov Disord 2026;41(Suppl_1):S1300-S1301.

Figure 1. Forest plot of pooled MD of motor outcomes.

Figure 2. Funnel plot with confidence intervals of the studies included.

Subthalamic Deep Brain Stimulation Produces Consistent Improvements in Sleep Quality and Daytime Sleepiness in Parkinson’s Disease: A Systematic Review and Meta-analysis

Title: Subthalamic Deep Brain Stimulation Produces Consistent Improvements in Sleep Quality and Daytime Sleepiness in Parkinson’s Disease: A Systematic Review and Meta-analysis

Authors: Mya C. Schiess, Juan D. Martinez-Lemus, Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, and Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

This study aims to determine the effects of subthalamic nucleus deep brain stimulation (STN‑DBS) on sleep quality and daytime sleepiness in Parkinson’s disease (PD).

Background

Sleep disturbances are among the most prevalent and disabling non‑motor symptoms (NMS) in PD. While STN‑DBS is an established therapy for motor symptoms, its impact on nocturnal sleep quality and daytime somnolence remains variably reported. The Parkinson’s Disease Sleep Scale (PDSS) and the Epworth Sleepiness Scale (ESS) provide validated frameworks for assessing distinct dimensions of sleep dysfunction.

Design/Methods

A systematic review and meta-analysis of longitudinal unilateral and bilateral STN‑DBS studies were conducted using PubMed-indexed articles. Nine studies reporting PDSS outcomes (n =286) and eight studies reporting ESS outcomes (n =190) were included. Extracted variables included sample sizes, mean change from baseline, standard errors, and follow-up duration. Data were synthesized using an inverse‑variance model with fixed‑effects. Heterogeneity was assessed using I² and tau², and prediction intervals were calculated.

Results

Most participants (93.68%) underwent bilateral STN‑DBS. STN‑DBS was associated with a significant pooled mean change from baseline in PDSS scores of 21.23 points (95% CI: 11.59 to 30.87) indicating substantial improvement in overall sleep quality [Figure 1]. Improvement peaked at six months. Heterogeneity was negligible (I² = 0%; tau² = 0), with a  prediction interval of 9.61 to 32.86.  ESS outcomes also improved significantly, with a pooled mean change from baseline of –3.62 (95% CI: –5.09 to –2.14) [Figure 2]. Heterogeneity for ESS was also minimal (I² = 0%; tau² = 0).

Conclusions

STN‑DBS yields robust and reproducible improvements in both nocturnal sleep quality and daytime somnolence in PD. The consistency across PDSS and ESS outcomes supports the utility of DBS for sleep‑related NMS and highlights the value of standardized measurement tools in evaluating DBS effects.

Citation

Schiess MC, Martinez-Lemus JD, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Subthalamic Deep Brain Stimulation Produces Consistent Improvements in Sleep Quality and Daytime Sleepiness in Parkinson’s Disease: A Systematic Review and Meta-analysis. Mov Disord 2026;41(Suppl_1):S1304-S1306.

Figure 1. Forest plot of pooled mean change from baseline in MD of PDSS scores after STN-DBS.

Figure 2. Forest plot of pooled mean change from baseline in MD of ESS scores after STN-DBS.

Telerehabilitation Versus Conventional Therapy in Parkinson’s Disease: Evidence from Randomized Controlled Trials

Title: Telerehabilitation Versus Conventional Therapy in Parkinson’s Disease: Evidence from Randomized Controlled Trials

Authors: Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, Jorge Patino, Andrew McGarry, and Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To compare the effects of telerehabilitation and conventional rehabilitation on motor function and quality of life (QoL) in patients with Parkinson’s disease (PD).

Background

Telerehabilitation typically involves the remote delivery of physical therapy, exercise coaching, and functional training through video‑based platforms. It has emerged as an alternative model of providing rehabilitation for PD, potentially overcoming barriers related to access, mobility, and cost. However, its comparative effectiveness relative to conventional in‑person rehabilitation remains debated.

Design/Methods

A systematic review and meta‑analysis were conducted using PubMed to identify randomized controlled trials (RCTs) comparing telerehabilitation with conventional rehabilitation in adults with PD. The measured outcomes were motor (MDS UPDRS‑III) and QoL (PDQ‑39/PDQ‑8). Pooled analyses were performed using inverse‑variance methods. Mean differences (MD) and standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated. Random‑effects models were applied in the presence of significant heterogeneity.

Results

Six RCTs encompassing 283 participants evaluated QoL outcomes, and four RCTs with 249 participants assessed motor outcomes. Meta‑analysis of MDS UPDRS‑III scores showed no statistically significant difference between telerehabilitation and conventional therapy (MD 1.66 points, 95% CI −7.87 to 11.18; I2= 94%) [Figure 1]. For QoL, pooled analysis demonstrated no significant advantage of either intervention (SMD −0.32, 95% CI −1.06 to 0.43; I2 = 71%) [Figure 2]. Across individual trials, telerehabilitation achieved outcomes comparable to conventional rehabilitation.

Conclusions

Evidence from RCTs suggests that telerehabilitation provides benefits in motor function and QoL similar to those of conventional rehabilitation in PD. Despite substantial heterogeneity, telerehabilitation appears to be a viable alternative to in‑person therapy, particularly for patients with limited access to traditional care. However, its applicability in real‑world settings may be limited by insurance policy coverage, which can restrict access to or reimbursement for remote rehabilitation services. Further large‑scale, standardized RCTs are needed to refine optimal delivery models.

Citation

Caprara AL, Rissardo JP, Patino J, McGarry A, Walker I. Telerehabilitation Versus Conventional Therapy in Parkinson’s Disease: Evidence from Randomized Controlled Trials. Mov Disord 2026;41(Suppl_1):S1364.

Figure 1. Forest plot of pooled MD of motor outcomes.

Figure 2. Forest plot of pooled SMD of quality of life outcomes.

Smell as a Diagnostic Signature: Systematic Review and Meta-Analysis of UPSIT Accuracy in Distinguishing Parkinson’s Disease from Essential Tremor

Title: Smell as a Diagnostic Signature: Systematic Review and Meta-Analysis of UPSIT Accuracy in Distinguishing Parkinson’s Disease from Essential Tremor

Authors: Mya C. Schiess, Juan D. Martinez-Lemus, Jamir Pitton Rissardo, Jorge Patino, Ana Leticia Fornari Caprara, Andrew McGarry, and Ian Walker

Conference: 2026 International Congress of Parkinson's Disease, Seoul, Korea

Objective

To evaluate the diagnostic performance of the University of Pennsylvania Smell Identification Test (UPSIT) in differentiating Parkinson’s disease (PD) from essential tremor (ET) using published PubMed-indexed studies.

Background

Hyposmia is a common nonmotor feature of PD and is typically absent or mild in ET. Olfactory testing, particularly UPSIT, has emerged as an accessible, noninvasive adjunct to improve diagnostic accuracy, especially in early tremor‑predominant presentations where clinical overlap is frequent.

Design/Methods

A systematic review and meta-analysis was performed using PubMed‑indexed articles only. Inclusion criteria were: (1) studies employing UPSIT, (2) direct comparison between PD and ET, and (3) sufficient data to extract sensitivity and specificity. Studies assessing other parkinsonian syndromes were excluded. Diagnostic accuracy measures were extracted from eligible publications and aggregated from the data compiled. MetaDTA was utilized for data synthesis. HSROC curves were generated to summarize the sensitivity and specificity of each study.

Results

Seven studies met the inclusion criteria, comprising 454 PD patients and 239 ET patients [Figure 1]. Pooled analysis demonstrated a sensitivity of 78% (95% CI: 74–82%) [Figure 2] for detecting PD‑associated olfactory dysfunction and a specificity of 91% (95% CI: 86–94%) [Figure 3] for distinguishing PD from ET. Most studies reported specificity ≥90%, indicating the strong discriminatory value of UPSIT in the differential diagnosis of tremor. Variability in sensitivity was observed, likely reflecting disease stage and cutoff definition. Most studies showed a high risk of bias due to nonrandom patient selection and unblinded olfactory testing.

Conclusions

UPSIT demonstrates high specificity and moderate sensitivity for differentiating PD from ET, supporting its role as a practical adjunct in the diagnostic evaluation of tremor syndromes. Marked olfactory impairment strongly favors PD over ET, particularly when motor features are equivocal. UPSIT should be interpreted in conjunction with clinical assessment and alongside biomarkers rather than as a standalone diagnostic tool.

Citation

Schiess MC, Martinez-Lemus JD, Rissardo JP, Patino J, Caprara AL, McGarry A, Walker I. Smell as a Diagnostic Signature: Systematic Review and Meta-Analysis of UPSIT Accuracy in Distinguishing Parkinson’s Disease from Essential Tremor. Mov Disord 2026;41(Suppl_1):S1099-S1100.

Figure 1. HSROC plot of UPSIT for distinguishing PD from ET.

Figure 2. Forest plot of the sensitivity of UPSIT for distinguishing PD from ET.

Figure 3. Forest plot of the specificity of UPSIT for distinguishing PD from ET.

250. Accepted

249. Accepted

248. Accepted

247. Accepted

246. Accepted