Reply to: “Alcohol Intake and Parkinson's Symptoms Following Diagnosis”

We thank Mischley and Farahnik for their thoughtful letter ¹ and for contributing complementary data on the association between alcohol intake and symptom burden among individuals with Parkinson's disease (PD). Their focus on post‐diagnosis symptom burden addresses a dimension that remains underexplored in the current literature.

As highlighted in our systematic review and meta‐analysis, most available evidence has focused on PD risk rather than post‐diagnosis outcomes. ¹ Importantly, our review included progression‐related evidence, although these data were limited and methodologically heterogeneous. ¹ In particular, Paul et al. ² examined PD progression and mortality rather than incident PD and their data were therefore narratively synthesized rather than pooled; they reported a reduced hazard of progression milestones among ever‐consumers compared with never‐consumers. Accordingly, our review did not overlook post‐diagnosis outcomes but rather identified them as an underdeveloped area in which the available data were insufficiently homogeneous for quantitative pooling. In this context, the contribution by Mischley and Farahnik is valuable because it adds post‐diagnosis, symptom‐focused data to a literature that remains sparse. However, their findings should be interpreted as complementary and hypothesis‐generating rather than confirmatory, given the cross‐sectional design and potential for reverse causation, residual confounding, and selection bias.

Their emphasis on wine is also noteworthy in this regard. In our review, ¹ subtype analyses suggested a modest inverse pooled association between wine consumption and PD risk under both comparator frameworks, that is, compared with abstainers and low‐level drinkers. However, this finding should be interpreted cautiously, as the wine analysis was based on a limited number of studies. Specifically, Kenborg et al. ³ reported consistent inverse associations, whereas Kim et al. ⁴ and Peters et al. ⁵ reported null or heterogeneous findings, and the pooled estimate showed moderate heterogeneity (I ² = 52.3%). These patterns underscore that the apparent wine signal remains tentative, rather than definitive.

These considerations also apply directly to the findings of Mischley and Farahnik. In our review, apparent inverse associations between alcohol consumption and PD risk were sensitive to study design, exposure definition, and comparator selection, with biases such as reverse causation and “sick quitter” effects potentially inflating the protective estimates. ¹ In Mischley and Farahnik study, where recent alcohol intake and symptom burden were assessed cross‐sectionally after diagnosis, the more immediate concerns are reverse causation and residual confounding: individuals with milder disease may be more likely to maintain alcohol consumption, particularly wine, as part of broader social and dietary behaviors. Accordingly, these findings are best interpreted as hypothesis‐generating rather than evidence of a protective effect on the course of PD.

We agree that the biological mechanisms proposed by Mischley and Farahnik are interesting. However, at present, such mechanistic explanations remain speculative and cannot distinguish behavioral correlations from true neurobiological effects. This is particularly important considering the limited and inconsistent evidence from genetic and Mendelian randomization studies in the broader alcohol–PD literature. ¹ For this reason, neither our review nor the authors' symptom‐focused analysis should be interpreted as supporting alcohol use as a preventive or therapeutic strategy in PD.

Future studies should clearly distinguish between incident PD risk, longitudinal disease progression, and cross‐sectional symptom burden after diagnosis. Progress in this area will require longitudinal designs with repeated exposure assessments, careful control for confounding, and integration of clinical, behavioral, and genetic data.

We appreciate Mischley and Farahnik's contribution to this ongoing discussion and agree that advancing this area requires a more nuanced and methodologically robust evidence base.

Author Roles

(1) Research Project: A. Conception, B. Design, C. Literature Search, D. Data Screening, E. Data Extraction, F. Meta‐Analysis, G. Data Interpretation, H. Interpretation of Findings, I. Methodological Support and Literature Interpretation, J. Provided Statistical and Methodological Advice, K. Provided Clinical Expertise in Movement Disorders, L. Supervision; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique, C. Approved the Final Version.

S.H.: 1A, 1B, 1H, 3A, 3B, 3C.

M.E.: 1B, 1H, 3A, 3B, 3C.

M.M.: 1I, 1J, 2C, 3B, 3C.

A.O.: 1H, 3B, 3C.

E.P.: 1I, 3B, 3C.

I.B.: 1J, 2C, 3B, 3C.

J.J.: 1L, 3B, 3C.

D.P.: 1A, 1G, 1K, 3B, 3C.

N.K.: 1A, 1B, 1G, 1L, 3B, 3C.

All authors met the International Committee of Medical Journal Editors (ICMJE) criteria for authorship. All authors contributed substantially to the conception and design of the study, acquisition and analysis of data, drafting and revising the manuscript, approved the final version to be published, and agreed to be accountable for all aspects of the work.

Financial Disclosures of All Authors (for the Preceding 12 Months)

None.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.