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The association between smoking and Huntington’s disease symptom onset and progression — results from Enroll-HD: The observational cohort study of people with Huntington’s disease

Year: 2025
Type: article
Abstract: AIM OF THE STUDY: To assess the impact of tobacco smoking on the onset of Huntington's disease (HD) and the progression of its motor and cognitive symptoms. CLINICAL RATIONALE OF THE STUDY: HD is an incurable neurodegenerative disorder. Therefore, identifying lifestyle factors with an impact of its progression is of particular interest. Tobacco smoking influences the course of neurodegenerative disorders. It has been shown to be a risk factor for dementia, but, on the contrary, seems to have a protective role in Parkinson's disease. MATERIAL AND METHODS: This study used Periodic Dataset 4 of the Enroll-HD database, from which a cohort of 2,438 HD subjects (799 presymptomatic) with four consecutive annual visits (three years of observation) was extracted. Logistic regression models were used to assess the effect of lifetime smoking on progression to the symptomatic phase. In the premanifest, Cox proportional regression model was applied to estimate the hazard ratio of HD diagnosis for smokers and nonsmokers during the three-year observation period. Multivariate linear regression models were used to investigate the relationship between smoking and the progression of HD clinical measures. RESULTS: It was found that current female smokers were at a higher risk of progressing to the symptomatic phase of HD than nonsmokers [hazard ratio (HR): 1.35, p = 0.023, 95% confidence interval (CI): 1.04-1.56]. For the symptomatic HD cohort, regardless of sex, smoking was associated with faster progression of motor symptoms, as measured by the Total Motor Score (p = 0.035, 95% CI: 0.04-0.9), as well as cognitive impairment, as measured by the Stroop Word Reading test (p = 0.04, 95% CI: 0.1-0.9). CONCLUSIONS AND CLINICAL IMPLICATIONS: It was presented that lifetime and current smoking are environmental factors that may be associated with an increased risk of HD progression, particularly in female HD gene carriers. This supports the recommendation that HD mutation carriers avoid smoking.
DOI: 10.5603/pjnns.107176
Language: English
Open Access status: bronze
OpenAlex ID: W4415168316
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