Overview: Smoking as a Modifiable Factor in Huntington’s Disease
Huntington’s disease (HD) is a progressive, currently incurable neurodegenerative disorder. While genetics set the stage, modifiable environmental factors may influence when symptoms start and how quickly they advance. A recent analysis using Periodic Dataset 4 from Enroll-HD examined 2,438 individuals, including 799 presymptomatic carriers with four consecutive annual visits, to assess whether lifetime and current smoking affected conversion to symptomatic HD and changes in established clinical measures over three years.
Key Finding: Greater Onset Risk for Women Who Smoke
The study identified a sex-specific signal: among presymptomatic HD gene carriers, current female smokers faced a higher risk of converting to symptomatic disease than nonsmokers. The hazard ratio was 1.35, with a p value of 0.023 and a 95% confidence interval of 1.04 to 1.56. This suggests that smoking avoidance counseling could be particularly impactful for female gene carriers when discussing risk management and surveillance timing. While the finding does not imply causation, it reinforces the importance of integrating lifestyle counseling into genetic risk discussions.
Progression in Symptomatic HD: Motor and Cognitive Decline Accelerated by Smoking
In participants who already met criteria for symptomatic HD, smoking was associated with faster deterioration in both motor and cognitive domains. The study reported a statistically significant worsening on the Total Motor Score (p = 0.035; 95% CI 0.04–0.9). Cognitive decline, measured by the Stroop Word Reading test, also progressed more rapidly in smokers (p = 0.04; 95% CI 0.1–0.9). Clinically, this pattern translates to earlier and sharper impairment in daily functioning, which can influence multidisciplinary care planning and the prioritization of smoking cessation interventions within care teams.
Clinical Implications: How to Use These Findings in Practice
For clinicians, the findings underscore several practical steps:
- Systematic smoking assessment: Incorporate routine smoking status checks into every HD visit, including presymptomatic individuals who carry the gene but are not yet symptomatic.
- Cessation counseling tailored to HD: Provide or refer for targeted smoking cessation support, acknowledging potential interactions with neurological symptoms and medications.
- Close monitoring of motor and cognitive trajectories: In smokers with HD or premanifest carriers, schedule more frequent evaluations of motor function and cognitive performance to detect emerging decline early.
- Individualized care planning: Use smoking status as a factor when prioritizing rehabilitation, physical therapy, and cognitive interventions within a multidisciplinary team.
It is important to communicate that the study demonstrates associations rather than definitive causation. Nonetheless, given the known health risks of smoking and the potential for accelerated HD progression, clinicians should err on the side of proactive cessation support as part of comprehensive HD management.
Limitations and Next Steps
While the Enroll-HD data provide important signals, researchers caution that more work is needed to understand the biological mechanisms linking smoking to HD progression and to determine whether quitting after diagnosis modifies the trajectory. Future studies could explore dose-response effects, the impact of quitting on long-term outcomes, and potential interactions with other lifestyle factors.
Bottom Line for Care Teams
The association between smoking and faster Huntington’s disease progression, particularly among women, highlights smoking cessation as a meaningful, modifiable target in HD care. Clinicians should integrate routine smoking history, offer tailored cessation resources, and closely monitor motor and cognitive changes in smokers to optimize multidisciplinary management and improve quality of life for people living with HD or carrying the genetic risk.
Reference: Witkowski G et al. The association between smoking and Huntington’s disease symptom onset and progression: results from Enroll-HD. Neurol Neurochir Pol. 2025; doi:10.5603/pjnns.107176.
