Why This Matters for Clinical Practice
HUNTINGTON’S disease is progressive and incurable, so modifiable factors that influence symptom onset and progression are clinically relevant. Using Periodic Dataset 4 from Enroll-HD, investigators evaluated 2,438 individuals, including 799 presymptomatic carriers with four consecutive annual visits. The analysis tested whether lifetime and current smoking were associated with conversion to symptomatic disease and with changes in established clinical measures over three years.
Smoking and Huntington’s Disease: Onset Signal in Women
Among premanifest participants, current female smokers had a higher risk of progressing to symptomatic Huntington’s disease compared with nonsmokers. The hazard ratio was 1.35 with a p value of 0.023 and a confidence interval from 1.04 to 1.56. This sex specific signal suggests that counseling female gene carriers on smoking avoidance may be particularly important when discussing risk management and timing of surveillance.
Faster Progression of Motor and Cognitive Impairment
In the symptomatic cohort, smoking was associated with more rapid deterioration in both motor and cognitive domains. Worsening on the Total Motor Score reached statistical significance with a p value of 0.035 and a confidence interval between 0.04 and 0.9. Cognitive decline on the Stroop Word Reading test was also faster in smokers, with a p value of 0.04 and a confidence interval between 0.1 and 0.9. These findings align with a clinically observable pattern of accelerated impairment that could inform multidisciplinary care planning and prioritization of cessation support.
Clinical Takeaways
The study supports smoking as an environmental factor associated with increased risk of Huntington’s disease progression, with a notable effect in female carriers. For clinicians, the results reinforce routine smoking status assessment, targeted cessation counseling, and close monitoring of motor and cognitive trajectories in smokers with Huntington’s disease or in premanifest carriers.
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.
