Overview: Smoking as a Modifiable Factor in Huntington’s Disease
Huntington’s disease (HD) is a progressive, incurable neurodegenerative disorder. While genetic timing largely governs onset, environmental and lifestyle factors can modulate how quickly symptoms emerge and 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 determine whether lifetime and current smoking influence conversion to symptomatic disease and changes in established clinical measures over a three-year span.
This work adds to a growing body of evidence that smoking is a modifiable environmental factor with tangible implications for HD management. The findings carry particular weight for clinicians who counsel people at risk for HD and those living with the disease, highlighting opportunities to optimize care through targeted cessation efforts and vigilant monitoring of disease progression.
Key Finding 1: A Female-Specific Signal for Onset Risk
Among premanifest participants, current smoking was associated with a higher risk of converting to symptomatic HD in women, compared with nonsmokers. The hazard ratio was 1.35, with a p value of 0.023 and a 95% confidence interval from 1.04 to 1.56. While the signal requires further replication, the sex-specific pattern suggests that counseling female gene carriers on smoking avoidance may be particularly important when discussing risk management and the timing of surveillance strategies.
Since women often navigate different social and biological factors that intersect with HD risk, this finding underscores the value of personalized risk communication. Clinicians should consider integrating gender-aware discussions about smoking into routine genetic counseling and HD risk assessments, especially for those who carry the HD mutation but are not yet symptomatic.
Key Finding 2: Faster Motor and Cognitive Decline in Smokers
In the symptomatic HD cohort, smoking correlated with a more rapid deterioration in both motor and cognitive domains. Specifically, motor decline measured by the Total Motor Score showed a statistically significant worsening (p = 0.035; 95% CI 0.04 to 0.9). Cognitive decline, assessed with the Stroop Word Reading test, also progressed more quickly among smokers (p = 0.04; 95% CI 0.1 to 0.9).
The convergence of motor and cognitive deterioration in smokers aligns with clinically observable patterns, emphasizing the need for multidisciplinary care planning. For patients and families, this means recognizing smoking as a contributor to the pace of functional decline and prioritizing interventions that support cessation alongside physical and cognitive rehabilitation programs.
Implications for Management and Care Planning
From a care framework perspective, these results support incorporating routine smoking status assessments into HD management. This includes documenting smoking history, current use, and cessation attempts as part of baseline and follow-up evaluations. For current smokers with HD or premanifest carriers at risk, clinicians should:
- Provide targeted cessation counseling with a focus on HD-specific concerns, including potential impacts on motor and cognitive trajectories.
- Coordinate with pharmacologic and behavioral cessation strategies that consider interactions with HD medications and comorbid conditions.
- Monitor motor and cognitive trajectories more closely in smokers, with earlier or more frequent follow-ups to detect accelerated decline.
- Engage multidisciplinary teams—neurology, behavioral health, physical therapy, speech-language pathology—in a proactive plan that supports cessation alongside rehabilitation.
Clinical Takeaways for Practice
The Enroll-HD analysis reinforces smoking as an environmental factor associated with faster progression in Huntington’s disease, with a notable signal in female carriers. For clinicians, the practical implications are clear:
- Incorporate routine smoking status assessment into HD clinics, including both premanifest individuals and those with established disease.
- Offer personalized cessation counseling, emphasizing the potential to influence symptom onset timing and progression rates.
- Monitor motor and cognitive outcomes with an awareness that smoking may accelerate decline, informing timely adjustments to care plans.
- Discuss smoking avoidance as part of risk management discussions for gene carriers and consider scheduling surveillance with thoughts to the patient’s sex and overall risk profile.
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.
