Substance abuse may hasten motor onset of Huntington disease: Evaluating the Enroll-HD database

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To investigate the relationship between substances of abuse and age at motor onset (AMO) in patients with Huntington disease (HD) in a large and diverse patient population.


This was a retrospective, observational study of the Enroll-HD database. Participants were determined to belong to 1 of 3 substance abuse groups: (1) tobacco abusers, (2) alcohol abusers, and (3) drug abusers. A group of participants who had never abused substances served as a control group. The average AMO of patients in the substance abuse groups was compared to the control group. The number of CAG repeats was used as a covariate in all analyses.


The average difference in AMOs of participants in the tobacco (n = 566), alcohol (n = 374), and drug abuse groups (n = 217) compared to the control group (n = 692) were 2.3 (F1, 1,258 = 33.8, p < 0.0001), 1.0 (F1, 1,066 = 4.2, p = 0.04), and 3.3 (F1, 909 = 29.7, p < 0.0001) years earlier, respectively. In all substance abuse groups, the AMO was lowered to a greater degree in female participants than it was in male participants.


Substances of abuse have a strong effect on the AMO in patients with HD. These effects seem to be amplified in women with HD compared to men. These results may provide a safe intervention capable of adding disease-free years to patients with HD.

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