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BackgroundCognitive decline has been reported in Huntington disease (HD), as well as in the period before diagnosis of motor symptoms (i.e., pre-HD). However, the severity, frequency, and characterization of cognitive difficulties have not been well-described. Applying similar cutoffs to those used in mild cognitive impairment (MCI) research, the current study examined the rates of subtle cognitive dysfunction (e.g., dysfunction that does not meet criteria for dementia) in pre-HD.MethodsUsing baseline data from 160 non-gene-expanded comparison participants, normative data were established for cognitive tests of episodic memory, processing speed, executive functioning, and visuospatial perception. Cutoff scores at 1.5 standard deviations below the mean of the comparison group were then applied to 575 gene-expanded pre-HD participants from the observational study, PREDICT-HD, who were stratified by motor signs and genetic risk for HD.ResultsNearly 40% of pre-HD individuals met criteria for MCI, and individuals closer to HD diagnosis had higher rates of MCI. Nonamnestic MCI was more common than amnestic MCI. Single-domain MCI was more common than multiple-domain MCI. Within the nonamnestic single-domain subtype, impairments in processing speed were most frequent.ConclusionsConsistent with the Alzheimer disease literature, MCI as a prodromal period is a valid concept in pre-HD, with nearly 40% of individuals showing this level of impairment before diagnosis. Future studies should examine the utility of MCI as a marker of cognitive decline in pre-HD.

Objective: To determine whether tetrabenazine (TBZ) use is associated with an increased incidence of depression and/or suicidal ideation., Methods: In this retrospective cross-sectional study of the Enroll-HD database, we used multiple logistic regression analyses to determine whether TBZ use is associated with an increased incidence of depression and/or suicidal ideation. For both dependent variables (depression and suicidality), separate analyses were conducted on (1) all participants, (2) only participants with a history of depression, and (3) only participants with no history of depression. Adjustments were made for CAG repeat length, total motor score, total functional capacity, Symbol Digit Modalities Test score, sex, disease duration, history of depression (when applicable), antipsychotic use, and antidepressant use., Results: Compared to participants who were not using TBZ (n = 3,548), TBZ users (n = 543) did not have an increased risk of depression (odds ratio [OR] = 0.78, p = 0.064). Participants taking TBZ actually had a relatively lower risk of suicidality (OR = 0.61, p = 0.043). Among only participants with a history of depression, those using TBZ had a lower incidence of depression (OR = 0.71, p = 0.016) and suicidal ideation (OR = 0.57, p = 0.028) compared to those not using TBZ. Finally, among only participants with no history of depression, TBZ use was not associated with a higher incidence of depression (OR = 1.59, p = 0.18) or suicidality (OR = 1.43, p = 0.66) compared to those who were not using TBZ., Conclusions: TBZ use was not associated with an increased incidence of depression or suicidality. These findings suggest that TBZ may be safe to use in patients with Huntington disease who have a history of depression., (© 2018 American Academy of Neurology.)

Objective: 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., Methods: 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., Results: 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 ( F 1, 1,258 = 33.8, p < 0.0001), 1.0 ( F 1, 1,066 = 4.2, p = 0.04), and 3.3 ( F 1, 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., Conclusions: 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., (© 2017 American Academy of Neurology.)

Background: Outcome studies have generally not indicated significant cognitive disturbances after cingulotomy. There is now considerable evidence that the cingulate may play an important role in emotional behavior and attention., Objective: To characterize impairments of attention associated with bilateral lesions of the anterior cingulate cortex produced by cingulotomy., Methods: Twelve patients who underwent cingulotomy for treatment of intractable pain were administered tests of attention, executive functions, response intention and production, and a broad range of other neurocognitive functions before surgery and again 3 and 12 months after surgery. Data from this within-subjects repeated-measures design were analyzed by multivariate analysis of variance procedures., Results: After cingulotomy, patients initially had executive and attentional impairments. By 12 months, these had resolved into more circumscribed deficits, with greatest impairments on tasks requiring intention and spontaneous response production, and milder impairments of focused and sustained attention. Other aspects of attention and other cognitive functions were generally unaffected., Conclusion: The anterior cingulate cortex modulates response intention and focused attention.