Background and Objectives Individuals with cerebellar ataxia (CA) can develop impulsive behavioral symptoms, often resulting in negative interpersonal consequences, detrimentally affecting their quality of life. Limited evidence exists concerning impulsivity in CA and its associated behavioral changes. We assessed impulsive traits in CA using the Barratt Impulsivity Scale (BIS-11) and compared them with those of Parkinson disease (PD) to investigate the differences in the impulsive trait profiles between CA and PD. Methods We conducted a dual-center cross-sectional study with individuals with CA and PD enrolled through consecutive sampling from movement disorders clinics at Columbia University Medical Center and Vanderbilt University Medical Center, respectively. Age-matched controls were recruited at the respective institutions. Participants were excluded if they had prior or comorbid neurologic and psychiatric diseases known to be associated with impulsivity. All participants completed the BIS-11 questionnaire as a measure of impulsive traits. We used a general linear model and a least absolute shrinkage and selection operation regression to compare the total, subscale, and individual items of the BIS-11 scores between groups. Subgroup analyses were performed to isolate cerebellar contributions to impulsivity from potential effects of extracerebellar pathology and dopaminergic dysfunction or medications. Results A total of 190 participants—90 age-matched controls, 50 participants with CA, and 50 with PD—completed the assessments. Persons with CA reported 9.7% higher BIS-11 scores than controls (p < 0.001), while persons with PD reported 24.9% higher scores than controls (p < 0.001). In CA, the most affected domain of impulsivity was nonplanning. In contrast, persons with PD noted greater impulsivity across the nonplanning, attentional, and motor domains. Discussion Impulsivity in CA is uniquely driven by the nonplanning trait, unlike in PD. This suggests that the cerebellum and basal ganglia may differentially govern impulsive behaviors with the cerebellum contributing to the brain circuitry of impulsivity in a domain-specific manner.

Objective: Impulsive decision‐making is characterized by actions taken without considering consequences. Patients with Parkinson's disease (PD) who receive dopaminergic treatment, especially dopamine agonists, are at risk of developing impulsive–compulsive behaviors (ICBs). We assessed impulse‐related changes across a large heterogeneous PD population using the Barratt impulsivity scale (BIS‐11) by evaluating BIS‐11 first‐ and second‐order factors.Methods: We assessed a total of 204 subjects: 93 healthy controls (HCs), and 68 ICB– and 43 ICB + PD patients who completed the BIS‐11. Using a general linear model and a least absolute shrinkage and selection operation regression, we compared BIS‐11 scores between the HC, ICB– PD, and ICB + PD groups.Results: Patients with PD rated themselves as more impulsive than HCs in the BIS‐11 total score, second‐order attention domain, and first‐order attention and self‐control domains. ICB + patients recorded higher total scores as well as higher scores in the second‐order non‐planning domain and in self‐control and cognitive complexity than ICB– patients.Interpretation: These results indicate that the patients with PD show particular problems with attentional control, whereas ICB + patients show a distinct problem in cognitive control and complexity. Additionally, it appears that all patients with PD are more impulsive than their age‐ and sex‐matched healthy peers. Increased impulsivity may be a result of the disease course, or attributed to dopaminergic medication use, but these results emphasize the importance of the cognitive components of impulsivity in patients with PD.

Impulsivity is inherent to behavioral disorders such as substance abuse and binge eating. While the role of dopamine in impulse behavior is well established, γ-aminobutyric acid (GABA) therapies have promise for the treatment of maladaptive behaviors. In Parkinson disease (PD), dopaminergic therapies can result in the development of impulsive and compulsive behaviors, and this clinical syndrome shares similar pathophysiology to that seen in addiction, substance abuse, and binge-eating disorders. We hypothesized that impulsive PD patients have a reduced thalamic GABAergic response to dopamine therapy. To test this hypothesis, we employed GABA magnetic resonance spectroscopy, D2-like receptor PET imaging, and clinical and quantitative measures of impulsivity in PD patients (n = 33), before and after dopamine agonist administration. We find a blunted thalamic GABA response to dopamine agonists in patients with elevated impulsivity (p = 0.027). These results emphasize how dopamine treatment differentially augments thalamic GABA concentrations, which may modify behavioral impulsivity.

Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using magnetic resonance imaging, normalized to healthy values, comparing measurements from ∼1 month before to 12 to 24 months after HSCT (n = 11; age, 33.3 ± 8.9 years; 389 ± 150 days after HSCT) with age-, race- and sex-matched values from healthy adults without sickle trait (n = 28; age, 30.2 ± 5.6 years). Before transplant, 7 patients had neurological indications for transplant (eg, overt stroke) and 4 had nonneurological reasons for haploidentical bone marrow transplant (haplo-BMT). All received haplo-BMT from first-degree relatives (parent, sibling, or child donor) with reduced-intensity preparation and maintained engraftment. Before transplant, CBF was elevated (CBF, 69.11 ± 24.7 mL/100 g/min) compared with that of controls (P = .004). Mean CBF declined significantly after haplo-BMT (posttransplant CBF, 48.2 ± 13.9 mL/100 g/min; P = .003). OEF was not different from that of controls at baseline and did not change significantly after haplo-BMT (pretransplant, 43.1 ± 6.7%; posttransplant, 39.6 ± 7.0%; P = .34). After transplant, CBF and OEF were not significantly different from controls (CBF, 48.2 ± 13.4 mL/100 g/min; P = .78; and OEF, 39.6 ± 7.0%; P > .99). CMRO2 did not change significantly after haplo-BMT (pretransplant, 3.18 ± 0.87 mL O2/100 g/min; posttransplant, 2.95 ± 0.83; P = .56). Major complications of haplo-BMT included 1 infection-related death and 1 severe chronic graft-versus-host disease. Haplo-BMT in adults with SCD reduces CBF to that of control values and maintains OEF and CMRO2 on average at levels observed in healthy adult controls. The trial was registered at www.clinicaltrials.gov as #NCT01850108.

Understanding age-related changes in cerebral blood flow (CBF, rate of blood delivery to brain tissue) in sickle cell anemia (SCA) is a prerequisite to incorporating CBF as a marker of brain health. CBF decreases from school-age through adulthood in nonanemic people. In SCA, CBF is generally increased to compensate for anemia, but knowledge of age-related norms is limited. We hypothesized that age-related CBF trajectories differ for SCA vs nonanemic healthy persons: CBF increases from childhood to early adulthood in SCA to compensate for reduced blood oxygen content and then plateaus because of reduced vasodilatory capacity with older age. Children and adults with SCA and race-matched controls (hemoglobin [Hb] AA) aged 6-45 years were enrolled in an observational cross-sectional study from 2014 to 2023 at an academic and community health center. History of overt stroke or arterial stenosis >50% were exclusions. Brain MRIs were performed at 3T with arterial-spin-labeling measurements of gray matter CBF. Regression analyses assessed how age, imaging markers of ischemia, Hb, and arterial oxygen saturation (SpO₂) related to CBF. In 192 Black participants with SCA (N = 126; mean age = 18.7 ± 9.0 years, 52.4% female) or without SCA (N = 66; mean age = 22.4 ± 9.7 years, 54.5% female), total Hb was lower in SCA (mean Hb = 8.9 ± 1.3 g/dL) vs control (mean Hb = 13.4 ± 1.5 g/dL) participants (p < 0.001) and did not differ with age in the SCA group. SpO₂ was reduced in SCA (median SpO₂ = 96%; interquartile range [IQR] = 94-97.4%) vs controls (median SpO₂ = 98%, IQR = 97-99%, p < 0.001). In SCA participants, SpO₂ was lower in adults (median SpO₂ = 95%, IQR = 94%-97%, p = 0.001) compared with children (SpO₂ = 96.5%, IQR = 95%-98.2%). Regression analyses, including an interaction between age and group (SCA vs control), showed that CBF increases in SCA by 5.03 mL/100 g/min per decade (95% CI 1.70-8.37) and plateaus at approximately age 30-35 years. In controls, CBF decreased by -5.20 mL/100 g/min per decade (95% CI -8.96 to -1.94). The divergent age dependency of CBF between SCA and non-anemic persons may be explained by a gradient of increasing CBF with age required to compensate for reductions in blood oxygen content in SCA, with possible exhaustion of cerebral vasodilatory abilities in the fourth decade of life. Longitudinal studies are needed.

Patients with sickle cell disease (SCD) are at elevated risk of silent cerebral infarcts and strokes; however, they frequently lack established stroke risk factors (eg, macrovascular arterial steno-occlusion) and the mechanisms underlying such events are incompletely characterized. This study evaluated cerebral hemometabolism with respect to imaging markers of vascular shunting in 143 participants with SCD, including 73 pediatric (aged 6-17 years) and 70 adult (aged 18-40 years) participants using 3-Tesla brain magnetic resonance imaging (MRI). Vascular shunting was assessed in each patient using a previously published ordinal venous hyperintensity score (VHS) of 0, 1, or 2 on cerebral blood flow-weighted MRI. Participants with VHS of 2, indicative of the most rapid arteriovenous transit, had significantly reduced blood oxygen content (CaO2; 10.90 ± 1.69 mL O2/100 mL blood), oxygen extraction fraction (OEF; 33.52% ± 5.54%), and cerebral metabolic rate of oxygen consumption (CMRO2; 2.91 ± 0.69 mL O2/100 g tissue per minute) compared with their counterparts with VHS = 0 (CaO2 = 12.42 ± 1.58 mL O2/100 mL blood; OEF = 39.03% ± 3.80%; CMRO2 = 3.77 ± 0.84 mL O2/100 g tissue per minute) or VHS = 1 (CaO2 = 11.86 ± 1.73 mL O2/100 mL blood; OEF = 36.37% ± 5.11%; CMRO2 = 3.59 ± 0.78 mL O2/100 g tissue per minute). Both pediatric and adult patients with SCD presenting with greater imaging evidence of vascular shunting had mildly reduced OEF and CMRO2. These findings highlight that imaging markers of vascular shunting are associated with significant, albeit mild, evidence of reduced OEF and CMRO2 in patients with SCD.