Bryan Bernard’s research while affiliated with Rush University Medical Center and other places

Background: The criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown. Methods: The MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychological assessment to define PD-MCI (n = 467). Risk for developing PDD was examined using a Cox model. Global cognitive tests were compared to neuropsychological test batteries (Level I&II) in determining risk for PDD. Results: PD-MCI based on a global cognitive test (MMSE or MoCA) increases the hazard for developing PDD (respectively HR = 2.57, P = 0.001; HR = 4.14, P = <0.001). The C-statistics for MMSE (0.72) and MoCA (0.70) were lower than those based on neuropsychological tests (Level I = 0.82; Level II = 0.81). Sensitivity, specificity and diagnostic accuracy balance was best in Level II. Conclusion: MMSE and MoCA predict conversion to PDD. However, Level II neuropsychological assessment seems the preferred assessment for PD-MCI.

Objective To compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and non-carriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). Methods Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and non-carriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. Results Data were available for 367 subjects: 58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects who were longitudinal followed (range 36 to 60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/year more than GBA-DBS- subjects (95% CI = -2.35, -1.69), 1.71 points/year more than GBA+DBS- subjects (95% CI = -2.14, -1.28), and 1.49 points/year more than GBA-DBS+ subjects (95% CI = -1.80, -1.18). Interpretation Although non-randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the pre-surgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS and alternative options may be considered. This article is protected by copyright. All rights reserved.

Background Few studies assess the relationships between nonmotor aspects of experiences of daily living and cognitive functioning in Parkinson's disease (PD). Objective To evaluate the relationships among the Movement Disorders Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part I items and neuropsychological tests in PD.Methods: We assessed 151 PD patients with the MDS‐UPDRS part I and a battery of cognitive tests focused on the following 5 cognitive domains: attention/working memory, executive functioning, recent memory, language, visuoperception. Raw scores for individual cognitive tests were transformed to z scores, and cognitive domain scores were calculated by averaging z scores within each domain. Individual items from the MDS‐UPDRS part I were entered in a stepwise linear regression analysis assessing item contribution to cognitive domain scores. Results The MDS‐UPDRS part I item scores for hallucinations and psychosis and light headedness on standing predicted attention/working memory domain scores ( P = 0.004). These same item scores, along with apathy, depressed mood, and dopamine dysregulation syndrome, predicted executive functioning ( P = 0.044). The apathy and dopamine dysregulation syndrome items predicted language ( P = 0.006). In addition, the cognitive impairment and sleep items were predictors of recent memory ( P = 0.031). None of the items were predictors of visuoperception ( P = 0.006). Other part I items were not significantly related to cognitive domain scores. Conclusions Specific nonmotor MDS‐UPDRS part I items, particularly mood, behavior, and autonomic‐related items, exhibited significant relationships with cognitive domains. The highest number of items were predictive of the executive functioning domain, which is the hallmark cognitive dysfunction in PD.

Huntington’s disease (HD) is characterized by motor, cognitive, and psychiatric dysfunction. HD progression causes loss of automaticity, such that previously automatic tasks require greater attentional resources. Dual-task (DT) paradigms and fast-paced gait may stress the locomotor system, revealing deficits not seen under single-task (ST). However, the impact of gait “stress tests” on HD individuals needs further investigation. Therefore, the aims of this study were to investigate whether: 1) fast-paced and dual-task walking uncover deficits in gait and turning not seen under single-task, 2) cognitive and gait outcomes relate to fall incidence, and 3) gait deficits measured with wearable inertial sensors correlate with motor symptom severity in HD as measured by the Unified Huntington’s disease Rating Scale-total motor score (UHDRS-TMS). Seventeen HD (55 ± 9.7 years) and 17 age-matched controls (56.5 ± 9.3 years) underwent quantitative gait testing via a 25m, two-minute walk test with APDMTM inertial sensors. Gait was assessed under a 1) ST, self-selected pace, 2) fast-as-possible (FAP) pace, and 3) verbal fluency DT. The UHDRS-TMS and a cognitive test battery were administered, and a retrospective fall history was obtained. During ST, DT, and FAP conditions, HD participants demonstrated slower gait, shorter stride length, and greater lateral step and stride length variability compared to controls (p<0.00001 to 0.034). Significant dual-task costs (DTC) were observed for turns; HD participants took more time (p = 0.013) and steps (p = 0.028) to complete a turn under DT compared to controls. Higher UHDRS-TMS correlated with greater stride length variability, less double-support, and more swing-phase time under all conditions. Decreased processing speed was associated with increased gait variability under ST and FAP conditions. Unexpectedly, participant’s self-reported falls did not correlate with any gait or turn parameters. HD participants demonstrated significantly greater DTC for turning, which is less automatic than straight walking, requiring coordination of body segments, anticipatory control, and cortical regulation. Turn complexity likely makes it more susceptible to cognitive interference in HD.

BACKGROUND Huntington's disease (HD) is characterized by chorea, balance and gait impairments and cognitive deficits, which increase fall risk. Dual task (DT) and environmentally challenging paradigms reflect balance related to everyday life. Furthermore, the impact of cognitive deficits on balance dysfunction and falls in HD is unknown. OBJECTIVE To determine the impact of DT interference, sensory feedback, and cognitive performance on balance and falls in HD. METHODS Seventeen participants with HD (55 + 9.7 years) and 17 age‐matched controls (56.5 + 9.3 years) underwent quantitative balance testing with APDMTM inertial sensors. Postural sway was assessed during conditions of manipulated stance, vision, proprioception and cognitive demand. The DT was a concurrent verbal fluency task. Neuropsychological assessments testing multiple cognitive domains were also administered. RESULTS HD participants exhibited significantly greater total sway area, jerk, and variability under single‐task (ST) and DT conditions compared to controls (p = 0.0002 to < 0.0001). They also demonstrated greater DT interference with vision removed for total sway area (p = 0.01) and variability (p = 0.02). Significantly worse postural control was observed in HD with vision removed and reduced proprioception (p=0.001 to 0.01). Decreased visuospatial performance correlated with greater total sway and jerk (p = 0.01; 0.009). No balance parameters correlated with retrospective falls in HD. CONCLUSION HD participants have worse postural control under DT, limited proprioception/vision and greater DT interference with a narrowed base and no visual input. These findings may have implications for designing motor and cognitive strategies to improve balance in HD. This article is protected by copyright. All rights reserved.

Background: Executive function and information processing speed deficits occur in fragile X premutation carriers (PMC) with and without fragile X-associated tremor/ataxia syndrome (FXTAS). Gait is negatively impacted by cognitive deficits in many patient populations resulting in increased morbidity and falls but these relationships have not been studied in FXTAS. Research question: We sought to investigate the associations between executive function and information processing speed and gait, turning and falls in PMC with and without FXTAS compared to healthy controls. Methods: Global cognition and the cognitive domains of information processing speed, attention, response inhibition, working memory and verbal fluency were tested with a neuropsychological test battery in 18 PMC with FXTAS, 15 PMC without FXTAS, and 27 controls. An inertial sensor based instrumented Timed Up and Go was employed to test gait, turns and functional mobility. Results: Lower information processing speed was significantly associated with shorter stride length, reflecting slower gait speed, in PMC with FXTAS (p = 0.0006) but not PMC without FXTAS or controls. Lower response inhibition was also significantly associated with slower turn-to-sit times in PMC with FXTAS (p = 0.034) but not in those without FXTAS or controls. Lower information processing speed (p = 0.012) and working memory (p = 0.004), were significantly correlated with a greater number of self-reported falls in the past year in FXTAS participants. Significance: This is the first study demonstrating that worse executive function and slower information processing speed is associated with reduced gait speed and functional mobility, as well as with a higher retrospective fall history in participants with FXTAS. This information may be important in the design of cognitive and motor interventions for this neurodegenerative disorder.