Potential Prodromal Digital Postural Sway Markers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Detected via Dual-Tasking and Sensory Manipulation.

FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene premutation carriers (PMCs) and is characterized by cerebellar ataxia, tremor, and cognitive deficits that negatively impact balance and gait and increase fall risk. Dual-tasking (DT) cognitive-motor paradigms and challenging balance conditions may have the capacity to reveal markers of FXTAS onset. Our objectives were to determine the impact of dual-tasking and sensory and stance manipulation on balance in FXTAS and potentially detect subtle postural sway deficits in FMR1 PMCs who are asymptomatic for signs of FXTAS on clinical exam. Participants with FXTAS, PMCs without FXTAS, and controls underwent balance testing using an inertial sensor system. Stance, vision, surface stability, and cognitive demand were manipulated in 30 s trials. FXTAS participants had significantly greater total sway area, jerk, and RMS sway than controls under almost all balance conditions but were most impaired in those requiring vestibular control. PMCs without FXTAS had significantly greater RMS sway compared with controls in the feet apart, firm, single task conditions both with eyes open and closed (EC) and the feet together, firm, EC, DT condition. Postural sway deficits in the RMS postural sway variability domain in asymptomatic PMCs might represent prodromal signs of FXTAS. This information may be useful in providing sensitive biomarkers of FXTAS onset and as quantitative balance measures in future interventional trials and longitudinal natural history studies.

Outdoor Nighttime Light Exposure (Light Pollution) is Associated with Alzheimer's Disease.

Alzheimer's disease (AD) prevalence has increased in the last century which can be attributed to increased lifespan, but environment is also important. This study evaluated the relationship between outdoor nighttime light exposure and AD prevalence in the United States. Higher outdoor nighttime light was associated with higher prevalence of AD. While atrial fibrillation, diabetes, hyperlipidemia, hypertension, and stroke were associated more strongly with AD prevalence than nighttime light intensity, nighttime light was more strongly associated with AD prevalence than alcohol abuse, chronic kidney disease, depression, heart failure, and obesity. Startlingly, nighttime light exposure more strongly associated with AD prevalence in those under the age of 65 than any other disease factor examined. These data indicate a need to investigate how nighttime light exposure influences AD pathogenesis.

Directional Deep Brain Stimulation Programming: Is the Segment Clearly Identifiable and Stable Over Time?

BACKGROUND: In our early experience programming directional deep brain stimulation (d-DBS) in PD, we found the optimal directional segment changed over time in some patients. To determine the frequency/reasons for this we examined whether (1) different programmers would identify the same segment as "optimal"; and (2) the same programmer would select the same "optimal" segment over time. We hypothesized there would be a moderately high level of agreement on optimal electrode selection between different assessors and repeated assessments by the same evaluator. METHODS: This was a prospective, double-blind investigation evaluating the reliability and stability of programming d-DBS. Each patient underwent a mono-polar survey four times (2 time points by 2 separate assessors). The primary aim was the inter-rater agreement of selecting the optimal electrode at 1 and 6 months. The secondary aim was to determine the intra-rater agreement of selecting the optimal electrode from 1 to 6 months. RESULTS: Twenty-one patients were enrolled. There was fair inter-rater agreement at 1 month and moderate at 6 months. There was minimal intra-rater agreement between 1 and 6 months. DISCUSSION: The data refuted our hypothesis. Potential reasons for low agreement include (1) the arduous/subjective nature of identifying the optimal electrode in d-DBS systems, especially in well-placed electrodes; and/or (2) acute changes to the location of stimulation delivery offering temporary improvement in symptoms. Key takeaways gathered were it may, (1) behoove the programmer to explore different electrode montages after a period of time; and (2) be more efficient to review the directional electrode montage only when dictated by clinical symptoms/disease progression.

Digital gait markers to potentially distinguish fragile X-associated tremor/ataxia syndrome, Parkinson's disease, and essential tremor.

Background: Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disease that affects carriers of a 55-200 CGG repeat expansion in the fragile X messenger ribonucleoprotein 1 (FMR1) gene, may be given an incorrect initial diagnosis of Parkinson's disease (PD) or essential tremor (ET) due to overlapping motor symptoms. It is critical to characterize distinct phenotypes in FXTAS compared to PD and ET to improve diagnostic accuracy. Fast as possible (FP) speed and dual-task (DT) paradigms have the potential to distinguish differences in gait performance between the three movement disorders. Therefore, we sought to compare FXTAS, PD, and ET patients using quantitative measures of functional mobility and gait under self-selected (SS) speed, FP, and DT conditions. Methods: Participants with FXTAS (n = 22), PD (n = 23), ET (n = 20), and controls (n = 20) underwent gait testing with an inertial sensor system (APDM™). An instrumented Timed Up and Go test (i-TUG) was used to measure movement transitions, and a 2-min walk test (2MWT) was used to measure gait and turn variables under SS, FP, and DT conditions, and dual-task costs (DTC) were calculated. ANOVA and multinomial logistic regression analyses were performed. Results: PD participants had reduced stride lengths compared to FXTAS and ET participants under SS and DT conditions, longer turn duration than ET participants during the FP task, and less arm symmetry than ET participants in SS gait. They also had greater DTC for stride length and velocity compared to FXTAS participants. On the i-TUG, PD participants had reduced sit-to-stand peak velocity compared to FXTAS and ET participants. Stride length and arm symmetry index during the DT 2MWT was able to distinguish FXTAS and ET from PD, such that participants with shorter stride lengths were more likely to have a diagnosis of PD and those with greater arm asymmetry were more likely to be diagnosed with PD. No gait or i-TUG parameters distinguished FXTAS from ET participants in the regression model. Conclusion: This is the first quantitative study demonstrating distinct gait and functional mobility profiles in FXTAS, PD, and ET which may assist in more accurate and timely diagnosis.