The latest medical research on Neurodegenerative Disorders

Sleep disorders have a prevalence of 30% to 70% in post-stroke individuals. The presence of sleep disorders and poor sleep quality after stroke can affect important functions and lead to worse outcomes. However, most studies are restricted to the acute post-stroke stage only.

To investigate the frequency of self-reported sleep alterations in a sample of chronic stroke individuals and to identify which self-reported sleep alterations were associated with disability.

Prospective exploratory study. Self-reported sleep alterations were measured by the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale, and STOP-Bang Questionnaire. The dependent variable was measured 3 years after the first contact by the Modified Rankin Scale (mRS). Step-wise multiple linear regression analysis was employed to identify which sleep alterations were associated with disability.

Sixty-five individuals with stroke participated. About 67.7% of participants had poor sleep quality, 52.4% reported insomnia symptoms, 33.9% reported excessive daytime sleepiness, and 80.0% were classified as intermediate or high risk for obstructive sleep apnea. Only risk for obstructive sleep apnea was significantly associated with disability and explained 5% of the variance in the mRS scores.

Self-reported sleep alterations had a considerable frequency in a sample of chronic stroke individuals. The risk of obstructive sleep apnea was associated with disability in the chronic stage of stroke. Sleep alterations must be considered and evaluated in the rehabilitation process even after a long period since the stroke onset.

Direct-to-participant online reporting facilitates the conduct of clinical research by increasing access and clinically meaningful patient engagement.

We assessed feasibility of online data collection from adults with diagnosed Huntington's disease (HD) who directly reported their problems and impact in their own words.

Data were collected online from consenting United States residents who self-identified as 1) having been diagnosed with Huntington's disease, 2) able to ambulate independently, and 3) self-sufficient for most daily needs. Data for this pilot study were collected using the Huntington Study Group myHDstory online research platform. The Huntington Disease Patient Report of Problems (HD-PROP), an open-ended questionnaire, was used to capture verbatim bothersome problems and functional impact. Natural language processing, human-in-the-loop curation of verbatim reports involving clinical and experience experts, and machine learning classified verbatim-reports into clinically meaningful symptoms.

All 8 questionnaires in the online pilot study were completed by 345 participants who were 60.9% men, 34.5±9.9 (mean±SD) years old, and 9.5±8.4 years since HD diagnosis. Racial self-identification was 46.4% Caucasian, 28.7% African American, 15.4% American Indian/Alaska Native, and 9.5% other. Accuracy of verbatim classification was 99%. Non-motor problems were the most frequently reported symptoms; depression and cognitive impairment were the most common.

Online research participation was feasible for a diverse cohort of adults who self-reported an HD diagnosis and predominantly non-motor symptoms related to mood and cognition. Online research tools can help inform what bothers HD patients, identify clinically meaningful outcomes, and facilitate participation by diverse and under-represented populations.

Balance and walking capacity are often impaired in people with motor incomplete spinal cord injury (iSCI), frequently resulting in reduced functional ambulation and participation. This study aimed to assess the efficacy of walking adaptability training compared to similarly dosed conventional locomotor and strength training for improving walking capacity, functional ambulation, balance confidence, and participation in ambulatory people with iSCI.

We conducted a 2-center, parallel-group, pragmatic randomized controlled trial. Forty-one people with iSCI were randomized to 6 weeks of (i) walking adaptability training (11 hours of Gait Real-time Analysis Interactive Lab (GRAIL) training-a treadmill in a virtual reality environment) or (ii) conventional locomotor and strength training (11 hours of treadmill training and lower-body strength exercises). The primary measure of walking capacity was maximal walking speed, measured with an overground 2-minute walk test. Secondary outcome measures included the Spinal Cord Injury Functional Ambulation Profile (SCI-FAP), the Activities-specific Balance Confidence (ABC) scale, and the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P).

No significant difference in maximal walking speed between the walking adaptability (n = 17) and conventional locomotor and strength (n = 18) training groups was found 6 weeks after training at follow-up (-0.05 m/s; 95% CI = -0.12-0.03). In addition, no significant group differences in secondary outcomes were found. However, independent of intervention, significant improvements over time were found for maximal walking speed, SCI-FAP, ABC, and USER-P restrictions scores. Conclusions. Our findings suggest that walking adaptability training may not be superior to conventional locomotor and strength training for improving walking capacity, functional ambulation, balance confidence, or participation in ambulatory people with iSCI.

Dutch Trial Register; Effect of GRAIL training in iSCI.

Microglia play important roles in maintaining brain homeostasis and neurodegeneration. The discovery of genetic variants in genes predominately or exclusively expressed in myeloid cells, such as Apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2), as the strongest risk factors for Alzheimer's disease (AD) highlights the importance of microglial biology in the brain. The sequence, structure and function of several microglial proteins are poorly conserved across species, which has hampered the development of strategies aiming to modulate the expression of specific microglial genes. One way to target APOE and TREM2 is to modulate their expression using antisense oligonucleotides (ASOs).

In this study, we identified, produced, and tested novel, selective and potent ASOs for human APOE and TREM2. We used a combination of in vitro iPSC-microglia models, as well as microglial xenotransplanted mice to provide proof of activity in human microglial in vivo.

We proved their efficacy in human iPSC microglia in vitro, as well as their pharmacological activity in vivo in a xenografted microglia model. We demonstrate ASOs targeting human microglia can modify their transcriptional profile and their response to amyloid-β plaques in vivo in a model of AD.

This study is the first proof-of-concept that human microglial can be modulated using ASOs in a dose-dependent manner to manipulate microglia phenotypes and response to neurodegeneration in vivo.