Spinal Muscular Atrophy Treatment in Patients Identified by Newborn Screening-A Systematic Review.

BACKGROUND: In spinal muscular atrophy, clinical trial results indicated that disease-modifying treatments are highly effective when given prior to symptom onset, which has prompted newborn screening programs in growing number of countries. However, prognosis of those patients cannot be inferred from clinical trials conducted in presymptomatic individuals, as in some cases disease presents very early. METHODS: we conducted a systematic review of articles published up to January 2023. RESULTS: Among 35 patients with three SMN2 copies treated before 42 days of age and followed-up for at least 18 months, all but one achieved autonomous ambulation. Of 41 patients with two SMN2 copies, who were non-symptomatic at treatment initiation, all achieved a sitting position independently and 31 were able to walk. Of 16 patients with two SMN2 copies followed-up for at least 18 months who presented with symptoms at treatment onset, 3 achieved the walking milestone and all but one were able to sit without support. CONCLUSIONS: evaluation of data from 18 publications indicates that the results of early treatment depend on the number of SMN2 copies and the initial neurological status of the patient.

Effort during prolonged wakefulness is associated with performance to attentional and executive tasks but not with cortical excitability in late-middle-aged healthy individuals.

OBJECTIVE: Sleep loss negatively affects brain function with repercussion not only on objective measures of performance but also on many subjective dimensions, including effort perceived for the completion of cognitive processes. This may be particularly important in aging, which is accompanied by important changes in sleep and wakefulness regulation. We aimed to determine whether subjectively perceived effort covaried with cognitive performance in healthy late-middle-aged individuals. METHOD: We assessed effort and performance to cognitive tasks in 99 healthy adults (66 women; 50-70 years) during a 20-hr wake extension protocol, following 7 days of regular sleep and wake times and a baseline night of sleep in the laboratory. We further explored links with cortical excitability using transcranial magnetic stimulation coupled to electroencephalography. RESULTS: Perceived effort increased during wake extension and was highly correlated to subjective metrics of sleepiness, fatigue, and motivation, but not to variations in cortical excitability. Moreover, effort increase was associated with decreased performance to some cognitive tasks (psychomotor vigilance and two-back working memory task). Importantly, effort variations during wakefulness extension decreased from age 50 to 70 years, while more effort is associated with worse performance in older individuals. CONCLUSION: In healthy late-middle-aged individuals, more effort is perceived to perform cognitive tasks, but it is not sufficient to overcome the performance decline brought by lack of sleep. Entry in the seventh decade may stand as a turning point in the daily variations of perceived effort and its link with cognition. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Genetic risk for insomnia is associated with objective sleep measures in young and healthy good sleepers.

Insomnia disorder (ID) is the second most common neuropsychiatric disorder. Its socioeconomic burden is enormous while diagnosis and treatment are difficult. A novel approach that reveals associations between insomnia genetic propensity and sleep phenotypes in youth may help understand the core of the disease isolated from comorbidities and pave the way for new treatments. We obtained quantitative nocturnal sleep electroencephalogram (EEG) features in 456 participants (18-31y, 49 women). Sleep EEG was recorded during a baseline night following at least 7 days of regular sleep times. We then assessed daytime sleep onset latency in a subsample of N = 359 men exposed to manipulations affecting sleep pressure. We sampled saliva or blood for polygenic risk score (PRS) determination. The PRS for ID was computed based on genome-wide common single nucleotide polymorphism assessments. Participants also completed a battery of behavioral and cognitive tests. The analyses revealed that the PRS for ID was negatively associated with cumulated EEG power in the delta (0.5-4 Hz) and theta (4-8 Hz) bands across rapid eye movement (REM) and non-REM sleep (p ≤ .0026; ß ≥ -0.13) controlling for age, sex and BMI. The PRS for ID was also negatively associated with daytime likelihood of falling asleep (ß = -0.19, p = .0009). Other explorations for associations with non-baseline-nights, cognitive measures, and mood did not yield significant results. These results propose that the need or the ability to fall asleep and to generate slow brain activity during sleep may constitute the core sleep-related risk factors for developing ID.

Alzheimer's disease genetic risk and sleep phenotypes in healthy young men: association with more slow waves and daytime sleepiness.

STUDY OBJECTIVES: Sleep disturbances and genetic variants have been identified as risk factors for Alzheimer's disease (AD). Our goal was to assess whether genome-wide polygenic risk scores (PRS) for AD associate with sleep phenotypes in young adults, decades before typical AD symptom onset. METHODS: We computed whole-genome PRS for AD and extensively phenotyped sleep under different sleep conditions, including baseline sleep, recovery sleep following sleep deprivation, and extended sleep opportunity, in a carefully selected homogenous sample of 363 healthy young men (22.1 years ± 2.7) devoid of sleep and cognitive disorders. RESULTS: AD PRS was associated with more slow-wave energy, that is, the cumulated power in the 0.5-4 Hz EEG band, a marker of sleep need, during habitual sleep and following sleep loss, and potentially with larger slow-wave sleep rebound following sleep deprivation. Furthermore, higher AD PRS was correlated with higher habitual daytime sleepiness. CONCLUSIONS: These results imply that sleep features may be associated with AD liability in young adults, when current AD biomarkers are typically negative, and support the notion that quantifying sleep alterations may be useful in assessing the risk for developing AD.