Sleep fragmentation despite intact rest-activity patterns in premanifest Huntington's disease: An actigraphy study.

OBJECTIVE: Sleep research in Huntington's disease (HD) has primarily focused on manifest HD, with significantly less attention given to premanifest HD (Pre-HD). Therefore, we investigated sleep and rest-activity patterns in people with Pre-HD versus healthy controls (HC). METHODS: We conducted a cross-sectional study including 36 Pre-HD and 48 HC participants. Pre-HD participants were stratified into three groups according to their proximity to estimated diagnosis, using a cytosine-adenine-guanine (CAG) and current age-based predictive model: NEAR (<9 years to diagnosis), MID (9-15 years to diagnosis) and FAR (>15 years to diagnosis). Sleep and rest-activity patterns were assessed using wrist-worn actigraphy, a sleep diary, and sleep questionnaires. RESULTS: NEAR and MID groups experienced higher fragmentation index than HC and FAR groups. NEAR and MID groups also exhibited greater WASO than the FAR group. NEAR and MID groups showed lower intra-daily variability (IV) than HC and FAR groups, with the NEAR group also being more active in the most active 10 h (M10). Groups did not differ on subjective sleep measures, inter-daily stability (IS), sleep regularity index, relative amplitude, or amount of activity in the least active 5 h (L5). Considering all Pre-HD participants, fewer years to diagnosis, higher CAG-age-product (CAP) scores (a measure of cumulative exposure to the HD-causing gene mutation) and larger CAG repeat lengths correlated with higher WASO, fragmentation index, L5, IS, and lower sleep efficiency and IV. Higher CAP score correlated with higher M10. CONCLUSIONS: Despite intact rest-activity patterns and similar subjective sleep quality to HC, greater sleep fragmentation is a prominent and early feature in Pre-HD. Therefore, reducing sleep fragmentation may be a potential target for sleep intervention in HD. Longitudinal studies using larger samples are needed to assess sleep across the disease spectrum and its impact on clinical outcomes, like cognition.

Subjective awareness of sleepiness while driving in younger and older adults.

Understanding whether drivers can accurately assess sleepiness is essential for educational campaigns advising drivers to stop driving when feeling sleepy. However, few studies have examined this in real-world driving environments, particularly among older drivers who comprise a large proportion of all road users. To examine the accuracy of subjective sleepiness ratings in predicting subsequent driving impairment and physiological drowsiness, 16 younger (21-33 years) and 17 older (50-65 years) adults drove an instrumented vehicle for 2 h on closed loop under two conditions: well-rested and 29 h sleep deprivation. Sleepiness ratings (Karolinska Sleepiness Scale, Likelihood of Falling Asleep scale, Sleepiness Symptoms Questionnaire) were obtained every 15min, alongside lane deviations, near crash events, and ocular indices of drowsiness. All subjective sleepiness measures increased with sleep deprivation for both age groups (p < 0.013). While most subjective sleepiness ratings significantly predicted driving impairment and drowsiness in younger adults (OR: 1.7-15.6, p < 0.02), this was only apparent for KSS, likelihood of falling asleep, and "difficulty staying in the lane for the older adults" (OR: 2.76-2.86, p = 0.02). This may be due to an altered perception of sleepiness in older adults, or due to lowered objective signs of impairment in the older group. Our data suggest that (i) younger and older drivers are aware of sleepiness; (ii) the best subjective scale may differ across age groups; and (iii) future research should expand on the best subjective measures to inform of crash risk in older adults to inform tailored educational road safety campaigns on signs of sleepiness.

Sleep, alertness and performance across a first and a second night shift in mining haul truck drivers.

This study examined the impact of first and second night shift work on sleep and performance in mining haul truck drivers. Sleep-wake patterns were monitored using wrist actigraphy. The Karolinska Sleepiness Scale (KSS), Psychomotor Vigilance Test (PVT) and a truck simulator were administered at the start and end of the first (N1) or second (N2) night shift (19:00-07:00 h). Participants were categorised into those who demonstrated a decline in performance (increase of one or more PVT lapses [reaction time >500 msec] from the start to the end of shift) or those who did not demonstrate a decline in performance (no increase in lapses) from the start to the end of shift. Total sleep time (TST) was longer in the 24 h prior to N1 (9.05 ± 1.49 h) compared to N2 (5.38 ± 1.32 h). PVT lapses and the slowest 10% of reaction times were similar at the start and end of N1, while greater impairments on these outcomes were observed at the end of N2 compared to the end of N1 (p < .05). In contrast, subjective sleepiness was equally impaired at the end of both night shifts. PVT performance (lapses and slowest 10% of reaction times) and drive violations demonstrated a similar direction of change on N1 and N2. Participants who demonstrated a decline in performance showed reduced TST in the 48 h prior to shifts compared to those who demonstrated no decline in performance across the shift. Likely due to short sleep prior, the end of N2 was associated with pronounced performance impairments on the PVT and drive violations compared to the start of the shift. The findings suggest that drive violations may be more sensitive to sleep loss compared to the other driving measures examined in this study. This study also emphasizes the need for adequate recovery sleep between night shifts.

On-road driving impairment following sleep deprivation differs according to age.

Impaired driving performance due to sleep loss is a major contributor to motor-vehicle crashes, fatalities, and serious injuries. As on-road, fully-instrumented studies of drowsy driving have largely focused on young drivers, we examined the impact of sleep loss on driving performance and physiological drowsiness in both younger and older drivers of working age. Sixteen 'younger' adults (M = 24.3 ± 3.1 years [21-33 years], 9 males) and seventeen 'older' adults (M = 57.3 ± 5.2, [50-65 years], 9 males) undertook two 2 h drives on a closed-loop track in an instrumented vehicle with a qualified instructor following (i) 8 h sleep opportunity the night prior (well-rested), and (ii) after 29-h of total sleep deprivation (TSD). Following TSD, both age groups displayed increased subjective sleepiness and lane departures (p < 0.05), with younger drivers exhibiting 7.37 × more lane departures, and 11 × greater risk of near crash events following sleep loss. While older drivers exhibited a 3.5 × more lane departures following sleep loss (p = 0.008), they did not have a significant increase in near-crash events (3/34 drives). Compared to older adults, younger adults had 3.1 × more lane departures (p = < 0.001), and more near crash events (79% versus 21%, p = 0.007). Ocular measures of drowsiness, including blink duration, number of long eye closures and PERCLOS increased following sleep loss for younger adults only (p < 0.05). These results suggest that for older working-aged adults, driving impairments observed following sleep loss may not be due to falling asleep. Future work should examine whether this is attributed to other consequences of sleep loss, such as inattention or distraction from the road.

I think I'm sleepy, therefore I am - Awareness of sleepiness while driving: A systematic review.

Driver drowsiness contributes to 10-20% of motor vehicle crashes. To reduce crash risk, ideally drivers would be aware of the drowsy state and cease driving. The extent to which drivers can accurately identify sleepiness remains under much debate. We systematically examined whether individuals are aware of sleepiness while driving, and whether this accurately reflects driving impairment, using meta-analyses and narrative review. Within this scope, there is high variability in measures of subjective sleepiness, driving performance and physiologically-derived drowsiness, and statistical analyses. Thirty-four simulated/naturalistic driving studies were reviewed. To summarise, drivers were aware of sleepiness, and this was associated to physiological drowsiness and driving impairment, such that high levels of sleepiness significantly predicted crash events and lane deviations. Subjective sleepiness was more strongly correlated (i) with physiological drowsiness compared to driving outcomes; (ii) under simulated driving conditions compared to naturalistic drives; and (iii) when examined using the Karolinska sleepiness scale (KSS) compared to other measures. Gaps remain in relation to how age, sex, and varying degrees of sleep loss may influence this association. This review provides evidence that drivers are aware of drowsiness while driving, and stopping driving when feeling 'sleepy' may significantly reduce crash risk.

An evaluation and comparison of commercial driver sleepiness detection technology: a rapid review.

Objective. Sleepiness-related motor vehicle crashes, caused by lack of sleep or driving during night-time hours, often result in serious injury or fatality. Sleepiness detection technology is rapidly emerging as a sleepiness risk mitigation strategy for drivers. Continuous monitoring technologies assess and alert to driver sleepiness in real-time, while fit for duty technologies provide a single assessment of sleepiness state. The aim of this rapid review was to evaluate and compare sleepiness detection technologies in relation to specifications, cost, target consumer group and validity.Approach. We evaluated a range of sleepiness detection technologies suitable for consumer groups ranging from regular drivers in private vehicles through to work-related drivers within large businesses.Main results. Continuous monitoring technologies typically ranged between $100 and $3000 AUD and had ongoing monthly costs for telematics functionality and manager alerts. Fit for duty technologies had either a one-off purchase cost or a monthly subscription cost. Of concern, the majority of commercial continuous monitoring technologies lacked scientific validation. While some technologies had promising findings in terms of their ability to detect and reduce driver sleepiness, further validation work is required. Field studies that evaluate the sensitivity and specificity of technology alerts under conditions that are regularly experienced by drivers are necessary. Additionally, there is a need for longitudinal naturalistic driving studies to determine whether sleepiness detection technologies actually reduce sleepiness-related crashes or near-crashes.Significance. There is an abundance of sleepiness detection technologies on the market, but a majority lacked validation. There is a need for these technologies and their validation to be regulated by a driver safety body. Otherwise, consumers will base their technology choices on cost and features, rather than the ability to save lives.

Awareness of sleepiness: Temporal dynamics of subjective and objective sleepiness.

We systematically examined the temporal relationships between subjective sleepiness and both physiological drowsiness and performance impairment in a controlled laboratory setting. Eighteen healthy young adults (8 women; MAGE  = 21.44 ± 3.24 years) underwent 40 hr of extended wakefulness, completing a bihourly Karolinska Sleepiness Scale (KSS) and 10-min Psychomotor Vigilance Task (PVT). Microsleeps and slow eye movements (SEMs) were scored during the PVT. KSS scores increased 3 hr prior to performance impairment (p < .001) and 4-6 hr prior to physiological sleepiness (p < .001). There were strong within-subject correlations between KSS and PVT lapses (r = 0.75, p < .001) and physiological drowsiness (r > 0.60, p < .001). Between-subjects product-moment correlations were more modest but showed a significant positive increase across time awake, suggesting that subjective sleepiness and objective outcomes were more tightly correlated after sleep loss. Cross-correlations showed significant positive correlations at 0-lag (p < .034); however, a high proportion of participants showed maximal correlations at positive lags, suggesting KSS was associated with future objective impairment. Within individuals, subjective sleepiness was highly correlated with objective impairment, between-subject correlations were more modest, possibly due to interindividual vulnerability to sleep loss. These results suggest that subjective sleepiness represents an inbuilt early warning system for subsequent drowsiness and performance impairment.

The validity of the pupillographic sleepiness test at shorter task durations.

The pupillographic sleepiness test (PST) is an accurate predictor of alertness failure and performance impairment across sleep deprivation. At 11 min in duration, the task is considered too long to be used in occupational or roadside settings. We therefore investigated the predictive capacity of the PST at seven shortened test durations. Eighteen healthy young adults (aged 21.4 ± 3.2 years, 10 men) underwent 40 h of continuous wakefulness, completing an 11-min PST and a 10-min psychomotor vigilance task (PVT) every 2 h. Waking electroencephalography was recorded and scored for microsleeps during PVTs. The PST was divided into eight equal 82-s blocks and the predictive capacity of the pupillary unrest index (PUI) calculated at descending PST durations by systematically removing blocks. PUI increased significantly with time awake for all test durations (p < .0001), with a similar amplitude of PUI observed for test durations of 5.5 min and longer. While all test durations accurately predicted PVT impairment (AUC: 0.72-0.86, p < .001) and microsleep (AUC: 0.74-0.84, p < .0001), 5.5 min was the shortest duration where accuracy remained high across level and type of impairment (AUC: 0.79-0.86). For the 5.5-min duration, the positive predictive value (PPV) and negative predictive value (NPV) were on average 50.1% and 89.4%, respectively, and were comparable to the full 11-min task (PPV: 49.2%; NPV: 91%). The PST can be shortened to 5.5 min without compromising accuracy in detecting performance impairment or physiological drowsiness. The PST is an ideal candidate for fitness-for-duty or fitness-to-drive testing, and future studies should examine its predictive capacity, at shorter durations, against operationally relevant outcomes.

Acoustic slow wave sleep enhancement via a novel, automated device improves executive function in middle-aged men.

STUDY OBJECTIVES: As slow-wave activity (SWA) is critical for cognition, SWA-enhancing technologies provide an exciting opportunity to improve cognitive function. We focus on improving cognitive function beyond sleep-dependent memory consolidation, using an automated device, and in middle-aged adults, who have depleted SWA yet a critical need for maximal cognitive capacity in work environments. METHODS: Twenty-four healthy adult males aged 35-48 years participated in a randomized, double-blind, cross-over study. Participants wore an automated acoustic stimulation device that monitored real-time sleep EEG. Following an adaptation night, participants were exposed to either acoustic tones delivered on the up phase of the slow-wave (STIM) or inaudible "tones" during equivalent periods of stimulation (SHAM). An executive function test battery was administered after the experimental night. RESULTS: STIM resulted in an increase in delta (0.5-4 Hz) activity across the full-night spectra, with enhancement being maximal at 1 Hz. SWA was higher for STIM relative to SHAM. Although no group differences were observed in any cognitive outcomes, due to large individual differences in SWA enhancement, higher SWA responders showed significantly improved verbal fluency and working memory compared with nonresponders. Significant positive associations were found between SWA enhancement and improvement in these executive function outcomes. CONCLUSIONS: Our study suggests that (1) an automated acoustic device enhances SWA; (2) SWA enhancement improves executive function; (3) SWA enhancement in middle-aged men may be an important therapeutic target for enhancing cognitive function; and (4) there is a need to examine interindividual responses to acoustic stimulation and its effect on subsequent cognitive function. CLINICAL TRIAL REGISTRATION: This study has been registered with the Australian New Zealand Clinical Trials Registry. "The efficacy of acoustic tones in slow-wave sleep enhancement and cognitive function in healthy adult males". https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371548&isReview=true. REGISTRATION: ACTRN12617000399392.

Associations between sleep and verbal memory in subjective cognitive decline: A role for semantic clustering.

Age-related reductions in slow wave activity (SWA) and increased fragmentation during sleep play a key role in memory impairment. As the prefrontal cortex is necessary for the control processes relevant to memory encoding, including utilisation of internal heuristics such as semantic clustering, and is preferentially vulnerable to sleep disturbance, our study examined how SWA and sleep fragmentation relates to memory performance in individuals with Subjective Cognitive Decline (SCD). Thirty older adults with SCD (Mean Age = 69.34, SD = 5.34) completed a neurocognitive test battery, including the California Verbal Learning Test, which was used to assess semantic clustering. One week later, participants were admitted to the laboratory for a two night visit. SWA and sleep fragmentation were captured using sleep polysomnography. Next-day memory performance was tested using the Rey Auditory Verbal Learning Test. Poorer sleep (reduced SWA; increased arousals) was associated with reduced semantic clustering, which mediated impairment on verbal memory and learning tests conducted both the day after sleep was recorded (for both SWA and arousals), and a week prior (for arousals only). We demonstrate semantic clustering mediated the well described associations between sleep and verbal memory. As these strategies are a component of cognitive training interventions, future research may examine the role of simultaneous sleep interventions for improving cognitive training outcomes.

Pupillary instability as an accurate, objective marker of alertness failure and performance impairment.

Pupillary instability reflects alterations in autonomic nervous system activity and has been shown to reflect change in alertness. However, the extent to which it can predict subsequent performance impairment and alertness failure is not clear. Eighteen healthy young adults (group age = 21.44 ± 3.24 years, 10 men) underwent 40 hr of continuous wakefulness, completing an 11-min Pupillographic Sleepiness Test (PST), the Karolinska Sleepiness Scale and a 10-min Psychomotor Vigilance Task (PVT) every 2 hr. Waking electroencephalography was recorded continuously and scored for microsleeps and slow eye movements (SEMs) during PVTs. Pupillary instability was sensitive to time awake, significantly increasing after 18 hr of wakefulness. The time course of impairment was almost identical to PVT lapses, microsleeps and SEMs. Receiver operating characteristic curve analysis demonstrated reasonable sensitivity and specificity of pupillary instability in correctly classifying PVT lapses, microsleeps and SEMs above individual baseline thresholds (all AUC values >0.78, p < 0.0001). Preliminary cut-off scores ranging from 10 to 11.5 mm/min for varying impairment thresholds are proposed for young adults. If reproducible in field settings, the PST may be a strong candidate as a fitness for duty/fitness to drive tool for detecting drowsiness-related impairment.

Advanced Circadian Timing and Sleep Fragmentation Differentially Impact on Memory Complaint Subtype in Subjective Cognitive Decline.

BACKGROUND: Increased sleep fragmentation and advanced circadian timing are hallmark phenotypes associated with increased age-related cognitive decline. Subjective cognitive decline (SCD) is considered a prodromal stage of neurodegeneration and dementia; however, little is known about how sleep and circadian timing impact on memory complaints in SCD. OBJECTIVE: To determine how sleep and circadian timing impact on memory complaint subtypes in older adults with SCD. METHODS: Twenty-five older adults with SCD (mean age = 69.97, SD = 5.33) completed the Memory Functioning Questionnaire to characterize their memory complaints. They also underwent neuropsychological assessment, and completed 1 week of at-home monitoring of sleep with actigraphy and sleep diaries. This was followed by a two-night laboratory visit with overnight polysomnography and a dim light melatonin onset assessment to measure circadian timing. RESULTS: Advanced circadian timing was associated with greater memory complaints, specifically poorer memory of past events (r = -0.688, p = 0.002), greater perceived decline over time (r = -0.568, p = 0.022), and increased reliance on mnemonic tools (r = -0.657, p = 0.004). Increased sleep fragmentation was associated with reduced self-reported memory decline (r = 0.529, p = 0.014), and reduced concern about everyday forgetfulness (r = 0.435, p = 0.038). CONCLUSION: Advanced circadian timing was associated with a number of subjective memory complaints and symptoms. By contrast, sleep fragmentation was linked to lowered perceptions of cognitive decline, and less concern about memory failures. As circadian disruption is apparent in both MCI and Alzheimer's disease, and plays a key role in cognitive function, our findings further support a circadian intervention as a potential therapeutic tool for cognitive decline.

Impairment due to combined sleep restriction and alcohol is not mitigated by decaying breath alcohol concentration or rest breaks.

OBJECTIVE: Epidemiological and laboratory-based driving simulator studies have shown the detrimental impact of moderate, legal levels of alcohol consumption on driving performance in sleepy drivers. As less is known about the time course of decaying alcohol alongside performance impairment, our study examined impairment and recovery of performance alongside decaying levels of alcohol, with and without sleep restriction. METHODS: Sixteen healthy young males (18-27 years) underwent 4 counterbalanced conditions: Baseline, Alcohol (breath alcohol concentration [BrAC] < 0.05%), Sleep Restriction (5 hr time in bed), and Combined. Participants consumed alcohol (or control drink) ~4.5 hr post wake (12:30 p.m.). To test on the descending limb of alcohol, attention and vigilance test batteries commenced 1 hr after consumption and were completed every 30 min for 2 hr (1:30 p.m.-3:30 p.m.). RESULTS: The Combined condition impaired subjective and objective sleepiness. Here, performance deficits peaked 90 min after alcohol consumption or 30 min after the BrAC peak. Performance did not return to baseline levels until 2.5 hr following consumption, despite receiving rest breaks in between testing. CONCLUSIONS: These findings suggest that (a) falling BrACs are an inadequate guide for performance/safety and (b) rest breaks without sleep are not a safety measure for mitigating performance impairment when consuming alcohol following restricted sleep.