"The worst thing is lying in bed thinking 'I want a cigarette'" a qualitative exploration of smoker's and ex-smoker's perceptions of sleep during a quit attempt and the use of cognitive behavioural therapy for insomnia to aid cessation.

Smokers report poorer sleep quality than non-smokers and sleep quality deteriorates further during cessation, increasing risk of smoking relapse. Despite the use of cognitive behavioural therapy for insomnia (CBT-I) to aid quit attempts emerging in the area, little is known about smokers and ex smoker's experiences of sleep during a quit attempt or their perceptions of CBT-I. This study addresses this gap by exploring smoker's and ex-smoker's experiences of the link between smoking and sleep and how this may change as a function of smoking/smoking abstinence. It also explores views of traditional CBT-I components (i.e., perceived feasibility, effectiveness, barriers of use). We conducted semi-structured interviews with current and recently quit smokers (n = 17) between January and September 2022. The framework method was used for analysis. Four themes addressing research questions were described. These included: 1) A viscous cycle; poor sleep quality and negative psychological state during cessation; 2) Perceived engagement and effectiveness; the importance of feasibility, experience, value, identity and psychological state in assessing CBT-I as a cessation tool; 3) Striking a balance; tailoring CBT-I to reduce psychological overload in a time of lifestyle transition; and 4) Personalisation and digital delivery helping overcome psychological barriers during cessation. The analysis suggested during quit attempts smokers experienced a range of sleep problems that could increase risk of relapse due to a negative impact on psychological state. It also revealed participants thought that CBT-I is something they would use during a quit attempt but suggested changes and additions that would improve engagement and be better tailored to quitting smokers. Key additions included the integration of smoking-based cognitive restructuring, starting the intervention prior to a quit attempt, and the need for personalisation and tailoring.

Associations between self-reported sleep quality, fatigue severity, factors associated with successful cessation, and cessation beliefs among regular smokers.

BACKGROUND: Smokers report poorer sleep than non-smokers and sleep quality deteriorates further during cessation, increasing risk of smoking relapse. Better understanding of the relationship between sleep and relapse-related outcomes could inform novel approaches to smoking cessation support. The aim of this study was to investigate same day associations of self-reported sleep quality and fatigue severity with factors associated with successful cessation and cessation beliefs, among regular smokers. METHODS: This cross-sectional observational study (n=412) collected self-reported sleep quality, fatigue severity, and factors associated with successful cessation and cessation beliefs among regular smokers via an online survey (60% male). RESULTS: There was evidence of an association between sleep quality (SQ) and reduced 24hr (ß = -0.12, p = 0.05) and lifetime (ß = -0.09, p = 0.04) abstinence self-efficacy. In addition, poorer SQ and higher fatigue severity (FS) were associated with increased smoking urges (SQ: ß = 0.27, p < .001; FS: ß = 0.32, p < .001), increased barriers to cessation (SQ: ß = 0.19, p < .001; FS: ß = 0.32, p < .001), and increased perceived risks to cessation (SQ: ß = 0.18, p < .001; FS: ß = 0.26, p < .001). Fatigue severity was weakly associated with increased perceived benefits to cessation (ß = 0.12, p = .017). CONCLUSIONS: Self-reported sleep quality and fatigue severity were associated with multiple factors associated with successful cessation and cessation beliefs. Further research is needed to extend these findings by using different methods to identify the temporal direction of associations and causality. IMPLICATIONS: This study is the first to examine associations between sleep quality, fatigue severity, and factors associated with successful cessation and cessation beliefs. Findings show that both sleep quality and fatigue severity are associated with multiple factors associated with successful cessation and could be modifiable targets for future smoking cessation interventions. Furthermore, our data suggest that fatigue severity has an independent effect on multiple factors associated with successful cessation when accounting for sleep quality. This indicates that fatigue, independent of sleep quality, could be an important factor in a quit attempt.

Automated Real-World Video Analysis of Sit-to-Stand Transitions Predicts Parkinson's Disease Severity.

Introduction: Technology holds the potential to track disease progression and response to neuroprotective therapies in Parkinson's disease (PD). The sit-to-stand (STS) transition is a frequently occurring event which is important to people with PD. The aim of this study was to demonstrate an automatic approach to quantify STS duration and speed using a real-world free-living dataset and look at clinical correlations of the outcomes, including whether STS parameters change when someone withholds PD medications. Methods: Eighty-five hours of video data were collected from 24 participants staying in pairs for 5-day periods in a naturalistic setting. Skeleton joints were extracted from the video data; the head trajectory was estimated and used to estimate the STS parameters of duration and speed. Results: 3.14 STS transitions were seen per hour per person on average. Significant correlations were seen between automatic and manual STS duration (Pearson rho - 0.419, p = 0.042) and between automatic STS speed and manual STS duration (Pearson rho - 0.780, p < 0.001). Significant and strong correlations were seen between the gold-standard clinical rating scale scores and both STS duration and STS speed; these correlations were not seen in the STS transitions when the participants were carrying something in their hand(s). Significant differences were seen at the cohort level between control and PD participants' ON medications' STS duration (U = 6,263, p = 0.018) and speed (U = 9,965, p < 0.001). At an individual level, only two participants with PD became significantly slower to STS when they were OFF medications; withholding medications did not significantly change STS duration at an individual level in any participant. Conclusion: We demonstrate a novel approach to automatically quantify and ecologically validate two STS parameters which correlate with gold-standard clinical tools measuring disease severity in PD.

L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults.

Introduction: Millions of people worldwide take medications such as L-DOPA that increase dopamine to treat Parkinson's disease. Yet, we do not fully understand how L-DOPA affects sleep and memory. Our earlier research in Parkinson's disease revealed that the timing of L-DOPA relative to sleep affects dopamine's impact on long-term memory. Dopamine projections between the midbrain and hippocampus potentially support memory processes during slow wave sleep. In this study, we aimed to test the hypothesis that L-DOPA enhances memory consolidation by modulating NREM sleep. Methods: We conducted a double-blind, randomised, placebo-controlled crossover trial with healthy older adults (65-79 years, n = 35). Participants first learned a word list and were then administered long-acting L-DOPA (or placebo) before a full night of sleep. Before sleeping, a proportion of the words were re-exposed using a recognition test to strengthen memory. L-DOPA was active during sleep and the practice-recognition test, but not during initial learning. Results: The single dose of L-DOPA increased total slow-wave sleep duration by approximately 11% compared to placebo, while also increasing spindle amplitudes around slow oscillation peaks and around 1-4 Hz NREM spectral power. However, behaviourally, L-DOPA worsened memory of words presented only once compared to re-exposed words. The coupling of spindles to slow oscillation peaks correlated with these differential effects on weaker and stronger memories. To gauge whether L-DOPA affects encoding or retrieval of information in addition to consolidation, we conducted a second experiment targeting L-DOPA only to initial encoding or retrieval and found no behavioural effects. Discussion: Our results demonstrate that L-DOPA augments slow wave sleep in elderly, perhaps tuning coordinated network activity and impacting the selection of information for long-term storage. The pharmaceutical modification of slow-wave sleep and long-term memory may have clinical implications. Clinical trial registration: Eudract number: 2015-002027-26; https://doi.org/10.1186/ISRCTN90897064, ISRCTN90897064.

Understanding how people with Parkinson's disease turn in gait from a real-world in-home dataset.

INTRODUCTION: Turning in gait digital parameters may be useful in measuring disease progression in Parkinson's disease (PD), however challenges remain over algorithm validation in real-world settings. The influence of clinician observation on turning outcomes is poorly understood. Our objective is to describe a unique in-home video dataset and explore the use of turning parameters as biomarkers in PD. METHODS: 11 participants with PD, 11 control participants stayed in a home-like setting living freely for 5 days (with two sessions of clinical assessment), during which high-resolution video was captured. Clinicians watched the videos, identified turns and documented turning parameters. RESULTS: From 85 hours of video 3869 turns were evaluated, averaging at 22.7 turns per hour per person. 6 participants had significantly different numbers of turning steps and/or turn duration between "ON" and "OFF" medication states. Positive Spearman correlations were seen between the Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale III score with a) number of turning steps (rho = 0.893, p < 0.001), and b) duration of turn (rho = 0.744, p = 0.009) "OFF" medications. A positive correlation was seen "ON" medications between number of turning steps and clinical rating scale score (rho = 0.618, p = 0.048). Both cohorts took more steps and shorter durations of turn during observed clinical assessments than when free-living. CONCLUSION: This study shows proof of concept that real-world free-living turn duration and number of turning steps recorded can distinguish between PD medication states and correlate with gold-standard clinical rating scale scores. It illustrates a methodology for ecological validation of real-world digital outcomes.

T2 heterogeneity as an in vivo marker of microstructural integrity in medial temporal lobe subfields in ageing and mild cognitive impairment.

A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n = 49) compared to healthy older controls (n = 99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in CA1-3 and entorhinal cortex and volume of entorhinal cortex showed some ability to predict cognitive decline, where absolute T2 could not, however further studies are required to verify this result. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative diseases and the study of brain-behaviour relationships.

T2 heterogeneity: a novel marker of microstructural integrity associated with cognitive decline in people with mild cognitive impairment.

BACKGROUND: Early Alzheimer's disease (AD) diagnosis is vital for development of disease-modifying therapies. Prior to significant brain tissue atrophy, several microstructural changes take place as a result of Alzheimer's pathology. These include deposition of amyloid, tau and iron, as well as altered water homeostasis in tissue and some cell death. T2 relaxation time, a quantitative MRI measure, is sensitive to these changes and may be a useful non-invasive, early marker of tissue integrity which could predict conversion to dementia. We propose that different microstructural changes affect T2 in opposing ways, such that average 'midpoint' measures of T2 are less sensitive than measuring distribution width (heterogeneity). T2 heterogeneity in the brain may present a sensitive early marker of AD pathology. METHODS: In this cohort study, we tested 97 healthy older controls, 49 people with mild cognitive impairment (MCI) and 10 with a clinical diagnosis of AD. All participants underwent structural MRI including a multi-echo sequence for quantitative T2 assessment. Cognitive change over 1 year was assessed in 20 participants with MCI. T2 distributions were modelled in the hippocampus and thalamus using log-logistic distribution giving measures of log-median value (midpoint; T2µ) and distribution width (heterogeneity; T2σ). RESULTS: We show an increase in T2 heterogeneity (T2σ; p < .0001) in MCI compared to healthy controls, which was not seen with midpoint (T2µ; p = .149) in the hippocampus and thalamus. Hippocampal T2 heterogeneity predicted cognitive decline over 1 year in MCI participants (p = .018), but midpoint (p = .132) and volume (p = .315) did not. Age affects T2, but the effects described here are significant even after correcting for age. CONCLUSIONS: We show that T2 heterogeneity can identify subtle changes in microstructural integrity of brain tissue in MCI and predict cognitive decline over a year. We describe a new model that considers the competing effects of factors that both increase and decrease T2. These two opposing forces suggest that previous conclusions based on T2 midpoint may have obscured the true potential of T2 as a marker of subtle neuropathology. We propose that T2 heterogeneity reflects microstructural integrity with potential to be a widely used early biomarker of conditions such as AD.

Effects of Parkinson's disease and dopamine on digit span measures of working memory.

RATIONALE: Parkinson's disease (PD) impairs working memory (WM)-the ability to maintain items in memory for short periods of time and manipulate them. There is conflicting evidence on the nature of the deficits caused by the disease, and the potential beneficial and detrimental effects of dopaminergic medication on different WM processes. OBJECTIVES: We hypothesised that PD impairs both maintenance and manipulation of items in WM and dopaminergic medications improve this in PD patients but impair it in healthy older adults. METHODS: We tested 68 PD patients ON and OFF their dopaminergic medication, 83 healthy age-matched controls, and 30 healthy older adults after placebo and levodopa administration. We used the digit span, a WM test with three components (forwards, backwards, and sequence recall) that differ in the amount of manipulation required. We analysed the maximum spans and the percentage of lists correctly recalled, which probe capacity of WM and the accuracy of the memory processes within this capacity, respectively. RESULTS: PD patients had lower WM capacity across all three digit span components, but only showed reduced percentage accuracy on the components requiring manipulation (backwards and sequence spans). Dopaminergic medication did not affect performance in PD patients. In healthy older adults, levodopa did not affect capacity, but did impair accuracy on one of the manipulation components (sequence), without affecting the other (backwards). CONCLUSIONS: This suggests that the deficit of maintenance capacity and manipulation accuracy in PD patients is not primarily a dopaminergic one and supports a potential "overdosing" of intact manipulation mechanisms in healthy older adults by levodopa.