Sleep in Normal Aging

The impact of Alzheimer’s disease (AD) and its related dementias is rapidly expanding, and its mitigation remains an urgent social and technical challenge. To date there are no effective treatments or interventions for AD, but recent studies suggest that alcohol consumption is correlated with the risk of developing dementia. In this review, we synthesize data from preclinical, clinical, and epidemiological models to evaluate the combined role of alcohol consumption and serotonergic dysfunction in AD, underscoring the need for further research on this topic. We first discuss the limitations inherent to current data-collection methods, and how neuropsychiatric symptoms common among AD, alcohol use disorder, and serotonergic dysfunction may mask their co-occurrence. We additionally describe how excess alcohol consumption may accelerate the development of AD via direct effects on serotonergic function, and we explore the roles of neuroinflammation and proteostasis in mediating the relationship between serotonin, alcohol consumption, and AD. Lastly, we argue for a shift in current research to disentangle the pathogenic effects of alcohol on early-affected brainstem structures in AD.

Sleep strongly supports the formation of adaptive immunity, e.g., after vaccination. However, the underlying mechanisms remain largely obscure. Here we show in healthy humans that sleep compared to nocturnal wakefulness specifically promotes the migration of various T-cell subsets towards the chemokine CCL19, which is essential for lymph-node homing and, thus, for the initiation and maintenance of adaptive immune responses. Migration towards the inflammatory chemokine CCL5 remained unaffected. Incubating the cells with plasma from sleeping participants likewise increased CCL19-directed migration, an effect that was dependent on growth hormone and prolactin signaling. These findings show that sleep selectively promotes the lymph node homing potential of T cells by increasing hormonal release, and thus reveal a causal mechanism underlying the supporting effect of sleep on adaptive immunity in humans.

The bidirectional relationship between sleep and pain problems has been extensively demonstrated but despite all the accumulating evidence, their shared mechanisms are currently not fully understood. This review examined the association between sleep disturbances, defined as a broad array of sleep-related outcomes (eg, poor quality, short duration, insomnia), and endogenous pain modulation (EPM) in healthy and clinical populations. Our search yielded 6,151 references, and 37 studies met the eligibility criteria. Qualitative results showed mixed findings regarding the association between sleep disturbances and temporal summation of pain (TSP) and conditioned pain modulation (CPM), with poor sleep more commonly associated with decreased pain inhibition in both populations. Quantitative results indicated that such associations were not statistically significant, neither in healthy populations when EPM outcomes were assessed for changes pre-/post-sleep intervention (TSP: .31 [95%CI: −.30 to .92]; P = .321; CPM: .40 [95%CI: −.06 to .85] P = .088) nor in clinical populations when such association was assessed via correlation (TSP: −.00 [95%CI: −.22 to .21] P = .970; CPM: .12 [95%CI: −.05 to .29]; P = .181). For studies that reported results by sex, meta-analysis showed that experimental sleep disturbances impaired pain inhibition in females (1.43 [95%CI: .98–1.88]; P < .001) but not in males (−.30 [95%CI: −2.69 to 1.60]; P = .760). Only one study investigating the association between sleep disturbances and offset analgesia was identified, while no studies assessing spatial summation of pain were found. Overall, this review provides a comprehensive overview of the association between sleep disturbances and EPM function, emphasizing the need for further investigation to clarify specific mechanisms and phenotypic subtypes.

This review shines a light on the association between sleep disturbances and endogenous pain modulation function. Qualitatively, we found a frequent association between reduced sleep quality and impaired pain inhibition. However, quantitatively such an association was not corroborated. Sex-specific effects were observed, with females presenting sleep-related impaired pain inhibition but not males.

Perform a secondary analysis examining the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for depression symptom responses, and explore changes in potential target mechanisms.

Secondary analysis of a randomized controlled trial with convenience age subsamples (younger (20–49 year; n = 52) versus and older (50–71 years; n = 35)).

Community mental health clinics.

Eighty-seven adults with serious mental illness.

TranS-C versus treatment as usual (TAU).

Outcomes were depression symptoms (Quick Inventory of Depression Symptoms), insomnia symptoms (Insomnia Severity Index), and objective sleep-wake rhythm measures (interdaily stability and relative amplitude).

Depression response rates (≥50% symptom reductions) were higher in the TranS-C (35.0%) than the TAU (8.8%) group 6-months postintervention (χ² = 10.3, p = 0.001). There was a medium effect of TranS-C versus TAU on depression symptoms 6-months postintervention (Cohen's d = −0.40, 95% confidence interval (CI): −0.81, 0.01). In both age groups, there were large treatment effects on insomnia symptoms post-treatment (Cohen's d >0.90). In the older subsample, there were additionally medium treatment effects on post-treatment interdaily stability (Cohen's d = 0.60, 95% CI: −0.11, 1.61). Post-treatment reductions in insomnia symptoms correlated with depression symptom reduction 6-months later in the younger subsample (Spearman rho = 0.59, n = 20, p = 0.008). In older adults, postintervention increases in interdaily stability correlated with depression symptom reductions 6-months later (Spearman rho = −0.52, n = 15, p = 0.049).

Confirmatory trials are needed, given the low age-specific sample sizes here, to determine if TranS -C's produces durable depression responses by increasing sleep-wake rhythm stability in older adults and improving insomnia symptoms in younger adults.

The authors evaluated preliminary efficacy of a behavioral intervention that targets sleep/sleep-wake rhythms, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C), for depression symptoms in people with serious mental illness. TranS-C was associated with higher depression response rates than treatment as usual 6-months postintervention. The degree of depression symptom response 6-months later was related to the degree of treatment phase improvements in interdaily stability (in older adults) and reduction in insomnia severity (in younger adults).

A pragmatic nonpharmacologic intervention, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction, has preliminary efficacy for improving sleep-wake factors and depression symptoms.

Finding typical patterns - phenotypes - of sleep behaviors characterizing parasomnias in different age and sex groups.

We analyzed YouTube videos on sleep-related behaviors likely representing parasomnias. We applied the search terms “sleepwalking”, “somnambulism”, “sleep eating”, “sleep sex”, “sleep talking”, and “aggression in sleep” in six languages. We classified those persons shown on the videos into estimated biological sex and age (child, adult, elderly) groups. We scored the activity types by a self-made scale and applied binary logistic regression to analyze the association between sleep behaviors versus sex and age groups by the STATA package, providing a 95% confidence interval and the probability of statistical significance.

224 videos (102 women, 68 children, 16 adults, and 40 elderly people) were scored. Elderly people had significantly (P < 0.012) lower odds of sleepwalking compared to adults and children. Adult females performed complex manual activities during sleepwalking more often than males (P < 0.012). Elderly males had 40-fold odds compared to adults and children, to perform aggressive movements and 70-fold odds of complex movements in bed, compared to adults. Elderly people presented emotional behaviors less frequently than adults (P < 0.004), and females showed them twice as often as males. Adults sleep-talked full sentences more often than children and elderly people (P < 0.001).

Our results support the existence of age- and sex-specific parasomnia phenotypes, denoting possible safety measures. The remarkably low odds of sleepwalking in the elderly highlight the possibility of different pathomechanisms in higher age groups compared to children.

Parasomnias present highly variable clinical forms and often cause injuries. Identifying typical phenotypes may help risk management and imply theoretical conclusions. Our study supports the existence of age-specific parasomnia phenotypes. We found that adult women have a high risk of performing dangerous activities during sleep, and elderly males often move violently in bed, likely representing dream enactment behaviors. Elderly people of both sexes have low odds of sleep ambulation- likely representing somnambulism; compared to adults and children, constituting a descending “age slope” of somnambulism that might reflect different underlying pathomechanisms in children versus adults and the elderly.