Sleep duration, sleep efficiency, and amyloid ß among cognitively healthy later-life adults: a systematic review and meta-analysis.

BACKGROUND: Abnormal amyloid ß (Aß) deposits in the brain are a hallmark of Alzheimer's disease (AD). Insufficient sleep duration and poor sleep quality are risk factors for developing AD. Sleep may play a role in Aß regulation, but the magnitude of the relationship between sleep and Aß deposition remains unclear. This systematic review examines the relationship between sleep (i.e., duration and efficiency) with Aß deposition in later-life adults. METHODS: A search of PubMed, CINAHL, Embase, and PsycINFO generated 5,005 published articles. Fifteen studies met the inclusion criteria for qualitative syntheses; thirteen studies for quantitative syntheses related to sleep duration and Aß; and nine studies for quantitative syntheses related to sleep efficiency and Aß. RESULTS: Mean ages of the samples ranged from 63 to 76 years. Studies measured Aß using cerebrospinal fluid, serum, and positron emission tomography scans with two tracers: Carbone 11-labeled Pittsburgh compound B or fluorine 18-labeled. Sleep duration was measured subjectively using interviews or questionnaires, or objectively using polysomnography or actigraphy. Study analyses accounted for demographic and lifestyle factors. Based on 13 eligible articles, our synthesis demonstrated that the average association between sleep duration and Aß was not statistically significant (Fisher's Z = -0.055, 95% CI = -0.117 ~ 0.008). We found that longer self-report sleep duration is associated with lower Aß (Fisher's Z = -0.062, 95% CI = -0.119 ~ -0.005), whereas the objectively measured sleep duration was not associated with Aß (Fisher's Z = 0.002, 95% CI = -0.108 ~ 0.113). Based on 9 eligible articles for sleep efficiency, our synthesis also demonstrated that the average association between sleep efficiency and Aß was not statistically significant (Fisher's Z = 0.048, 95% CI = -0.066 ~ 0.161). CONCLUSION: The findings from this review suggest that shorter self-reported sleep duration is associated with higher Aß levels. Given the heterogeneous nature of the sleep measures and outcomes, it is still difficult to determine the exact relationship between sleep and Aß. Future studies with larger sample sizes should focus on comprehensive sleep characteristics and use longitudinal designs to better understand the relationship between sleep and AD.

Context-specific emergence and growth of the SARS-CoV-2 Delta variant.

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing-and not the number of importations-were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529).

Association of Sleep With Risk of Alzheimer's Disease Mortality: NIH-AARP Diet and Health Study.

OBJECTIVES: Alzheimer's disease (AD) and related dementias contribute to one in three senior deaths. Lifestyle factors, including sleep, may contribute to AD risk and mortality; however, current evidence on sleep and AD mortality is mixed. METHODS: We used data from the NIH-AARP Diet and Health Study. Sleep duration and napping were self-reported and AD death were ascertained via linkage to the National Death Index. RESULTS: Long sleep and napping were both associated with increased AD mortality. Specifically, 9+ hr of sleep was associated with 50% increase (hazard ratio = 1.50, 95% CI = [1.17, 1.92]) in AD mortality when compared 7 to 8 hr, while napping for 1+ hr was associated with 29% increase (1.29 [1.08, 1.55]) when compared with no napping. Results appeared to be stronger in men and remained after removing AD deaths within first 5 years after baseline. DISCUSSION: Long sleep and napping may predict higher AD mortality in the older population.

Cross-sectional and prospective associations between self-reported sleep characteristics and cognitive function in men and women: The Midlife in the United States study.

Sleep behaviour is an important contributing factor in healthy human ageing and cognitive function. Previous studies have linked sleep deficiency with cognitive decline in older adults. However, there is need for more prospective investigations that focus on specific domains of cognitive function. The present study analysed cross-sectional and prospective associations between self-reported sleep and cognitive function in the Midlife in the United States (MIDUS) study. Weekday and weekend sleep duration and habitual sleep quality were obtained via questionnaire data. Brief Test of Adult Cognition by Telephone was conducted to assess overall cognitive function, as well as episodic memory and executive function. We found significant trend for both long weekday and weekend sleep (>8 hr) and lower episodic memory scores in the overall sample. Sex-specific cross-sectional analysis demonstrated men with longer weekend sleep duration have lower overall cognitive function scores, and a negative association between weekend sleep and episodic memory scores. Women demonstrated a positive association between weekend sleep duration and executive function scores. There was no prospective significance for overall or sex-specific analysis. Our present results suggest that sleep duration may contribute to cognitive function, and future studies should include objective sleep measurements and focus on the potential cognitive benefits of improving sleep to further elucidate this association.

Protocol for a type 1 hybrid effectiveness/implementation clinical trial of collaborative specialty care for Veterans with Gulf War Illness.

AIMS: We describe a clinical trial which is seeking to determine the effectiveness and understand implementation outcomes for tele-collaborative specialty care for Veterans with Gulf War Illness (GWI). MAIN METHODS: This study will be a hybrid type 1 randomized effectiveness-implementation trial comparing tele-collaborative specialty care to electronic consultation for Gulf War Veterans with GWI (N = 220). In tele-collaborative specialty care, the specialty provider team will deliver health coaching and problem-solving treatment to Veterans and recommend a plan for analgesic optimization. In electronic consultation, the specialty provider team will make a one-time recommendation to the primary care team for locally delivered health coaching, problem-solving treatment and analgesic optimization. The primary aim will be to determine the effectiveness of tele-collaborative specialty care as compared to electronic consultation to reduce disability related to GWI. Our secondary aim will be to understand implementation outcomes. SIGNIFICANCE: There is a need to improve care for Veterans with GWI. A potentially useful model to improve care is tele-collaborative specialty care, where the specialists work with the primary care provider to synergistically treat the patients. DISCUSSION: This is the first clinical trial to prospectively compare different models of care for Veterans with GWI. This responds to multiple calls for research to improve treatment for Veterans with GWI, including from the National Academy of Medicine.

Mobility in Blue-Green Spaces Does Not Predict COVID-19 Transmission: A Global Analysis.

Mobility restrictions during the COVID-19 pandemic ostensibly prevented the public from transmitting the disease in public places, but they also hampered outdoor recreation, despite the importance of blue-green spaces (e.g., parks and natural areas) for physical and mental health. We assess whether restrictions on human movement, particularly in blue-green spaces, affected the transmission of COVID-19. Our assessment uses a spatially resolved dataset of COVID-19 case numbers for 848 administrative units across 153 countries during the first year of the pandemic (February 2020 to February 2021). We measure mobility in blue-green spaces with planetary-scale aggregate and anonymized mobility flows derived from mobile phone tracking data. We then use machine learning forecast models and linear mixed-effects models to explore predictors of COVID-19 growth rates. After controlling for a number of environmental factors, we find no evidence that increased visits to blue-green space increase COVID-19 transmission. By contrast, increases in the total mobility and relaxation of other non-pharmaceutical interventions such as containment and closure policies predict greater transmission. Ultraviolet radiation stands out as the strongest environmental mitigant of COVID-19 spread, while temperature, humidity, wind speed, and ambient air pollution have little to no effect. Taken together, our analyses produce little evidence to support public health policies that restrict citizens from outdoor mobility in blue-green spaces, which corroborates experimental studies showing low risk of outdoor COVID-19 transmission. However, we acknowledge and discuss some of the challenges of big data approaches to ecological regression analyses such as this, and outline promising directions and opportunities for future research.

Context-specific emergence and growth of the SARS-CoV-2 Delta variant.

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta’s invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

Context-specific emergence and growth of the SARS-CoV-2 Delta variant.

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases 1-3 . The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions 4,5 . Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta's invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

Adolescent sleep characteristics and body-mass index in the Family Life, Activity, Sun, Health, and Eating (FLASHE) Study.

Sleep may play a role in overweight and obesity in adolescents. The objective of this study is to investigate the relationships between sleep duration and timing and overweight and obesity status in adolescents, with a special emphasis on weekday-weekend difference in sleep characteristics as well as sex-specific relationships. We examined 1,254 U.S. adolescents (12-17 years) self-reported sleep duration, timing, weekday-weekend differences in duration and timing in relation to overweight and obesity. We found an inverse association between sleep duration and overweight and obesity. Compared to 8-9 h of sleep, short sleep (< 7 h) on weekdays was associated with higher odds of overweight and obesity [Odds ratio (95% confidence interval), 1.73 (1.00, 2.97)] in the overall population, while long sleep (10+ h) on weekends was associated with lower odds, but only in males [0.56 (0.34, 0.92)]. We also found that a larger weekday-weekend difference in sleep duration was associated with overweight and obesity in females, but not in males. Specifically, the odds of overweight and obesity were significantly higher among females reporting longer sleep on weekends than weekdays by ≥ 2 h [2.31 (1.15, 4.63)] when compared to those reporting little weekday-weekend differences. Sleep timing, or weekday-weekend differences in sleep timing, were not associated with overweight and obesity in the overall population, although we found suggestive evidence linking later weekend sleep with overweight and obesity in females. Our findings support a role of sleep in adolescent obesity and suggest sex-differences in this relationship that warrant future studies.

Reduced blood pressure responsiveness to skeletal muscle metaboreflex activation in older adults following inorganic nitrate supplementation.

The vasoactive molecule nitric oxide (NO) contributes to regulation of blood pressure (BP) at rest and during exercise. Age-related exaggerated increased BP responses during exercise have been proposed to be due in part to a decreased NO bioavailability and possibly an enhanced skeletal muscle metaboreflex. In the present study we sought to determine if age-related differences in BP responses to skeletal muscle metaboreflex activation exist. Additionally, since NO bioavailability can be improved with exogenous nitrate (NO3-) via the nitrate-nitrite-NO pathway, we tested the hypothesis that inorganic NO3- supplementation would reduce BP responses to muscle metaboreflex activation in healthy older adults. 13 older adults (67 ±â€¯1 years) participated in a randomized, double-blind, placebo controlled crossover study consisting of four weeks of NO3- supplementation [beetroot powder; 250 mg (∼4.03 mmol) of NO3- and 20 mg (∼0.29 mmol) of NO2-] and four weeks of placebo (beetroot powder devoid of NO3-/NO2-). Skeletal muscle metaboreflex testing consisted of isometric handgrip exercise (IHG) at 30% of maximal voluntary contraction immediately followed by post exercise forearm ischemia (PEI), which was achieved by inflation of a rapid pressure cuff (240 mmHg) around the upper arm. BP responses were analyzed as the change (Δ) from baseline to the end of IHG and PEI. An additional 10 young adults (25 ±â€¯1 years) were recruited to serve as a reference cohort and address if BP responses to skeletal muscle metaboreflex activation were greater with aging. BP responses to IHG were similar between the young and older adults. However, older adults demonstrated a greater increase in systolic BP during PEI (P < 0.05). Plasma NO3- and NO2-were increased following NO3- supplementation in older adults (P < 0.01). ΔSystolic BP (19 ±â€¯2 vs. 13±3 mmHg, P < 0.05), ΔDiastolic BP (7 ±â€¯1 vs. 5±1 mmHg, P < 0.05) and ΔMean arterial pressure (11 ±â€¯1 vs. 8±2 mmHg, P < 0.05) were reduced during PEI following four weeks of NO3-supplementation, whereas placebo had no effect on ΔSystolic BP (16 ±â€¯2 vs. 17±2 mmHg), ΔDiastolic BP (5 ±â€¯1 vs. 7±1 mmHg), and ΔMean arterial pressure (8 ±â€¯1 vs. 10±1 mmHg) during PEI (all P > 0.05). These data suggest that inorganic NO3- supplementation attenuates skeletal muscle metaboreflex mediated increases in BP during exercise in older adults.

Inorganic nitrate supplementation attenuates peripheral chemoreflex sensitivity but does not improve cardiovagal baroreflex sensitivity in older adults.

Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BRA) or devoid of (BRP) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O2) and reported as the slope of the relationship between O2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BRA (from -0.14 ± 0.04 to -0.05 ± 0.02 l·min-1·%[Formula: see text]-1, P = 0.01) versus BRP (from -0.10 ± 0.05 to -0.11 ± 0.05 l·min-1·%[Formula: see text]-1, P = 0.80), with no differences in heart rate responsiveness (BRA: from -0.47 ± 0.06 to -0.33 ± 0.04 beats·min-1·%[Formula: see text]-1, BRP: from -0.48 ± 0.07 to -0.42 ± 0.06 beats·min-1·%[Formula: see text]-1) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BRA and BRP (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BRA) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.

Influence of chronic endurance exercise training on conduit artery retrograde and oscillatory shear in older adults.

PURPOSE: With aging, there tends to be an increase in retrograde and oscillatory shear in peripheral conduit arteries of humans. Whether the increase in shear rate is due to the aging process or an effect of a less active lifestyle that often accompanies aging is unknown. Therefore, we examined whether chronic endurance exercise training attenuates conduit artery retrograde and oscillatory shear in older adults. METHODS: Brachial and common femoral artery mean blood velocities and diameter were determined via Doppler ultrasound under resting conditions, and shear rate was calculated in 13 young (24 ± 2 years), 17 older untrained (66 ± 3 years), and 16 older endurance exercise-trained adults (66 ± 7 years). RESULTS: Brachial artery retrograde (-9.1 ± 6.4 vs. -12.6 ± 9.4 s(-1); P = 0.35) and oscillatory (0.14 ± 0.08 vs. 0.14 ± 0.08 arbitrary units; P = 0.99) shear were similar between the older trained and untrained groups, whereas brachial artery retrograde and oscillatory shear were greater in older untrained compared to young adults (-5.0 ± 3.4, 0.08 ± 0.05 s(-1) arbitrary units, P = 0.017 and 0.048, respectively). There was no difference between the young and older trained brachial retrograde (P = 0.29) and oscillatory (P = 0.07) shear. Common femoral artery retrograde (-6.3 ± 2.9 s(-1)) and oscillatory (0.21 ± 0.08 arbitrary units) shear were reduced in older trained compared to the older untrained group (-10.4 ± 4.1 and 0.30 ± 0.09 s(-1) arbitrary units, both P = 0.005 and 0.006, respectively), yet similar to young adults (-7.1 ± 3.5 and 0.19 ± 0.06 s(-1) arbitrary units, P = 0.81 and 0.87, respectively). CONCLUSION: Our results suggest that chronic endurance exercise training in older adults ameliorates retrograde and oscillatory shear rate patterns, particularly in the common femoral artery.

Acute dietary nitrate supplementation enhances compensatory vasodilation during hypoxic exercise in older adults.

We have previously demonstrated that aging reduces the compensatory vasodilator response during hypoxic exercise due to blunted nitric oxide (NO) signaling. Recent evidence suggests that NO bioavailability can be augmented by dietary nitrate through the nitrate-nitrite pathway. Thus we tested the hypothesis that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise, particularly in older adults. Thirteen young (25 ± 1 yr) and 12 older (64 ± 2 yr) adults performed rhythmic forearm exercise at 20% of maximum voluntary contraction during normoxia and hypoxia (∼80% O2 saturation); both before (control) and 3 h after beetroot juice (BR) consumption. Forearm vascular conductance (FVC; ml·min(-1)·100 mmHg(-1)) was calculated from forearm blood flow (ml/min) and blood pressure (mmHg). Compensatory vasodilation was defined as the relative increase in FVC due to hypoxic exercise (i.e., % increase compared with respective normoxic exercise trial). Plasma nitrite was determined from venous blood samples obtained before the control trials and each of the exercise trials (normoxia and hypoxia) after BR. Consumption of BR increased plasma nitrite in both young and older adults (P < 0.001). During the control condition, the compensatory vasodilator response to hypoxic exercise was attenuated in older compared with young adults (3.8 ± 1.7% vs. 14.2 ± 1.2%, P < 0.001). Following BR consumption, compensatory vasodilation did not change in young (13.7 ± 3.3%, P = 0.81) adults but was substantially augmented in older adults (11.4 ± 2.1%, P < 0.01). Our data suggest that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise in older but not young adults.

Treatment of chronic mechanical spinal pain with intravenous pamidronate: a review of medical records.

We explored the effect of intravenous infusions of a bisphosphonate, pamidronate, in the management of chronic mechanical spinal pain, a worldwide public health problem in terms of lost workdays, medical treatment costs, and suffering. Bisphosphonates have an anti-nociceptive effect in animals. In humans, intravenous pamidronate relieves numerous painful conditions, including metastatic bone pain, ankylosing spondylitis, rheumatoid arthritis, and complex regional pain syndrome. We reviewed the charts of 25 patients who had experienced disabling spinal pain for several years, and whom we treated with intravenous pamidronate. None had a history of osteoporotic vertebral fractures or metastatic disease. Pain rating scores decreased in 91% of patients: on a 0-10 numeric rating scale, the mean pain change was -3.6 points and mean percentage change was -41% (P<0.0001). There was no increase in opioid or nonopioid analgesic medications associated with pain relief. The apparent analgesic effect of pamidronate for chronic mechanical spinal pain needs to be confirmed with placebo-controlled trials.