Cardiovascular disease hospitalizations among women who undergo fertility treatment.

RESEARCH QUESTION: Are women who receive fertility treatment at increased risk of cardiovascular disease (CVD) hospitalization compared with women who do not? DESIGN: A retrospective cohort study of all women registered for fertility treatment at Monash IVF between 1998 and 2014. This cohort was linked to the Victorian Admitted Episodes Dataset, which contains records of all hospital admissions in the Australian state of Victoria. Age- and Index of Relative Socioeconomic Disadvantage (IRSD)-adjusted relative risks of CVD hospitalization for women who did or did not undergo fertility treatment were determined using Poisson regression. Risks were calculated overall by CVD subtype and stratified by area-based social disadvantage using IRSD fifths, number of stimulated cycles and mean oocytes per cycle. RESULTS: Of 27,262 women registered for fertility treatment, 24,131 underwent treatment and 3131 did not. No significant difference was found in risk of CVD hospitalization between treated and untreated women overall (adjusted RR 0.93, 95% 0.82 to 1.05) or by CVD subtype. The admission risk for CVD was significantly lower in treated women who had a mean of fewer than five oocytes per cycle (adjusted RR 0.80, 95% CI 0.70 to 0.92) compared with untreated women. Treated women residing in areas within the second IRSD fifth were less likely to be hospitalized for CVD compared with untreated women (age-adjusted RR 0.66, 95% CI 0.49 to 0.89). CONCLUSIONS: Fertility treatment is not associated with increased risk of CVD hospitalization. Lower risk among some subgroups of treated women may be explained by social disadvantage.

The association between sleep duration and muscle sympathetic nerve activity.

PURPOSE: Sleep duration is associated with risk of hypertension and cardiovascular diseases. It is thought that shorter sleep increases sympathetic activity. However, most studies are based on acute experimental sleep deprivation that have produced conflicting results. Furthermore, there are limited data available on habitual sleep duration and gold-standard measures of sympathetic activation. Hence, this study aimed to assess the association between habitual sleep duration and muscle sympathetic nerve activity. METHODS: Twenty-four participants aged ≥ 18 years were included in the study. Sleep was assessed using at-home 7-day/night actigraphy (ActiGraph™ GT3X-BT) and sleep questionnaires (Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale). Microelectrode recordings of muscle sympathetic nerve activity were obtained from the common peroneal nerve. Participants were categorised into shorter or longer sleep duration groups using a median split of self-report and actigraphy sleep measures. RESULTS: Compared to longer sleepers, shorter sleepers averaged 99 ± 40 min and 82 ± 40 min less sleep per night as assessed by self-report and objective measures, respectively. There were no differences in age (38 ± 18 vs 39 ± 21 years), sex (5 male, 7 female vs 6 male, 6 female), or body mass index (23 ± 3 vs 22 ± 3 kg/m2) between shorter and longer sleepers. Expressed as burst frequency, muscle sympathetic nerve activity was higher in shorter versus longer sleepers for both self-report (39.4 ± 12.9 vs 28.4 ± 8.5 bursts/min, p = 0.019) and objective (37.9 ± 12.4 vs 28.1 ± 8.8 bursts/min, p = 0.036) sleep duration. CONCLUSIONS: Shorter sleep duration assessed in a home setting was associated with higher muscle sympathetic nerve activity. Sympathetic overactivity may underlie the association between short sleep and hypertension.

Long term all-cause and cardiovascular disease mortality among women who undergo fertility treatment.

OBJECTIVES: To compare age-adjusted all-cause and CVD mortality, relative to the general female population, for women registered for fertility treatment who received it and those who did not. DESIGN: Prospective cohort study; analysis of Monash IVF clinical registries data, 1975-2018, linked with National Death Index mortality data. PARTICIPANTS: All women who registered for fertility treatment at Monash IVF (Melbourne, Victoria), 1 January 1975 - 1 January 2014, followed until 31 December 2018. MAIN OUTCOME MEASURES: Standardised mortality ratios (SMRs) for all-cause and CVD mortality, for women who did or did not undergo fertility treatment; SMRs stratified by area-level socio-economic disadvantage (SEIFA Index of Relative Socioeconomic Disadvantage [IRSD]) and (for women who underwent treatment), by stimulated cycle number and mean oocytes/cycle categories. RESULTS: Of 44 149 women registered for fertility treatment, 33 520 underwent treatment (66.4%), 10 629 did not. After adjustment for age, both all-cause (SMR, 0.58; 95% CI, 0.54-0.62) and CVD mortality (SMR, 0.41; 95% CI, 0.32-0.53) were lower than for the general female population. All-cause mortality was similar for women registered with Monash IVF who did (SMR, 0.55; 95% CI, 0.50-0.60) or did not undergo fertility treatment (SMR, 0.63; 95% CI, 0.56-0.70). The SMR was lowest for both treated and untreated women in the fifth IRSD quintile (least disadvantage), but the difference was statistically significant only for untreated women. CVD mortality was lower for registered women who underwent fertility treatment (SMR, 0.29; 95% CI, 0.19-0.43) than for those who did not (SMR, 0.58; 95% CI, 0.42-0.81). CONCLUSION: Fertility treatment does not increase long term all-cause or CVD mortality risk. Lower mortality among women registered for fertility treatment probably reflected their lower socio-economic disadvantage.

Prone sleeping affects cardiovascular control in preterm infants in NICU.

BACKGROUND: Prone sleeping is used in preterm infants undergoing intensive care to improve respiratory function, but evidence suggests that this position may compromise autonomic cardiovascular control. To test this hypothesis, this study assessed the effects of the prone sleeping position on cardiovascular control in preterm infants undergoing intensive care treatment during early postnatal life. METHODS: Fifty-six preterm infants, divided into extremely preterm (gestational age (GA) 24-28 weeks, n = 23) and very preterm (GA 29-34 weeks, n = 33) groups, were studied weekly for 3 weeks in prone and supine positions, during quiet and active sleep. Heart rate (HR) and non-invasive blood pressure (BP) were recorded and autonomic measures of HR variability (HRV), BP variability (BPV), and baroreflex sensitivity (BRS) using frequency analysis in low (LF) and high (HF) bands were assessed. RESULTS: During the first 3 weeks, prone sleeping increased HR, reduced BRS, and increased HF BPV compared to supine. LF and HF HRV were also lower prone compared to supine in very preterm infants. Extremely preterm infants had the lowest HRV and BRS measures, and the highest HF BPV. CONCLUSIONS: Prone sleeping dampens cardiovascular control in early postnatal life in preterm infants, having potential implications for BP regulation in infants undergoing intensive care.

Improved sleep efficiency is associated with reduced cardio-metabolic risk: Findings from the MODERN trial.

Poor sleep increases cardio-metabolic risk, but limited information on the impact of sleep for the improvement of cardio-metabolic health exists. This analysis examined the impact of sleep on a health and lifestyle modification programme to reduce cardio-metabolic disease risk factors. Secondary analysis of the MODERN randomised controlled trial to reduce cardio-metabolic risk was undertaken at baseline and 24-month follow-up. Participants aged 40-70 years (n = 121) with three or more cardio-metabolic risk factors were randomised to a health and lifestyle modification intervention (n = 59) or usual care (n = 62), and underwent 7 day/night actigraphy to assess total sleep time, sleep efficiency (%), number of awakenings/night and physical activity levels. Blood pressure, blood lipid and glycaemic levels, anthropometric and diet measures were collected. The mean age was 59 ± 7 years and 37% were male. Baseline sleep measures were not different between groups. At the 24-month follow-up, both groups showed improvements in cardio-metabolic risk factors, albeit the change in blood pressure was greater in the intervention compared with the usual care group (systolic blood pressure: -11 versus -4 mmHg, p = .014). There were no differences between groups for diet, physical activity or sleep parameters. An increase in sleep efficiency was independently associated with lower systolic blood pressure (ß = -2.117, p = .002) and higher high-density lipoprotein levels (ß = 0.040, p = .033); an increase in total sleep time was associated with lower low-density lipoprotein levels (ß = -0.003, p = .038) at 24 months. Overall, improvement in sleep quality over time was beneficial to reduce blood pressure and lipid levels. These findings highlight sleep as a potential target to reduce cardio-metabolic risk.

Sleep quantity and quality and cardiometabolic risk factors in Indigenous Australians.

Poor sleep is associated with increased risk of cardiovascular disease (CVD). Indigenous Australians have 1.3 times higher risk of CVD compared to non-indigenous Australians. However, there are limited data describing sleep problems and cardiometabolic risk in this population. This study aimed to investigate sleep quantity and quality in indigenous Australians and assess its association with cardiometabolic risk. Two hundred and forty-five indigenous Australians aged > 18 years were recruited via convenience sampling from communities in the Northern Territory and Queensland. Sleep quantity and quality was assessed subjectively with questionnaires including the Epworth Sleepiness Scale. In a sub-population (n = 46), objective sleep assessment was performed over three nights of actigraphy. Cardiometabolic risk measures included glycated haemoglobin, lipids, anthropometric measurements and sitting blood pressure. Sleep duration measured subjectively and objectively averaged 7.5 ± 2.0 hr/night; however, over one-third of participants (self-report 35%; actigraphy 39%) obtained < 7 hr/night. Overall, more than a third of participants experienced poor-quality sleep, with 27% reporting severe daytime sleepiness (ESS score > 10) and a high number of objectively measured awakenings/night (6 ± 4). Short sleep duration (<6 hr/night) measured both subjectively and objectively was an independent predictor of diastolic (ß = 5.37, p = .038) and systolic blood pressure (ß = 14.30, p = .048). More objectively measured night-time awakenings were associated with increased glycated haemoglobin levels (ß = 0.07, p = .020) and greater sleep fragmentation was associated with lower high-density lipoprotein levels (ß = -0.01, p = .025). A large proportion of indigenous Australians experienced short sleep durations and had significant sleep disruption. Poor sleep quantity and quality may contribute to heightened cardiometabolic risk in this population.

Effects of Prone Sleeping on Cerebral Oxygenation in Preterm Infants.

OBJECTIVE: To determine the effect of prone sleeping on cerebral oxygenation in preterm infants in the neonatal intensive care unit. STUDY DESIGN: Preterm infants, divided into extremely preterm (gestational age 24-28 weeks; n = 23) and very preterm (gestational age 29-34 weeks; n = 33) groups, were studied weekly until discharge in prone and supine positions during active and quiet sleep. Cerebral tissue oxygenation index (TOI) and arterial oxygen saturation (SaO2) were recorded. Cerebral fractional tissue extraction (CFOE) was calculated as CFOE = (SaO2 - TOI)/SaO2. RESULTS: In extremely preterm infants, CFOE increased modestly in the prone position in both sleep states at age 1 week, in no change in TOI despite higher SaO2. In contrast, the very preterm infants did not have position-related differences in CFOE until the fifth week of life. In the very preterm infants, TOI decreased and CFOE increased with active sleep compared with quiet sleep and with increasing postnatal age. CONCLUSION: At 1 week of age, prone sleeping increased CFOE in extremely preterm infants, suggesting reduced cerebral blood flow. Our findings reveal important physiological insights in clinically stable preterm infants. Further studies are needed to verify our findings in unstable preterm infants regarding the potential risk of cerebral injury in the prone sleeping position in early postnatal life.

Comparison of the longitudinal effects of persistent periodic breathing and apnoea on cerebral oxygenation in term- and preterm-born infants.

KEY POINTS: Periodic breathing and apnoea were more common in preterm compared to age-matched term-born infants across the first 6 months after term-corrected age. Periodic breathing decreased with age in both term and preterm infants. Apnoea duration was not different between groups; however, the decline in apnoea index with postnatal age observed in the term infants was not seen in the preterm infants. Falls in tissue oxygenation index (brain TOI) associated with apnoeas were greater in the preterm infants at all three ages studied. The clinical significance of falls in brain TOI during periodic breathing and apnoea on neurodevelopmental outcome is unknown and warrants further investigations. ABSTRACT: Periodic breathing and short apnoeas are common in infants, particularly those born preterm, but are thought to be benign. The aim of our study was to assess the incidence and impact of periodic breathing and apnoea on heart rate, oxygen saturation and brain tissue oxygenation index (TOI) in infants born at term and preterm over the first 6 months after term equivalent age. Nineteen term-born infants (38-42 weeks gestational age) and 24 preterm infants (born at 27-36 weeks gestational age) were studied at 2-4 weeks, 2-3 months and 5-6 months post-term-corrected age during sleep. Periodic breathing episodes were defined as three or more sequential apnoeas each lasting ≥3 s and apnoeas as ≥3 s in duration. The mean duration of periodic breathing episodes was longer in term infants than in preterm infants at 2-4 weeks (P < 0.05) and at 5-6 months (P < 0.05); however, the nadir in TOI was significantly less in the term infants at 2-3 months (P < 0.001). Apnoea duration was not different between groups; however, the decline in apnoea index with postnatal age observed in the term infants was not seen in the preterm infants. Falls in TOI associated with apnoeas were greater in the preterm infants at all three ages studied. In conclusion, periodic breathing and short apnoeas were more common in infants born preterm and falls in cerebral oxygenation were greater than in the term group. The clinical significance of this on neurodevelopmental outcome is unknown and warrants further investigations.

The effect of sex and prematurity on the cardiovascular baroreflex response in sheep.

NEW FINDINGS: What is the central question of this study? Late preterm infants are often assumed to escape long-term morbidities known to impact earlier preterm offspring. Is this true for the cardiovascular system? What is the main finding and its importance? We show that late preterm birth is a risk factor for cardiovascular dysfunction in early adulthood and is influenced by sex. Early signs of cardiovascular dysfunction might predispose to heart disease in adulthood. Very preterm infants have an increased risk of cardiovascular disease; however, the effects of a late preterm birth on future cardiovascular function are not known. We hypothesized that after a late preterm birth, the well-described impairments in heart rate variability and baroreflex sensitivity would persist into adulthood. To test this hypothesis, sheep born preterm (0.9 gestation; nine male and seven female) or term (11 male and six female) underwent surgery at 14 months of age for insertion of femoral arterial and venous catheters and a femoral flow probe. After recovery, heart rate variability was assessed, followed by a baroreflex challenge (using the vasoactive agents phenylephrine and sodium nitroprusside) in conscious adult lambs. Our data demonstrate decreased low-frequency normalised units (LFnu) and low-frequency/high-frequency ratio in female but not male ex-preterm sheep at rest. When challenged, mature male ex-preterm sheep have an increased blood pressure response but dampened heart rate baroreflex response. We show that even a late preterm birth leads to cardiovascular dysfunction in adulthood. These early signs of cardiovascular dysfunction might underpin the later hypertension and increased risk of heart disease observed in adults born preterm. These findings are particularly important because late preterm infants are often assumed to escape the long-term morbidities known to impact on very preterm and extremely preterm offspring.

Effects of foetal growth restriction and preterm birth on cardiac morphology and function during infancy.

AIM: To investigate the effects of foetal growth restriction (FGR) and prematurity on cardiac morphology and function in infancy. We hypothesised that FGR and prematurity would both alter cardiac development. METHODS: Cardiac morphology and function were evaluated in 24 preterm FGR infants (p-FGR) and 23 preterm and 19 term appropriately grown for gestational age infants (p-AGA and t-AGA, respectively) by conventional echocardiography and Tissue Doppler Imaging. p-FGR and p-AGA infants were studied on postnatal day 1 and all groups were studied at one-and six-months post-term age. RESULTS: p-FGR infants demonstrated increased cardiac sphericity compared to AGA peers on postnatal day 1 (p = 0.004) and at one-month post-term age (p = 0.004). Posterior and relative wall thickness increased overtime in the p-FGR group only (p < 0.05). Systolic function was not different between groups. E/e' ratio was higher in both preterm groups compared to the term group at one-month post-term age (p = 0.01). No statistically significant group differences were found at six-months post-term age. CONCLUSION: Foetal growth restriction was associated with subtle cardiac morphological changes, whereas both prematurity and FGR were associated with subclinical alterations in diastolic function.

Fetal-growth-restricted preterm infants display compromised autonomic cardiovascular control on the first postnatal day but not during infancy.

BackgroundFetal growth restriction (FGR) is associated with increased perinatal mortality and long-term cardiovascular and neurodevelopmental sequelae. We hypothesized that FGR impacts on the development of autonomic heart rate and blood pressure control, contributing to unfavorable short- and long-term outcomes following FGR.MethodsWe studied 25 preterm FGR and 22 preterm and 19 term appropriate for gestational age (AGA) infants. Preterm neonates were studied on postnatal day 1, and all infants were studied at 1 and 6 months post-term age. To investigate autonomic cardiovascular control, we examined heart rate variability (HRV) and baroreflex sensitivity using spectral power and transfer-function analyses.ResultsPreterm FGR neonates exhibited higher heart rates and reduced HRV compared with preterm AGA controls on postnatal day 1. No significant differences were found between the three groups at 1 or 6 months post-term age.ConclusionPreterm FGR neonates display compromised HRV on postnatal day 1, which may suggest increased vulnerability to circulatory instability. This may predispose these neonates to systemic and cerebral hypoperfusion and increase the risk of long-term neurodevelopmental sequelae. Differences were no longer found at 1 and 6 months post-term age, suggesting that the maturation of autonomic cardiovascular control may be preserved following FGR.

Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy.

Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. One of the main causes of IUGR is uteroplacental vascular insufficiency. Under these circumstances of chronic oxygen and nutrient deprivation, the growth-restricted fetus often displays typical circulatory changes, which in part represent adaptations to the suboptimal intrauterine environment. These fetal adaptations aim to preserve oxygen and nutrient supply to vital organs such as the brain, the heart, and the adrenals. These prenatal circulatory adaptations are thought to lead to an altered development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities. In this review, we discuss the alterations to cardiovascular structure, function, and control that have been observed in growth-restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency. We also discuss the current knowledge on early life surveillance and interventions to prevent progression into chronic disease.

Dummy/pacifier use in preterm infants increases blood pressure and improves heart rate control.

BACKGROUND: Preterm infants are at increased risk of sudden infant death syndrome (SIDS). Use of a dummy/pacifier is thought to be protective against SIDS; accordingly, we assessed the effects of dummy/pacifier use on blood pressure, cerebral oxygenation, and heart rate control over the first 6 mo of life after term corrected age (CA) when SIDS risk is greatest. METHODS: Thirty-five preterm infants were studied longitudinally at 2-4 wk, 2-3 mo, and 5-6 mo CA. Cardiac control was assessed from spectral indices of heart rate variability (HRV) in the low frequency (LF) and the high frequency (HF) range, and the ratio of HF/LF indicating sympathovagal balance was calculated. RESULTS: Overall, at 2-3 mo, mean arterial pressure was significantly higher in the supine position in dummy/pacifier users in both quiet sleep (70 ± 2 vs. 60 ± 2 mm Hg; P < 0.05) and active sleep (74 ± 3 vs. 69 ± 2 mm Hg; P < 0.05). Dummy/pacifier users had higher LF HRV and LF/HF ratio and lower HF HRV. CONCLUSION: Dummy/pacifier use increased blood pressure during sleep, at the age of greatest SIDS risk. Overall, LF HRV was elevated and HF HRV reduced in dummy/pacifier users, suggesting that dummy use alters cardiac control in preterm infants.

Discrimination of sleep states using continuous cerebral bedside monitoring (amplitude-integrated electroencephalography) compared to polysomnography in infants.

AIM: Limited two-channel electroencephalography (EEG) and amplitude-integrated EEG (aEEG) monitorings are being increasingly used; however, these measurements have not been compared with polysomnographic monitoring, the gold standard for determining infant sleep states. We aimed to determine the accuracy of two-channel EEG and aEEG recordings in defining sleep states and wakefulness in term infants compared to polysomnographic monitoring. METHODS: Sleep was assessed in eight healthy term born infants (mean: 34 ± 3 days), using simultaneous polysomnography (Compumedics S-Series) and a two-channel EEG monitor (Brainz BRM2). EEG intensity, 90% spectral edge frequency (SEF), aEEG amplitude frequency bands were analysed in 30-second epochs during quiet sleep, active sleep and awake as determined by polysomnography. RESULTS: BRM2-recorded EEG accurately identified quiet sleep from active sleep for EEG intensity (p = 0.003), SEF (p = 0.001) and aEEG amplitude (p = 0.003) and quiet sleep from awake, but not active sleep from awake. Frequency band analysis showed that wake could be identified by changes in absolute power (p = 0.015) and frequency as a percentage of total power (p = 0.03). CONCLUSION: We demonstrate that limited two-channel EEG monitoring can distinguish quiet sleep from active sleep and may be suitable for investigating the development of sleep in infants in the neonatal intensive care setting.

Gestational age at birth affects maturation of baroreflex control.

OBJECTIVES: To assess the effect of prone sleeping, the major risk factor for sudden infant death syndrome, in the control of blood pressure (BP) in preterm infants born across a range of gestational ages. STUDY DESIGN: Daytime polysomnography was performed at 2-4 weeks, 2-3 months, and 5-6 months postterm age. The participants were 21 very preterm (mean gestation 29.4 ± 0.3 weeks), 14 preterm (mean gestation 33.1 ± 0.3 weeks), and 17 term (mean gestation 40.1 ± 0.3 weeks). BP was measured via a Finometer cuff (Finapres Medical Systems, Amsterdam, The Netherlands) placed around the wrist. Data were recorded both supine and prone. Baroreflex sensitivity (BRS) was calculated via cross-spectral analysis of spontaneous fluctuations in BP. RESULTS: BRS was lower in the prone position in very preterm infants at 2-4 weeks in active sleep (P < .05). Maturation of BRS was delayed in very preterm compared with both preterm and term infants. CONCLUSIONS: Maturation of BRS after term-equivalent age is altered in very preterm infants. Reduced BRS may result in an impaired ability of very preterm infants to respond to cardiovascular stress during infancy and may predispose them to cardiovascular disease later in life.

Pacifier use does not alter sleep and spontaneous arousal patterns in healthy term-born infants.

AIM: Impaired arousal from sleep has been implicated in sudden infant death syndrome (SIDS). Sleeping in the prone position is a major risk factor for SIDS. Epidemiological studies have shown that pacifier use decreases the risk of SIDS, even when infants sleep prone. We examined spontaneous arousability in infants slept prone and supine over the first 6 months of life and hypothesised that spontaneous arousals would be increased in pacifier users, particularly in the prone position. METHODS: Healthy term infants (n = 30) were studied on three occasions over the first 6 months after birth. Spontaneous cortical arousals and subcortical activations were scored and converted into frequency per hour of sleep. RESULTS: There was no effect of pacifier use on total time spent sleeping or awake or the number of spontaneous awakenings at any age. There was also no effect of pacifier use on the frequency or duration of the total number of spontaneous arousals or on cortical arousals and subcortical activations. CONCLUSION: Pacifier use did not alter infant spontaneous arousability at any of the three ages studied, in either the prone or supine sleeping position. Any preventative effect of pacifiers for SIDS may be through physiological mechanisms other than increased arousability.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians.

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016-2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40-70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

Association of the Sleep Regularity Index With Incident Dementia and Brain Volume.

BACKGROUND AND OBJECTIVES: Irregular sleep may increase the risk of cardiometabolic conditions, but its association with incident dementia is unclear. The aim of this study was to assess the association between sleep regularity, that is, the day-to-day consistency in sleep-wake patterns and the risk of incident dementia and related brain MRI endophenotypes. METHODS: We used Cox proportional hazard models to investigate the relationships between sleep regularity and incident dementia in 88,094 UK Biobank participants. The sleep regularity index (SRI) was calculated as the probability of being in the same state (asleep/awake) at any 2 time points 24 hours apart, averaged over 7 days of accelerometry. RESULTS: The mean age of the sample was 62 years (SD = 8), 56% were women, and the median SRI was 60 (SD = 10). There were 480 cases of incident dementia over a median 7.2 years of follow-up. Following adjustments for demographic, clinical, and genetic confounders (APOE ε4), there was a nonlinear association between the SRI and dementia hazard (p [global test of spline term] < 0.001) with hazard ratios (HRs) following a U-shape pattern. HRs, relative to the median SRI, were 1.53 (95% CI 1.24-1.89) for participants with SRI at the 5th percentile (SRI = 41) and 1.16 (95% CI 0.89-1.50) for those with SRI at the 95th percentile (SRI = 71). In a subset with brain MRI (n = 15,263), gray matter and hippocampal volume tended to be lowest at the extremes of the SRI. DISCUSSION: Sleep regularity displayed a U-shaped association with risk of incident dementia. Irregular sleep may represent a novel dementia risk factor.

Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology.

BACKGROUND AND OBJECTIVES: Both short and long sleep duration were previously associated with incident dementia, but underlying mechanisms remain unclear. We evaluated how self-reported sleep duration and its change over time associate with (A)myloid, (T)au, (N)eurodegeneration, and (V)ascular neuroimaging markers of Alzheimer disease. METHODS: Two Framingham Heart Study overlapping samples were studied: participants who underwent 11C-Pittsburg Compound B amyloid and 18F-flortaucipir tau PET imaging and participants who underwent an MRI. MRI metrics estimated neurodegeneration (total brain volume) and cerebrovascular injuries (white matter hyperintensities [WMHs] volume, covert brain infarcts, free-water [FW] fraction). Self-reported sleep duration was assessed and split into categories both at the time of neuroimaging testing and approximately 13 years before: short ≤6 hours. average 7-8 hours, and long ≥9 hours. Logistic and linear regression models were used to examine sleep duration and neuroimaging metrics. RESULTS: The tested cohort was composed of 271 participants (age 53.6 ± 8.0 years; 51% male) in the PET imaging sample and 2,165 participants (age 61.3 ± 11.1 years; 45% male) in the MRI sample. No fully adjusted association was observed between cross-sectional sleep duration and neuroimaging metrics. In fully adjusted models compared with consistently sleeping 7-8 hours, groups transitioning to a longer sleep duration category over time had higher FW fraction (short to average ß [SE] 0.0062 [0.0024], p = 0.009; short to long ß [SE] 0.0164 [0.0076], p = 0.031; average to long ß [SE] 0.0083 [0.0022], p = 0.002), and those specifically going from average to long sleep duration also had higher WMH burden (ß [SE] 0.29 [0.11], p = 0.007). The opposite associations (lower WMH and FW) were observed in participants consistently sleeping ≥9 hours as compared with people consistently sleeping 7-8 hours in fully adjusted models (ß [SE] -0.43 [0.20], p = 0.028; ß [SE] -0.019 [0.004], p = 0.020). Each hour of increasing sleep (continuous, ß [SE] 0.12 [0.04], p = 0.003; ß [SE] 0.002 [0.001], p = 0.021) and extensive increase in sleep duration (≥2 hours vs 0 ± 1 hour change; ß [SE] 0.24 [0.10], p = 0.019; ß [SE] 0.0081 [0.0025], p = 0.001) over time was associated with higher WMH burden and FW fraction in fully adjusted models. Sleep duration change was not associated with PET amyloid or tau outcomes. DISCUSSION: Longer self-reported sleep duration over time was associated with neuroimaging biomarkers of cerebrovascular pathology as evidenced by higher WMH burden and FW fraction. A longer sleep duration extending over time may be an early change in the neurodegenerative trajectory.

The treatment of sleep dysfunction to improve cognitive function: A meta-analysis of randomized controlled trials.

OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) evaluates if treating sleep disturbances improves cognitive function over at least 12 weeks. METHODS: Multiple data sources were searched until November 1, 2021. RCTs were included if they examined the effect of an intervention (behavioral or medical) on sleep and cognition in an adult sample with sleep disturbances and had an intervention duration and follow-up of at least 12 weeks. Two independent reviewers located 3784 studies; 16 satisfied the inclusion criteria. Primary outcomes included the broad cognitive domains of visual processing, short-term memory, long-term storage and retrieval, processing speed, and reaction time. RESULTS: Most trials were conducted in participants with obstructive sleep apnea (OSA; N = 13); the most studied intervention was continuous positive airway pressure (CPAP; N = 10). All RCTs were 12 months in duration or less. The estimates of mean pooled effects were not indicative of significant treatment effect for any primary outcome. Although the interventions reduced daytime sleepiness (Hedge's g, 0.51; 95% confidence interval, 0.29-0.74; p < 0.01), this did not lead to cognitive enhancement. CONCLUSIONS: Overall, there was insufficient evidence to suggest that treating sleep dysfunction can improve cognition. Further studies with longer follow-up duration and supporting biomarkers are needed.