To determine the relationship between sleep quality and CSF markers of Alzheimer disease (AD) pathology in late midlife.
We investigated the relationship between sleep quality and CSF AD biomarkers ...in a cohort enriched for parental history of sporadic AD, the Wisconsin Registry for Alzheimer's Prevention. A total of 101 participants (mean age 62.9 ± 6.2 years, 65.3% female) completed sleep assessments and CSF collection and were cognitively normal. Sleep quality was measured with the Medical Outcomes Study Sleep Scale. CSF was assayed for biomarkers of amyloid metabolism and plaques (β-amyloid 42 Aβ42), tau pathology (phosphorylated tau p-tau 181), neuronal/axonal degeneration (total tau t-tau, neurofilament light NFL), neuroinflammation/astroglial activation (monocyte chemoattractant protein-1 MCP-1, chitinase-3-like protein 1 YKL-40), and synaptic dysfunction/degeneration (neurogranin). To adjust for individual differences in total amyloid production, Aβ42 was expressed relative to Aβ40. To assess cumulative pathology, CSF biomarkers were expressed in ratio to Aβ42. Relationships among sleep scores and CSF biomarkers were assessed with multiple regression, controlling for age, sex, time between sleep and CSF measurements, and CSF assay batch.
Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater AD pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42. There were no significant associations between sleep and NFL or neurogranin.
Self-report of poor sleep was associated with greater AD-related pathology in cognitively healthy adults at risk for AD. Effective strategies exist for improving sleep; therefore sleep health may be a tractable target for early intervention to attenuate AD pathogenesis.
Sleeping brain activity reflects brain anatomy and physiology. The aim of this study was to use high density (256 channel) electroencephalography (EEG) during sleep to characterize topographic ...changes in sleep EEG power across normal aging, with high spatial resolution. Sleep was evaluated in 92 healthy adults aged 18-65 years old using full polysomnography and high density EEG. After artifact removal, spectral power density was calculated for standard frequency bands for all channels, averaged across the NREM periods of the first 3 sleep cycles. To quantify topographic changes with age, maps were generated of the Pearson's coefficient of the correlation between power and age at each electrode. Significant correlations were determined by statistical non-parametric mapping. Absolute slow wave power declined significantly with increasing age across the entire scalp, whereas declines in theta and sigma power were significant only in frontal regions. Power in fast spindle frequencies declined significantly with increasing age frontally, whereas absolute power of slow spindle frequencies showed no significant change with age. When EEG power was normalized across the scalp, a left centro-parietal region showed significantly less age-related decline in power than the rest of the scalp. This partial preservation was particularly significant in the slow wave and sigma bands. The effect of age on sleep EEG varies substantially by region and frequency band. This non-uniformity should inform the design of future investigations of aging and sleep. This study provides normative data on the effect of age on sleep EEG topography, and provides a basis from which to explore the mechanisms of normal aging as well as neurodegenerative disorders for which age is a risk factor.
Abstract Midlife may be an ideal window for intervention in Alzheimer's disease (AD). To determine whether sleep is associated with early signs of AD neuropathology (amyloid deposition) in late ...midlife, we imaged brain amyloid deposits using positron emission tomography with C-11Pittsburgh Compound B (PiB), and assessed sleep with the Epworth Sleepiness Scale and the Medical Outcomes Study Sleep Scale in 98 cognitively healthy adults (aged 62.4 ± 5.7 years) from the Wisconsin Registry for Alzheimer's Prevention. We used multiple regressions to test the extent to which sleep scores predicted regional amyloid burden. Participants reporting less adequate sleep, more sleep problems, and greater somnolence on the Medical Outcomes Study had greater amyloid burden in AD-sensitive brain regions (angular gyrus, frontal medial orbital cortex, cingulate gyrus, and precuneus). Amyloid was not associated with reported sleep amount, symptoms of sleep-disordered breathing, trouble falling asleep, or Epworth Sleepiness Scale. Poor sleep may be a risk factor for AD and a potential early marker of AD or target for preventative interventions in midlife.
Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive ...impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk.
Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined.
Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers.
Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.
Determine stability of individual differences in executive function, cognitive processing speed, selective visual attention, and maintenance of wakefulness during simulated sustained operations with ...combined sleep restriction and circadian misalignment.
Twenty healthy adults (eight female), aged 25.7 (±4.2 SD), body mass index (BMI) 22.3 (±2.1) kg/m2 completed an 18-day protocol twice. Participants maintained habitual self-selected 8-hour sleep schedules for 2 weeks at home prior to a 4-day laboratory visit that included one sleep opportunity per day: 8 hours on night 1, 3 hours on night 2, and 3 hours on mornings 3 and 4. After 3 days of unscheduled sleep at home, participants repeated the entire protocol. Stability and task dependency of individual differences in performance were quantified by intra-class correlation coefficients (ICC) and Kendall's Tau, respectively.
Performance on Stroop, Visual Search, and the Maintenance of Wakefulness Test were highly consistent within individuals during combined sleep restriction and circadian misalignment. Individual differences were trait-like as indicated by ICCs (0.54-0.96) classified according to standard criteria as moderate to almost perfect. Individual differences on other performance tasks commonly reported in sleep studies showed fair to almost perfect ICCs (0.22-0.94). Kendall's rank correlations showed that individual vulnerability to sleep restriction and circadian misalignment varied by task and by metric within a task.
Consistent vulnerability of higher-order cognition and maintenance of wakefulness to combined sleep restriction and circadian misalignment has implications for the development of precision countermeasure strategies for workers performing safety-critical tasks, e.g. military, police, health care workers and emergency responders.
Background
Inflammatory cascades accompany α‐synuclein overexpression in brain aging. Sleep spindles, neural oscillations supporting memory and neuroplasticity, are also vulnerable to the effects of ...aging. However, relationships between α‐synuclein, chronic central inflammation, and age‐related sleep spindle deficits remain unexplored. Here, we examined relationships between glial activation, α‐synuclein, and local sleep spindle expression during non‐rapid eye movement (NREM) sleep.
Method
Polysomnography with 256‐channel electroencephalography (EEG) was conducted on 58 cognitively unimpaired older adults (61.4±6.3 years, 38 female). Absolute fast spindle power (FSP; 13‐16Hz) during NREM sleep was obtained from EEG data using multitaper spectral analysis. Cerebrospinal fluid (CSF) biomarkers were measured using exploratory Roche NeuroToolKit assays (automated robust prototype immunoassays, Roche Diagnostics International Ltd). Measurements of soluble triggering receptor expressed on myeloid cells 2 (sTREM2, denoting microglial activation), α‐synuclein (denoting neurodegeneration), and glial fibrillary acidic protein (GFAP, denoting astrocytic activation) were correlated with FSP across scalp topography, after normalizing sTREM2 (log(x)) and α‐synuclein (1/x). These correlations were corrected for multiple comparisons using threshold‐free cluster enhancement (TFCE; 5000 permutations). PROCESSv3.5 (model 6, SPSS) was used to test indirect effects of age, inflammation, and α‐synuclein on FSP, controlling for apnea‐hypopnea index (AHI), sex, and time between CSF draw and sleep study.
Result
FSP was correlated with GFAP (Pearson’s r=‐0.325, p<0.05), log10(sTREM2) (r=‐0.327, p<0.05), and 1/α‐synuclein (r=0.503, p<0.001), with associations overlapping at 13 fronto‐central derivations Fig. 1‐3. This overlap was unique and specific to the 13‐16Hz range. Supporting the association between α‐synuclein and synaptic degeneration, log10(neurogranin), a marker of synaptic integrity, was associated with both 1/α‐synuclein (r=‐0.821, p<0.001) and FSP (r=‐0.421, p=0.001). A serial mediation modeled from age to GFAP, 1/α‐synuclein, and averaged FSP Fig. 4, showed a significant, unstandardized indirect effect of ‐0.00186310 (5000‐sample bootstrapped 99% confidence interval ‐0.00518986, ‐0.00004027). Another serial mediation modeled from age to log10(sTREM2), 1/α‐synuclein, and averaged FSP Fig. 4, revealed a significant, unstandardized indirect effect of ‐0.00298193 (bootstrapped 99% confidence interval ‐0.00732707, ‐0.00015208).
Conclusion
Microglial and astrocytic activation in aging may disrupt fronto‐central fast spindle expression through individual associations with α‐synuclein‐related synaptic degeneration. Contextualizing these findings with age‐related accumulation of other neuropathologies, and associated cognitive impairments, requires further work.
Support: R56AG052698, P50AG033514.
Sleep and plasticity in schizophrenia Sprecher, Kate E; Ferrarelli, Fabio; Benca, Ruth M
Current topics in behavioral neurosciences,
01/2015, Volume:
25
Journal Article
Peer reviewed
Open access
Schizophrenia is a devastating mental illness with a worldwide prevalence of approximately 1%. Although the clinical features of the disorder were described over one hundred years ago, its ...neurobiology is still largely elusive despite several decades of research. Schizophrenia is associated with marked sleep disturbances and memory impairment. Above and beyond altered sleep architecture, sleep rhythms including slow waves and spindles are disrupted in schizophrenia. In the healthy brain, these rhythms reflect and participate in plastic processes during sleep. This chapter discusses evidence that schizophrenia patients exhibit dysfunction of sleep-mediated plasticity on a behavioral, cellular, and molecular level and offers suggestions on how the study of sleeping brain activity can shed light on the pathophysiological mechanisms of the disorder.
Abdominal obesity, particularly common in centrally obese males, may have a negative impact on upper airway (UA) function during sleep. For example, cranial displacement of the diaphragm with raised ...intra-abdominal pressure may reduce axial tension exerted on the UA by intrathoracic structures and increase UA collapsibility during sleep.
This study aimed to examine the effect of abdominal compression on UA function during sleep in obese male obstructive sleep apnea patients.
Participants slept in a sound-insulated room with physiologic measurements controlled from an adjacent room.
Fifteen obese (body mass index: 34.5 +/- 1.1 kg/m2) male obstructive sleep apnea patients (apnea-hypopnea index: 58.1 +/- 6.8 events/h) aged 50 +/- 2.6 years participated.
Gastric (PGA) and transdiaphragmatic pressures (P(DI)), UA closing pressure (UACP), UA airflow resistance (R(UA)), and changes in end-expiratory lung volume (EELV) were determined during stable stage 2 sleep with and without abdominal compression, achieved via inflation of a pneumatic cuff placed around the abdomen. UACP was assessed during brief mask occlusions.
Abdominal compression significantly decreased EELV by 0.53 +/- 0.24 L (P=0.045) and increased PGA (16.2 +/- 0.8 versus 10.8 +/- 0.7 cm H2O, P < 0.001), P(DI) (11.7 +/- 0.9 versus 7.6 +/- 1.2 cm H2O, P < 0.001) and UACP (1.4 +/- 0.8 versus 0.9 +/- 0.9 cm H2O, P = 0.039) but not R(UA)(6.5 +/- 1.4 versus 6.9 +/- 1.4 cm H2O x L/s, P=0.585).
Abdominal compression negatively impacts on UA collapsibility during sleep and this effect may help explain strong associations between central obesity and obstructive sleep apnea.
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