Sleep oscillation-specific associations with Alzheimer’s disease CSF biomarkers : novel roles for sleep spindles and tau

Background: Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ42, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals. Methods: One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ42, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time. Results: Spindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ42, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD. Conclusions: Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline

Investigation of plume dynamics during picosecond laser ablation of H13 steel using high-speed digital holography

Ablation of H13 tool steel using pulse packets with repetition rates of 400 and 1000 kHz and pulse energies of 75 and 44μJ, respectively, is investigated. A drop in ablation efficiency (defined here as the depth per pulse or μm/μJ) is shown to occur when using pulse energies of E$_{pulse}$>44μJ, accompanied by a marked difference in crater morphology. A pulsed digital holographic system is applied to image the resulting plumes, showing a persistent plume in both cases. Holographic data are used to calculate the plume absorption and subsequently the fraction of pulse energy arriving at the surface after traversing the plume for different pulse arrival times. A significant proportion of the pulse energy is shown to be absorbed in the plume for E$_{pulse}$>44μJ for pulse arrival times corresponding to > 1 MHz pulse repetition rate, shifting the interaction to a vapour-dominated ablation regime, an energetically costlier ablation mechanism.This work was collaboratively carried out under EPSRC Grant Number EP/K030884/1, as part of the EPSRC Centre for Innovative Manufacturing in Laser-based Production Processes. One of the authors acknowledges his PhD studentship by the Federal Government of Nigeria (TETFUND) in conjunction with the Federal University of Petroleum Resources Effurun (FUPRE)

Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study

Rationale: Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer’s disease. However, how sleep apnea affects longitudinal risk for Alzheimer’s disease is less well understood. Objectives: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. Methods: Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. Measurements and Main Results: We found that severity of OSA indices (AHIall [F1,88 = 4.26; P < 0.05] and AHI4% [F1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in ADPiB-mask (Alzheimer’s disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F1,28 = 2.96, P = 0.09; and F1,28 = 2.32, not significant, respectively). Conclusions: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly

Microbial load on medicinal plants sold in Bini markets, Nigeria

669-672Microbiological analysis was carried out on samples of 20 medicinal plants obtained from open markets in Benin and her environs. The standard plate count technique on Nutrient agar (NA) was used to determine the total aerobic bacterial count, mannitol salt agar and Baird-Parker agar for staphylococcal count, MacConkey agar for coliform count and potato dextrose agar for fungal counts. The purified bacterial and fungal isolates were then characterized and identified. All the samples examined contained microorganisms. The bacterial count ranged from 1.0×10³ cfu/g to 9.8×10⁴ cfu/g with Aframomum meleguata, Onyokea gore and Khaya ivorensis having the highest count of 9.8 × 10⁴cfu/g; 9.4 × 10³ cfu/g and 8.8×10³ cfu/g, respectively and Justicia flava had the lowest count of 1.0 × 10³ cfu/g. The fungal counts were high in all the samples examined. The bacterial isolates were identified as Staphylococcus aureus (50.0%), Staphylococcus epidermidis (25.0%), Escherichia coli (10.0%) and Bacillus subtilis (40.0%) while fungal isolates included Aspergillus niger (85.0%) and Penicillium species (50.0%). The presence of these microorganisms in the samples could be due to improper handling and storage procedures as most of the samples were kept in bags on cold floors in very humid tropical stores (stalls)

Obstructive Sleep Apnea and Longitudinal Alzheimer's disease biomarker changes

Study Objectives: To determine the effect of self-reported clinical diagnosis of obstructive sleep apnea (OSA) on longitudinal changes in brain amyloid PET and CSF biomarkers (A beta 42, T-tau, and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI), and Alzheimer's disease (AD) elderly. Methods: Longitudinal study with mean follow-up time of 2.52 +/- 0.51 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI, and 325 AD elderly. Main outcomes were annual rate of change in brain amyloid burden (i.e. longitudinal increases in florbetapir PET uptake or decreases in CSF A beta 42 levels); and tau protein aggregation (i.e. longitudinal increases in CSF total tau [T-tau] and phosphorylated tau [P-tau]). Adjusted multilevel mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate of biomarker change differed between participants with and without OSA. Results: In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B =.06, 95% CI =.02,.11 and B =.08, 95% CI =.05, .12, respectively) and decrease in CSF A beta 42 levels (B = -2.71, 95% CI = -3.11, -2.35 and B = -2.62, 95% CI = -3.23, -2.03, respectively); as well as increases in CSF T-tau (B = 3.68, 95% CI = 3.31, 4.07 and B = 2.21, 95% CI = 1.58, 2.86, respectively) and P-tau (B = 1.221, 95% CI = 1.02, 1.42 and B = 1.74, 95% CI = 1.22, 2.27, respectively); compared with OSA- participants. No significant variations in the biomarker changes over time were seen in the AD group. Conclusions: In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD

Associations of Alzheimer’s disease Plasma Biomarkers' and slow wave sleep within Black and White Cognitively Normal Older‐Adults

Abstract Background We studied whether plasma levels of Aβ40, Aβ42, Aβ42/Aβ40, Tau, tau/Aβ42 and NfL are associated with slow wave sleep, and if this association varied within non‐Hispanic Whites and Blacks/African‐Americans. Method This was a cross‐sectional analysis of baseline data from 171 cognitively normal older‐adults, volunteering in active NYU studies on memory and sleep. Plasma Aβ40, Aβ42, Tau and NfL were measured using single molecule array (SIMOA). Non‐rapid eye movement sleep (NREM) slow wave sleep (SWS) duration was assessed from 2 nights of in‐lab NPSGs. Associations of NREM SWS duration and plasma AD biomarker levels were examined by applying adjusted generalized linear models and Pearson correlation analysis after data normalization. Analyses were adjusted for age, sex, BMI, race, and education. Result Of the 171 subjects (128 Whites and 43 Blacks), 112 (65.5%) were females, and mean (SD) age was 68.6 (6.6) years, BMI was 27.6 (6.1) kg/m**2, and education was 16.9 (2.1). There were no racial differences in age, sex, and BMI, SWS and AHI4%. In comparison to whites, blacks had significantly lower years of education (14.2 vs. 17.2, p <.01). Black/African‐American subjects had significantly lower plasma Aβ40 (248.3 vs. 262.5 pg/ml) and NfL levels (11.4 vs. 15.2 pg/ml). p<.05 for both. There were no significant racial differences in levels of plasma Aβ42, Aβ42/Aβ40, Tau, Tau/Aβ40 and Tau/Aβ42. NREM SWS duration was not associated with plasma Aβ42, Aβ40 or tau in the overall sample. However, in Whites, SWS negatively correlated with plasma Aβ42 (r = ‐0.28, p< = 0.05). In Black/African‐Americans, SWS positively correlated with plasma Aβ42 (r = 0.48, p = 0.05). In Whites, SWS negatively correlated with plasma Aβ40 (r = ‐0.087, p = 0.72), though not significant. In Black/African‐Americans, SWS positively correlated with plasma Aβ40 levels (r = 0.32, p = 0.04). In Whites, SWS negatively correlated with plasma Tau (r = ‐0.153, p = 0.27), though not significant. In Black/African‐Americans, SWS positively correlated with plasma Tau levels (r = 0.52, p = 0.04). NREM SWS was not associated with plasma tau/Aβ42, plasma tau/Aβ40 or plasma NfL in the overall sample and across racial‐subgroups. Conclusion Race‐specific relationships between NREM SWS and plasma Aβ42, Aβ40 & Tau might propose differences in SDOH mechanisms that may affect sleep and AD‐risk in older‐adults

Self‐reported obstructive sleep apnea, amyloid and tau burden, and Alzheimer's disease time‐dependent progression

Introduction: Obstructive sleep apnea (OSA) is associated with Alzheimer's disease (AD) biomarkers in cognitively normal (CN) and mild cognitive impaired (MCI) participants. However, independent and combined effects of OSA, amyloid beta (A beta) and tauaccumulation on AD time-dependent progression risk is unclear. Methods: Study participants grouped by biomarker profile, as described by the A/T/N scheme, where "A" refers to aggregated A beta "T" aggregated tau, and "N" to neurodegeneration, included 258 CN (OSA-positive [OSA+] [A+TN+ n = 10, A+/TN- n = 6, A-/TN+ n = 10,A-/TN- n = 6 and OSA-negative [OSA-] [A+TN+ n = 84, A+/TN-n = 11, A-/TN+ n = 96, A-/TN- n = 36]) and 785 MCI (OSA+ [A+TN+ n = 35, A+/TN-n = 15, A-/TN+ n = 25, A-/TN- n =16] and OSA- [A+TN+ n = 388, A+/TN- n = 28, A-/TN+ n = 16], A-/TN- n = 114]) older-adults from the Alzheimer's Disease Neuroimaging Initiative cohort. Cox proportional hazards regression models estimated the relative hazard of progression from CN-to-MCI and MCI-to-AD, among baseline OSA CN and MCI patients, respectively. Multi-level logistic mixed-effects models with random intercept and slope investigated the synergistic associations of self-reported OSA, A beta, and tau burden with prospective cognitive decline. Results: Independent of TN-status (CN and MCI), OSA+/A beta+ participants were approximately two to four times more likely to progress to MCI/AD (P < .001) and progressed 6 to 18 months earlier (P <.001), compared to other participants combined (ie, OSA+/A beta-, OSA-/A beta+, and OSA-/A beta-). Notably, OSA+/A beta- versus OSA-/A beta- (CN and MCI) and OSA+/TN- versus OSA-/TN-(CN) participants showed no difference in the risk and time-to-MCI/AD progression. Mixed effects models demonstrated OSA synergism with Ag (CN and MCI [beta = 1.13, 95% confidence interval (CI), 0.74 to 1.52, and beta = 1.18, 95%CI, 0.82 to 1.54]) respectively, and with tau (MCI [beta = 1.31, 95% CI, 0.87 to 1.47]), P < .001 for all. Discussion: OSA acts in synergism with Aa and with tau, and all three acting together result in synergistic neurodegenerative mechanisms especially as A beta and tau accumulation becomes increasingly abnormal, thus leading to shorter progression time to MCI/AD in CN and MCI-OSA patients, respectively

Interactive Associations of Neuropsychiatry Inventory-Questionnaire Assessed Sleep Disturbance and Vascular Risk on Alzheimer's Disease Stage Progression in Clinically Normal Older Adults

Background: To determine whether sleep disturbance (SD) and vascular-risk interact to promote Alzheimer's disease (AD) stage-progression in normal, community-dwelling older adults and evaluate their combined risk beyond that of established AD biomarkers.Methods: Longitudinal data from the National Alzheimer's Coordinating Center Uniform-Dataset. SD data (i.e., SD+ vs. SD-), as characterized by the Neuropsychiatric Inventory-Questionnaire, were derived from 10,600 participants at baseline, with at-least one follow-up visit. A subset (n = 361) had baseline cerebrospinal fluid (CSF) biomarkers and MRI data. The Framingham heart study general cardiovascular disease (FHS-CVD) risk-score was used to quantify vascular risk. Amnestic mild cognitive impairment (aMCI) diagnosis during follow-up characterized AD stage-progression. Logistic mixed-effects models with random intercept and slope examined the interaction of SD and vascular risk on prospective aMCI diagnosis.Results: Of the 10,600 participants, 1,017 (9.6%) reported SD and 6,572 (62%) were female. The overall mean (SD) age was 70.5 (6.5), and follow-up time was 5.1 (2.7) years. SD and the FHS-CVD risk-score were each associated with incident aMCI (aOR: 1.42 and aOR: 2.11, p < 0.01 for both). The interaction of SD and FHS-CVD risk-score with time was significant (aOR: 2.87, p < 0.01), suggesting a synergistic effect. SD and FHS-CVD risk-score estimates remained significantly associated with incident aMCI even after adjusting for CSF (A beta, T-tau, P-tau) and hippocampal volume (n = 361) (aOR: 2.55, p < 0.01), and approximated risk-estimates of each biomarker in the sample where data was available.Conclusions: Clinical measures of sleep and vascular risk may complement current AD biomarkers in assessing risk of cognitive decline in older adults