Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults.

Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.

Cardiorespiratory fitness and circadian rhythms in adolescents: a pilot study.

Although cardiorespiratory fitness (CRF), an important marker of youth health, is associated with earlier sleep/wake schedule, its relationship with circadian rhythms is unclear. This study examined the associations between CRF and rhythm variables in adolescents. Eighteen healthy adolescents (10 females and 8 males; Mage = 14.6 ± 2.3 yr) completed two study visits on weekdays bracketing an ambulatory assessment during summer vacation. Visit 1 included in-laboratory CRF assessment (peak V̇o2) using a ramp-type progressive cycle ergometry protocol and gas exchange measurement, which was followed by 7-14 days of actigraphy to assess sleep/wake patterns and 24-h activity rhythms. During Visit 2, chronotype, social jetlag (i.e., the difference in midsleep time between weekdays and weekends), and phase preference were assessed using a questionnaire, and hourly saliva samples were collected to determine the dim light melatonin onset (DLMO) phase. All analyses were adjusted for sex, pubertal status, and physical activity. Greater peak V̇o2 was associated with earlier sleep/wake times and circadian phase measures, including acrophase, UP time, DOWN time, last activity peak (LAP) time, and chronotype (all P < 0.05). Peak V̇o2 was negatively associated with social jetlag (P = 0.02). In addition, the mixed-model analysis revealed a significant interaction effect between peak V̇o2 and actigraphy-estimated hour-by-hour activity patterns (P < 0.001), with the strongest effects observed at around the time of waking (0600-1000). In healthy adolescents, better CRF was associated with an earlier circadian phase and increased activity levels notably during the morning. Future studies are needed to investigate the longitudinal effects of the interactions between CRF and advanced rhythms on health outcomes.NEW & NOTEWORTHY In healthy adolescents, better cardiorespiratory fitness, as assessed by the gold standard measure [laboratory-based assessment of peak oxygen consumption (V̇o2)], was associated with earlier circadian timing of sleep/wake patterns, rest-activity rhythms and chronotype, and less social jetlag. These findings highlight the close interrelationships between fitness and rhythms and raise the possibility that maintaining higher cardiorespiratory fitness levels alongside earlier sleep/wake schedule and activity rhythms may be important behavioral intervention targets to promote health in adolescents.

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity and verbal memory.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults.

Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality-graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes-map onto central tenets of memory consolidation theory and sleep-related processing. Findings indicate that greater network integration is tied to overnight emotional memory retention via NREM SWS expression. Greater hippocampal and amygdala influence over network organization supports emotional memory retention, and hippocampal or amygdala control over information flow are differentially associated with distinct stages of memory processing. These centrality measures are also tied to the local expression and coupling of key sleep oscillations tied to sleep-dependent memory consolidation. These findings suggest that measures of intrinsic network connectivity may predict the capacity of brain functional networks to acquire, consolidate, and retrieve emotional memories.

Nocturnal Delta Power is Associated With Lower Next-Day Pain But Not Pain Catastrophizing: Results From a Cohort of Female Participants With Temporomandibular Joint Pain.

Existing data demonstrate reduced delta power during sleep in patients with depression and chronic pain. However, there has been little examination of the relationship between delta power and pain-reports, or pain-catastrophizing. We recruited female participants (n = 111) with insomnia and temporomandibular disorder, and measured nocturnal and daytime measures of pain and pain catastrophizing, and calculated relative nocturnal delta (0.5-4 Hz) power during sleep. We fit linear regression models, and further examined the moderating effect of depressive symptom severity. Lower relative delta power across the whole night was significantly associated with greater nocturnal pain (B = -20.276, P = .025, R2 = 0.214). Lower relative delta power during the first-third of the night, was associated with greater nocturnal pain (B = -17.807, p = 0.019, R2 = 0.217), next-day pain (B = 13.876, P = .039, R2 = 0.195), and next-morning pain (B = -15.751, P = .022, R2 = 0.198). Lower relative delta power during the final-third of the night was significantly associated with greater nocturnal (B = -17.602, P = .029, R2 = 0.207) and next-morning pain (3rd: B = -14.943, P = .042, R2 = 0.187). Depressive symptom severity did not moderate these relationships. Delta power was not significantly associated with nocturnal or daytime pain catastrophizing. These findings demonstrate that greater relative delta power during sleep is associated with lower nocturnal and next-day pain in patients with temporomandibular disorder. This data may guide the use of sleep interventions in clinical pain populations, with the aim of improving pain outcomes. PERSPECTIVE: This article presents data demonstrating an association between increased nocturnal delta power and reduced next-day pain. These findings may help promote interventions which aim to increase nocturnal delta power in clinical pain populations, with the goal of improving pain outcomes.

Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to ß-amyloid positivity.

STUDY OBJECTIVES: Fast frequency sleep spindles are reduced in aging and Alzheimer's disease (AD), but the mechanisms and functional relevance of these deficits remain unclear. The study objective was to identify AD biomarkers associated with fast sleep spindle deficits in cognitively unimpaired older adults at risk for AD. METHODS: Fifty-eight cognitively unimpaired, ß-amyloid-negative, older adults (mean ±â€…SD; 61.4 ±â€…6.3 years, 38 female) enriched with parental history of AD (77.6%) and apolipoprotein E (APOE) ε4 positivity (25.9%) completed the study. Cerebrospinal fluid (CSF) biomarkers of central nervous system inflammation, ß-amyloid and tau proteins, and neurodegeneration were combined with polysomnography (PSG) using high-density electroencephalography and assessment of overnight memory retention. Parallelized serial mediation models were used to assess indirect effects of age on fast frequency (13 to <16Hz) sleep spindle measures through these AD biomarkers. RESULTS: Glial activation was associated with prefrontal fast frequency sleep spindle expression deficits. While adjusting for sex, APOE ε4 genotype, apnea-hypopnea index, and time between CSF sampling and sleep study, serial mediation models detected indirect effects of age on fast sleep spindle expression through microglial activation markers and then tau phosphorylation and synaptic degeneration markers. Sleep spindle expression at these electrodes was also associated with overnight memory retention in multiple regression models adjusting for covariates. CONCLUSIONS: These findings point toward microglia dysfunction as associated with tau phosphorylation, synaptic loss, sleep spindle deficits, and memory impairment even prior to ß-amyloid positivity, thus offering a promising candidate therapeutic target to arrest cognitive decline associated with aging and AD.

Incidence and risk factors for post-penetrating keratoplasty glaucoma.

Purpose: To carry out a prospective study to analyze the incidence and various preoperative, intraoperative, and postoperative risk factors for the development of PPKG. Methods: A total of 207 patients were analyzed prospectively, who were operated for penetrating keratoplasty (PK) in a tertiary eye care hospital between the time period of August 1, 2017 and February 28, 2018 and were followed up till the sixth month. Each patient was analyzed at every visit to determine the factors responsible for post-keratoplasty glaucoma. Results: Out of 207 eyes, post-PK glaucoma developed in 84 cases, which yielded an incidence of 41%. Incidence of PPKG (Post PK glaucoma) in various conditions was as follows: in repeat PK 62%, in perforated corneal ulcer 33%, in nonperforated corneal ulcer 29%, in corneal scar including adherent leukoma 37.2%, and in pseudophakic bullous keratopathy and aphakic bullous keratopathy, 14% and 80%, respectively. In age- and sex-adjusted multivariate analysis, the significant risk factors were age (P-value- 0.006), presence of PAS (P-value 0.001), and fellow eye glaucoma (P-value 0.04). Aphakia and combined surgery were not found to be significant. Conclusion: Our study recommends a meticulous examination of the fellow eye to assess the presence of glaucoma as it can increase the suspicion of glaucoma in the eye to be operated. The presence of PAS and age are important risk factors for developing PPKG. The risk of developing PPKG increases exponentially as the number of risk factors increases, but the presence of more than three risk factors does not add to the development of PPKG.

Post penetrating keratoplasty infectious keratitis: Clinico-microbiological profile and predictors of outcome.

PURPOSE: To study the clinico-microbiological profile, outcomes and prognostic factors of post penetrating keratoplasty (PKP) infectious keratitis. METHODS: Retrospective review of medical records of 78 patients with post PKP infectious keratitis presenting between January 2014 and December 2018. Demographic, clinical and microbiological profile was documented and predictors of treatment and graft success were evaluated using univariate and subsequent multivariate logistic regression analysis. RESULTS: Mean age of patients was 52.17 ± 15.51 years and mean infiltrate size was 19.39 ± 19.68 mm2. Mean duration of presentation with infection post PKP was 11.66 ± 10.65 months. Culture positivity was seen in 64 eyes (82.05%). Bacterial growth was observed in 47 eyes (60.25%), fungal growth in 17 (21.79%) and no microbiological growth in 14 eyes (17.94%). At 3 months the visual acuity (VA) improved in 37 eyes (47.44%), did not change in 27 (34.62%) and deteriorated in 14 (17.95%). Graft failure was noted in 53 eyes (73.08%). Surgical intervention was needed in 47 (60.25%) eyes of which most common was therapeutic PKP in 32 eyes (41.02%). Treatment failure was noted with fungal infection (p = 0.05), poorer vision at presentation (p = 0.02), larger infiltrate area (p = 0.002) and graft infection developing before 1 year (p = 0.02). Graft failure was noted with associated endophthalmitis (p = 0.02), poorer VA at presentation (p = 0.01) and larger infiltrate area (p = 0.02). CONCLUSION: Post PKP infectious keratitis is a sight threatening ocular condition. It is associated with high incidence of graft failure and frequently requires surgical intervention. Fungal etiology, larger infiltrate size, poorer vision at presentation and associated endophthalmitis carries a poorer prognosis.

Aerobic fitness and the sleeping brain of adolescents-a pilot study.

STUDY OBJECTIVES: Aerobic fitness (AF) and sleep are major determinants of health in adolescents and impact neurocognitive and psychological development. However, little is known about the interactions between AF and sleep during the developmental transition experienced across adolescence. This study aimed to consider the relationships between AF and habitual sleep patterns and sleep neurophysiology in healthy adolescents. METHODS: Subjects (mean age = 14.6 ± 2.3 years old, range 11-17, 11 females) were evaluated for AF (peak VO2 assessed by ramp-type progressive cycle ergometry in the laboratory), habitual sleep duration and efficiency (7-14 days actigraphy), and topographic patterns of spectral power in slow wave, theta, and sleep spindle frequencies in non-rapid eye movement (NREM) sleep using overnight polysomnography (PSG) with high-density electroencephalography (hdEEG, 128 channels). RESULTS: Significant relationships were observed between peak VO2 and habitual bedtime (r = -0.650, p = .009) and wake-up time (r = -0.603, p = .017), with greater fitness associated with going to bed and waking up earlier. Peak VO2 significantly predicted slow oscillations (0.5-1 Hz, p = .018) and theta activity (4.5-7.5 Hz, p = .002) over anterior frontal and central derivations (p < .001 and p = .001, respectively) after adjusting for sex and pubertal development stage. Similar associations were detected for fast sleep spindle activity (13-16 Hz, p = .006), which was greater over temporo-parietal derivations. CONCLUSIONS: Greater AF was associated with a more mature pattern of topographically-specific features of sleep EEG known to support neuroplasticity and cognitive processes and which are dependent on prefrontal cortex and hippocampal function in adolescents and adults. AF was also correlated with a smaller behavioral sleep phase delay commonly seen during adolescence.

Resuming eye bank services during the COVID-19 pandemic: Experience and inferences.

PURPOSE: The aim of this study was to formulate a methodological approach for resuming eye bank services during COVID-19 pandemic. METHODS: Eye bank operations were temporarily halted in March after the government-mandated "Lockdown" in response to COVID-19 pandemic. Before restarting eye bank operations in May, we studied sources of exposure, performed risk assessment, instituted additional process validations and redefined the Standard Operating Procedures (SOPs) in consultation with the guidelines published by the Eye bank Association of India and All India Ophthalmological Society. The eye bank staff were rigorously trained before and after operations were restarted. We conducted a survey at the end of July to gauge staff attitude and reaction. RESULTS: Eye banks services resumed on 20th May 2020. Since reopening till the end of July total 41 keratoplasties have been done. 91.75% of all keratoplasties done were therapeutic surgeries and 17% of the surgeries were done using glycerine preserved tissues. No staff had COVID-19 symptoms when the operations restarted and none developed symptoms up to the end of July. All eye bank staff were aware of COVID-19 pandemic and 86% said they felt safe working at the eye bank. 86% of the staff said that they received adequate training and 66% of the staff expressed that they always received proper PPE and kits. Overall, 93% of the staff expressed that the measures taken by the eye bank ensured their safety. CONCLUSION: Based on our experience we suggest the following activities for planned resumption of eye bank services during the pandemic: Exposure Risk Analysis, Personal Protective Equipment usage training, SOP Revision and staff training on modified SOPs. Criteria based selection of donor sources, participatory planning involving the staff and double-checking at critical process junctions helped us in managing a smooth transition.

Effect of timolol maleate (0.5%) in the management of myopic regression post laser-assisted in-situ keratomileusis: Clinical and topographical outcomes.

PURPOSE: The aim of this study was to analyze the effect of timolol maleate (0.5%) eye drops in the treatment of myopic regression after laser-assisted in-situ keratomileusis (LASIK). METHODS: The study was conducted at a tertiary care eye hospital in north India between April 2017 & March 2018 as a prospective interventional study. Patients who underwent uneventful myopic LASIK with hansatome mechanical keratome and presented with regression were included in the study. Baseline demographic characteristics, time to presentation with regression best-corrected visual acuity (BCVA), refraction, intraocular pressure, central corneal thickness and keratometry were recorded at baseline and at each follow-up visit. The enrolled patients were prescribed timolol maleate (0.5%) eyedrops twice daily. They were followed up every month till 3 months on timolol maleate (0.5%) eyedrops and at 6 months post stopping the treatment. RESULTS: Twenty-nine eyes of 15 patients were enrolled in the study. Mean pre LASIK spherical equivalent (SE) was - 7.48 ± 2.9 Diopters (Range-3.125 to -11.75 Diopters) and mean regression spherical equivalent was -1.02 ± 1.1 Diopters. There was a decrease in mean SE from presentation (intervention start point) up to 6 months follow-up (-1.34 ± 0.89 to -0.30 ± 0.29 Diopters). While posterior corneal curvature (K1 and K2 Back) changed significantly over treatment period (P = 0.0029, P = 0.0024 respectively), changes in anterior corneal curvature (K1 and K2 Front) were not significant (P = 0.05, P = 0.06 respectively). Central corneal thickness (CCT) and intraocular pressure (IOP) did not change significantly over treatment course. CONCLUSION: Timolol maleate (0.5%) eyedrop is an effective modality for the treatment of refractive regression post LASIK circumventing the need for laser re-treatment in such patients. The most probable mechanism is reversal of the anterior bowing of the cornea in response to intraocular pressure changes.

Curvularia infection of corneoscleral tunnel.

Corneoscleral tunnel infection is a potentially sight threatening complication of cataract surgery. Microbiological investigations are mandatory and early surgical intervention helps in achieving favourable outcomes. Fungal infection of tunnel incisions can pose a diagnostic and therapeutic challenge. We report a case of post-operative tunnel infection with curvularia. Prompt surgical intervention and intensive topical therapy helped attain a good tectonic as well as visual recovery.

Awareness regarding eye donation among staff of a tertiary eye care hospital in North India.

PURPOSE: To assess the awareness, knowledge and attitude regarding eye donation in staff of a tertiary eye care hospital in North India. METHODS: A prospective, cross-sectional study was conducted on the employees of a tertiary eye care centre (urban area) along with its four secondary centres (rural area). Socio-demographic profile, awareness, knowledge and attitude of 507 employees regarding eye donation were evaluated through a pretested, self-administered questionnaire. Knowledge-based questions were scored. RESULTS: Of the 507 participants, 327 (64.5%) participants were from medical/paramedical field (Group 1) and 180 (35.5%) were from non-medical field (Group 2). Awareness about eye donation was 99%. Twenty (3.95%) participants scored poor (0-8), 90 (17.75%) had a fair score (9-16) and 397 (78.30%) had a good score (17-24). Good knowledge was found in significantly more (P = 0.01) participants in Group 1 (77.37%) as compared to Group 2 (70.1%). Four hundred and fifty-seven (90.13%) participants were willing to pledge their eyes for donation, the prime motivational force being spreading vision to the blind [346 (68.24%)]. The perceived reasons for not pledging were religious [28 (5.52%)], thought of family getting upset [29 (5.72%)] and scepticism regarding proper usage of tissue [64 (12.62%)]. CONCLUSION: The study demonstrated that although there is a substantial awareness about eye donation, there are certain lacunae in the knowledge and perceptions among staff of an eye care hospital. With the correct knowledge and attitude, they can contribute by creating awareness and motivating the people for eye donation while carrying out their routine hospital activities.

Impact of quality assurance on utilization of corneal tissues in a community Eye Bank.

PURPOSE: To determine the linkage between Quality Assurance Program (QAP) and increase in utilization of donor corneas at a community Eye Bank. METHODS: A donor cornea is defined as utilized when it is used for cornea transplant. Two metrics, utilization rate (UR) and non-utilization rate (NUR), were defined. The Eye Bank implemented QAP from 2011. As a part of QAP, detailed gap analysis of tissue utilization was performed. Four major categories causing non-utilization of recovered corneas were identified. These categories were poor "Tissue Quality", "Seropositive" donor blood sample, "Medical History" of donor, and donor "Blood Sample Issues." The years 2008-2011 were labelled the pre-intervention period, and the years 2012-2017 were labelled the post-intervention period. Annual UR and annual NUR for the four categories of non-utilization from the pre and the post-intervention periods were statistically compared. RESULTS: In the pre-intervention period, the Eye Bank recovered 1425 donor corneas in total and transplanted 762. In the post-intervention period, the Eye Bank recovered 6661 corneas in total and transplanted 4393. The UR improved from 53.47% (762/1425) in the pre-intervention period to 65.95% (4393/6661) in the post-intervention period (P < 0.001). NUR in "Tissue Quality" category decreased from 34.32% to 29.7% from the pre to the post-intervention period (P < 0.001). NUR in "Blood Sample Issues" category reduced from 3.23% to 0.32% from the pre to the post-intervention period (P < 0.001). NUR in "Medical History" category decreased from 5.68% to 0.33% from the pre to the post-intervention period (P < 0.001). CONCLUSIONS: The study indicates that QAP improves UR of recovered corneas. In countries with a shortage of donor corneas, increasing utilization of recovered corneas can lead to an increase in corneal transplants. Implementation of QAP at the Eye Bank can be a means of achieving this outcome.