The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people.

Background: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-ß42 (Aß42), total tau (t-tau), and phosphorylated tau181 (p-tau), as well as the trajectories of these CSF measures obtained longitudinally. Results: A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aß-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aß42 (ß=-12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (ß = 26.812, p = 0.019) and p-tau (ß = 3.441, p = 0.015), but not Aß42. In the NYU cohort alone, subjects classified as Aß+ (n = 38) displayed a stronger association between the NLR and t-tau (ß = 100.476, p = 0.037) compared to Aß- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. Conclusions: We report associations between the NLR and Aß42 in the older ADNI cohort, and between the NLR and t-tau and p-tau181 in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.

Obstructive Sleep Apnea and Alzheimer's Disease Pathology: Is Sleep Architecture the Missing Key?

Impairments of the sleep architecture due to disrupted sleep in individuals with obstructive sleep apnea (OSA) may result in reduced slow wave sleep (SWS), intermittent hypoxemia, and excessive day time sleepiness- all factors that have been shown to impact Alzheimer's disease (AD) risk. In this commentary, we comment on the work by Cavuoto and colleagues in which they examine the associations between nocturnal hypoxemia or sleep disruptions (during SWS) and amyloid-ß burden in individuals with OSA. We review the findings in the context of other similar studies and highlight the strengths and weaknesses of these published studies. We note the importance of examining these relationships longitudinally with a large sample size, including considering sleep health disparities, vascular components, and multiple cognitive domain tests.

Discrimination Predicts Suboptimal Adherence to CPAP Treatment and Mediates Black-White Differences in Use.

BACKGROUND: Although racial and ethnic differences in CPAP adherence for OSA are widely established, no studies have examined the influence of perceived racial discrimination on CPAP usage, to our knowledge. RESEARCH QUESTION: (1) Do Black adults with OSA report experiencing greater amounts of discrimination than non-Hispanic White adults? (2) Is discrimination associated with poorer CPAP adherence over time, independent of self-identified race? (3) Does discrimination mediate the relationship between self-identified Black race and CPAP usage? STUDY DESIGN AND METHODS: In this prospective study, Black and non-Hispanic White adults with OSA initiating CPAP were enrolled from two sleep centers and completed questionnaires including sociodemographics, perceived discrimination, daytime sleepiness, insomnia symptoms, and depressive symptoms. Perceived discrimination was measured using the Everyday Discrimination Scale (EDS). Black and White group comparisons for baseline sociodemographic variables, sleep symptoms, and perceived discrimination were performed with Student t test or χ2/Fisher exact test, as appropriate. A linear regression model was completed with self-identified Black race and EDS total score as the primary independent variables of interest and mean daily CPAP usage at 30 and 90 days serving as the dependent outcomes. This regression modeling was repeated after adjusting for psychosocial variables known to be associated with CPAP usage. EDS total score was explored as a potential mediator of the association between self-identified Black race and mean daily CPAP adherence at 30 and 90 days. RESULTS: The sample for this analysis consisted of 78 participants (31% female, 38% Black) with a mean age of 57 ± 14 years. Sixty percent of the Black adults reported they experienced racial discrimination at least a few times each year. Relative to White adults, Black adults were also more likely to indicate more than one reason for discrimination (27% vs 4%, P = .003). Adjusting for discrimination, self-identified Black race was associated with 1.4 (95% CI, -2.3 to -0.4 h; P = .006) and 1.6 (95% CI, -2.6 to -0.6 h; P = .003) fewer hours of mean daily CPAP usage at 30 and 90 days, respectively. In the fully adjusted model, a 1-unit change in the total discrimination score (more discrimination) was associated with a 0.08-h (95% CI, 0.01-0.15 h; P = .029) and 0.08-h (95% CI, 0.01-0.16 h; P = .045) change in mean daily CPAP usage at 30 and 90 days, respectively. INTERPRETATION: Adults with OSA who encountered racial discrimination experienced greater decrement in CPAP usage than those who did not experience racial discrimination.

The effects of social support and support types on continuous positive airway pressure use after 1month of therapy among adults with obstructive sleep apnea.

BACKGROUND: The relationship between perceived social support and continuous positive airway pressure remains understudied among individuals with obstructive sleep apnea. The aim of this prospective cohort study was to determine if baseline perceived social support and subtypes predict regular continuous positive airway pressure use after 1month of therapy. METHODS: Adults with obstructive sleep apnea initiating continuous positive airway pressure therapy were recruited from sleep clinics in New York City. Demographics, medical history, and comorbidities were obtained from patient interview and review of medical records. Objective continuous positive airway pressure adherence data was collected at the first clinical follow-up. RESULTS: Seventy-five participants (32% female; non-Hispanic Black 41%; mean age of 56 ± 14years) provided data. In adjusted analyses, poorer levels of overall social support, and subtypes including informational/emotional support, and positive social interactions were associated with lower continuous positive airway pressure use at 1month. Relative to patients reporting higher levels of support, participants endorsing lower levels of overall social support, positive social interaction and emotional/informational support had 1.6 hours (95% CI: 0.5,2.7, hours; p = .007), 1.3 hours (95% CI: 0.2,2.4; p = .026), and 1.2 hours (95% CI: 0.05,2.4; p = .041) lower mean daily continuous positive airway pressure use at 1month, respectively. CONCLUSION: Focusing on social support overall and positive social interaction particularly, could be an effective approach to improve continuous positive airway pressure adherence in patients at risk of suboptimal adherence.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

A Social Media-Based Diabetes Intervention for Low-Income Mandarin-Speaking Chinese Immigrants in the United States: Feasibility Study.

BACKGROUND: Chinese immigrants bear a high diabetes burden and face significant barriers to accessing diabetes self-management education (DSME) and counseling programs. OBJECTIVE: The goal of this study was to examine the feasibility and acceptability and to pilot test the potential efficacy of a social media-based DSME intervention among low-income Chinese immigrants with type 2 diabetes (T2D) in New York City. METHODS: This was a single group pretest and posttest study in 30 Chinese immigrants with T2D. The intervention included 24 culturally and linguistically tailored DSME videos, focusing on diabetes education and behavioral counseling techniques. Over 12 weeks, participants received 2 brief videos each week via WeChat, a free social media app popular among Chinese immigrants. Primary outcomes included the feasibility and acceptability of the intervention. Feasibility was evaluated by recruitment processes, retention rates, and the video watch rate. Acceptability was assessed via a satisfaction survey at 3 months. Secondary outcomes, that is, hemoglobin A1c (HbA1c), self-efficacy, dietary intake, and physical activity, were measured at baseline, 3 months, and 6 months. Descriptive statistics and paired 2-sided t tests were used to summarize the baseline characteristics and changes before and after the intervention. RESULTS: The sample population (N=30) consisted of mostly females (21/30, 70%) who were married (19/30, 63%), with limited English proficiency (30/30, 100%), and the mean age was 61 (SD 7) years. Most reported an annual household income of

Platelet Function Is Associated With Dementia Risk in the Framingham Heart Study.

Background Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD. Methods and Results We examined associations of baseline platelet function with incident dementia risk in the community-based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause-specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow-up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper-responders, as well as the platelet response to 0.1 µmol/L epinephrine. Conclusions Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20-year follow-up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.

Discrimination and Hypertension Among Older African Americans and Caribbean Blacks: The Moderating Effects of John Henryism.

OBJECTIVES: Discrimination is a major contributor to health disparities between Black and White older adults. Although the health effects of discrimination are well established, less is known about factors that may intervene in the discrimination-health connection, such as coping strategies. The study aim was to determine whether John Henryism (JH; high-effort coping) moderates the association between racial discrimination and hypertension in nationally representative samples of older African Americans and Caribbean Blacks. METHODS: The analytic sample was drawn from the National Survey of American Life-Reinterview, which was conducted 2001-2003, and included African Americans (N = 546) and Caribbean Blacks (N = 141) aged 55 and older. Study variables included racial discrimination, JH, and hypertension. Logistic regressions, which controlled key sociodemographic differences, were used to test the study aim. RESULTS: Among both Black ethnic groups, discrimination and JH were not associated with hypertension. For African Americans low and moderate in JH, discrimination was unrelated to hypertension; discrimination was positively associated with hypertension for African Americans high in JH. For Caribbean Blacks, discrimination was positively associated with hypertension among respondents low in JH. Among Caribbean Blacks moderate and high in JH, discrimination was not associated with hypertension. DISCUSSION: The findings indicate that JH, in the face of discrimination, is associated with hypertension of older African Americans but may be an effective coping strategy for older Caribbean Blacks due to cultural and sociodemographic differences between the 2 ethnic groups. Future research should investigate the differing mechanisms by which JH influences health in heterogeneous older Black populations.

Exploring the combined effects of sleep apnea and APOE-e4 on biomarkers of Alzheimer's disease.

Objective: We determined the interactive associations of apolipoprotein e4 (APOE-e4), and obstructive sleep apnea (OSA) on biomarkers of Alzheimer's disease and examined for racial/ethnic differences of this association. Methods: We used data from the National Alzheimer's Coordinating Center Uniform Dataset (NACC UDS). All participants undergo annual observations, including demographic survey, battery of neuropsychological tests, blood draw (with genotyping), and a clinical evaluation with medical and cognitive/dementia status assessment, while a subset of participants have cerebrospinal fluid (CSF) biomarkers and neuroimaging data. Biomarkers of AD were characterized as the presence of abnormally low amyloid in CSF, via validated Aß42 cut off protocols, and total segmented hippocampal volume, and volume of white matter hyper intensities (WMH). While clinical markers (to preview cognitive relationships) were characterized via the Montreal Cognitive Assessment (MOCA). Results: Biomarker and clinical marker data were derived from 1,387 participants at baseline (mean age = 69.73 ± 8.32; 58.6% female; 13.7% Black/African American), 18.4% of the sample had sleep apnea, and 37.9% were APOE-e4 carriers. Our results confirmed previous reports that OSA and APOE-e4 were independently associated with AD through abnormal levels of amyloid (F (1,306) = 4.27; p = 0.040; F (1,285) = 60.88; p < 0.000, respectively), WMH volume (F (1,306) = 4.27; p = 0.040; F (1,285) = 60.88; p < 0.000, respectively), and MOCA scores (F (1,306) = 4.27; p = 0.040; F (1,285) = 60.88; p < 0.000, respectively). No significant interaction between OSA and APOE-e4 relative to amyloid emerged, however, race stratified analyses indicated the interaction of OSA and APOE-e4 and was significantly associated with WMH and hippocampal volume in Black/African American, but not white participants. Conclusion: OSA and APOE-e4 are interactively associated with WHM in Black/African Americans. This interaction may partially explicate increased levels of risk in this population.

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 (Aß, 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.

The Neutrophil to Lymphocyte Ratio Is Associated With the Risk of Subsequent Dementia in the Framingham Heart Study.

Objective: Active neutrophils are important contributors to Alzheimer's disease (AD) pathology through the formation of capillary stalls that compromise cerebral blood flow (CBF) and through aberrant neutrophil signaling that advances disease progression. The neutrophil to lymphocyte ratio (NLR) is a proxy of neutrophil-mediated inflammation, and higher NLR is found in persons diagnosed with clinical AD. The objective of this study was to investigate whether increased NLR in older adults is independently associated with the risk of subsequent dementia. Methods: We examined associations of baseline NLR with incident dementia risk in the community-based Framingham Heart Study (FHS) longitudinal cohorts. The association between NLR and risk of dementia was evaluated using the cumulative incidence function (CIF) and inverse probability-weighted Cox proportional cause-specific hazards regression models, with adjustment for age, sex, body mass index (BMI), systolic and diastolic blood pressure, diabetes, current smoking status, low-density lipoprotein (LDH), high-density lipoprotein (LDL), total cholesterol, triglycerides, and history of cardiovascular disease (CVD). Random forest survival models were used to evaluate the relative predictive value of the model covariates on dementia risk. Results: The final study sample included 1,648 participants with FHS (average age, 69 years; 56% women). During follow-up (median, 5.9 years), we observed 51 cases of incident dementia, of which 41 were AD cases. Results from weighted models suggested that the NLR was independently associated with incident dementia, and it was preceded in predictive value only by age, history of CVD, and blood pressure at baseline. Conclusion: Our study shows that individuals with higher NLR are at a greater risk of subsequent dementia during a 5.9-year follow-up period. Further evaluating the role of neutrophil-mediated inflammation in AD progression may be warranted.

Ambient Stimuli Perpetuate Nighttime Sleep Disturbances in Hospital Patients With TBI.

BACKGROUND AND OBJECTIVES: The effect of the ambient environment, sound, light, and movement, on the nighttime rest-activity of patients hospitalized with moderate-severe traumatic brain injury (TBI) is poorly understood. The purpose of this study was to examine how sound, light, and movement in these patients' hospital rooms may contribute to nighttime awakenings. METHODS: An observational design was used with 18 adult participants on a neuroscience step-down unit diagnosed with moderate-severe TBI. For up to five consecutive nights, actigraphy was used to capture nighttime awakenings while a custom-made multisensory device captured sound, light, and movement exposures in the participant's room. RESULTS: Participants were awake for 24% (or about 3 hr) of the time during the designated nighttime period of 8 pm to 8 am. Average nighttime exposures of sound was 52 dB, light was nine lumens, and movement, measured as a proportion, was 0.28% or 28%. With each stimuli exposure set at its average, there was a 20% probability of participant nighttime awakenings. Clinically meaningful reductions of movement in and out the participant's room and elevated sound significantly decreases the participant's probability of nighttime awakenings (p < .05), but reductions in light did not. CONCLUSION: The ambient environment seems to impede restful sleep in immediate post-injury phase of patients with moderate-severe TBI.

Association between Influenza Vaccination and severe COVID-19 outcomes at a designated COVID-only hospital in Brooklyn.

Maintaining influenza vaccination at high coverage has the potential to prevent a proportion of COVID-19 morbidity and mortality. We examined whether flu-vaccination is associated with severe corona virus disease 2019 (COVID-19) disease, as measured by intensive care unit (ICU)-admission, ventilator-use, and mortality. Other outcome measures included hospital length of stay and total ICU days. Our findings showed that flu-vaccination was associated with a significantly reduced likelihood of an ICU admission especially among aged <65 and non-obese patients. Public health promotion of flu-vaccination may help mitigate the overwhelming demand for critical COVID-19 care pending the large-scale availability of COVID-19 vaccines.

Effects of obstructive sleep apnea on human spatial navigational memory processing in cognitively normal older individuals.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) prevalence increases with age, but whether OSA-related sleep disruption could interrupt the processing of previously encoded wake information thought to normally occur during sleep in cognitively normal older adults remains unknown. METHODS: Fifty-two older (age = 66.9 ± 7.7 years, 56% female), community-dwelling, cognitively normal adults explored a 3-D maze environment and then performed 3 timed trials before (evening) and after (morning) sleep recorded with polysomnography with a 20-minute morning psychomotor vigilance test. RESULTS: Twenty-two (22) participants had untreated OSA [apnea-hypopnea index (AHI4%) ≥ 5 events/h] where severity was mild on average [median (interquartile range); AHI4% = 11.0 (20.7) events/h] and 30 participants had an AHI4% < 5 events/h. No significant differences were observed in overnight percent change in completion time or in the pattern of evening presleep maze performance. However, during the morning postsleep trials, there was a significant interaction between OSA group and morning trial number such that participants with OSA performed worse on average with each subsequent morning trial, whereas those without OSA showed improvements. There were no significant differences in morning psychomotor vigilance test performance, suggesting that vigilance is unlikely to account for this difference in morning maze performance. Increasing relative frontal slow wave activity was associated with better overnight maze performance improvement in participants with OSA (r = .51, P = .02) but not in those without OSA, and no differences in slow wave activity were observed between groups. CONCLUSIONS: OSA alters morning performance in spatial navigation independent of a deleterious effect on morning vigilance or evening navigation performance. Relative frontal slow wave activity is associated with overnight performance change in older participants with OSA, but not those without.

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 (Aß) and tau-accumulation 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 Aß, "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 = 164, 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, Aß, and tau burden with prospective cognitive decline. RESULTS: Independent of TN-status (CN and MCI), OSA+/Aß+ 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+/Aß-, OSA-/Aß+, and OSA-/Aß-). Notably, OSA+/Aß- versus OSA-/Aß- (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 Aß (CN and MCI [ß = 1.13, 95% confidence interval (CI), 0.74 to 1.52, and ß = 1.18, 95%CI, 0.82 to 1.54]) respectively, and with tau (MCI [ß = 1.31, 95% CI, 0.87 to 1.47]), P < .001 for all. DISCUSSION: OSA acts in synergism with Aß and with tau, and all three acting together result in synergistic neurodegenerative mechanisms especially as Aß and tau accumulation becomes increasingly abnormal, thus leading to shorter progression time to MCI/AD in CN and MCI-OSA patients, respectively.

Obstructive Sleep Apnea and Its Treatment in Aging: Effects on Alzheimer's disease Biomarkers, Cognition, Brain Structure and Neurophysiology.

Here we review the impact of obstructive sleep apnea (OSA) on biomarkers of Alzheimer's disease (AD) pathogenesis, neuroanatomy, cognition and neurophysiology, and present the research investigating the effects of continuous positive airway pressure (CPAP) therapy. OSA is associated with an increase in AD markers amyloid-ß and tau measured in cerebrospinal fluid (CSF), by Positron Emission Tomography (PET) and in blood serum. There is some evidence suggesting CPAP therapy normalizes AD biomarkers in CSF but since mechanisms for amyloid-ß and tau production/clearance in humans are not completely understood, these findings remain preliminary. Deficits in the cognitive domains of attention, vigilance, memory and executive functioning are observed in OSA patients with the magnitude of impairment appearing stronger in younger people from clinical settings than in older community samples. Cognition improves with varying degrees after CPAP use, with the greatest effect seen for attention in middle age adults with more severe OSA and sleepiness. Paradigms in which encoding and retrieval of information are separated by periods of sleep with or without OSA have been done only rarely, but perhaps offer a better chance to understand cognitive effects of OSA than isolated daytime testing. In cognitively normal individuals, changes in EEG microstructure during sleep, particularly slow oscillations and spindles, are associated with biomarkers of AD, and measures of cognition and memory. Similar changes in EEG activity are reported in AD and OSA, such as "EEG slowing" during wake and REM sleep, and a degradation of NREM EEG microstructure. There is evidence that CPAP therapy partially reverses these changes but large longitudinal studies demonstrating this are lacking. A diagnostic definition of OSA relying solely on the Apnea Hypopnea Index (AHI) does not assist in understanding the high degree of inter-individual variation in daytime impairments related to OSA or response to CPAP therapy. We conclude by discussing conceptual challenges to a clinical trial of OSA treatment for AD prevention, including inclusion criteria for age, OSA severity, and associated symptoms, the need for a potentially long trial, defining relevant primary outcomes, and which treatments to target to optimize treatment adherence.

Obstructive sleep apnea, cognition and Alzheimer's disease: A systematic review integrating three decades of multidisciplinary research.

Increasing evidence links cognitive-decline and Alzheimer's disease (AD) to various sleep disorders, including obstructive sleep apnea (OSA). With increasing age, there are substantial differences in OSA's prevalence, associated comorbidities and phenotypic presentation. An important question for sleep and AD researchers is whether OSA's heterogeneity results in varying cognitive-outcomes in older-adults compared to middle-aged adults. In this review, we systematically integrated research examining OSA and cognition, mild cognitive-impairment (MCI) and AD/AD biomarkers; including the effects of continuous positive airway pressure (CPAP) treatment, particularly focusing on characterizing the heterogeneity of OSA and its cognitive-outcomes. Broadly, in middle-aged adults, OSA is often associated with mild impairment in attention, memory and executive function. In older-adults, OSA is not associated with any particular pattern of cognitive-impairment at cross-section; however, OSA is associated with the development of MCI or AD with symptomatic patients who have a higher likelihood of associated disturbed sleep/cognitive-impairment driving these findings. CPAP treatment may be effective in improving cognition in OSA patients with AD. Recent trends demonstrate links between OSA and AD-biomarkers of neurodegeneration across all age-groups. These distinct patterns provide the foundation for envisioning better characterization of OSA and the need for more sensitive/novel sleep-dependent cognitive assessments to assess OSA-related cognitive-impairment.