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Abstract Introduction Decreased sleep spindle oscillations were previously associated with cognitive decline in older adults, increased tau levels, and phenoconversion to dementia in patients with Parkinson disease (PD). We analyzed quantitative sleep spindle measures to determine if this biomarker was associated with particular neurodegenerative disorder syndromes. Methods Sleep spindle oscillations ascertained in patients broadly characterized as presumed Parkinsonian-spectrum disorders (PSD), which included the subtypes dementia with Lewy Bodies/Parkinson Disease Dementia (DLB/PDD, n=16), PD (n=16), isolated REM sleep behavior disorder (iRBD, n=19), and progressive supranuclear palsy (PSP, n=13), were compared with non-PSD subtypes Alzheimer Disease dementia (AD, n=22), mild cognitive impairment (MCI, n=35), and normal cognition (NC, n=61). Sleep Profiler studies were conducted in all participants. The automated spindle detection algorithms recognized temporal excursions in the alpha (8-12 Hz) and sigma (12-16 Hz) power of 250 milliseconds or greater, with spindle duration being the sum of all spindle elapsed times. Night-to-night variability was assessed in PSP=13, PD=16, DLB/PDD=12, AD=17, MCI=25, and NC=53. Statistical analyses included intraclass correlations (ICC) and Bland-Altman plots for two-night data, and Mann-Whitney U-tests and multiple logistic regression applied to sleep-time weight-averaged spindle-durations. Results The night-to-night spindle-duration ICC was 0.95 (P<0.0001), with a Bland-Altman bias of 0.05+/-2.83 minutes. Spindle-duration was independently associated with PSD versus non-PSD groups (P=0.017, OR 1.08, 95%-CI 1.01-1.15), but not significantly associated with age (P=0.12, OR 1.03, 95%-CI 0.99-1.07) or sex (P=0.54). When stratified by subtype, age was associated with spindle-duration when NC were compared to AD and MCI (P=0.0003, OR 1.10, 95%-CI 1.04-1.16) and when iRBD were compared to DLB/PDD, PD and PSP (P<0.05, OR 1.00, 95%-CI 0.89-1.13)Spindle-durations were reduced in PSP (0.9+/-2.1) and DLB/PDD (2.0+/-5.1) when individually compared to AD (3.2+/-7.1), iRBD (3.3+/-3.4), PD (5.3+/-6.6), MCI (5.3+/-9.7), and NC (8.0+/-11.1) subtypes (all P<0.05). AD patients also exhibited lower spindle-durations than NC (P=0.03). Conclusion Auto-detected sleep spindle-durations exhibited excellent night-to-night reliability in both NC and patients with neurologic disorders. Decreased sleep spindle-duration was independently associated with PSP and DLB/PDD, and in AD. Reduced sleep spindle duration may be a distinct sleep biomarker for those disorders likely indicating thalamocortical dysfunction. Support (If Any) NIA grants: R44AG050326, R44AG054256, P30AG62677 and R34AG56639.

Abstract Introduction The severity of REM sleep without atonia, a prodromal biomarker for synucleinopathy-related neurodegenerative disorders, is influenced by selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine retake inhibitor (SNRI) use. This study investigates whether SSRI/SNRIs similarly impacts the severity of Non-REM hypertonia (NRH), a biomarker independently associated with patients broadly characterized with presumed Parkinsonian-spectrum disorders (PSD). Methods In this multi-center study, the relationship between NRH and SSRI/SNRIs was evaluated in PSD patients [Lewy Body/Parkinson Disease Dementia (DLB/PDD=16), Parkinson Disease (PD=16), isolated REM sleep behavior disorder (iRBD=19), and progressive supranuclear palsy (PSP=12)], and non-PSD subjects [Alzheimer Disease (AD=22), mild cognitive impairment (MCI=35), and normal cognition (NC=61)]. Studies were conducted with the Sleep Profiler in all participants. NRH was auto-detected based on persistently elevated electromyographic (EMG) power relative to delta, theta, and sigma bands. Abnormal-NRH was based on a threshold of >5% of sleep time, and weight-averaged by sleep time, in the 75% of studies with two-nights of data. Statistical analyses included multiple logistic regression, Fisher Exact, and Mann-Whitney U tests. Results Across all 181 records, 38% had abnormal-NRH and 24% used SSRI/SNRIs (P<0.005). No differences were observed in the distributions of NRH for those with NRH-only vs. those with combined NRH and SSRI/SNRI use (n=45, 14.5+/-7.7% versus n=24, 18.6+/-11.6%, respectively; P=0.19). Abnormal-NRH was associated with the PSD versus non-PSD groups (P<0.0001, odds-ratio=14.0) and SSRI/SNRI use (P<0.05, odds-ratio=2.4), but not age and sex. Within the PSD and non-PSD groups, the frequency of abnormal-NRH was 75% vs. 19% (P<0.0001), and SSRI/SNRI use was 32% vs. 19% (P=0.07), respectively. The distributions of abnormal-NRH in the PSD and non-PSD subgroups ranged from PSP=92%, DLB/PDD=81%, PD=56% ,and RBD=74% versus MCI=26%, and NC=16%, AD=14%, respectively. By comparison, distributions of SSRI/SNRI use were DLB/PDD=50%, RBD=42%, PSP=33%, and PD=0% in the PSD subgroups, compared to MCI=34%, AD=23%, and NC=10% in the non-PSD subgroups. Conclusion Abnormal non-REM hypertonia exhibited a very strong association with Parkinsonian-spectrum disorder diagnoses (odds-ratio=14.0) and a relatively weaker association with selective serotonin reuptake inhibitor or serotonin-norepinephrine retake inhibitor use (odds-ratio=2.4), suggesting a finding that reflects an interactive, rather than causal inference. Support (If Any) NIA grants R44AG050326, R44AG054256, P30AG62677 and R34AG56639.

Background: Each year, nearly 700,000 Americans suffer from strokes, resulting in 150,000 deaths and significant disability among survivors. Despite advances in therapeutic options for acute stroke within a critical time window, patient delay in seeking medical attention remains a significant barrier to improving outcomes. In a recent study of the effect of marital status on the timing of presentation for medical care in patients with chest pain, married men presented earlier than married women. In this study, we hypothesize that marital status is a predictor of earlier health-seeking behavior following the onset of stroke symptoms. Methods: We conducted a retrospective review of 100 patients with acute stroke symptoms in our stroke alert quality initiative database who were brought by Emergency Medical Services (EMS) to the Mayo Clinic Hospital, Arizona between December 1, 2010 and June 30, 2011. Nine patients were excluded due to lack of data. The database contains the following information for each patient: age, gender, marital status, the time of symptom awareness, and the time of EMS dispatch. Using both an independent samples t-Test and ANOVA, we compared the time from symptom awareness to EMS dispatch both between married and single patients, and between men and women, (married and single). Results: The mean age of the 91 patients studied was 76 years (SD = 12.5 years) and 52% were women. Forty-five patients (49.5%) were married, and 46 (50.5%) were single. The mean time from symptom awareness to EMS activation was 52 minutes (median 21.0, SD 87.3, range 2-519 minutes.) Categorized by marital status, married patients activated EMS earlier that single patients, but this difference was not significant (43 versus 60 minutes, p=0.35.). Analyzing the data separately for gender, we found that married men activated EMS significantly earlier than married women (26 versus 72 minutes, p=0.04.). Single men activated EMS earlier than single women, but this difference was not significant (50 versus 66 minutes, p=0.60.) Conclusions: Among persons with acute stroke symptoms, earlier medical-seeking behavior was seen in married compared to single persons, and particularly in married men. We plan to analyze a larger sample of patients, and if these preliminary findings are confirmed, we will conduct a prospective study evaluating reasons why married men with stroke symptoms seek medical attention earlier.

AbstractBackgroundNeurodegenerative disease (NDD) is associated with sleep disturbances, including decreased stage N3 and REM sleep and reduced spindle activity. Further, supine sleep position may impact NDD risk by altering glymphatic clearance. This study evaluated conventional and exploratory sleep metrics in the differentiation of subjects with normal cognition (NC) and patients with Alzheimer’s disease dementia (AD) and alpha‐synucleinopathies (α‐Syn).MethodHome sleep data were acquired across multiple study sites using the self‐applied Sleep ProfilerTM, including 44 NC subjects (age=69+5.0), 22 patients diagnosed with AD (age=75+7.1) and 25 with α‐Syn (Parkinson’s disease=14, Parkinson’s disease with Dementia or Dementia with Lewy Bodies=11; age=69+6.9). Recordings were auto‐staged and technically reviewed, with 86% of the records having two‐night averages. Logistic regression and Mann‐Whitney U tests were used to characterize group differences based on age, conventional sleep metrics (i.e., sleep efficiency, sleep onset (SO), awakenings, percent of sleep time (%) in REM,N1, N2 and N3, and sleep spindles) and exploratory sleep measures [i.e., % supine, % Light N2 (L2=N2 epochs absent of spindles with K‐complexes and/or alpha or EMG (>40 Hz) intrusion), % NREM sleep with hypertonia (NRSH=>4 consecutive epochs with persistently elevated EMG power relative to delta and theta power) and % atypical N3 (AN3=epochs staged N3 with low theta and sigma power relative to delta, alpha, beta and EMG)].ResultAD were older than both NC and α‐Syn patients (p<0.005). Both AD and α‐Syn had lower %REM and greater %supine than NC (p<0.005), and %NRSH was greater in α‐Syn than NC or AD (p<0.005). Based on logistic regression, AD was differentiated from NC based on age, %REM, %L2 (p<0.05) and %supine (p=0.06). α‐Syn was distinguished from NC using both conventional (%N3 and SO, p<0.05) and exploratory sleep metric (%AN3 and %NRSH, p<0.05; %supine, p=0.06). Age (p=0.05) and %NRSH (p<0.01) were the only metrics that differentiated α‐Syn from AD.ConclusionObjective home sleep profiles hold promise for differentiating NDD patients from NC. The sleep metrics that provided the greatest distinction between NDD and NC were %REM, %supine and NRSH, while only NRSH distinguished AD from α‐Syn patients. Further confirmatory studies are underway.

Abstract Purpose Compare agreements between polysomnography-based (PSG) diagnosis of isolated REM-sleep-behavior-disorder (iRBD) and Non-REM-Hypertonia (NRH), a novel biomarker independently associated with synucleinopathy-related neurodegenerative diseases. Methods Sixteen patients with histories of dream-enactment-behavior (DEB)(women=38%; age:64.6±13.0) underwent PSG with simultaneously-recorded Sleep Profiler (SP). Two boarded sleep neurologists independently characterized iRBD. Physician1 combined abnormal qualitative REM-sleep-without-atonia (RSWA) by submental electromyography, with video-confirmation of probably DEB. Physician2 relied solely on qualitative RSWA. SP was auto-staged, technically reviewed, and reprocessed for automated abnormal NRH detection. Kappa scores measured physician and NRH agreements. Results In the 14 records with REM sleep, iRBD was characterized in: Physician1=64%, Physician2=79%, NRH=71% of the records. Across the three methods, unanimous iRBD agreement occurred in 57% of the records (positive=7, negative=1). The between-physician agreement in iRBD classifications was fair (kappa=0.32). The agreement between NRH and Physician1 was moderate (kappa=0.52) versus slight with Physician2 (kappa=0.05). NRH comparisons to consensus physician agreement yielded one false-positive and one false-negative iRBD finding. Physician2 classified: a) iRBD in two cases that were negative by Physician1 and NRH, and b) one negative case that Physician1 and NRH characterized as iRBD. Physician1 identified one negative case that was classified iRBD by Physician2 and NRH. Additionally, NRH was abnormal in one of the two records with no REM sleep. Discussion NRH may assist in iRBD risk assessment, given it agreed with at least one physician in 86% of the cases and the between-physician iRBD agreement was only fair. NRH also characterized iRBD-risk in patients with insufficient REM sleep for RSWA assessment.

Abstract Purpose Evaluate the sleep staging agreement between polysomnography (PSG) and Sleep Profiler (SP) in patients with suspected isolated REM-sleep-behavior-disorder. Methods Twenty-six patients with reported dream-enactment-behavior (Site1=16, Site2=10; 27% women; age 64±13 years) underwent a diagnostic PSG with simultaneously recorded SP. A registered sleep-technologist at each site performed PSG-staging, while SP was auto-staged and technically reviewed/edited. Across technicians, the initial staging was blinded. Site1 then performed unblinded restaging of PSG=N3(N2) vs. SP=N2(N3) epochs, while Site2 conducted a blinded, carefully-targeted restaging of N3. Statistics included Cohen’s kappa and Chi-square analyses. Results Agreement between SP and Site1 vs. Site2 were significantly different for Wake (kappa:Site1=0.816;Site2=0.650;combined=0.736), stage N1 (kappa:Site1=0.149;Site2=0.228;combined=0.188), stage N2 (kappa:Site1=0.632;Site2=0.718;combined=0.659), stage N3 (kappa:Site1=0.715;Site2=0.368;combined=0.525) and REM (kappa:Site1=0.827;Site2=0.719;combined=0.766)(all P&lt;0.001). After restaging of N3, the kappa values improved at Site1 (unblinded:N2=0.659/N3=0.883) and Site2 (blinded:N2=0.775/N3=0.736)(combined:N2=0.735/N3=0.851). The proportion of PSG-epochs restaged from N3 to N2 was 17% at Sites1 and 38% at Site2 (P&lt;0.001), while Site1 had fewer remaining PSG=N3 vs. SP=N2 conflicts (5.6% vs. 20.8%, P&lt;0.001). Compared to Site2, Site1 had a superior: REM kappa due to fewer SP=N2 disagreements (8.5% vs. 16.8%, P&lt;0.001), and Wake kappa resulting from fewer SP=N1 (6.6 vs. 15.6%, P&lt;0.001) and SP=N2 conflicts (5.9 vs. 12.0%, P&lt;0.001). Conversely, the Site1 N1 kappa was inferior due to greater SP=wake disagreement (41.6% vs. 19.8%, P&lt;0.001). Discussion N3 was excessively stage by both PSG technicians before restaging. At Site1, Wake, N3, and REM had almost-perfect-agreement with SP, while N2 had substantial-agreement. At Site2 and across-site, substantial-agreement was observed for Wake, N2, N3, and REM.

Background: Atrial fibrillation (AF) is an important modifiable and independent risk factor for stroke. AF is associated with 2-4% annual risk for first time stroke and about 8% annually for recurrent stroke. Anticoagulant therapy reduces the risk by 60%, while the relative risk reduction (RRR) obtained from antiplatelet therapy is only 20%. The effect is more robust for secondary than for primary prevention. Risk stratification schemes are utilized to assess an individual’s risk of future stroke and to determine the optimal antithrombotic or anticoagulation regimen for stroke prevention. Despite Warfarin’s superiority over antiplatelet therapy to reduce the risk of AF related systemic embolism, Warfarin is largely underutilized. The aim of this study was to determine the frequency and reasons behind withholding anticoagulation in patient with AF related cardioembolic stroke in our institution. Method: We extracted patients from our Get With The Guideline’s (GWTG) database who were admitted to Mayo Clinic AZ between January 2004 and December 2009. Two authors (TK and NL) independently identified all patients with the diagnosis of atrial fibrillation who were not prescribed Warfarin therapy upon discharge, then reviewed to identify the reason(s) why anticoagulation was not initiated. Factors such as discharge disposition (home, acute rehabilitation, long term nursing facility, hospice, other) and functional status (able to ambulate independently, with assistance, unable to ambulate, or not documented) were also assessed to help support the decision process. Results: From a total of 1295 patients, 305 with AF were identified. Patients who expired 48 (3.7%) from un-related causes were excluded. Of the 257 patients, 206 (80.2%) were anticoagulated and 51 (19.8%) were not anticoagulated. We found that in the anticoagulated group, patients discharged home were more likely to receive anticoagulation (89.2%), followed by those discharged to acute rehabilitation and skilled nursing facilities (77%). Those discharged to hospice were the least likely to receive anticoagulation (6.4%). In addition, patients with greater functional ability were also more likely to receive anticoagulation (independent 89.8%, vs. assisted 76.7%, vs. non-ambulatory 33.3%; p<0.0001). Reasons to withhold anticoagulation therapy at discharge included terminal illness/comfort measures only (40.0%); risk/discomfort due to bleeding (24%); risk of falls (13.0%); and patient refusal (9.0%). Discussion: Based on the results, we conclude that functional status and disposition at discharge are significant factors influencing the decision to anticoagulate after cardioembolic stroke attributed to AF.

Abstract Microaspiration, or silent aspiration, is commonly suspected in patients with refractory respiratory symptoms, including unexplained chronic cough, asthma, chronic obstructive pulmonary disease, bronchiolitis, bronchiectasis, and idiopathic pulmonary fibrosis. This suspicion is driven by the high prevalence of gastroesophageal reflux in these otherwise disparate disorders. Frequently, patients receive aggressive treatment for gastroesophageal reflux disease as a means of treating their underlying respiratory conditions, even in the absence of overt symptoms of reflux. However, clinical trials have not demonstrated a clear impact on outcomes with this strategy, and in some instances there may be potential for harm. Mechanistic studies have increasingly used gastric biomarkers obtained directly from the airways to confirm the association between reflux and respiratory disease, but results are limited by methodologic flaws and correlation. The best evidence of aspiration directly causing respiratory disorders is the histopathologic detection of foreign bodies. For most of the other chronic respiratory disorders, microaspiration may be uncommon or a secondary aggravating factor, as in patients with acute exacerbations of chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis. In some cases, microaspiration is probably not a significant factor at all, such as in unexplained chronic cough. It is important to distinguish between conditions in which aspiration is primarily or directly causal and conditions in which aspiration may be indirectly aggravating, to help identify whether interventions targeting reflux and aspiration precautions should be recommended to patients. Our clinical review examines some of the evidence supporting reflux-aspiration as a mechanism for several chronic respiratory disorders and offers some management considerations when reflux-aspiration is suspected.