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AbstractINTRODUCTIONGiven the close interactions between the retina and the brain, retinal amyloid imaging may serve as a diagnostic and prognostic tool for Alzheimer's disease and related dementias. This retrospective study investigated multivariable associations between retinal perivascular amyloid and cognitive domains.METHODSIntegrated analysis of retinal perivascular amyloid imaging, neuropsychological assessment, and brain magnetic resonance imaging in adults with and without cognitive impairment (N = 26; mean age: 65 ± 7 years; 50% female). Correlations between perivascular amyloid plaque burden and cognitive domains were evaluated with linear regression and interactions with hippocampal volumetry were explored.RESULTSHigher perivascular and periarteriolar amyloid plaque count in the secondary small and tertiary branches were associated with poorer verbal and visual memory in this cohort (p = 0.005–0.009). Higher perivascular amyloid burden interacted with hippocampal atrophy to worsen visual memory (p = 0.033).DISCUSSIONRetinal perivascular amyloid may serve as a non‐invasive marker for cognitive impairment and may shed insight into pathological changes in the brain.Highlights In vivo retinal perivascular amyloid plaque counts are associated with poorer memory. Retinal perivascular amyloid interacted with hippocampal atrophy to worsen memory. Retinal amyloid imaging is a potential biomarker for neurodegenerative diseases.

Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.

BACKGROUND AND OBJECTIVES: It remains unclear whether decompressive craniectomy (DC) is beneficial in patients who suffer symptomatic intracerebral hemorrhage (sICH) after acute ischemic stroke (AIS). We sought to study the effect of DC on functional outcomes in patients with sICH after AIS who underwent mechanical thrombectomy (MT). METHODS: Patients with AIS from anterior circulation large vessel occlusion who underwent MT and subsequently developed sICH were identified from the Stroke Thrombectomy and Aneurysm Registry database. The primary outcome was acceptable 90-day functional neurological outcome, defined as modified Rankin scale (mRS) 0-3. Multivariable logistic regression and propensity-score matching were used to identify and quantify risk factors. RESULTS: Of 464 patients identified with sICH after AIS after MT, 97 patients (20.9%) underwent DC. Patients who underwent DC were more likely to be female ( P < .001), younger ( P < .001), have a measured medical comorbidity, have higher baseline mRS ( P = .02), and have higher-grade hemorrhages ( P = .01). At 90 days, 14% of patients had the primary outcome of mRS 0-3 and 56% had died. The primary outcome was observed in 11 patients who underwent DC (11%) and 55 (15%) of those without DC (odds ratio [OR] 0.7, 95% CI 0.4-1.4, P = .40). DC did not affect mRS shift at 90 days ( P = .10) but was associated with lower mortality (OR 0.5, 95% CI 0.3-0.8, P = .01). Multivariable analysis demonstrated that DC decreased the odds of primary outcome (adjusted OR 0.2, 95% CI 0.02-0.9, P = .045), but did not affect mortality ( P = .94), mRS shift ( P = .50), or length of stay ( P = .90). Propensity-matched analysis similarly demonstrated that non-DC patients were more likely to achieve the primary outcome (24% vs 8%, P = .045). CONCLUSION: In patients with sICH after AIS after MT, those selected for DC had less favorable outcomes and similar rates of mortality at 90 days.

Background: Evaluation of the performance of Cobas ® Pulse (Roche Diagnostics GmbH, Mannheim, Germany), a new blood glucose (BG) monitoring system (BGMS; referred to here as BGMSA) intended for point-of-care testing using samples from patients in diverse clinical settings by intended point-of-care test operators. Methods: Arterial, capillary, venous, or heel stick whole blood (WB) samples from patients in non-critical and critical care settings were collected and analyzed using BGMSA and the Nova StatStrip ® BGMS (Nova Biomedical, Waltham, MA; referred to here as BGMSB), and a hexokinase comparator (Cobas 6000 Analyzer Series; Roche Diagnostics GmbH). The blood glucose measurement accuracy was assessed by the Food and Drug Administration guidance criteria. Results: Two studies are presented. In the first, 2678 samples (622 arterial, 706 capillary, 1203 venous, 147 heel stick) were collected from 1577 patients in 14 US and three European sites. All accuracy criteria were met for arterial and venous samples considering all data combined. BGMSA showed better accuracy than BGMSB for arterial, venous, and heel stick, and similar results to BGMSB for capillary WB vs venous comparator. No endogenous interference from pO 2 , hematocrit, and sodium was identified. BGMSA was also accurate when analyzing contrived samples used to show accuracy over a wide range of glucose concentrations, alone and when combined with extreme hematocrit. In the second study, 117 capillary fingerstick samples collected at one US site were measured on both BGMSA and the comparator, and all accuracy criteria were met. No clinically significant medical risks were observed via Diabetes Technology Society Error Grids. Conclusions: BGMSA was effective for determining blood glucose in venous, arterial, neonatal arterial, neonatal heel stick, and capillary WB samples.

Background Endovascular therapy (EVT) for stroke due to distal or medium vessel occlusion (DMVO) is safe. Due to the distinct anatomical characteristics of DMVOs, further evaluation of EVT is crucial to determine which devices may yield better outcomes. Methods A retrospective analysis of adults with DMVO treated in 37 centers (11 countries) was queried. The primary outcome of favorable shift in 90-day modified Rankin Scale (mRS) was compared between patients treated with Trevo versus other devices on first pass using 1:1 propensity score matching (PSM) with multivariable adjustment. Secondary outcomes included the number of pass attempts, final thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), improvement in National Institutes of Health Stroke Scale (NIHSS) at 24h, and 90-day mortality. Results Of the 1115 included patients, 264 (24%) were treated with Trevo (PSM cohort of 261 per group). Trevo use was not associated with a favorable 90-day mRS shift (proportional odds ratio [OR] 1.10, 95% confidence interval [CI] 0.80–1.51). Trevo was associated with fewer passes (adjusted β=-0.25, 95% CI −0.48 - −0.03), higher odds of TICI 2b-3 (adjusted OR 1.97, 95% CI 1.11–3.49), and a greater 24h NIHSS improvement (adjusted β= −1.74, 95% CI −3.11 - −0.36), with no difference in sICH or mortality (p>0.05). Results were similar in sensitivity analyses. Conclusions We observed no safety concerns with Trevo as compared to other EVT devices for DMVO recanalization. There was a signal of better technical efficacy and early clinical improvement.

Abstract Introduction The majority of adults with inflammatory bowel disease (IBD) experience disability which is not fully explained by disease activity. Up to 80% of adults with IBD experience poor sleep health, which is associated with disability in other populations; however, the relationship between disability and sleep health among patients with IBD is largely unexamined. The purpose of this study was to compare the sleep health characteristics of those with and without IBD-related disability. Methods We recruited adults (18 to 59 years old) with IBD from a single academic medical center from 2022 to 2024. We measured disease activity using the Manitoba IBD Index and sleep using the PROMIS Sleep Disturbance and PROMIS Sleep-Related Impairment scales, the Insomnia Severity Index, and 14 days of wrist-worn actigraphy (Phillips Spectrum Plus, Phillips Respironics). We asked participants how many days they missed or had at least 50% reduced productivity in paid work or household work or missed leisure activities in the last 3 months related to their IBD. Disability was defined as missing six or more day over three months. We conducted bivariate analyses and logistic regressions to study associations. Results Among 83 adults with IBD [mean age = 40.4 years (SD 10.7), 59 (71.1%) were female, 56 (71.1%) had Crohn’s disease], and 49 (62.0%) had IBD-related disability. Patients with disability had more severe sleep disturbance (56.4 vs. 51.0, p &lt;.001), sleep-related impairment (58.3 vs 50.3, p &lt;.001), more severe insomnia (12.7 vs. 9.4, p =.029), and actigraph-measured higher wake after sleep onset (41.6 minutes vs. 34.0 minutes, p = 0.012) and lower sleep efficiency (85.1% vs. 87.9%, p = 0.032) compared to those without disability. After controlling for age and disease activity, sleep-related impairment (OR = 1.1, 95% CI 1.03, 1.15) was independently associated with disability. Conclusion Patients with IBD-related disability experience poor sleep health. Sleep related daytime impairment uniquely contributed to disability when controlling for disease activity. Sleep interventions need to be tested in adults with IBD to determine if they are effective at addressing disability in this population. Support (if any) Mayo Clinic Bonner Fund

Abstract Introduction Identifying central sleep apnea (CSA) during home sleep apnea testing is important to guide appropriate treatment for sleep-disordered breathing (SDB) and underlying cardiovascular conditions, including heart failure and atrial fibrillation. SANSA (Huxley Medical, Inc.) is a multi-diagnostic chest-worn monitor capable of detecting SDB, cardiac arrhythmias, and heart function. Using polysomnography (PSG) as a reference, we developed a machine learning (ML) method to classify respiratory events from this monitor as central or obstructive. Methods Data was analyzed from ninety-five subjects with suspected SDB who wore the chest monitor simultaneously with PSG overnight. To address known scoring heterogeneity of CSA, PSG records were scored for central apneas by two core laboratories (Core 1 and Core 2). Core 1 annotations from twenty-eight records were first used to train a random forest classifier to differentiate obstructive (N=680) and central events (N=388). The model used oximetry, respiratory effort, and snoring to classify events based on effort, duration, and other features. A five-fold cross validation was used to evaluate event-level performance. The model was then used to estimate subject-level CAI for all subjects and compared with Core 2 scores. Results Algorithm event-level sensitivity and specificity to detect central events was 72.7% and 81.0%. Subject-level CAI for all records between the chest monitor and Core 2 had a correlation coefficient of 0.90 and root mean squared error (RMSE) of 4.6 events/hour, versus 0.82 and 4.7 events/hour comparing Core 1 and Core 2. Sensitivity and specificity to detect CAI≥10 events/hour was 80.0% (4/5) and 98.9% (89/90), compared to 100% (3/3) and 98.9% (91/92) for CAI≥15. Conclusion An ML algorithm to differentiate obstructive and central events collected from the chest-worn monitor demonstrated favorable event-level performance and comparable CAI agreement to that between two PSG core laboratories. Home-based CSA detection alongside cardiac monitoring could identify high risk patients for expedited therapy, cardiology referral, or follow-up PSG. These results motivate further validation in a larger cohort as well as investigation of outcomes related to time to evaluation and management. Support (if any) National Science Foundation; Georgia Research Alliance; Huxley Medical, Inc.