Citations

Abstract Introduction Sleep-disordered breathing (SDB) is a potentially modifiable risk factor for the prevention of dementia, of which Alzheimer’s disease (AD) is the most common cause. However, there is a lack of longitudinal evidence relating SDB to AD pathology >20 years later. We examined the association between late-midlife SDB and late-life brain β-amyloid (Aβ) deposition—a hallmark of AD—assessed approximately 23 years later. Methods The Atherosclerosis Risk in Communities (ARIC) Study is an ongoing prospective cohort study initiated in 1987. Participants at two ARIC sites (Washington County, Maryland; Minneapolis, Minnesota) with primarily White participants also completed polysomnography (PSG) in the Sleep Heart Health Study (SHHS) in 1995-98. SDB measures included apnea-hypopnea index (AHI; number of apneas + hypopneas with ≥3% oxygen desaturation/hour of sleep), arousal index, and percentage of total sleep time in apnea, in hypopnea, and with oxygen saturation < 90%. A subset of participants completed florbetapir positron emission tomography (PET) scans through several ARIC ancillary studies (2011-2025 including the ARIC Sleep-PET study). We defined Aβ deposition as a global standardized uptake value ratio (SUVR) >1.2 (vs. SUVR ≤1.2). We used Poisson regression with robust standard errors to estimate relative risk (RR) of Aβ deposition by SDB, adjusting for demographics and vascular risk factors, and applied inverse probability attrition weighting to account for selective drop-out. Results Among 186 dementia-free participants (mean age=59 years at PSG and 82 years at PET scan, 58% female, 98% White), every 10% increase in total sleep time in hypopnea was associated with higher risk of Aβ deposition (RR=1.40, 95% confidence interval [CI]: 1.03, 1.91). When compared to no SDB (AHI < 5), moderate to severe SDB (AHI ≥15) was associated with elevated Aβ deposition (RR=2.36, 95% CI: 1.22, 4.57); mild SDB (AHI 5 to < 15) was not (RR=1.05, 95% CI: 0.53, 2.07). Conclusion SDB in late midlife was associated with greater risk of Aβ deposition approximately 23 years later. SDB may play a role in the early stages of AD pathogenesis. Future longitudinal studies are needed to optimize strategies for screening and treating SDB for dementia prevention. Support (if any) Supported in part by RF1AG050745.

Abstract Introduction Klinefelter syndrome (KS) is a chromosomal condition marked by hypogonadism and disturbances in hormonal regulation. The relationship between KS and co-occurring sleep disorders has not been extensively characterized, creating a need for more detailed investigation. Methods We identified individuals with Klinefelter syndrome (KS) evaluated at our institution between January 2000 and December 2025 using ICD-9 and ICD-10-CM codes. Electronic health records were then manually reviewed to confirm KS status and to exclude miscoded entries. For confirmed cases, we extracted data on sleep-related complaints, diagnoses, diagnostic testing (overnight oximetry, polysomnography, home sleep testing), and treatment. Sleep disorders were categorized operationally: obstructive sleep apnea (OSA), central sleep apnea (CSA), insomnia, hypersomnia/narcolepsy, or other according to documented clinician diagnosis or diagnostic test results. When structured Sleep Center data were available, these were included. We summarized cohort characteristics using means (± SD) or medians (interquartile range) as appropriate. For comparison between subgroups (e.g., those with vs without documented sleep-disordered breathing), we applied Welch’s t-test and binomial proportion tests. Analyses were conducted using Python scripts and spreadsheet software. Results Nearly one-third of patients with confirmed KS in this series had either diagnosed or suspected obstructive sleep apnea (OSA), substantially exceeding prevalence estimates in the general population. The frequency of central sleep apnea (CSA) was comparable to that seen in the general population, however its occurrence without usual predisposing factors suggests a predisposition toward idiopathic CSA in KS. Circadian rhythm disorders were rare, occurring in < 1% of the cohort. Notably, nearly 75% of KS patients with documented sleep-related symptoms had never undergone formal evaluation in a Sleep Center. Conclusion The observed rate of presumed idiopathic CSA among individuals with KS suggests the possibility of KS-specific mechanisms affecting ventilatory control stability. Additionally, there appeared to be a larger prevalence of OSA in this patient population. Notably, approximately three-quarters of KS patients who reported sleep-related symptoms had never undergone a formal Sleep Medicine assessment, highlighting a significant gap in structured evaluation that may relate to limited access to specialized care, referral patterns, or other systemic barriers, and warrants additional study. Support (if any) None

Abstract Introduction Narcolepsy and idiopathic hypersomnia (IH) are characterized by excessive daytime sleepiness. They can be caused by deficiency of orexin/hypocretin, a neuropeptide that regulates sleep and wakefulness. It is estimated that 1 in 2000 people in the United States of America have been diagnosed with some form of narcolepsy or idiopathic hypersomnia. Around the world, about 3 million people are narcoleptic. Little data are available regarding the lifestyle factors in these patients. In this study, we sought to find whether lifestyle factors, including diet and physical activity are associated with the severity of sleepiness in narcolepsy and idiopathic hypersomnia. Methods We collaborated with “Hypersomnia Foundation” and “Wake Up Narcolepsy” who distributed our survey to their subscribers. The survey consisted of a series of four short subsurveys asking about the substance use, diet (MiniEAT screen), exercise (IPAQ questionnaire), and daytime sleepiness (Epworth Sleepiness Scale). The survey was anonymous and included baseline characteristics, diagnosis (Narcolepsy type 1 (NT1), Narcolepsy type 2 (NT2), or Idiopathic Hypersomnia (IH)). We considered hypersomnolence and moderate to severe hypersomnolence to be present if ESS >10 and ≥15, respectively. Results We received total of 377 individual responses. Of those, 191 responders had IH, 97 had NT1 and 89 had NT2. Median age was 31 (25, 42) and 323 identified as females, 44 males and 10 others. Median ESS was 15 (12, 18), where 285 responders had ESS >10 (76%) and 194 (51%) had ESS >/=15. The ressponders with NT1 had significantly higher median ESS: 17 (12,19), than NT2: 15 (10, 17), or IH: 15(12, 17) responders (p< 0.01). In multiple univariate analyses, none of the baseline characteristics, habits (smoking, alcohol or caffeine), dietary consumption (fruit, vegetable, legumes/nuts/seeds, whole or refined grains, dairy and fish/seafood) or exercise (vigourous, moderate or walking) had significant association with the degree of responders’ subjective sleepiness. Conclusion Most survey responders continue to be excessively sleepy, particularly those with NT1. There were no apparent univariate associations of underlying hypersomnolence with the baseline characteristics, habits, diet and exercise levels. Disorders of central hypersomnolence are of complex nature without easily identifiable modifiers. Support (if any) Mayo Clinic CRISP

Abstract Introduction Sleep regularity has been shown to be a stronger predictor of mortality compared to sleep duration, though the underlying mechanisms are incompletely understood. Heart rate variability (HRV), a measure of cardiac autonomic modulation, is associated with cardiovascular morbidity and mortality. While HRV is traditionally analyzed using linear methods (e.g., frequency-domain analyses), there is growing interest in nonlinear measures to assess the dynamic complexity of cardiac regulation. However, the influence of sleep regularity on both linear and nonlinear HRV is unclear. We therefore assessed the association between sleep regularity and HRV in healthy adults. Methods HRV was obtained in 12 participants (6 female) via electrocardiography during 10-min supine rest and assessed using linear (high frequency [HF]; low frequency [LF]/HF ratio) and nonlinear (detrended fluctuation analysis [DFA]-α1 and -α2) indices. Sleep regularity was quantified using the standard deviation (SD) of diary-determined sleep onset across ~14 days. Participants were classified as regular (SD< 1h; n=5) or irregular sleepers (SD>=1h; n=7). Irregular sleepers were instructed to maintain a consistent sleep onset (±30min) for 12-weeks. Differences between groups were assessed using independent t-tests and relationships between SD sleep onset and HRV were assessed using Pearson correlation analyses. Results There were no differences between groups in age (mean±SD, irregular vs. regular, respectively; 30.7±7.8 vs. 27.2±8.5y; p=0.23), sleep onset timing (24:38±1:45 vs. 23:37±1:14; p=0.14), or DFA-α2 (0.27±0.11 vs. 0.36±0.20; p=0.16). At baseline, irregular sleepers had higher SD sleep onset (1.4±0.4 vs. 0.8±0.2h; p< 0.01), LF/HF ratio (2.4±1.8 vs. 0.6±0.5%; p=0.03), DFA-α1 (1.10±0.22 vs. 0.81±0.20; p=0.02), and lower HF (37.1±20.5 vs. 63.1±7.1nu; p=0.02). In the entire sample, SD sleep onset was inversely correlated with HF (r=-0.63; p=0.02) and positively correlated with LF/HF ratio (r=0.75; p< 0.01) and DFA-α1(r=0.61; p=0.03) at baseline. At 12-weeks, the change in SD sleep onset was inversely correlated with change in HF (r=-0.79; p< 0.01) and positively correlated with change in LF/HF ratio (r=0.77; p< 0.01) and DFA-α1(r=0.66; p=0.01). Conclusion Irregular sleep patterns are associated with altered cardiac regulatory dynamics and may be one mechanism contributing to adverse outcomes. Improving sleep regularity may be a potential interventional target to improve the autonomic balance and cardiovascular adaptation. Support (if any)

OBJECTIVE Adamantinomatous craniopharyngioma (ACP) is a rare type of brain tumor that affects a wide age range, from children to older adults. Due to the rarity of the disease, existing studies are predominantly limited to single-center or single-surgeon experiences, often lacking statistical power and generalizability. The aim of this study was to address this gap by providing a comprehensive analysis of ACP outcomes based on a large multicenter cohort from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). METHODS This multicenter retrospective cohort study was conducted via the RAPID consortium and assessed patients with histologically confirmed ACP treated surgically between August 2000 and November 2024 at high-volume pituitary centers across the United States. RESULTS Among the 359 patients (206 male, median age at primary surgery of 47 years) included in the analysis, 76% underwent endoscopic transsphenoidal surgery and 22% underwent craniotomy. Gross-total resection was achieved in 45% and subtotal resection in 47%. Notably, 120 of 311 patients (39%) presented with preoperative hypothalamic-pituitary axis dysfunction. Following all treatments, permanent hypothyroidism was reported in 40% of patients, adrenal insufficiency in 33%, and arginine vasopressin deficiency in 19%. Of 263 patients who underwent primary surgery, radiation therapy was administered in 84 (32%). Progression-free survival (PFS) declined from 66% at 1 year to 31% at 6 years. In the multivariable analysis, independent predictors of worse PFS included subtotal resection (HR 0.22, 95% CI 0.11–0.42; p = 0.001), partial resection (HR 0.11, 95% CI 0.04–0.28, p = 0.001), larger tumor size (HR 0.77, 95% CI 0.64–0.94; p = 0.009), and tumor extension beyond the sella and suprasellar regions (HR 0.21, 95% CI 0.06–0.74; p = 0.016). Primary surgery and salvage surgery groups showed comparable PFS. CONCLUSIONS In this large multicenter cohort study, gross-total resection was achieved in fewer than half of patients and was independently associated with improved PFS. Approximately one-third of patients underwent radiation therapy after primary surgery. These findings provide robust evidence supporting the prognostic value of extent of resection and inform contemporary treatment algorithms for ACP. The high incidence of postoperative endocrinopathy underscores the need for individualized multidisciplinary long-term care. While the retrospective design is a limitation, the multicenter approach enhances the generalizability of these results.

OBJECTIVE Protocols for intraoperative mapping during awake craniotomy vary widely. The aim of this study was to evaluate how the number and type of intraoperative neuropsychological paradigms administered via NeuroMapper, a tablet-based platform, during awake glioma surgery affect positive mapping rates, return to work (RTW), and oncological outcomes. Factors associated with the operative duration and early postoperative neurological deficits were of additional interest. METHODS This single-center retrospective study included patients with diffuse low- and high-grade gliomas who underwent awake craniotomy with NeuroMapper-guided mapping between 2018 and 2024. Primary outcomes were RTW, progression-free survival (PFS), and overall survival (OS); operative duration and early postoperative deficits were secondary outcomes. Covariate balancing propensity score (CBPS) analysis was used to address confounding by tumor grade, with all postweighting standardized mean differences < 0.10. A weighted logistic regression model assessed RTW, and CBPS-weighted Cox models assessed PFS and OS. Linear regression was used to analyze intraoperative variables, operative duration, and early postoperative deficits. RESULTS Of 189 patients included in the analysis, 65 had LGG (median age 39 years) and 124 had HGG (median age 56 years). Mapping complexity varied, with 1–6 tasks used (median 4). Weighted multivariate logistic regression analysis identified the following independent predictors of RTW: preoperative Karnofsky Performance Status score ≥ 80 (OR 1.37, p = 0.039), absence of recurrent disease (OR 0.30, p < 0.001), use of 5–6 paradigms (OR 1.54, p = 0.047), positive mapping (OR 2.41, p = 0.017), and subtotal resection (OR 4.43, p = 0.002). Intraoperative seizure, early postoperative deficit, and the resection technique were not significant. IDH mutation status was associated with improved PFS (HR 0.15, p < 0.001), while subtotal resection was associated with worsened PFS (HR 3.00, p < 0.001). Positive mapping was associated with better OS (HR 0.57, p = 0.04). The operative duration was unaffected by mapping variables but was longer in patients with obesity (β = 0.28, p = 0.038). CONCLUSIONS Positive NeuroMapper-guided mapping of more diverse linguistic functions was associated with RTW and longer OS. Additionally, mapping complexity did not prolong surgery times, supporting potential standardization.

OBJECTIVE Communicating hydrocephalus may occur following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs), yet identifying individual patient risk factors associated with this post-SRS complication remains a challenge. This study examined predictors of nonobstructive ventricular enlargement and symptomatic communicating hydrocephalus following primary SRS treatment for VS via a single-center institutional cohort review and meta-analysis of the literature. METHODS A retrospective single-institution cohort study and systematic literature review and meta-analysis examining post-SRS communicating hydrocephalus in VS was performed. RESULTS The institutional cohort consisted of 634 patients who received primary SRS as treatment for VS. The cohort was 51.6% female, with a median age of 64 (range 18–89) years. Following SRS treatment, 364 patients (57.4%) experienced tumor shrinkage, 218 (34.4%) had no change in the size of their lesion, and 52 (8.2%) experienced tumor growth. Nonobstructive ventricular enlargement was observed in 23 patients (3.6%) following SRS treatment, of whom 9 (39.1%) remained asymptomatic and 14 (60.9%) required placement of a ventriculoperitoneal (VP) shunt, with a median time to shunt placement of 8 months. In the multivariate analysis, patients ≥ 65 years old (p = 0.038), SRS target volume ≥ 5 cm 3 (p < 0.001), maximum SRS dose ≥ 26 Gy (p = 0.015), and tumor growth at the most recent follow-up (p = 0.002) were associated with an increased risk of post-SRS ventricular enlargement. Similarly, patients with older age (p = 0.049), increased SRS target volume (p = 0.002), and tumor growth (p = 0.016) were at an increased risk of symptomatic communicating hydrocephalus requiring VP shunt placement. Twenty-nine studies, including the cohort in this study, met inclusion criteria in the meta-analysis. Of the pooled 7825 patients, the overall incidence of hydrocephalus following SRS was 5%, and a subanalysis of 7081 patients demonstrated the incidence of symptomatic hydrocephalus requiring a VP shunt to be 4%. In this subanalysis, the overall shunting rate in patients who experienced post-SRS ventriculomegaly was 92%. Among individual studies in the literature, increased tumor size was most commonly found to be a statistically significant risk factor for post-SRS hydrocephalus. CONCLUSIONS Approximately 5% of patients may experience nonobstructive ventricular enlargement following primary SRS treatment for VS. However, not all patients may be symptomatic and require shunting. Patients who are older (≥ 65 years), those with larger tumor volumes, and those with post-SRS tumor growth may be at increased risk of communicating hydrocephalus and may benefit from closer clinical monitoring.

ABSTRACT Aims Exercise capacity is a powerful predictor of cardiovascular risk. In patients unable to exercise, body composition analysis can potentially be used to estimate cardiorespiratory fitness. We developed a body composition “fitness” score, then validated its utility in two external populations. Methods and Results We included patients from four sites undergoing single photon emission computed tomography (SPECT) and twelve sites undergoing positron emission tomography (PET). We quantified body composition using deep learning. We evaluated associations between body composition and good exercise capacity (defined as completing ≥7 minutes on a Bruce protocol) then developed a body composition “fitness” score. We then assessed the associations of “fitness” score with exercise capacity and all-cause mortality in external populations. In total, 36471 patients were included with median age 67 (interquartile range 58 – 74). Median skeletal muscle density was higher among patients with good exercise capacity. In the external SPECT population, the body composition “fitness” score had higher prediction performance for good exercise capacity (AUC 0.771, 95% CI 0.752 – 0.789) than age (AUC 0.717, p<0.01). In the external PET population, high body composition “fitness” score was associated with lower cardiovascular death (adjusted hazard ratio 0.70, 95% CI 0.62 – 0.79, p<0.001). Conclusions We demonstrated that a comprehensive body composition “fitness” score could identify patients with good cardiorespiratory fitness. This approach transforms routinely acquired CT data into a surrogate marker of fitness which can be applied in patients undergoing PET, or other CT imaging, where exercise testing is not performed. Graphical Abstract Overview of study design. The overall population (n=36471) was split as outlined above. Body composition was analyzed from available computed tomography imaging. The distribution of body composition measures were analyzed in the combined single photon emission computed tomography (SPECT) populations. A body composition “fitness” score was derived to predict good exercise capacity in the internal population, with associations assessed in the two external testing populations.

Abstract Human genomic studies link reduced CUB domain-containing protein 1 (CDCP1) expression with myocardial recovery in heart failure. While CDCP1 regulates cardiac fibroblast proliferation in vitro, it’s in vivo role in cardiac fibrosis remains unclear. Using a Cdcp1 -knockout (KO) angiotensin II/phenylephrine mouse model, we show that Cdcp1 deletion reduces echocardiographic left ventricular mass, histologic cardiac fibrosis, and pro-fibrotic gene expression, along with decreased fibroblast activation and inflammatory markers. Spatial transcriptomics identified a pressure overload–expanded fibroblast subpopulation enriched for growth factor and TGF-β signaling (FB5), which was markedly attenuated in Cdcp1 -KO hearts, alongside reduction of a pro-inflammatory cardiomyocyte subtype (CM4). Complementary studies in human ventricular fibroblasts demonstrate that CDCP1 knockdown reduced extracellular matrix gene expression and collagen I deposition. These findings establish CDCP1 as a regulator of cardiac fibrotic remodeling in vivo and open avenues for its further investigation as a potential therapeutic target.