Association of Nonmodifiable Risk Factors With Alzheimer Disease Blood Biomarkers in Community-Dwelling Adults in the ESTHER Study
This population-based study on dementia biomarkers found that P-tau181 was dependent on age and APOEe4; NfL on age and sex; and GFAP on age, sex, APOEe4, and menopause status. GFAP levels and rate of increase were higher in women, especially in premenopausal participants.
KEY FINDINGS: This population-based study on dementia biomarkers found that P-tau181 was dependent on age and APOEe4; NfL on age and sex; and GFAP on age, sex, APOEe4, and menopause status. GFAP levels and rate of increase were higher in women, especially in premenopausal participants. Future research should confirm these findings and further explore the role of menopause in dementia pathogenesis among women.
BACKGROUND: Dementia-related blood biomarkers are the future of large-scale dementia risk stratification; however, the extent to which phosphorylated tau (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are associated with nonmodifiable risk factors has yet to be confirmed in the community, and the role of menopause has yet to be investigated. Therefore, the aim of this study was to examine the association of age, sex, APOEe4 status, and menopause, with dementia-related blood biomarker levels (P-tau181, NfL, and GFAP) and rate of change over 11 years in longitudinal biomarker measurements in community-dwelling adults.
DETAILS: Within this German population-based Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen in der älteren Bevölkerung cohort study (n = 9,940), a nested case-control study of 1,026 participants (1:1, without dementia during follow-up: incident dementia during follow-up) aged 50-75 years at baseline followed over 17 years was conducted. Blood biomarker measurements (P-tau181, NfL, and GFAP) were completed in blood from baseline, 8-year, and 11-year follow-ups, and cross-sectional and longitudinal regression analyses were used to assess the association with age, sex, APOEe4, and menopause. The mean age of participants was 64 years, and women accounted for slightly over half (54%) of the sample. Age was cross-sectionally and longitudinally significantly associated with all dementia-related biomarkers (p < 0.001). NfL and GFAP levels more strongly correlated (Spearman R = 0.55 and 0.49) with age at baseline than P-tau181 levels (Spearman R = 0.21). Women experienced significantly higher levels and rates of increase in GFAP (p < 0.001) while men experienced higher levels of NfL after adjusting for age and APOEe4 (p < 0.01). APOEe4 status was significantly associated with baseline and longitudinal levels of P-tau181 (baseline β = 0.30, p < 0.05) and GFAP (baseline β = 15.84, p < 0.001). Of interest, premenopausal status was significantly associated with higher GFAP levels after adjusting for age, sex, and APOEe4 (β = 19.09, p < 0.05).
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Source: Stocker, H., Beyer, L., Trares, K., et al. Association of Nonmodifiable Risk Factors With Alzheimer Disease Blood Biomarkers in Community-Dwelling Adults in the ESTHER Study. American Academy of Neurology. 2025; 104(9): 213500. Published: May 27, 2025. DOI: 10.1212/WNL.000000000021350.
Fear of Disease Progression and Resilience Parallelly Mediated the Effect of Post-Stroke Fatigue on Post-Stroke Depression
An interprofessional effort to minimize patient interruptions at night in an intensive care unit setting led to improved patient sleep quality and sustainable practice changes.
KEY FINDINGS: FOP and resilience parallelly mediated the effect of PSF on PSD, which may provide a novel perspective for healthcare professionals in preventing PSD. Targeted interventions aiming at reducing PSF, lowering FOP levels and enhancing resilience may be possible ways to alleviate PSD.
BACKGROUND: Purpose of the study is to explore the effect of post-stroke fatigue (PSF) on post-stroke depression (PSD) and examine the mediating effects of fear of disease progression (FOP) and resilience between PSF and PSD. This study enriched the literature by exploring the effect of PSF on PSD and further examining the mediating effects of FOP and resilience between PSF and PSD. Findings emphasized the important effects of PSF, FOP and resilience on PSD.
DETAILS: A total of 315 stroke patients participated in the questionnaire survey between November 2022 and June 2023. Data were collected using the General Information Questionnaire, Fatigue Severity Scale, Fear of Disease Progression Questionnaire-Short Form, Connor-Davidson Resilience Scale-10 Item and Hospital Anxiety and Depression Scale-Depression Subscale. Data were analysed by descriptive analysis, Mann-Whitney U-test, Kruskal-Wallis H-test, Pearson or Spearman correlation, hierarchical regression analysis and mediation analysis. PSF had a significant positive total effect on PSD (ß = .354, 95% CI: .251, .454). Additionally, FOP and resilience played a partial parallel-mediating role in the relationship between PSF and PSD (ß = .202, 95% CI: .140, .265), and the total indirect effect accounted for 57.06% of the total effect.
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Source: Ning, L., Fu, Y., Wang, Y., et al. (20245). Fear of Disease Progression and Resilience Parallelly Mediated the Effect of Post-Stroke Fatigue on Post-Stroke Depression: A Cross-Sectional Study. J Clin Nurs. 2025; 34(5): 1753-1764. Published: May, 2025. DOI: 10.1111/jocn.17323.
Distribution of Port-Wine Birthmarks and Glaucoma Outcomes in Sturge-Weber Syndrome
Lower eyelid and choroidal angiomas were associated with glaucoma diagnosis, suggesting a spatial relationship with SWS findings. However, leptomeningeal angiomas were not associated, possibly because these are further from the eye.
KEY FINDINGS: Lower eyelid and choroidal angiomas were associated with glaucoma diagnosis, suggesting a spatial relationship with SWS findings. However, leptomeningeal angiomas were not associated, possibly because these are further from the eye.
BACKGROUND: Objective of the study is to identify which features of Sturge-Weber syndrome (SWS) were most associated with glaucoma onset, severity, and treatment failure at a tertiary care center.
DETAILS: Electronic health records were reviewed for all children with SWS presenting between 2014 and 2020. Examination and imaging findings from dermatology, neurology, and ophthalmology were collected. Logistic regression was used to identify factors associated with glaucoma-related outcomes. Primary outcomes included glaucoma development, progression to surgery, and treatment failure. Failure was defined as having a final intraocular pressure >21 mmHg, devastating complication, or <=20/200 vision. Twenty-three of 44 SWS patients (52.3%) developed glaucoma, and 6 of 23 patients (26.1%) had both eyes affected. Sixteen of 29 eyes (55.2%) required surgery, and 29.6% overall met our failure criteria (mean follow-up: 5.1 ± 4.3 years). Glaucoma diagnosis was associated with bilateral port-wine birthmarks (PWBs; odds ratio [OR] 5.9; 95% confidence interval [CI] 1.3-43.2), PWB with any lower eyelid involvement (OR 9.7, 95% CI 2.6-44.5), and choroidal hemangiomas (OR 3.8, 95% CI 1.1-13.8), but was not associated with upper eyelid or leptomeningeal angiomas, seizures, prior hemispherectomy, or pulsed-dye laser. Eyes that progressed to surgery were more likely to have PWB affecting the lower eyelid (OR 33.7, 95% CI 4.5-728.0). No clinical or demographic factors were associated with treatment failure. In most cases, angle surgery failed (72.7%) but was a temporizing measure before subconjunctival filtering surgery.
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Source: M. Vu, D., Gjerde, H., Elhusseiny, A. M., et al. (20245). Distribution of c and Glaucoma Outcomes in Sturge-Weber Syndrome. Ophthalmology Glaucoma. 2025; 8(2): 181-187. Published: March-April, 2025. DOI: 10.1016/j.ogla.2024.10.007.
A Pilot Randomized Control Trial of Holding During Hypothermia and Effects on Maternal and Infant Salivary Cortisol Levels
Authors demonstrate positive effects of holding during TH as evidenced by lower salivary cortisol for both mother and infant and decreased heart rate, respiratory rate, and blood pressure for the infant on day-2. Further research is needed to replicate these results, to understand the lack of infant response on day-3 and to assess correlation with cumulative morphine exposure.
KEY FINDINGS: Authors demonstrate positive effects of holding during TH as evidenced by lower salivary cortisol for both mother and infant and decreased heart rate, respiratory rate, and blood pressure for the infant on day-2. Further research is needed to replicate these results, to understand the lack of infant response on day-3 and to assess correlation with cumulative morphine exposure.
BACKGROUND: The lack of physical contact during therapeutic hypothermia (TH) is challenging for parents of newborns with hypoxic ischemic encephalopathy. Holding is often avoided due to concerns for effects on infant temperature and for dislodging equipment. Authors assessed the effect of holding during TH on maternal and infant salivary cortisol levels and on infant vital signs.
DETAILS: Prospective crossover study with infants randomized to a 30-minute session of holding on day-2 versus day-3 of TH. "No-holding" occurred on the alternate day at the same time. Pre- and post-holding salivary cortisol levels were compared between holding and no-holding conditions. Vital signs were collected at 2-minute intervals. Data was analyzed using mixed-effects models. Thirty-four mothers and infants were recruited. The median gestational age was 39 weeks, 16 (94%) had moderate encephalopathy and all were on morphine during TH. Salivary cortisol levels decreased after holding for infants on day-2 (P = .02) and mothers on day-2 and day-3 (P = .01). Infants held on day-2, but not on day-3, had lower heart rates, respiratory rates, and mean arterial pressures. Temperature and oxygen saturations were stable on both days.
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Source: Fox, L., Cutler, A., Kaneko-Tarui, T., et al. (20245). A Pilot Randomized Control Trial of Holding During Hypothermia and Effects on Maternal and Infant Salivary Cortisol Levels. Advances in Neonatal Care. 2025; 25(2): 173-180. Published: April, 2025. DOI: 10.1097/ANC.0000000000001239.
Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia
In this phase 3, double-blind, randomized, placebo-controlled trial in 256 people with schizophrenia, xanomeline-trospium was associated with a statistically significant and clinically meaningful reduction in Positive and Negative Syndrome Scale total score compared with placebo. Xanomeline-trospium was generally well tolerated; the most common adverse events were primarily gastrointestinal effects, which were mild or moderate in intensity and generally transient in nature.
KEY FINDINGS: Xanomeline-trospium was efficacious and well tolerated in people with schizophrenia experiencing acute psychosis. These findings, together with the previously reported and consistent results from the EMERGENT-1 and EMERGENT-2 trials, support the potential of xanomeline-trospium to be the first in a putative new class of antipsychotic medications without D2 dopamine receptor blocking activity.
BACKGROUND: A significant need exists for new antipsychotic medications with different mechanisms of action, greater efficacy, and better tolerability than existing agents. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation. In prior trials, xanomeline-trospium chloride was effective in reducing symptoms of psychosis and generally well tolerated in people with schizophrenia. Purpose of this study is to evaluate the efficacy and safety of xanomeline-trospium vs placebo in adults with schizophrenia.
DETAILS: EMERGENT-3 (NCT04738123) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 5-week trial of xanomeline-trospium in people with schizophrenia experiencing acute psychosis, conducted between April 1, 2021, and December 7, 2022, at 30 inpatient sites in the US and Ukraine. Data were analyzed from February to June 2023. Participants were randomized 1:1 to receive xanomeline-trospium chloride (maximum dose xanomeline 125 mg/trospium 30 mg) or placebo for 5 weeks. The prespecified primary end point was change from baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measures were change from baseline to week 5 in PANSS positive subscale score, PANSS negative subscale score, PANSS Marder negative factor score, Clinical Global Impression-Severity score, and proportion of participants with at least a 30% reduction in PANSS total score. Safety and tolerability were also evaluated. A total of 256 participants (mean [SD] age, 43.1 [11.8] years; 191 men [74.6%]; 156 of 256 participants [60.9%] were Black or African American, 98 [38.3%] were White, and 1 [0.4%] was Asian) were randomized (125 in xanomeline-trospium group and 131 in placebo group). At week 5, xanomeline-trospium significantly reduced PANSS total score compared with placebo (xanomeline-trospium , -20.6; placebo, -12.2; least squares mean difference, -8.4; 95% CI, -12.4 to -4.3; P < .001; Cohen d effect size, 0.60). Discontinuation rates due to treatment-emergent adverse events (TEAEs) were similar between the xanomeline-trospium (8 participants [6.4%]) and placebo (7 participants [5.5%]) groups. The most common TEAEs in the xanomeline-trospium vs placebo group were nausea (24 participants [19.2%] vs 2 participants [1.6%]), dyspepsia (20 participants [16.0%] vs 2 participants [1.6%]), vomiting (20 participants [16.0%] vs 1 participant [0.8%]), and constipation (16 participants [12.8%] vs 5 participants [3.9%]). Measures of extrapyramidal symptoms, weight gain, and somnolence were similar between treatment groups.
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Source: Kaul, I., Sawchak, S., Walling, D. P., et al. (2024). Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2024; 81(8): 749-756. Published: August, 2024. DOI: 10.1001/jamapsychiatry.2024.0785.
Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke
While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.
KEY FINDINGS: While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.
BACKGROUND: Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%.
DETAILS: Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high.
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Source: Bailey, A. M., Baum, R., Nestor, M .,et al. (2024). Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke: A Case Series. Advanced Emergency Nursing Journal. 2024; 46(2): 101-107. Published: April/June, 2024. DOI: 10.1097/TME.0000000000000512.
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