Reproductive hormones in relation to white matter hyperintensity volumes among midlife women.

INTRODUCTION: Although reproductive hormones are implicated in cerebral small vessel disease in women, few studies consider measured hormones in relation to white matter hyperintensity volume (WMHV), a key indicator of cerebral small vessel disease. Even fewer studies consider estrone (E1), the primary postmenopausal estrogen, or follicle-stimulating hormone (FSH), an indicator of ovarian age. We tested associations of estradiol (E2), E1, and FSH to WMHV among women. METHODS: Two hundred twenty-two women (mean age = 59) underwent hormone assays (E1, E2, FSH) and 3T brain magnetic resonance imaging. Associations of hormones to WMHV were tested with linear regression. RESULTS: Higher E2 (B[standard error (SE)] = -0.17[0.06], P = 0.008) and E1 (B[SE] = -0.26[0.10], P = 0.007) were associated with lower whole-brain WMHV, and higher FSH (B[SE] = 0.26[0.07], P = 0.0005) with greater WMHV (covariates age, race, education). When additionally controlling for cardiovascular disease risk factors, associations of E1 and FSH to WMHV remained. DISCUSSION: Reproductive hormones, particularly E1 and FSH, are important to women's cerebrovascular health. HIGHLIGHTS: Despite widespread belief that sex hormones are important to women's brain health, little work has considered how these hormones in women relate to white matter hyperintensities (WMH), a major indicator of cerebral small vessel disease. We considered relations of estradiol (E2), estrone (E1), and follicle-stimulating hormone (FSH) to WMH in midlife women. Higher E2 and E1 were associated with lower whole-brain WMH volume (WMHV), and higher FSH with higher whole-brain WMHV. Associations of E1 and FSH, but not E2, to WMHV persisted with adjustment for cardiovascular disease risk factors. Findings underscore the importance of E2 and FSH to women's cerebrovascular health.

Much lower prevalence and mortality of chronic obstructive pulmonary disease in Japan than in the US despite higher smoking rates: A meta analysis/systematic review.

BACKGROUND: A recent systematic review showed Japan's mortality from chronic obstructive pulmonary disease (COPD) is the lowest among 204 countries, despite notably higher smoking rates in men in Japan than in the US. This study aims to compare (1) trends in smoking rates, (2) trends in COPD mortality, and (3) the spirometry-based COPD prevalence in the general adult population between Japan and the US. METHODS: Age- and sex-specific smoking rates from the 1980s through 2010s and COPD mortality from 1999 through 2019 were obtained from national surveys and official statistics (International Classification of Diseases-10th codes J40-44), respectively. A systematic review and meta-analysis was performed to estimate COPD prevalence in Japan, while the National Health and Nutrition Examination Survey 2007-2012 was used for the US. A fixed ratio of 0.7 of forced expiratory volume in the first second of forced vital capacity was used to define COPD. RESULTS: Over the past four decades, men in Japan consistently had 20-30% higher smoking rates than their US counterparts. From 1999-2019, age-adjusted COPD mortality in men in Japan was only a third of the US, whereas that in women was less than a tenth in 2019. Synthesizing data from 11 studies, involving 89,955 participants, Japan's COPD prevalence was more than 10% lower than in the US in almost all age groups for both sexes. CONCLUSIONS: This study showed markedly lower rates of COPD in Japan than in the US. Investigating factors contributing to the paradoxical observations could lead to advancing COPD risk reduction strategies.

Changes in pituitary adenoma patient presentation and outcomes during the COVID pandemic at a Pituitary Center of Excellence.

PURPOSE: The COVID-19 pandemic caused significant disruption to the surgical care of patients. The aim of this study was to analyze the impact of the pandemic on endoscopic endonasal surgery (EES) for patients with a pituitary adenoma. METHODS: Patients from 2015 to 2022 that had EES for a pituitary adenoma were included in this study. Patients were separated into pre-COVID (January 2015-March 2020) and COVID (March 2020-September 2022) groups. Univariate analysis was done using chi-square, fisher exact tests, and t-tests to compare groups. RESULTS: This study included 492 patients that had EES for their pituitary adenoma. There were 314 patients in the pre-COVID group and 178 patients in the COVID group. Patients in the COVID group had a higher risk analysis index (RAI) frailty score (15 ± 10 pre-COVID vs. 20 ± 9 COVID, P < 0.001) and a higher American Society of Anesthesiology (ASA) physical status score (3 or 4) (72.0% pre-COVID vs. 81.9% COVID, P = 0.02). There were significantly more macroadenoma cases (87.6% pre-COVID vs. 94.4% COVID, P = 0.02) and extrasellar surgical approaches (45.2% pre-COVID vs. 61.2% COVID, P < 0.001) during COVID. There was no significant difference in length of stay (LOS) and readmission rates between groups. CONCLUSIONS: Patients that presented during the pandemic tended to be more frail, have more comorbidities, and require additional extrasellar surgical approaches. Despite changes in clinical presentation and operative management, the LOS and readmission rate remained stable during COVID, supporting the safety of this procedure during the recent pandemic.

Neuroimaging with Rotterdam Scoring System and long-term outcomes in severe traumatic brain injury patients.

PURPOSE: The Rotterdam Scoring System (RSS) attempts to prognosticate early mortality and early functional outcome in patients with traumatic brain injury (TBI) based on non-contrast head computed tomography (CT) imaging findings. The purpose of this study was to identify the relationship between RSS scores and long-term outcomes in patients with severe TBI. METHODS: Consecutively treated patients with severe TBI enrolled between 2008 and 2011, in the prospective, observational, Brain Trauma Research Center database were included. The Glasgow Outcome Scale (GOS) was used to measure long-term functional outcomes at three, six, 12, and 24 months. GOS scores were categorized into favorable (GOS = 4-5) and unfavorable (GOS = 1-3) outcomes. RSS scores were calculated at the time of image acquisition. RESULTS: Of the 89 patients included, 74 (83.4%) were male, 81 (91.0%) were Caucasian, and the mean age of the cohort was 41.9 ± 18.5 years old. Patients with an RSS score of 3 and lower were more likely to have a favorable outcome with increased survival rates than patients with RSS scores greater than 3. CONCLUSIONS: The RSS score determined on the head CT scan acquired at admission in a cohort of patients with severe TBI correlated with long-term survival and functional outcomes up to two years following injury.

Association Between ß-Amyloid Accumulation and Incident Dementia in Individuals 80 Years or Older Without Dementia.

BACKGROUND AND OBJECTIVES: While the highest prevalence of dementia occurs in individuals older than 80 years, most imaging studies focused on younger populations. The rates of ß-amyloid (Aß) accumulation and the effect of Alzheimer disease (AD) pathology on progression to dementia in this age group remain unexplored. In this study, we examined the relationship between changes in Aß deposition over time and incident dementia in nondemented individuals followed during a period of 11 years. METHODS: We examined 94 participants (age 85.9 + 2.8 years) who had up to 5 measurements of Pittsburgh compound-B (PiB)-PET and clinical evaluations from 2009 to 2020. All 94 participants had 2 PiB-PET scans, 76 participants had 3 PiB-PET scans, 18 participants had 4 PiB-PET scans, and 10 participants had 5 PiB-PET scans. The rates of Aß deposition were compared with 120 nondemented individuals younger than 80 years (69.3 ± 5.4 years) from the Australian Imaging, Biomarker, and Lifestyle (AIBL) study who had 3 or more annual PiB-PET assessments. RESULTS: By 2020, 49% of the participants developed dementia and 63% were deceased. There was a gradual increase in Aß deposition in all participants whether they were considered Aß positive or negative at baseline. In a Cox model controlled for age, sex, education level, APOE-4 allele, baseline Mini-Mental State Examination, and mortality, short-term change in Aß deposition was not significantly associated with incident dementia (HR 2.19 (0.41-11.73). However, baseline Aß burden, cortical thickness, and white matter lesions volume were the predictors of incident dementia. Aß accumulation was faster (p = 0.01) in the older cohort (5.6%/year) when compared with AIBL (4.1%/year). In addition, baseline Aß deposition was a predictor of short-term change (mean time 1.88 years). DISCUSSION: There was an accelerated Aß accumulation in cognitively normal individuals older than 80 years. Baseline Aß deposition was a determinant of incident dementia and short-term change in Aß deposition suggesting that an active Aß pathologic process was present when these participants were cognitively normal. Consequently, age may not be a limiting factor for the use of the emergent anti-Aß therapies.

Trajectories of Sleep Over Midlife and Incident Cardiovascular Disease Events in the Study of Women's Health Across the Nation.

BACKGROUND: Up to 50% of women report sleep problems in midlife, and cardiovascular disease (CVD) is the leading cause of death in women. How chronic poor sleep exposure over decades of midlife is related to CVD risk in women is poorly understood. We tested whether trajectories of insomnia symptoms or sleep duration over midlife were related to subsequent CVD events among SWAN (Study of Women's Health Across the Nation) participants, whose sleep was assessed up to 16 times over 22 years. METHODS: At baseline, SWAN participants (n=2964) were 42 to 52 years of age, premenopausal or early perimenopausal, not using hormone therapy, and free of CVD. They completed up to 16 visits, including questionnaires assessing insomnia symptoms (trouble falling asleep, waking up several times a night, or waking earlier than planned ≥3 times/week classified as insomnia), typical daily sleep duration, vasomotor symptoms, and depressive symptoms; anthropometric measurements; phlebotomy; and CVD event ascertainment (ie, fatal or nonfatal myocardial infarction, stroke, heart failure, revascularization). Sleep trajectories (ie, insomnia, sleep duration) were determined by means of group-based trajectory modeling. Sleep trajectories were tested in relation to CVD in Cox proportional hazards models (multivariable models: site, age, race and ethnicity, education, CVD risk factors averaged over visits; additional covariates: vasomotor symptoms, snoring, depression). RESULTS: Four trajectories of insomnia symptoms emerged: low insomnia symptoms (n=1142 [39% of women]), moderate insomnia symptoms decreasing over time (n=564 [19%]), low insomnia symptoms increasing over time (n=590 [20%]), and high insomnia symptoms that persisted (n=668 [23%]). Women with persistently high insomnia symptoms had higher CVD risk (hazard ratio, 1.71 [95% CI, 1.19, 2.46], P=0.004, versus low insomnia; multivariable). Three trajectories of sleep duration emerged: persistently short (~5 hours: n=363 [14%]), moderate (~6 hours: n=1394 [55%]), and moderate to long (~8 hours: n=760 [30%]). Women with persistent short sleep had marginally higher CVD risk (hazard ratio, 1.51 [95% CI, 0.98, 2.33], P=0.06, versus moderate; multivariable). Women who had both persistent high insomnia and short sleep had significantly elevated CVD risk (hazard ratio, 1.75 [95% CI, 1.03, 2.98], P=0.04, versus low insomnia and moderate or moderate to long sleep duration; multivariable). Relations of insomnia to CVD persisted when adjusting for vasomotor symptoms, snoring, or depression. CONCLUSIONS: Insomnia symptoms, when persistent over midlife or occurring with short sleep, are associated with higher CVD risk among women.

Menopausal vasomotor symptoms and plasma Alzheimer disease biomarkers.

BACKGROUND: Identifying risk factors for Alzheimer disease in women is important as women compose two-thirds of individuals with Alzheimer disease. Previous work links vasomotor symptoms, the cardinal menopausal symptom, with poor memory performance and alterations in brain structure, function, and connectivity. These associations are evident when vasomotor symptoms are monitored objectively with ambulatory skin conductance monitors. OBJECTIVE: This study aimed to determine whether vasomotor symptoms are associated with Alzheimer disease biomarkers. STUDY DESIGN: Between 2017 and 2020, the MsBrain study enrolled 274 community-dwelling women aged 45 to 67 years who had a uterus and at least 1 ovary and were late perimenopausal or postmenopausal status. The key exclusion criteria included neurologic disorder, surgical menopause, and recent use of hormonal or nonhormonal vasomotor symptom treatment. Women underwent 24 hours of ambulatory skin conductance monitoring to assess vasomotor symptoms. Plasma concentrations of Alzheimer disease biomarkers, including amyloid ß 42-to-amyloid ß 40 ratio, phosphorylated tau (181 and 231), glial fibrillary acidic protein, and neurofilament light, were measured using a single-molecule array (Simoa) technology. Associations between vasomotor symptoms and Alzheimer disease biomarkers were assessed via linear regression models adjusted for age, race and ethnicity, education, body mass index, and apolipoprotein E4 status. Additional models adjusted for estradiol and sleep. RESULTS: A total of 248 (mean age, 59.06 years; 81% White; 99% postmenopausal status) of enrolled MsBrain participants contributed data. Objectively assessed vasomotor symptoms occurring during sleep were associated with significantly lower amyloid ß 42/amyloid ß 40, (beta, -.0010 [standard error, .0004]; P=.018; multivariable), suggestive of greater brain amyloid ß pathology. The findings remained significant after additional adjustments for estradiol and sleep. CONCLUSION: Nighttime vasomotor symptoms may be a marker of women at risk of Alzheimer disease. It is yet unknown if these associations are causal.

An ERK5-PFKFB3 axis regulates glycolysis and represents a therapeutic vulnerability in pediatric diffuse midline glioma.

Metabolic reprogramming in pediatric diffuse midline glioma is driven by gene expression changes induced by the hallmark histone mutation H3K27M, which results in aberrantly permissive activation of oncogenic signaling pathways. Previous studies of diffuse midline glioma with altered H3K27 (DMG-H3K27a) have shown that the RAS pathway, specifically through its downstream kinase, extracellular-signal-related kinase 5 (ERK5), is critical for tumor growth. Further downstream effectors of ERK5 and their role in DMG-H3K27a metabolic reprogramming have not been explored. We establish that ERK5 is a critical regulator of cell proliferation and glycolysis in DMG-H3K27a. We demonstrate that ERK5 mediates glycolysis through activation of transcription factor MEF2A, which subsequently modulates expression of glycolytic enzyme PFKFB3. We show that in vitro and mouse models of DMG-H3K27a are sensitive to the loss of PFKFB3. Multi-targeted drug therapy against the ERK5-PFKFB3 axis, such as with small-molecule inhibitors, may represent a promising therapeutic approach in patients with pediatric diffuse midline glioma.

Posttraumatic Stress Disorder Symptoms and Cardiovascular and Brain Health in Women.

Importance: Posttraumatic stress disorder (PTSD), cardiovascular disease (CVD), and Alzheimer disease are major public health issues, particularly for women. The implications of PTSD for cardiovascular and brain health for women is poorly understood. Objective: To assess whether PTSD symptoms among midlife women are associated with carotid intima media thickness (IMT), an indicator of carotid atherosclerosis; brain white matter hyperintensity volume (WMHV), an indicator of brain small vessel disease; and cognitive performance and to test a modifying role of the APOEε4 genotype. Design, Setting, and Participants: In this cross-sectional study, participants were enrolled between 2016 to 2021 and completed questionnaires (PTSD Checklist-Civilian Version), physical measures, phlebotomy, neuropsychological testing, a carotid ultrasonographic examination, and 3-Tesla brain magnetic resonance imaging. Participants included community-based women ages 45 to 67 years without a history of CVD, stroke, or dementia. Data were analyzed from July 2022 to September 2023. Exposures: PTSD symptoms. Main Outcomes and Measures: Outcomes of interest were associations of PTSD symptoms with carotid IMT, brain WMHV, and cognition, assessed in linear regression models. Interactions by APOEε4 were tested. Covariates included age, race and ethnicity, education, and CVD risk factors. Results: Among 274 participants (mean [SD] age, 59.03 [4.34] years; 6 Asian participants [2.2%]; 48 Black participants [17.5%]; 215 White participants [78.5%]; 5 multiracial participants [1.8%]), 64 participants (24.71%) were APOEε4 genotype carriers. Higher PTSD symptoms were associated with greater carotid IMT (multivariable ß = 0.07 [95% CI, 0.01 to 0.13]; P = .03). Associations of PTSD symptoms with neurocognitive outcomes significantly varied by APOEε4 status. Among women with APOEε4, PTSD symptoms were associated with greater whole-brain WMHV (ß = 0.96 [95% CI, 0.30 to 1.63]; P = .009), periventricular WMHV (ß = 0.90 [95% CI, 0.24 to 1.56]; P = .02), deep WMHV (ß = 1.21 [95% CI, 0.23 to 2.20]; P = .01), and frontal WMHV (ß = 1.25 [95% CI, 0.05 to 2.45]; P = .04), as well as with poorer cognition, specifically attention and working memory (ß = -3.37 [95% CI, -6.12 to -0.62]; P = .02), semantic fluency (ß = -6.01 [95% CI, -10.70 to -1.31]; P = .01), perceptual speed (ß = -12.73 [95% CI, -20.71 to -4.75]; P = .002), and processing speed (ß = -11.05 [95% CI, -17.80 to -4.30]; P = .002) in multivariable models. Conclusions and Relevance: In this cross-sectional study of midlife women, greater PTSD symptoms were associated with higher carotid atherosclerosis and, among women who were APOEε4 carriers, greater brain small vessel disease and poorer cognitive performance. These findings point to the adverse implications of PTSD symptoms for cardiovascular and neurocognitive health among women in midlife, particularly for women who are APOEε4 carriers.

Percutaneous glycerol rhizolysis of the trigeminal ganglion for the treatment of idiopathic and classic trigeminal neuralgia: Outcomes and complications.

BACKGROUND AND PURPOSE: Patients with idiopathic trigeminal neuralgia (TN) with absent arterial contact or venous contact only and classic TN with morphological changes of the trigeminal nerve secondary to venous compression are not routinely recommended microvascular decompression at our institution. In patients with these anatomical subtypes of TN, limited data exists describing the outcomes of percutaneous glycerol rhizolysis (PGR) of the trigeminal ganglion (TG). METHODS: We performed a retrospective single-center cohort study and analyzed outcomes and complications after PGR of the TG. Clinical outcome after PGR of the TG was assessed via the Barrow Neurological Institute (BNI) Pain Scale. RESULTS: Forty-five patients underwent a total of 66 PGRs of the TG. At short-term follow-up, 58 procedures (87.9%) resulted in a BNI score of I (i.e., freedom from pain without medication). At a median follow-up of 3.07 years, 18 procedures (27.3%) resulted in a BNI score of I, 12 procedures (18.1%) resulted in BNI score of IIIa, and 36 procedures (54.5%) resulted in a BNI score of IIIb-V. The median length of freedom from pain without medication was 1.5 years. Eighteen procedures (27.3%) caused hypesthesia and two (3.0%) caused paresthesias. There were no serious complications. CONCLUSION: In patients with these anatomical subtypes of TN there was a high rate of short-term pain relief for the first 1-2 years and thereafter a large proportion of patients experienced pain relapse. In this patient group, PGR of the TG represents a safe procedure that is efficacious in the short term.

Carotid intima media thickness and white matter hyperintensity volume among midlife women.

INTRODUCTION: Carotid atherosclerosis may be associated with brain white matter hyperintensities (WMH). Few studies consider women at midlife, a critical time for women's cardiovascular and brain health. We tested the hypothesis that higher carotid intima media thickness (IMT) would be associated with greater WMH volume (WMHV) among midlife women. We explored interactions by apolipoprotein E (APOE) ε4 status. METHODS: Two hundred thirty-nine women aged 45 to 67 underwent carotid artery ultrasound, phlebotomy, and magnetic resonance imaging (MRI). One hundred seventy participants had undergone an ultrasound 5 years earlier. RESULTS: Higher IMT was associated with greater whole brain (B[standard error (SE)] = 0.77 [.31], P = 0.01; multivariable) and periventricular (B[SE] = 0.80 [.30], P = 0.008; multivariable) WMHV. Associations were observed for IMT assessed contemporaneously with the MRI and 5 years prior to the MRI. Associations were strongest for APOE ε4-positive women. DISCUSSION: Among midlife women, higher IMT was associated with greater WMHV. Vascular risk is critical to midlife brain health, particularly for APOE ε4-positive women.

Long-term Benefits for Younger Patients with Aggressive Immediate Intervention following Severe Traumatic Brain Injury: A Longitudinal Cohort Analysis of 175 Patients from a Prospective Registry.

BACKGROUND: The prevalence of traumatic brain injury (TBI) continues to rise, in part as a reflection of a growing elderly population. Concomitantly, nihilism may exist following substantial neurotrauma from a myriad of commonplace mechanisms, such as traffic incidents, assaults, or falls. OBJECTIVE: This study assesses long-term outcomes following aggressive surgical intervention with invasive neuromonitoring to guard against nihilism, especially for patients with advantageous characteristics such as younger age. METHODS: A consecutive series of patients with severe TBI treated between 2008 and 2018 and enrolled into the Brain Trauma Research Center (BTRC) database, an Institutional Review Board (IRB 19030228) approved prospective, longitudinal cohort study, were extracted. Demographic and clinical data were analyzed. Long-term functional outcome was recorded with the eight-point Glasgow Outcome Scale-Extended (GOS-E) score at 3-, 6-, 12-, and 24-months by trained, qualified neuropsychology technicians. Chi-squared and analysis of variance tests were used to evaluate the relationship of age groups between different variables. RESULTS: For this analysis, 175 patients with severe TBI who were enrolled in the BTRC database and required decompressive hemicraniectomy during the study period were included. Over one-third of the patients with a severe TBI, who were aged 35 years and younger, had a favorable outcome. CONCLUSIONS: Despite enduring a severe TBI, a substantial percentage of younger patients achieved favorable outcomes following aggressive treatment. As such, establishing a prognosis should be deferred to allow for recovery via individualized rehabilitation, multidisciplinary support, and community reintegration programs to cope with various long-term psychological, cognitive, and functional disabilities.

Will nasal airway surgery improve my sense of smell? A prospective observational study.

BACKGROUND: The effect of nasal airway surgery on olfaction has not been well established. The goal of this study is to assess changes in olfaction after septoplasty with inferior turbinate reduction through both objective and patient-reported measures. METHODS: Prospective, observational study was conducted of patients with nasal airway obstruction presenting between July 2017 and October 2019 who underwent septoplasty with inferior turbinate reduction. Nasal airflow was characterized with the Nasal Obstruction Symptom Evaluation (NOSE) scale and an 11-point ease-of-breathing (EOB) Likert scale, and olfaction with an 11-point olfactory Likert scale and the 40-item University of Pennsylvania Smell Identification Test (UPSIT), pre- and postoperatively. Pearson correlations were used to assess the relationship between measures of nasal obstruction and olfaction. RESULTS: Among 80 patients, mean NOSE scores improved from 67.4 preoperatively to 19.6 postoperatively (p < 0.001). EOB Likert scores improved from a mean of 3.9/10 to 8.1/10 after surgery (p < 0.001). Olfactory Likert scores improved from a baseline of 6.1/10 preoperatively to 7.9/10 after surgery (p < 0.001). No statistically significant difference was noted in UPSIT testing pre- versus postoperatively. A moderate correlation was noted between the degree of change in NOSE scores and improved olfactory Likert scores (r = 0.51, p < 0.001), and similarly between the degree of change in EOB Likert scores and improved olfactory Likert scores (r = 0.55, p < 0.0001). CONCLUSIONS: Based on our data, subjective tests of olfaction may improve with nasal airway surgery in some patients. Changes in olfaction best correlate with the extent to which surgery can improve subjective nasal obstructive symptoms.

Current Trends in Subspecialty Fellowship Training for 1691 Academic Neurological Surgeons.

OBJECTIVE: Neurosurgical subspecialty fellowship training has become increasingly popular in recent decades. However, few studies have evaluated recent trends in postgraduate subspecialty education. This study aims to provide a detailed cross-sectional analysis of subspecialty fellowship training completion trends and demographics among U.S. academic neurosurgeons. METHODS: Academic clinical faculty (M.D. or D.O.) teaching at accredited neurosurgery programs were included. Demographic, career, and fellowship data were collected from departmental physician profiles and the American Association of Neurological Surgeons (AANS) membership database. Relative citation ratio scores were retrieved using the National Institutes of Health iCite tool. RESULTS: This study included 1691 surgeons (1756 fellowships) from 125 institutions. The majority (79.13%) reported fellowship training. Fellowship completion was more common among recent graduates (residency year >2000), as was training in multiple subspecialties (P < 0.0001). Spine was the most popular subspecialty (16.04%), followed by pediatrics (11.18%), and cerebrovascular (9.46%). The least common were trauma/critical care (2.52%) and peripheral nerve (1.26%). Spine, neuroradiology, and endovascular subspecialties grew in popularity over time. Pediatrics and spine were the most popular for females and males, respectively. Epilepsy and cerebrovascular had the most full professors, while endovascular and spine had the most assistant professors. Stereotactic/functional and epilepsy had the most Ph.Ds. Fellowship training correlated with higher weighted, but not mean, relative citation ratio scores among associate (P = 0.002) and full professors (P = 0.005). CONCLUSIONS: There is an emerging proclivity for additional fellowship training among young neurosurgeons, often in multiple subspecialties. These findings are intended to help guide professional decision-making and optimize the delivery of postgraduate education.

Menopausal Vasomotor Symptoms and White Matter Hyperintensities in Midlife Women.

BACKGROUND AND OBJECTIVES: The menopause transition is increasingly recognized as a time of importance for women's brain health. A growing body of work indicates that the classic menopausal symptom, vasomotor symptom (VMS), may be associated with poorer cardiovascular health. Other work links VMS to poorer cognition. We investigate whether VMS, when rigorously assessed using physiologic measures, are associated with greater white matter hyperintensity volume (WMHV) among midlife women. We consider a range of potential explanatory factors in these associations and explore whether VMS are associated with the spatial distribution of WMHV. METHODS: Women aged 45-67 years and free of hormone therapy underwent 24 hours of physiologic VMS monitoring (sternal skin conductance), actigraphy assessment of sleep, physical measures, phlebotomy, and 3 Tesla neuroimaging. Associations between VMS (24-hour, wake, and sleep VMS, with wake and sleep intervals defined by actigraphy) and whole brain WMHV were considered in linear regression models adjusted for age, race, education, smoking, body mass index, blood pressure, insulin resistance, and lipids. Secondary models considered WMHV in specific brain regions (deep, periventricular, frontal, temporal, parietal, and occipital) and additional covariates including sleep. RESULTS: The study sample included 226 women. Physiologically assessed VMS were associated with greater whole brain WMHV in multivariable models, with the strongest associations observed for sleep VMS (24-hour VMS, B[SE] = 0.095 [0.045], p = 0.032; Wake VMS, B[SE] = 0.078 [0.046], p = 0.089, Sleep VMS, B[SE] = 0.173 [0.060], p = 0.004). Associations were not accounted for by additional covariates including actigraphy-assessed sleep (wake after sleep onset). When considering the spatial distribution of WMHV, sleep VMS were associated with both deep WMHV, periventricular WMHV, and frontal lobe WMHV. DISCUSSION: VMS, particularly VMS occurring during sleep, were associated with greater WMHV. Identification of female-specific midlife markers of poor brain health later in life is critical to identify women who warrant early intervention and prevention. VMS have the potential to serve as female-specific midlife markers of brain health in women.

Neuropsychological Assessment of Community-Dwelling Older Adults in Almaty, Kazakhstan.

Cognitive impairment in older adults is a major public concern for Kazakhstan's aging population. We aimed to (1) administer a neuropsychological test battery (NTB) in domains relevant to aging-associated cognitive impairment in a sample of adults aged 60+ without dementia in Almaty, Kazakhstan; (2) investigate the associations between demographic factors and test performance; and (3) provide information on the distribution of NTB scores as preliminary local normative data relevant for this population. A cross-sectional evaluation of 276 participants aged 60+ in Almaty, Kazakhstan, was conducted using cognitive instruments including tests of memory, attention, language, executive functions, visuospatial abilities, and processing speed. Multiple linear regression analyses were used to examine the association of demographic factors with neuropsychological test performance. The results from the regression analysis showed that those who are younger, have more years of education, are women, and are of Russian ethnicity had significantly better performance. The current study illustrated (1) the feasibility of administering the NTB to older adults in the general population in Kazakhstan; (2) the preliminary local normative neuropsychological measures; and (3) their independent associations with age, education, gender, and ethnicity. The findings are a platform for future research on dementia and cognitive impairment in older adults in Kazakhstan.

Menopausal vasomotor symptoms and adiponectin among midlife women.

OBJECTIVE: Vasomotor symptoms (VMS) are prevalent symptoms that can have a negative impact on quality of life. VMS have also been linked to cardiovascular disease risk, yet the mechanisms underlying these associations have not been elucidated. Some initial works link VMS to adverse adipokine profiles or cytokines produced by adipose tissue. However, results are not entirely consistent and are based entirely on self-report VMS, which is influenced by a range of memory and reporting biases. The aim of this work was to test whether physiologically assessed VMS are associated with lower adiponectin, the most abundant adipokine in the body, controlling for confounding factors. We also consider whether adiponectin explains previously documented relationships between VMS and carotid atherosclerosis. METHODS: A total of 300 peri- and postmenopausal nonsmoking women aged 40 to 60 years enrolled in the MsHeart study comprised the analytic sample. Women were free of hormone therapy or other medications impacting VMS, insulin-dependent diabetes, and cardiovascular disease. Participants underwent ambulatory physiologic VMS monitoring, physical measures, a carotid ultrasound, and fasting phlebotomy. RESULTS: More frequent physiologically assessed VMS were associated with lower adiponectin ( B [SE] = -0.081 [0.028], P = 0.004; or 0.081 lower µg/mL in adiponectin for each additional VMS over 24 hours), controlling for age, race/ethnicity, education, insulin resistance, and waist circumference. Associations were not explained by endogenous estradiol. Adiponectin did not explain associations between VMS and carotid atherosclerosis. CONCLUSIONS: Physiologic VMS were associated with lower adiponectin after considering potential confounders. The role of adipokines in VMS and in links between VMS and health warrants further attention.

Time to Follow Commands in Severe Traumatic Brain Injury Survivors With Favorable Recovery at 2 Years.

BACKGROUND: The recovery of severe traumatic brain injury (TBI) survivors with long-term favorable outlook is understudied. Time to follow commands varies widely in this patient population but has important clinical implications. OBJECTIVE: To (1) evaluate time to follow commands in severe patients with TBI with favorable outcomes, (2) characterize their trajectory of recovery, and (3) identify predictors associated with delayed cognitive improvement. METHODS: Participants were recruited prospectively at a Level I trauma center through the Brain Trauma Research Center from 2003 to 2018. Inclusion criteria were age 16 to 80 years, Glasgow Coma Scale score ≤8 and motor score <6, and Glasgow Outcome Scale-Extended measure ≥4 at 2 years postinjury. RESULTS: In 580 patients, there were 229 (39.5%) deaths and 140 (24.1%) patients had favorable outcomes at 2 years. The mean age was 33.7 ± 14.5 years, median Glasgow Coma Scale was 7 (IQR 6-7), and median Injury Severity Score was 30 (IQR 26-38). The mean time to follow commands was 12.7 ± 11.8 days. On multivariable linear regression, the presence of diffuse axonal injury (B = 9.2 days [4.8, 13.7], P < .0001) or intraventricular hemorrhage (B = 6.4 days [0.5, 12.3], P < .035) was associated with longer time before following commands and patients who developed nosocomial infections (B = 6.5 days [1.6-11.4], P < .01). CONCLUSION: In severe TBI survivors with favorable outcomes, time to follow commands varied widely. Most patients began to follow commands within 2 weeks. Evidence of diffuse axonal injury, intraventricular hemorrhage, and infections can delay cognitive improvement in the acute period. Patients make considerable recovery up to 2 years after their injury.

Differential tractography as a dynamic imaging biomarker: A methodological pilot study for Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, psychiatric, and cognitive symptoms. Due to its diverse manifestations, the scientific community has long recognized the need for sensitive, objective, individualized, and dynamic disease assessment tools. We examined the feasibility of Differential Tractography as a biomarker to evaluate correlation of symptom severity and of HD progression at the individual level. Differential tractography is a novel tractography modality that maps pathways with axonal injury characterized by a decrease of anisotropic diffusion pattern. We recruited sixteen patients scanned at 0-, 6-, and 12-month intervals by diffusion MRI scans for differential tractography assessment and correlated its volumetric findings with the Unified Huntington's Disease Rating Scale (UHDRS). Deterministic fiber tracking algorithm was applied. Longitudinal data was modeled using the generalized estimating equation (GEE) model and correlated with UHDRS scores, in addition to Spearman correlation for cross-sectional data. Our results show that volumes of affected pathways revealed by differential tractography significantly correlated with UHDRS scores in longitudinal data (p-value < 0.001), and chronological changes in differential tractography also correlated with the changes in UHDRS (p-value < 0.001). This technique opens new clinical avenues as a clinical translational tool to evaluate presymptomatic and symptomatic gene positive individuals. Our results provide support that differential tractography has the potential to be used as a dynamic imaging biomarker to assess at the individual level in a non-invasive manner, disease progression in HD. Critically important, differential tractography proves to be a quantitative tool for following degeneration in presymptomatic patients, with potential applications in clinical trials.