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INTRODUCTION: Brain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study. METHODS: Dementia and stroke‐free participants underwent OLINK Proteomics profiling and MRI measurements within 5 years. Pairwise cross‐sectional analysis assessed 68 biomarkers with 13 brain MRI volumes, adjusting for covariates and familial correlations. RESULTS: Elevated CDCP1, IL6, OPG, and 4E.BP1 were related to smaller total cerebral brain volume (TCBV), whereas higher HGF, IL8, and MMP10 were associated with smaller TCBV, total and frontal white matter volumes. Higher SCF and TWEAK were associated with larger TCBV. In sex‐stratified analyses, associations were observed exclusively among males. DISCUSSION: We report several associations between inflammatory biomarkers and brain volumes, highlighting different associations within sex subgroups. Highlights: Higher CDCP1, IL6, OPG, and 4E.BP1 levels were associated with smaller TCBV.Higher levels of HGF, IL8 and MMP10 were associated with smaller TCBV, CWV and FWV.Higher levels of SCF and TWEAK, were associated with larger TCBV.Significance diminished in models adjusting for CVD risk factors.Associations were observed exclusively in males. [ABSTRACT FROM AUTHOR]

• Infertility was associated with a greater E/e′, a marker of diastolic dysfunction. • Women with infertility may experience earlier subclinical cardiac remodeling. Infertility has been shown to be associated with a greater risk of incident heart failure with preserved ejection fraction. We studied the association of infertility with subclinical markers of heart failure with preserved ejection fraction, including echocardiographic signs of cardiac remodeling and cardiac biomarkers. A history of infertility was ascertained in 2002 women enrolled in the Framingham Heart Study. We examined the association of infertility with echocardiographic measures and cardiac biomarkers with multivariable-adjusted linear regression models. Among 2002 women (mean age 40.84 ± 9.71 years), 285 (14%) reported a history of infertility. Infertility was associated with a greater E/e′ ratio (β = 0.120, standard error 0.057, P =.04), even after adjustment for common confounders. Infertility was not associated with other echocardiographic measures or cardiac biomarkers. Infertility was associated with a greater E/e′ ratio, a marker of diastolic dysfunction that may signal earlier subclinical cardiac remodeling in women with infertility. [ABSTRACT FROM AUTHOR]

Background: In men and women, sex steroid hormones are associated with increased risk of Alzheimer's disease (AD) dementia. In older men, lower levels of testosterone are associated with higher rates of AD dementia. The relationship between estradiol levels on AD dementia risk in post‐menopausal women, however, is less clear, with studies reporting protective, deleterious and no effects. Finally, higher levels of sex hormone binding globulin (SHBG), a glycoprotein that regulates, and actively influences sex hormones, has been consistently linked with increased risk for AD dementia. Studies have yet to examine mid‐life hormonal levels in association with later‐life in vivo AD biomarkers in cognitively healthy adults. Method: 175 women and 159 men from the Framingham Study 3rd Generation cohort underwent blood (hormones) collection in 2002‐2005, and 18F‐Flortaucipir (FTP)‐PET and 11C‐PiB‐PET scans in 2016‐2020 (Table1). We examined FTP‐PET signal (referenced to cerebellar grey) in six a priori regions that previously demonstrated sex differences (entorhinal, inferior temporal, rostral middle frontal, inf/sup parietal and lateral occipital). Linear regressions examined sex‐stratified analyses of free/total testosterone, estradiol, and SHBG in each region, adjusting for age, age2, PET camera and plasma‐PET date‐difference (mean = 15(±2)yrs). Separate models examined interactions with a neocortical PiB‐PET composite and APOEε4. Result: In men, elevated SHBG was associated with lower FTP‐PET in entorhinal (p = 0.007), inferior temporal (p = 0.04) and rostral middle frontal regions (p = 0.02; Table2). Higher total testosterone was marginally associated with lower FTP‐PET signal in the latter region (p = 0.06), but other relationships were apparent. In women, higher total testosterone associated with lower FTP‐PET signal in inferior temporal (p = 0.05) and parietal regions (p = 0.04). Women APOEε4 carriers with higher estradiol showed higher levels of entorhinal FTP‐PET signal (p = 0.03;Table3). Conclusion: Higher levels of SHBG are associated with lower risk of AD‐related comorbidities, such as osteoporosis, diabetes, and visceral weight gain. A strong link between higher SHBG levels and higher HDL‐cholesterol may suggest a potential protective cardiovascular pathway for men against higher tau burden later in life. A lack of protective effect of pre‐menopausal estradiol in female APOEε4 carriers supports the notion that the role of estrogen in AD risk is centered around timing of decline. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity is a known risk factor for atrial fibrillation (AF). Wearable devices, such as smartwatches, present an opportunity to investigate the relation between daily step count and AF risk. Objective: The objective of this study was to investigate the association between daily step count and the predicted 5-year risk of AF. Methods: Participants from the electronic Framingham Heart Study used an Apple smartwatch. Individuals with diagnosed AF were excluded. Daily step count, watch wear time (hours and days), and self-reported physical activity data were collected. Individuals' 5-year risk of AF was estimated, using the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)–AF score. The relation between daily step count and predicted 5-year AF risk was examined via linear regression, adjusting for age, sex, and wear time. Secondary analyses examined effect modification by sex and obesity (BMI≥30 kg/m2), as well as the relation between self-reported physical activity and predicted 5-year AF risk. Results: We examined 923 electronic Framingham Heart Study participants (age: mean 53, SD 9 years; female: n=563, 61%) who had a median daily step count of 7227 (IQR 5699-8970). Most participants (n=823, 89.2%) had a <2.5% CHARGE-AF risk. Every 1000 steps were associated with a 0.08% lower CHARGE-AF risk (P <.001). A stronger association was observed in men and individuals with obesity. In contrast, self-reported physical activity was not associated with CHARGE-AF risk. Conclusions: Higher daily step counts were associated with a lower predicted 5-year risk of AF, and this relation was stronger in men and participants with obesity. The utility of a wearable daily step counter for AF risk reduction merits further investigation. [ABSTRACT FROM AUTHOR]

Background: Smartphone apps and mobile health devices offer innovative ways to collect longitudinal cardiovascular data. Randomized evidence regarding effective strategies to maintain longitudinal engagement is limited. Objective: This study aimed to evaluate smartphone messaging interventions on remote transmission of blood pressure (BP) and heart rate (HR) data. Methods: We conducted a 2 × 2 × 2 factorial blinded randomized trial with randomization implemented centrally to ensure allocation concealment. We invited participants from the Electronic Framingham Heart Study (eFHS), an e-cohort embedded in the FHS, and asked participants to measure their BP (Withings digital cuff) weekly and wear their smartwatch daily. We assessed 3 weekly notification strategies to promote adherence: personalized versus standard; weekend versus weekday; and morning versus evening. Personalized notifications included the participant's name and were tailored to whether or not data from the prior week were transmitted to the research team. Intervention notification messages were delivered weekly automatically via the eFHS app. We assessed if participants transmitted at least one BP or HR measurement within 7 days of each notification after randomization. Outcomes were adherence to BP and HR transmission at 3 months (primary) and 6 months (secondary). Results: Of the 791 FHS participants, 655 (82.8%) were eligible and randomized (mean age 53, SD 9 years; 392/655, 59.8% women; 596/655, 91% White). For the personalized versus standard notifications, 38.9% (126/324) versus 28.8% (94/327) participants sent BP data at 3 months (difference=10.1%, 95% CI 2.9%-17.4%; P =.006), but no significant differences were observed for HR data transmission (212/324, 65.4% vs 209/327, 63.9%; P =.69). Personalized notifications were associated with increased BP and HR data transmission versus standard at 6 months (BP: 107/291, 36.8% vs 66/295, 22.4%; difference=14.4%, 95% CI 7.1- 21.7%; P <.001; HR: 186/281, 66.2% vs 158/281, 56.2%; difference=10%, 95% CI 2%-18%; P =.02). For BP and HR primary or secondary outcomes, there was no evidence of differences in data transmission for notifications sent on weekend versus weekday or morning versus evening. Conclusions: Personalized notifications increased longitudinal adherence to BP and HR transmission from mobile and digital devices among eFHS participants. Our results suggest that personalized messaging is a powerful tool to promote adherence to mobile health systems in cardiovascular research. Trial Registration: ClinicalTrials.gov NCT03516019; https://clinicaltrials.gov/ct2/show/NCT03516019 [ABSTRACT FROM AUTHOR]

Background: Inflammatory cytokines and chemokines related to the innate and adaptive immune system have been linked to neuroinflammation in Alzheimer's Disease (AD) dementia. We hypothesized that individual blood‐based inflammatory biomarkers would associate with cognitive function, brain magnetic resonance imaging (MRI) volumes, and risk for dementia in Framingham Heart Study (FHS) participants. Method: Protein biomarkers related to immune cells or associated with inflammatory responses including CD14, CD163, CD5L, CD56, CD40L, CXCL16, SDF1, DPP4, SGP130, sRAGE, and MPO were measured at FHS Offspring exam 7. We identified FHS Offspring participants who underwent neuropsychological (NP) testing (n = 2394) or brain MRI (n = 2135) within five years of the examination; and who were followed up 10 years after age 60 for incident all‐cause dementia (n = 1650). We used linear mixed effect models accounting for family relationships to investigate the associations between the protein biomarkers and NP test performance and brain MRI volumes and Cox proportional hazards models to examine the association with incident dementia. A false discovery rate (FDR) within each outcome set was computed to adjust for multiple testing and FDR ≤ 0.1 indicated significance. Result: Participants from the NP and MRI samples were on average 61 years old and 54% female. Participants from the incident dementia sample (mean age 68 years) included 126 incident dementia cases within 10 years. In addition to CD14 which has an established association, we observed significant associations between higher CD40L and MPO with poorer NP performance from the executive function domain. Higher CD5L levels were significantly associated with smaller total brain volumes (TCBV), whereas higher sRAGE was associated with larger TCBV. Associations persisted after further adjusting for APOE ϵ4 carrier status and cardiovascular risk factors. None of the protein biomarkers included were significantly associated with risk of incident dementia, with trend towards an association for CD5L. Conclusion: Since the proinflammatory factors CD5L, CD40L, sRAGE and MPO are associated with immune cells and are involved in vascular pathology, our study suggests the immune‐vascular axis is associated with cognitive and brain aging. If confirmed in other samples, our findings may provide informative biomarkers of abnormal brain aging. [ABSTRACT FROM AUTHOR]

Background: Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population. Aims: Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age. Methods: 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients' parameters. The whole cohort was divided into two groups based on the age of the patients (< 75 years old and ≥ 75 years old). Results: 47% of the patients were < 75 years old and 53% were ≥ 75 years old. The primary outcome, OS, does not show significant differences between the two subgroups if other basal parameters are considered. Considering clinical covariates in univariate models (p < 0.05) several clinical aspects have an impact on OS, except for age (p = 0.072). Age continues to have no significant impact on the OS (p = 0.274) even in multivariate models in the two groups. The toxic effects are similar in the two groups. Conclusions: Radium-223 prolongs survival in both younger and older patients at the same baseline condition and is a good option in the symptomatic mCRPC setting compared to other agents. [ABSTRACT FROM AUTHOR]

Background: Cognitively‐normal (CN) older women exhibit elevated tau‐PET signal in medial temporal and neocortical regions compared with men. The effect of menopause on tau deposition remains unclear. We explored menopausal status as a moderator of sex differences in tau deposition in middle‐aged adults. Method: 273 CN (Age=55yrs(±8), Female(n)=134, Post‐menopausal(n)=70) from the Framingham Study 3rd generation cohort underwent 18F‐Flortaucipir (FTP)‐PET and/or 11C‐Pittsburgh Compound‐B (PiB)‐PET scans. We examined FTP‐PET signal in four a priori regions that demonstrate large sex differences in CN older adults (entorhinal, rostral middle frontal, inferior parietal and lateral occipital). FTP‐PET and global PiB‐PET signal were referenced to cerebellar grey. Linear regression examined sex differences in each ROI, adjusting for age and PET camera. Separate models examined menopausal status (post‐menopause/pre‐menopause females), menopausal age (≤|>50 years), and interactions with APOEε4. Sensitivity analyses included age‐matched males ('pseudo‐premenopausal'/'pseudo‐menopausal') against the menopause groups to account for confounds with chronological age. Result: Middle‐aged females exhibited higher FTP‐PET signal in the inferior parietal, rostral middle frontal and lateral occipital regions than males by ∼0.04SUVr (p<0.009; Fig. 1). No sex or menopause differences were evident in PiB‐PET. Post‐menopausal females exhibited higher FTP‐PET signal in the lateral occipital lobe than pre‐menopausal (p=0.05; Fig. 2). Menopause age≤50 years corresponded with higher lateral occipital and rostral middle frontal FTP‐PET signal than >50years (p<0.05; Fig. 2). Post‐menopausal females maintained higher signal in lateral occipital, inferior parietal and rostral middle frontal regions compared with even age‐matched 'pseudo‐menopausal' males (Table 1). Finally, a significant menopause*APOEε4 interaction suggested that the menopause effect was only evident in APOEε4 non‐carriers, localized to the parietal lobe (p∼0.03; Fig. 3). Conclusion: Sex differences in tauopathy are apparent in CN individuals approximately 20 years earlier than previously demonstrated. Our findings suggest that sex differences are exacerbated by menopause, particularly when the age‐at‐menopause is below 50 years. Chronological age did not appear to confound the results, as age‐matched males exhibited significantly lower tau signal. Finally, the effect of APOEε4 carriership may ameliorate menopause effects; only pre‐menopausal APOEε4 non‐carriers appeared to exhibit protective effects of circulating estradiol relative to post‐menopausal non‐carriers. Future work will need to identify direct hormonal contributions, the impact of surgery and hormone‐therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study assessed the effects of a new interface that combined CPAP 10 cm H2O by using a helmet with high-flow nasal cannula (HFNC) at varying flows in healthy volunteers. Outcome measures included pharyngeal pressures, diaphragm kinetics, breathing frequency, the temperature inside the helmet, and comfort. METHODS: After baseline assessment during spontaneous breathing, HFNC was applied at flows of 30, 40, and 50 L/min. Successively, the volunteers underwent helmet CPAP at 10 cm H2O and CPAP + HFNC at flows of 30, 40, and 50 L/min. We measured the variations of pharyngeal pressures at end-expiration and end-inspiration, referenced to spontaneous breathing for HFNC and to CPAP for CPAP + HFNC, diaphragm displacement and thickness at end-expiration and thickness at end-inspiration, breathing frequency, the temperature inside the helmet, the occurrence of the fog effect, and comfort. RESULTS: Variations of pharyngeal pressures at end-inspiration changes were small overall and clinically unimportant. With the mouth closed, at increasing HFNC flow, variations of pharyngeal pressures at endexpiration increased during both HFNC (from 2.8 up to 7.7) and, to a lesser extent, CPAP + HFNC (from 2.7 up to 3.8) (P < .001 for all comparisons). These variations were attenuated during open-mouth breathing. HFNC > 40 L/min and CPAP + HFNC ≥ 40 L/min compared with spontaneous breathing and CPAP, respectively, increased diaphragm displacement (P = .001), thickness at end-inspiration and thickness at end-expiration (P < .003 for both). At all flows, breathing frequency was slightly, although significantly, lower with CPAP + HFNC than with HFNC alone (P < .003). The temperature inside the helmet increased slightly and insignificantly at flows of ≤40 L/min with CPAP + HFNC compared with CPAP alone. The fog effect never occurred, whereas comfort was always rated as optimal, without differences between trials. CONCLUSIONS: CPAP + HFNC was well tolerated, with no adverse effects. Based on our findings, there was no need to vary the CPAP level when adding HFNC. At least in healthy subjects, CPAP + HFNC at 30 L/min seemed to be the best combination. [ABSTRACT FROM AUTHOR]

OBJECTIVE: PANDAS are known as the spectrum of autoimmune pathologies related to a previous or current infection by group A beta-hemolytic streptococcus (SBEGA), dealing with several neuropsychiatric manifestations that mainly affect pediatric age. The main features consist of behavioral disease or movement disease characterized by acute-onset, presenting especially through infant period or adolescence. Specific manifestations, occurring during the progression of the disease, are the presence of otorhinolaryngologic symptoms (ENT) and orofacial movement disorders associated with temporomandibular joint pain. PATIENTS AND METHODS: We enrolled 130 children (5-15 years) with a clinical diagnosis of PANDAS between 2012 and 2018. Participants were assessed using ENT specific parameters, PSG to examine respiratory disorders and conventional audiological evaluation. Descriptive and comparative statistical analyses were performed with a control group of 51 healthy patients. RESULTS: The prevalence of ENT symptoms associated was significantly detected in 88 patients of 130 in Group A (relative frequency (%) 67.6; p=0.041) and in 51 patients of 130 in the control Group B (relative frequency (%) 39.2; p=0.063). In relation to prevalence of SDB, 54 subjects have presented nocturnal respiratory obstructive symptoms from mild to severe (relative frequency (%) 61.3; p=0.033) vs. 20 patients of Group B (relative frequency (%) 39.2; p=0.055). The obstructive severity average type was correlated to the consensual adenotonsillar development (size 3-4), (relative frequency (%) 45.4; p=0.047). The audiological deficits found were mostly of transmissive type with OME correlated and linked to the presence of occasional episodes of AOM. The four PANDAS patients who presented orobuccal dystonia (relative frequency (%) 4.54; p=0.091) achieved an improvement of the algic symptoms through the exercises of self-rehabilitation. CONCLUSIONS: Findings from our study show that respiratory diseases, characterizing a group of patients with pandas, are the direct consequences of the malformed or hypertrophic condition and suggesting in these conditions surgical therapy as an approaching tool. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study is to evaluate the haemodynamic and respiratory effects of dexmedetomidine vs. propofol in patients with OSAHS during the drug-induced sleep endoscopy (DISE), and analyze simultaneously the electromyography of genioglossus muscle. PATIENTS AND METHODS: We conducted a study on 50 patients with OSAHS; patients were subjected to DISE with simultaneous polygraphic cardiorespiratory measurement and electromyography of genioglossus muscle. Patients undergoing DISE were divided in two groups: in Group A (19 M; 8 W) was administered propofol TCI and in Group B (16 M; 7 W) was administered dexmedetomidine TCI. RESULTS: In Group A, a mean minimal SpO2 decreasing of 3.7% (p=0.000) and a mean SpO2 decreasing of 1.6% (p 0.001) was noticed, while there was an increase in BP20 of 14.8% (p=0.000) and HR20 of 11.1% (p=0.000). In Group B, it was showed a decreasing of mean minimal SpO2 and mean SpO2 values, about 1.8% (p=0.000) and 1.1% (p 0.009) respectively, while there was an increase of BP20 and HR20, about 8.7% (p=0.000) and 8% (p 0.002), respectively. Despite EMG activity comparing spontaneous sleep with propofol-DISE, there is a statistically significative change for the amplitude (p=0.040) and an increase of 7.01% for the area under the curve (AUC). Comparing spontaneous sleep with dexmedetomidine-DISE induced one, there is only an increase of 25.87% in the AUC. CONCLUSIONS: A greater worsening of the cardio- respiratory basal values was noted after sleep induction with Propofol and same results were obtained confronting EMG of genioglossus muscle data. [ABSTRACT FROM AUTHOR]

Highlights • A two-layer deep architecture for top-down saliency detection and fine-grained visual classification. • Driving a saliency detector with a specific goal results in better performance than fine-tuning pre-trained saliency models. • Providing explicitly saliency maps to visual classifiers increased classification performance. Abstract This paper presents an approach for saliency detection able to emulate the integration of the top-down (task-controlled) and bottom-up (sensory information) processes involved in human visual attention. In particular, we first learn how to generate saliency when a specific visual task has to be accomplished. Afterwards, we investigate if and to what extent the learned saliency maps can support visual classification in nontrivial cases. To achieve this, we propose SalClassNet , a CNN framework consisting of two networks jointly trained: a) the first one computing top-down saliency maps from input images, and b) the second one exploiting the computed saliency maps for visual classification. To test our approach, we collected a dataset of eye-gaze maps, using a Tobii T60 eye tracker, by asking several subjects to look at images from the Stanford Dogs dataset, with the objective of distinguishing dog breeds. Performance analysis on our dataset and other saliency benchmarking datasets, such as POET, showed that SalClassNet outperforms state-of-the-art saliency detectors, such as SalNet and SALICON. Finally, we also analyzed the performance of SalClassNet in a fine-grained recognition task and found out that it yields enhanced classification accuracy compared to Inception and VGG-19 classifiers. The achieved results, thus, demonstrate that 1) conditioning saliency detectors with object classes reaches state-of-the-art performance, and 2) explicitly providing top-down saliency maps to visual classifiers enhances accuracy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Deep neural networks have been used to estimate age from ECGs, the electrocardiographic age (ECG-age), which predicts adverse outcomes. However, this prediction ability has been restricted to clinical settings or relatively short periods. We hypothesized that ECG-age is associated with death and cardiovascular outcomes in the long-standing community-based FHS (Framingham Heart Study). METHODS: We tested the association of ECG-age with chronological age in the FHS cohorts in ECGs from 1986 to 2021. We calculated the gap between chronological and ECG-age (Δage) and classified individuals as having normal, accelerated, or decelerated aging, if Δage was within, higher, or lower than the mean absolute error of the model, respectively. We assessed the associations of Δage, accelerated and decelerated aging with death or cardiovascular outcomes (atrial fibrillation, myocardial infarction, and heart failure) using Cox proportional hazards models adjusted for age, sex, and clinical factors. RESULTS: The study population included 9877 FHS participants (mean age, 55±13 years; 54.9% women) with 34 948 ECGs. ECG-age was correlated to chronological age (r=0.81; mean absolute error, 9±7 years). After 17±8 years of follow-up, every 10-year increase of Δage was associated with 18% increase in all-cause mortality (hazard ratio [HR], 1.18 [95% CI, 1.12–1.23]), 23% increase in atrial fibrillation risk (HR, 1.23 [95% CI, 1.17–1.29]), 14% increase in myocardial infarction risk (HR, 1.14 [95% CI, 1.05–1.23]), and 40% increase in heart failure risk (HR, 1.40 [95% CI, 1.30–1.52]), in multivariable models. In addition, accelerated aging was associated with a 28% increase in all-cause mortality (HR, 1.28 [95% CI, 1.14–1.45]), whereas decelerated aging was associated with a 16% decrease (HR, 0.84 [95% CI, 0.74–0.95]). CONCLUSIONS: ECG-age was highly correlated with chronological age in FHS. The difference between ECG-age and chronological age was associated with death, myocardial infarction, atrial fibrillation, and heart failure. Given the wide availability and low cost of ECG, ECG-age could be a scalable biomarker of cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Women have a higher prevalence of dementia than men. We determined the association between female reproductive factors and risk of cognitive outcomes, including incident dementia, in a community‐based sample of cognitively healthy individuals. Method: Lifetime reproductive factors including age of menarche, age of menopause, reproductive lifespan (age of menopause minus age of menarche), number of live births, post‐menopausal hormone replacement therapy use, and serum estradiol and estrone concentrations were measured in 796 dementia‐free women [mean age 68.4 (SD 5.7) yr] from the Framingham Heart Study Offspring cohort at examination cycle seven (1998‐2001). We related reproductive factors to subsequent risk of incident dementia. Structural MRI brain measures and neurocognitive test performance were included as secondary outcomes. Result: During a median 10 [Q1‐Q3, 8.04‐10.0] year follow‐up, 138 participants developed dementia. On Cox proportional‐hazards analysis adjusting for age and education, a longer reproductive lifespan was associated with a reduced risk of incident dementia (HR 0.94, 95% CI 0.91‐0.98, p = 0.004) while earlier age of menopause of ≤49 vs 50‐51 years was associated with an increased dementia risk (HR 2.56, 95% CI 1.12‐5.88, p = 0.027). Earlier menopause (≤49 versus 50‐51 years) was cross‐sectionally associated with lower hippocampal volume (β±SE, ‐0.123±0.057, p = 0.03). Compared to no live births, 1‐2 live births (5.85±2.03, p = 0.004) and ≥3 live births (5.17±2.06, p = 0.01) were associated with greater total cerebral brain volume. Use of post‐menopausal HRT (0.15±0.055, p = 0.007) and elevated serum estradiol (0.058±0.027, p = 0.03) and estrone concentrations (0.078±0.029, p = 0.006) were cross‐sectionally associated with improved abstract reasoning (Similarities test). Compared to no live births, 1‐2 live births (0.20±0.08, p = 0.018) and ≥3 live births (0.25±0.08, p = 0.003) were also associated with superior visuospatial performance. Conclusion: Greater exposure to estrogen throughout a woman's reproductive life was associated with a lower risk of incident dementia and cross‐sectionally associated with larger brain volumes and enhanced cognitive performance. Our results suggest positive cognitive benefits of greater lifetime estrogen exposure and highlight the potential role of estrogen exposure in modifying the risk of dementia. [ABSTRACT FROM AUTHOR]

A novel, comprehensive health risk index for adults has been validated and is now ready for use to improve the health of individuals and populations. This health risk index provides an estimate of the avoidable risk of death for adults 30 years or older. It includes 12 evidence-based clinical and behavioral risk factors and was validated on discrimination and calibration using the NHANES (National Health and Nutrition Examination Survey) and Framingham Heart Study cohorts. The results from both cohorts were consistent and similar. Discrimination was good, and calibration was acceptable but tended to overpredict mortality risk for females in the higher-risk deciles. [ABSTRACT FROM AUTHOR]

Knowledge of juvenile dispersal is important for understanding population dynamics and for effective conservation, particularly of geographically isolated raptor populations. Here, we report the first documented case of a long-distance movement of an Egyptian VultureNeophron percnopterusfrom the French population to Sicily. This observation opens a new perspective for the conservation of the small and endangered Sicilian population of this species, providing evidence that persistence of the Italian population may be aided by new input from other countries. [ABSTRACT FROM PUBLISHER]

Introduction This study examined whether interarm differences in systolic blood pressure (IDSBP) ≥10 mm Hg were associated with the risk of incident dementia and subclinical brain injury. Methods Between 1992 and 1998, 2063 participants of the Framingham Heart Study underwent assessment of IDSBP with results related to the 10-year risk of incident dementia including clinically characterized Alzheimer's disease. Secondary outcomes included markers of subclinical brain injury on magnetic resonance imaging. Results High IDSBP were associated with a greater risk of incident dementia (hazard ratio [HR] 1.92; 95% confidence interval [CI], 1.09–3.40) and Alzheimer's disease (HR, 2.32; 95% CI, 1.29–4.18), but only in those who carried an apolipoprotein E ( APOE ) ε4 allele. IDSBP also predicted lower total brain volumes and more prevalent silent brain infarcts in those who were APOE ε4 positive. Discussion High IDSBP were associated with an increased risk of dementia, including clinical Alzheimer's disease, and subclinical brain injury in those who were APOE ε4 positive. [ABSTRACT FROM AUTHOR]