Plasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer's disease (AD). Studies have reported strong associations between p-tau and tau-PET that are mainly driven by ...differences between amyloid-positive and amyloid-negative patients. However, the relationship between p-tau and tau-PET is less characterized within cognitively impaired patients with a biomarker-supported diagnosis of AD. We conducted a head-to-head comparison between plasma p-tau217 and tau-PET in patients at the clinical stage of AD and further assessed their relationships with demographic, clinical, and biomarker variables.
We retrospectively included 87 amyloid-positive patients diagnosed with MCI or dementia due to AD who underwent structural MRI, amyloid-PET (
C-PIB), tau-PET (
F-flortaucipir, FTP), and blood draw assessments within 1 year (age = 66 ± 10, 48% female). Amyloid-PET was quantified in Centiloids (CL) while cortical tau-PET binding was measured using standardized uptake value ratios (SUVRs) referenced against inferior cerebellar cortex. Plasma p-tau217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. MRI-derived cortical volume was quantified with FreeSurfer. Mini-Mental State Examination (MMSE) scores were available at baseline (n = 85) and follow-up visits (n = 28; 1.5 ± 0.7 years).
Plasma p-tau217 and cortical FTP-SUVR were correlated (r = 0.61, p < .001), especially in temporo-parietal and dorsolateral frontal cortices. Both higher p-tau217 and FTP-SUVR values were associated with younger age, female sex, and lower cortical volume, but not with APOE-ε4 carriership. PIB-PET Centiloids were weakly correlated with FTP-SUVR (r = 0.26, p = 0.02), but not with p-tau217 (r = 0.10, p = 0.36). Regional PET-plasma associations varied with amyloid burden, with p-tau217 being more strongly associated with tau-PET in temporal cortex among patients with moderate amyloid-PET burden, and with tau-PET in primary cortices among patients with high amyloid-PET burden. Higher p-tau217 and FTP-SUVR values were independently associated with lower MMSE scores cross-sectionally, while only baseline FTP-SUVR predicted longitudinal MMSE decline when both biomarkers were included in the same model.
Plasma p-tau217 and tau-PET are strongly correlated in amyloid-PET-positive patients with MCI or dementia due to AD, and they exhibited comparable patterns of associations with demographic variables and with markers of downstream neurodegeneration.
Ebola Virus causes disease both in human and non-human primates especially in developing countries. In 2014 during its outbreak, it led to majority of deaths especially in some impoverished area of ...West Africa and its effect is still witnessed up till date.
We studied the spread of Ebola virus and obtained a system of equations comprising of eighteen equations which completely described the transmission of Ebola Virus in a population where control measures were incorporated and a major source of contacting the disease which is the traditional washing of dead bodies was also incorporated. We investigated the local stability of the disease-free equilibrium using the Jacobian Matrix approach and the disease- endemic stability using the center manifold theorem. We also investigated the global stability of the equilibrium points using the LaSalle's Invariant principle.
The result showed that the disease-free and endemic equilibrium where both local and globally stable and that the system exhibits a forward bifurcation.
Numerical simulations were carried out and our graphs show that vaccine and condom use is best for susceptible population, quarantine is best for exposed population, isolation is best for infectious population and proper burial of the diseased dead is the best to avoid further disease spread in the population and have quicker and better recovery.
Background
Plasma measurements of phosphorylated tau (ptau) have emerged as promising biomarkers for Alzheimer’s disease (AD). Studies have shown strong associations between ptau and tau‐PET that are ...mainly driven by the difference between amyloid‐positive and amyloid‐negative patients. However, the relationship between ptau and tau‐PET is not well characterized within patients with AD. We conducted a head‐to‐head comparison between plasma ptau‐217 and tau‐PET in patients at the clinical stage of AD and assessed biomarker relationships with demographic and clinical variables.
Methods
Eighty‐seven amyloid‐positive patients (age=66±10, 48% women) with mild cognitive impairment (n=53) or dementia (n=34) underwent structural MRI, amyloid‐PET (11C‐PIB), tau‐PET (18F‐flortaucipir, FTP), Mini‐Mental State Examination (MMSE, with 28 patients having longitudinal measures 1.5±0.7 years after baseline) and blood draw within a year. Mean cortical PET‐Standardized Uptake Value Ratio (SUVR) were extracted using FreeSurfer5.3. Plasma ptau‐217 concentrations were measured using an electrochemiluminescence‐based assay on the Meso Scale Discovery platform.
Results
Ptau‐217 and cortical FTP‐SUVR were strongly correlated (r=0.61, p<.001, Figure 1). Younger age and female sex, but not APOE4, were associated with higher ptau‐217 and FTP‐SUVR (Figure 2). Amyloid‐PET levels were mildly associated with FTP‐SUVR (r=0.26, p=0.02), not ptau‐217 (r=0.10, p=0.36, Figure 2). The relationship between ptau‐217 and cortical FTP‐SUVR was not modified by age, sex, APOE4, or PIB‐PET (interactions: p’s>0.25). In the whole group, ptau‐217 was associated with FTP‐SUVR in temporo‐parietal and dorsal prefrontal cortices (Figure 3A). However, ptau‐217‐FTP association patterns varied with amyloid burden: in patients with moderate amyloid (<97.7 Centiloids), ptau‐217 was more strongly associated with temporal FTP‐SUVR whereas associations were stronger in primary cortices in patient with higher amyloid levels (Figure 3B). Cross‐sectionally, higher ptau‐217 and FTP‐SUVR were independently associated with lower MMSE (Table 1; Figure 4A). In separate mixed effect models, higher baseline ptau‐217 and FTP‐SUVR were associated with more severe longitudinal decline in MMSE (Figure 4B); when both biomarkers were entered in the same model, only FTP‐SUVR remained significant (Table 2).
Conclusions
In amyloid‐PET‐positive patients with cognitive deficits, ptau‐217 and tau‐PET had comparable patterns of association with demographic and clinical variables. However, cross‐modal and clinical associations tended to be stronger for tau‐PET than ptau‐217.
Abstract Objectives The Latino population is one of the largest, most diverse, and fastest growing demographic groups in the U.S. While Latinos enjoy longer life spans and reduced mortality risk ...relative to non-Hispanic whites, they have higher rates of chronic health conditions such as diabetes and dementia and live more of their older years with poor health and disability. Such inequities point to the need for this research focused on examining resiliency strategies and barriers to successful aging among various U.S. Latino subgroups. Methods This qualitative paper used thematic content analysis to examine resiliency strategies and barriers to successful aging among Mexican immigrant women (n=40) residing in an underserved agricultural community and entering mid-life (mean = 49 years old). Results With regards to barriers to successful aging, three themes emerged: 1) stressful lifestyle in the U.S. compared to the participants’ home countries; 2) stress from expectations at home; 3) and stress due to work and the various components around work. The following four resiliency strategies emerged: 1) family as a motivation for moving forward in life and focusing on the success of children; 2) having a positive mindset; 3) praying to God for strength to overcome obstacles; and 4) self-care. Discussion Despite experiencing barriers to successful aging, participants practice various resiliency strategies to age successfully. Since many of the barriers identified are related to poverty-related stressors, systemic solutions addressing the social determinants of health are needed.
Background
Plasma measurements of phosphorylated tau (ptau) have emerged as promising biomarkers for Alzheimer’s disease (AD). Studies have shown strong associations between ptau and tau‐PET that are ...mainly driven by the difference between amyloid‐positive and amyloid‐negative patients. However, the relationship between ptau and tau‐PET is not well characterized within patients with AD. We conducted a head‐to‐head comparison between plasma ptau‐217 and tau‐PET in patients at the clinical stage of AD and assessed biomarker relationships with demographic and clinical variables.
Methods
Eighty‐seven amyloid‐positive patients (age=66±10, 48% women) with mild cognitive impairment (n=53) or dementia (n=34) underwent structural MRI, amyloid‐PET (11C‐PIB), tau‐PET (18F‐flortaucipir, FTP), Mini‐Mental State Examination (MMSE, with 28 patients having longitudinal measures 1.5±0.7 years after baseline) and blood draw within a year. Mean cortical PET‐Standardized Uptake Value Ratio (SUVR) were extracted using FreeSurfer5.3. Plasma ptau‐217 concentrations were measured using an electrochemiluminescence‐based assay on the Meso Scale Discovery platform.
Results
Ptau‐217 and cortical FTP‐SUVR were strongly correlated (r=0.61, p<.001, Figure 1). Younger age and female sex, but not APOE4, were associated with higher ptau‐217 and FTP‐SUVR (Figure 2). Amyloid‐PET levels were mildly associated with FTP‐SUVR (r=0.26, p=0.02), not ptau‐217 (r=0.10, p=0.36, Figure 2). The relationship between ptau‐217 and cortical FTP‐SUVR was not modified by age, sex, APOE4, or PIB‐PET (interactions: p’s>0.25). In the whole group, ptau‐217 was associated with FTP‐SUVR in temporo‐parietal and dorsal prefrontal cortices (Figure 3A). However, ptau‐217‐FTP association patterns varied with amyloid burden: in patients with moderate amyloid (<97.7 Centiloids), ptau‐217 was more strongly associated with temporal FTP‐SUVR whereas associations were stronger in primary cortices in patient with higher amyloid levels (Figure 3B). Cross‐sectionally, higher ptau‐217 and FTP‐SUVR were independently associated with lower MMSE (Table 1; Figure 4A). In separate mixed effect models, higher baseline ptau‐217 and FTP‐SUVR were associated with more severe longitudinal decline in MMSE (Figure 4B); when both biomarkers were entered in the same model, only FTP‐SUVR remained significant (Table 2).
Conclusions
In amyloid‐PET‐positive patients with cognitive deficits, ptau‐217 and tau‐PET had comparable patterns of association with demographic and clinical variables. However, cross‐modal and clinical associations tended to be stronger for tau‐PET than ptau‐217.
Background Familial cerebral cavernous alformation (CCM) is an autosomal dominant disease caused by mutations in
,
, or
. Cases typically present with multiple lesions, strong family history, and ...neurological symptoms, including seizures, headaches, or other deficits. Intracranial hemorrhage (ICH) is a severe manifestation of CCM, which can lead to death or long-term neurological deficits. Few studies have reported ICH rates and risk factors in familial CCM. We report ICH rates and assess whether CCM lesion burden, a disease severity marker, is associated with risk of symptomatic ICH during follow-up in a well-characterized cohort of familial CCM cases. Methods and Results We studied 386 patients with familial CCM with follow-up data enrolled in the Brain Vascular Malformation Consortium CCM Project. We estimated symptomatic ICH rates overall and stratified by history of ICH before enrollment. CCM lesion burden (total lesion count and large lesion size) assessed at baseline enrollment was tested for association with increased risk of subsequent ICH during follow-up using Cox regression models adjusted for history of ICH before enrollment, age, sex, and family structure and stratified on recruitment site. The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (
=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio HR, 1.37 per doubling of total lesion count 95% CI, 1.10-1.71,
=0.006). The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (
=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio HR, 1.37 per doubling of total lesion count 95% CI, 1.10-1.71,
=0.006). Conclusions Patients with familial CCM with prior history of an ICH event are at higher risk for rehemorrhage during follow-up. In addition, total CCM lesion burden is significantly associated with increased risk of subsequent symptomatic ICH; hence lesion burden may be an important predictor of patient outcome and aid patient risk stratification.
