scholarly journals Brain-age predicts subsequent dementia in memory clinic patients

2021 ◽  
Author(s):  
Francesca Biondo ◽  
Amelia Jewell ◽  
Megan Pritchard ◽  
Dag Aarsland ◽  
Claire J Steves ◽  
...  
Keyword(s):  
Cox Regression ◽  
Memory Clinic ◽  
Age Related ◽  
Increased Risk ◽  
Mri Scans ◽  
Neuroimaging Biomarkers ◽  
Clinic Practice ◽  
Practice Methods ◽  
Quantitative Neuroimaging ◽  
Brain Age

INTRODUCTION: Research into quantitative neuroimaging biomarkers of dementia risk rarely uses data representative of everyday clinic practice. METHODS: We analysed T1-weighted MRI scans from memory clinic patients (n=1140; 60.2% female and mean [SD] age of 70.0 [10.8] years) to derive "brain-age", an index of age-related brain health. We determined which patients went on to develop dementia (n=476) via linkage to electronic health records. RESULTS: Cox regression indicated a 3% increased risk of dementia per brain-PAD year (brain-PAD = brain-age minus chronological age), HR(95% CI)=1.03(1.02, 1.04), p<0.001, adjusted for age, age^2, sex, MMSE and normalised brain volume. Brain-PAD remained significant even with a minimum time-to-diagnosis of 3 years (HR=1.06) and with MMSE score above 26 (HR=1.03). DISCUSSION: Memory clinic patients with older appearing brains are more likely to receive a subsequent dementia diagnosis. These results from a "real-world" dataset suggest quantitative neuroimaging biomarkers like brain-age could be readily used in the clinic.

scholarly journals Evidence of Stage- and Age-Related Heterogeneity of Non-HLA SNPs and Risk of Islet Autoimmunity and Type 1 Diabetes: The Diabetes Autoimmunity Study in the Young

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Brittni N. Frederiksen ◽  
Andrea K. Steck ◽  
Miranda Kroehl ◽  
Molly M. Lamb ◽  
Randall Wong ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cox Regression ◽  
Islet Autoimmunity ◽  
Candidate Snps ◽  
Age Related ◽  
Increased Risk ◽  
Restricted Cubic Splines ◽  
Candidate Loci ◽  
Hispanic White

Previously, we examined 20 non-HLA SNPs for association with islet autoimmunity (IA) and/or progression to type 1 diabetes (T1D). Our objective was to investigate fourteen additional non-HLA T1D candidate SNPs for stage- and age-related heterogeneity in the etiology of T1D. Of 1634 non-Hispanic white DAISY children genotyped, 132 developed IA (positive for GAD, insulin, or IA-2 autoantibodies at two or more consecutive visits); 50 IA positive children progressed to T1D. Cox regression was used to analyze risk of IA and progression to T1D in IA positive children. Restricted cubic splines were used to model SNPs when there was evidence that risk was not constant with age.C1QTNF6(rs229541) predicted increased IA risk (HR: 1.57, CI: 1.20–2.05) but not progression to T1D (HR: 1.13, CI: 0.75–1.71). SNP (rs10517086) appears to exhibit an age-related effect on risk of IA, with increased risk before age 2 years (age 2 HR: 1.67, CI: 1.08–2.56) but not older ages (age 4 HR: 0.84, CI: 0.43–1.62).C1QTNF6(rs229541), SNP (rs10517086), andUBASH3A(rs3788013) were associated with development of T1D. This prospective investigation of non-HLA T1D candidate loci shows that some SNPs may exhibit stage- and age-related heterogeneity in the etiology of T1D.

scholarly journals Increased risk of Parkinson’s disease among patients with age-related macular degeneration

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Po-Yu Jay Chen ◽  
Lei Wan ◽  
Jung-Nien Lai ◽  
Chih Sheng Chen ◽  
Jamie Jiin-Yi Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Macular Degeneration ◽  
Cox Regression ◽  
Age Related Macular Degeneration ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Age Related ◽  
Increased Risk

Abstract Background This study aimed to investigate the risk of Parkinson’s disease (PD) among patients with age-related macular degeneration (AMD) and its association with confounding comorbidities. Methods A population-based retrospective cohort study was conducted using Longitudinal Health Insurance Database 2000 (LHID2000). We established AMD and non-AMD cohorts from January 1, 2000 to December 31, 2012 to determine the diagnosis of PD. A total of 20,848 patients were enrolled, with 10,424 AMD patients and 10,424 controls matched for age, sex, and index year at a 1:1 ratio. The follow-up period was from the index date of AMD diagnosis to the diagnosis of PD, death, withdrawal from the insurance program, or end of 2013. Multivariable Cox regression analysis was performed to examine the hazard ratio (HR) and 95% confidence interval (CI) for the risk of PD between the AMD and non-AMD cohorts. Result After adjusting for potential confounders, there was a higher risk of developing PD in the AMD cohort than in the non-AMD cohort (adjusted HR = 1.35, 95% CI = 1.16–1.58). A significant association could be observed in both female (aHR = 1.42, 95% CI = 1.13–1.80) and male (aHR = 1.28, 95% CI = 1.05–1.57) patients, aged more than 60 years (60–69: aHR = 1.51, 95% CI = 1.09–2.09, 70–79: aHR = 1.30, 95% CI = 1.05–1.60; 80–100: aHR = 1.40, 95% CI = 1.01–1.95), and with more than one comorbidity (aHR = 1.40, 95% CI = 1.20–1.64). A significant association between increased risk of PD and AMD was observed among patients with comorbidities of osteoporosis (aHR = 1.68, 95% CI = 1.22–2.33), diabetes (aHR = 1.41, 95% CI = 1.12–1.78) and hypertension (aHR = 1.36, 95% CI = 1.15–1.62) and medications of statin (aHR = 1.42, 95% CI = 1.19–1.69) and calcium channel blocker (CCB) (aHR = 1.32, 95% CI = 1.11–1.58). The cumulative incidence of PD was significantly higher over the 12-year follow-up period in AMD cohort (log-rank test, p < 0.001). Conclusions Patients with AMD may exhibit a higher risk of PD than those without AMD.

scholarly journals Role of RET genetic variants in MEN2-associated pheochromocytoma

2014 ◽  
Vol 170 (6) ◽  
pp. 821-828 ◽  
Author(s):  
Débora Rodrigues Siqueira ◽  
Lucieli Ceolin ◽  
Carla Vaz Ferreira ◽  
Mírian Romitti ◽  
Silvana Cavalcante Maia ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cox Regression Analysis ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Age Related ◽  
Increased Risk ◽  
Tertiary Teaching ◽  
Cox Proportional Hazard Models ◽  
Tertiary Teaching Hospital ◽  
Estimated Risk

Background: RET polymorphisms have been involved in the clinical presentation and prognosis of multiple endocrine neoplasia type 2 (MEN2)-associated medullary thyroid carcinoma.ObjectiveTo investigate the effect of RET variants on the penetrance of pheochromocytoma (PHEO) in MEN2 patients. Methods: The RET variants L769L, S836S, and G691S/S904S were evaluated in a cohort of 153 MEN2 patients attending a tertiary teaching hospital. A comparison of RET variant frequencies between patients with and without PHEO was performed. Kaplan–Meier curves and Cox regression analysis were used to estimate the effect of RET variants on the age-dependent penetrance.ResultsA total of 48 (31.4%) patients presented with MEN2-associated PHEOs. The mean age at diagnosis was 35.5±13.4 years, 60.4% of patients were women, and 92.8% had RET mutations at codon 634. The frequencies of RET polymorphisms were as follows: 20.1% L769L, 4.75% S836S, and 17.3% S904S/G691S. We did not observe any association between the frequencies of L769L, S836S, or S904S/G691S variants and PHEO development (all P>0.05). However, individuals carrying two RET polymorphic alleles had an increased estimated risk of PHEO (2.63; 95% CI, 1.4–5.0; P=0.004) and were younger at diagnosis when compared with those with one or no polymorphism (29.6±6.3 and 39.3±14.4 years respectively; P=0.006). Accordingly, additional analysis using Cox proportional hazard models demonstrated that the presence of two RET variants was associated with an increased risk for early PHEO development (hazard ratio, 5.99 (95% CI, 2.24–16.03); P<0.001).ConclusionsRET polymorphic alleles have an additive effect on the estimated risk of age-related PHEO penetrance in MEN2 patients.

scholarly journals Malnutrition According to GLIM Criteria Is Associated with Mortality and Hospitalizations in Rehabilitation Patients with Stable Chronic Obstructive Pulmonary Disease

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 369
Author(s):  
Vanesa Dávalos-Yerovi ◽  
Ester Marco ◽  
Dolores Sánchez-Rodríguez ◽  
Xavier Duran ◽  
Delky Meza-Valderrama ◽  
...  
Keyword(s):  
Hospital Admissions ◽  
Cox Regression ◽  
Negative Impact ◽  
Fat Free Mass ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Copd Patients ◽  
Increased Risk ◽  
Post Hoc

Malnutrition has a negative impact on patients with chronic pulmonary obstructive disease (COPD). The purpose of this study was to assess the prevalence of malnutrition, defined by the Global Leadership Initiative for Malnutrition (GLIM), in stable COPD patients referred to pulmonary rehabilitation, and to explore potential associations of malnutrition according to GLIM, and its components, with increased risk of mortality and hospitalizations in 2 years. In a post-hoc analysis of a prospective cohort of 200 rehabilitation patients with stable COPD, main outcome variables were hospital admissions, length of stay, and mortality during a 2-year follow-up. Covariates were malnutrition according to GLIM and its phenotypic criteria: unintentional weight loss, low body mass index (BMI), and low fat-free mass (FFM). Univariate and multivariate analysis were performed using logistic and proportional hazard Cox regression. Malnutrition according to GLIM showed 45% prevalence and was associated with increased mortality risk. Low age-related BMI and FFM were independently associated with mortality, which persisted after adjustment for age and lung function. Malnutrition and low BMI were also associated with increased risk of hospitalization. Malnutrition according to GLIM criteria was highly prevalent in rehabilitation patients with COPD and was associated with nearly 3 times greater mortality and hospitalization risk.

scholarly journals ATN classification and clinical progression in subjective cognitive decline

Neurology ◽  
2020 ◽  
Vol 95 (1) ◽  
pp. e46-e58 ◽  
Author(s):  
Jarith L. Ebenau ◽  
Tessa Timmers ◽  
Linda M.P. Wesselman ◽  
Inge M.W. Verberk ◽  
Sander C.J. Verfaillie ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Medial Temporal Lobe ◽  
Cox Regression ◽  
Subjective Cognitive Decline ◽  
Control Group ◽  
Amyloid Pet ◽  
Memory Clinic ◽  
Amyloid A ◽  
Risk Profiling ◽  
Increased Risk

ObjectiveTo investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD).MethodsWe classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF β-amyloid (A), CSF p-tau (T), and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants, follow-up was available (3 ± 2 years). As a control population, we included 124 participants without SCD.ResultsFifty-six (n = 385) participants had normal Alzheimer disease (AD) biomarkers (A–T–N–), 27% (n = 186) had non-AD pathologic change (A–T–N+, A–T+N–, A–T+N+), 18% (n = 122) fell within the Alzheimer continuum (A+T–N–, A+T–N+, A+T+N–, A+T+N+). ATN profiles were unevenly distributed, with A–T+N+, A+T–N+, and A+T+N+ containing very few participants. Cox regression showed that compared to A–T–N–, participants in A+ profiles had a higher risk of dementia with a dose–response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition.ConclusionsAmong individuals presenting with SCD at a memory clinic, those with a biomarker profile A–T+N+, A+T–N–, A+T+N–, and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A–T–N– individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic.

scholarly journals Do age, fitness and concomitant medications influence management and outcomes of CLL patients treated with ibrutinib?

2021 ◽  
Author(s):  
Alessandra Tedeschi ◽  
Anna Maria Frustaci ◽  
Francesca Romana Mauro ◽  
Annalisa Chiarenza ◽  
Marta Coscia ◽  
...  
Keyword(s):  
Rating Scale ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Age Related ◽  
Increased Risk ◽  
Severe Comorbidity ◽  
Cyp3a4 Inhibitors ◽  
Concomitant Medications ◽  
Ecog Ps

Functional reserve of organs and systems is known to be relevant in predicting immunochemotherapy tolerance. Age and comorbidities, assessed by the cumulative illness rating scale (CIRS), have been used to address chemotherapy intensity. In ibrutinib era it is still unclear whether age, CIRS and ECOG-PS retain their predictive role on treatment vulnerability. In this 712 CLL patients series treated with ibrutinib outside clinical trials, baseline ECOG-PS and neutropenia, resulted as the most accurate predictors of treatment feasibility and outcomes. Age did not independently influence survival and ibrutinib tolerance, indicating that not age per se, but age-related conditions may affect drug management. We confirmed the role of CIRS&gt;6 as a predictor of a poorer progression and event-free survival (PFS, EFS). The presence of a severe comorbidity was significantly associated with permanent dose reductions (PDR), not translating into worse outcomes. As expected, del(17p) and/or TP53mut and previous therapies affected PFS, EFS and overall survival. No study so far has analyzed the influence of concomitant medications and CYP3A-inhibitors with ibrutinib. In our series, these factors had no impact, though CYP3A4 inhibitors use correlated at Cox regression analysis, with an increased risk of PDR. Despite the limitation of its retrospective nature, this large study confirmed the role of ECOG-PS as the most accurate predictor of ibrutinib feasibility and outcomes and importantly neutropenia emerged as a relevant tool influencing patients vulnerability. Although CIRS&gt;6 retained a significant impact on PFS and EFS its value should be confirmed by prospective studies.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

Gene polymorphisms associated with an increased risk of exudative age-related macular degeneration in a Spanish population

2021 ◽  
pp. 112067212110026
Author(s):  
Pablo Gili ◽  
Leyre Lloreda Martín ◽  
José-Carlos Martín-Rodrigo ◽  
Naon Kim-Yeon ◽  
Laura Modamio-Gardeta ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Gene Polymorphisms ◽  
Age Related Macular Degeneration ◽  
Spanish Population ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Exudative Amd ◽  
Age Related ◽  
Increased Risk

Purpose: To identify the association between single-nucleotide polymorphisms (SNPs) in CFH, ARMS2, HTRA1, CFB, C2, and C3 genes and exudative age-related macular degeneration (AMD) in a Spanish population. Methods: In 187 exudative AMD patients and 196 healthy controls (61% women, mean age 75 years), 12 SNPs as risk factors for AMD in CFH (rs1410996, rs1061170, r380390), ARMS2 (rs10490924, rs10490923), HTRA1 (rs11200638), CFB (rs641153), C2 (rs547154, rs9332739), and C3 (rs147859257, rs2230199, rs1047286) genes were analyzed. Results: The G allele was the most frequent in CFH gene (rs1410996) with a 7-fold increased risk of AMD (OR 7.69, 95% CI 3.17–18.69), whereas carriers of C allele in CFH (rs1061170) showed a 3-fold increased risk for AMD (OR 3.22, 95% CI 1.93–5.40). In CFH (rs380390), the presence of G allele increased the risk for AMD by 2-fold (OR 2.52, 95% CI 1.47–4.30). In ARMS2 (rs10490924), the T-allele was associated with an almost 5-fold increased risk (OR 5.49, 95% CI 3.23–9.31). The A allele in HTRA1 (rs11200638) was more prevalent in AMD versus controls (OR 6.44, 95% CI 3.62–11.47). In C2 gene (rs9332739) the presence of C increased risk for AMD by 3-fold (OR 3.10, 95% CI 1.06–9.06). Conclusion: SNPs in CFH, ARMS2, HTRA1, and C2 genes were associated in our study with an increased risk for exudative AMD in Spanish patients.

scholarly journals Ten-year trends in epidemiology and outcomes of pediatric kidney replacement therapy in Europe: data from the ESPN/ERA-EDTA Registry

2021 ◽  
Author(s):  
Marjolein Bonthuis ◽  
Enrico Vidal ◽  
Anna Bjerre ◽  
Özlem Aydoğ ◽  
Sergey Baiko ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Cox Regression ◽  
Patient Survival ◽  
Healthcare Providers ◽  
Resource Planning ◽  
Policy Makers ◽  
Age Related ◽  
Kidney Replacement Therapy ◽  
Over Time ◽  
Related Population

Abstract Background For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We examined trends in incidence and prevalence of KRT and patient survival. Methods We included all children aged <15 years starting KRT 2007–2016 in 22 European countries participating in the ESPN/ERA-EDTA Registry since 2007. General population statistics were derived from Eurostat. Incidence and prevalence were expressed per million age-related population (pmarp) and time trends studied with JoinPoint regression. We analyzed survival trends using Cox regression. Results Incidence of children commencing KRT <15 years remained stable over the study period, varying between 5.5 and 6.6 pmarp. Incidence by treatment modality was unchanged over time: 2.0 for hemodialysis (HD) and peritoneal dialysis (PD) and 1.0 for transplantation. Prevalence increased in all age categories and overall rose 2% annually from 26.4 pmarp in 2007 to 32.1 pmarp in 2016. Kidney transplantation prevalence increased 5.1% annually 2007–2009, followed by 1.5% increase/year until 2016. Prevalence of PD steadily increased 1.4% per year over the entire period, and HD prevalence started increasing 6.1% per year from 2011 onwards. Five-year unadjusted patient survival on KRT was around 94% and similar for those initiating KRT 2007–2009 or 2010–2012 (adjusted HR: 0.98, 95% CI:0.71–1.35). Conclusions We found a stable incidence and increasing prevalence of European children on KRT 2007–2016. Five-year patient survival was good and was unchanged over time. These data can inform patients and healthcare providers and aid health policy makers on future resource planning of pediatric KRT in Europe.

Sign in / Sign up

Export Citation Format

Share Document