Abstract 011: Retinal Signs Are Associated With Increased 20-Year Dementia Risk in the Atherosclerosis Risk in Communities Study

Introduction: The microvascular contribution to dementia may be under-recognized because of the inability to visualize the brain microvasculature in vivo. Although the easily-imaged retinal vasculature may be a surrogate measure for that in the brain, large prospective studies of the relationship between retinal vascular signs and dementia are scarce. Hypothesis: Retinal signs are associated with greater subsequent risk of all-cause dementia and etiologic subtype over 20 years in 12482 men and women (mean age of 60 years when retinal signs were measured, 22% African American). Methods: Retinal signs were measured using fundus photography (1993-1995). Presence and etiology of dementia and mild cognitive impairment (MCI) were adjudicated using data collected in 2011-13, including a complete neuropsychological battery and brain magnetic resonance imaging (subset of participants). For participants not attending the 2011-13 visit, dementia cases were identified using the Telephone Interview for Cognitive Status–Modified or informant interview, or by hospitalization or death certificate code. Multivariable-adjusted Cox proportional hazards models and logistic regression were used to quantify the relationship of retinal signs with dementia risk and with etiologic subtype, respectively. Results: During a mean 16 years of follow-up, 1259 (10%) participants developed dementia. Moderate or severe (vs. no) retinopathy (hazard ratio [HR], 1.86; 95% CI: 1.36, 2.55) and generalized arteriolar narrowing, measured as the central retinal arteriolar equivalent (CRAE, narrowest quartile vs. widest three quartiles), (HR, 1.26; 95% CI: 1.09, 1.45) were associated with all-cause dementia. Results did not differ by diabetes, race or APOE ε4 genotype. Retinopathy was associated with cerebrovascular-related dementia and MCI (odds ratio, 2.66; 95% CI: 1.30, 5.42). Conclusions: Retinal photography captures small vascular signs in the eye that are related to increased dementia risk. Emerging techniques, such as optical coherence tomography angiography, may have the sensitivity to provide surrogate indices of microvascular lesions relevant to dementia in older adults.

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Association of circulating tumor cells (CTC) with survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a real-world cohort.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.59 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 59-59

Author(s):

Umang Swami ◽

Taylor Ryan McFarland ◽

Benjamin Haaland ◽

Adam Kessel ◽

Roberto Nussenzveig ◽

...

Keyword(s):

Real World ◽

Proportional Hazards ◽

De Novo ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Eligibility Criteria ◽

Free Survival ◽

Cox Proportional Hazards Models ◽

Risk Of Progression ◽

The Relationship

59 Background: In mCSPC, baseline CTC counts have been shown to correlate with PSA responses and progression free survival (PFS) in small studies in the context of androgen deprivation therapy (ADT) without modern intensification with docetaxel or novel hormonal therapy. Similar correlation of CTC count with PSA responses and PFS was recently reported from an ongoing phase 3 trial in mCSPC setting (SWOG1216) without reporting the association in the context of ADT intensification. Furthermore, none of these studies correlated CTCs with overall survival (OS). Herein we evaluated whether CTCs were associated with outcomes including OS in a real world mCPSC population treated with intensified as well as non-intensified ADT. Methods: Eligibility criteria: new mCSPC receiving ADT with or without intensification and enumeration of baseline CTCs by FDA cleared Cell Search CTC assay. The relationship between CTC counts (categorized as: 0, 1-4, and ≥5/7.5 ml) and both PFS and OS was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason, PSA at ADT initiation, de novo vs. non-de novo status, and ADT intensification vs. non-intensification therapy. Results: Overall 99 pts were identified. Baseline characteristics are summarized in Table. In unadjusted analyses, CTC counts of ≥5 as compared to 0 were strongly associated with inferior PFS (hazard ratio [HR] 3.38, 95% CI 1.85-6.18; p < 0.001) and OS (HR 4.44 95% CI 1.63-12.10; p = 0.004). In multivariate analyses, CTC counts of ≥5 as compared to 0 continued to be associated with inferior PFS (HR 5.49, 95% CI 2.64-11.43; p < 0.001) and OS (HR 4.00, 95% CI 1.31-12.23; p = 0.015). Within the ADT intensification subgroup also, high CTC counts were associated with poor PFS and OS. For PFS, the univariate HR for CTC ≥5 vs. 0 was 4.87 (95% CI 1.66-14.30; p = 0.004) and multivariate HR for CTC ≥5 vs. 0 was 7.43 (95% CI 1.92-28.82; p = 0.004). For OS, the univariate HR for CTC ≥5 vs. 0 was 15.88 (95% CI 1.93-130.58; p = 0.010) and multivariate HR for CTC ≥5 vs. 0 was 24.86 (95% CI 2.03-304.45; p = 0.012). Conclusions: To best of our knowledge this is the first study to show that high baseline CTC counts are strongly associated with inferior PFS as well as OS in pts with newly diagnosed mCSPC, even in those who received intensified ADT therapy. Identifying these pts at highest risk of progression and death can help with counselling and prognostication in clinics as well as design and enrollment in future clinical trials. [Table: see text]

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Illiteracy, dementia risk, and cognitive trajectories among older adults with low education

Neurology ◽

10.1212/wnl.0000000000008587 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2247-e2256 ◽

Cited By ~ 3

Author(s):

Miguel Arce Rentería ◽

Jet M.J. Vonk ◽

Gloria Felix ◽

Justina F. Avila ◽

Laura B. Zahodne ◽

...

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Independent Effect ◽

Growth Curve Models ◽

Cox Proportional Hazards Models ◽

Dementia Risk ◽

Incident Dementia ◽

Low Education

ObjectiveTo investigate whether illiteracy was associated with greater risk of prevalent and incident dementia and more rapid cognitive decline among older adults with low education.MethodsAnalyses included 983 adults (≥65 years old, ≤4 years of schooling) who participated in a longitudinal community aging study. Literacy was self-reported (“Did you ever learn to read or write?”). Neuropsychological measures of memory, language, and visuospatial abilities were administered at baseline and at follow-ups (median [range] 3.49 years [0–23]). At each visit, functional, cognitive, and medical data were reviewed and a dementia diagnosis was made using standard criteria. Logistic regression and Cox proportional hazards models evaluated the association of literacy with prevalent and incident dementia, respectively, while latent growth curve models evaluated the effect of literacy on cognitive trajectories, adjusting for relevant demographic and medical covariates.ResultsIlliterate participants were almost 3 times as likely to have dementia at baseline compared to literate participants. Among those who did not have dementia at baseline, illiterate participants were twice as likely to develop dementia. While illiterate participants showed worse memory, language, and visuospatial functioning at baseline than literate participants, literacy was not associated with rate of cognitive decline.ConclusionWe found that illiteracy was independently associated with higher risk of prevalent and incident dementia, but not with a more rapid rate of cognitive decline. The independent effect of illiteracy on dementia risk may be through a lower range of cognitive function, which is closer to diagnostic thresholds for dementia than the range of literate participants.

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Eosinophil count and mortality risk in incident hemodialysis patients

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz296 ◽

2020 ◽

Vol 35 (6) ◽

pp. 1032-1042

Author(s):

Duk-Hee Kang ◽

Yuji Lee ◽

Carola Ellen Kleine ◽

Yong Kyu Lee ◽

Christina Park ◽

...

Keyword(s):

Mortality Risk ◽

Eosinophil Count ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Time Varying ◽

Cox Proportional Hazards Models ◽

Lower Baseline ◽

All Cause Mortality ◽

Relationship Of ◽

The Relationship

Abstract Background Eosinophils are traditionally known as moderators of allergic reactions; however, they have now emerged as one of the principal immune-regulating cells as well as predictors of vascular disease and mortality in the general population. Although eosinophilia has been demonstrated in hemodialysis (HD) patients, associations of eosinophil count (EOC) and its changes with mortality in HD patients are still unknown. Methods In 107 506 incident HD patients treated by a large dialysis organization during 2007–11, we examined the relationships of baseline and time-varying EOC and its changes (ΔEOC) over the first 3 months with all-cause mortality using Cox proportional hazards models with three levels of hierarchical adjustment. Results Baseline median EOC was 231 (interquartile range 155–339) cells/μL and eosinophilia (>350 cells/μL) was observed in 23.4% of patients. There was a gradual increase in EOC over time after HD initiation with a median ΔEOC of 5.1 (IQR −53–199) cells/μL, which did not parallel the changes in white blood cell count. In fully adjusted models, mortality risk was highest in subjects with lower baseline and time-varying EOC (<100 cells/μL) and was also slightly higher in patients with higher levels (≥550 cells/μL), resulting in a reverse J-shaped relationship. The relationship of ΔEOC with all-cause mortality risk was also a reverse J-shape where both an increase and decrease exhibited a higher mortality risk. Conclusions Both lower and higher EOCs and changes in EOC over the first 3 months after HD initiation were associated with higher all-cause mortality in incident HD patients.

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Relationship Between Change in Serum Uric Acid and Ischemic Stroke in Chinese Hypertensive Patients

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.717128 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qiu-hong Tan ◽

Lin Liu ◽

Yu-qing Huang ◽

Yu-ling Yu ◽

Jia-yi Huang ◽

...

Keyword(s):

Uric Acid ◽

Ischemic Stroke ◽

Serum Uric Acid ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Elevated Risk ◽

Rank Test ◽

Hypertensive Patients ◽

Cox Proportional Hazards Models ◽

The Relationship

Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients.Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan–Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity.Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): <-32.6 μmol/L; middle (SUA stable): ≥-32.6 μmol/L, <40.2 μmol/L; high (SUA increase substantially): ≥40.2 μmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age < 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially.Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.

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Association between anticholinergic burden and dementia in UK Biobank

Innovation in Aging ◽

10.1093/geroni/igab046.3356 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 936-936

Author(s):

Jure Mur ◽

Simon Cox ◽

Riccardo Marioni ◽

Tom Russ ◽

Graciela Muniz-Terrera

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Anticholinergic Drugs ◽

Uk Biobank ◽

General Measure ◽

Future Studies ◽

Cox Proportional Hazards Models ◽

Dementia Risk ◽

Anticholinergic Burden

Abstract Previous studies on the association between the long-term use of anticholinergic drugs and dementia report heterogenous results. This variability could be due to, among other factors, different anticholinergic scales used, and differential effects of distinct classes of anticholinergic drugs. Here, we use 171,775 participants of UK Biobank with linked GP prescription records to calculate the cumulative annual anticholinergic burden (ACB) and ascertain dementia diagnoses through GP- and inpatient records. We then use Cox proportional hazards models to compare 13 anticholinergic scales and anticholinergic burden (ACB) due to different classes of drugs in their association with dementia. We find dementia to be more strongly predicted by ACB than by polypharmacy across most anticholinergic scales (standardised ORs range: 1.027-1.125). Furthermore, not only the baseline ACB, but the slope of the longitudinal trajectory of ACB (HR=1.094; 95% CI: 1.068-1.119) is predictive of dementia. However, the association between ACB and dementia holds only for some classes of drugs – especially antidepressants, antiepileptics, and high-ceiling antidiuretics. Moreover, we do not find a clear relationship between reported anticholinergic potency and dementia risk. The heterogeneity in findings on the association between ACB and dementia may in part be due to different effects for different classes of drugs. Future studies should establish such differences in more detail and further examine the practicality of using a general measure of anticholinergic potency as it relates to the risk of dementia.

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U-Shaped Association of Serum Uric Acid With All-Cause and Cause-Specific Mortality in US Adults: A Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz068 ◽

2019 ◽

Vol 105 (3) ◽

pp. e597-e609 ◽

Cited By ~ 1

Author(s):

Lihua Hu ◽

Guiping Hu ◽

Benjamin Ping Xu ◽

Lingjuan Zhu ◽

Wei Zhou ◽

...

Keyword(s):

Uric Acid ◽

Cohort Study ◽

Serum Uric Acid ◽

Inflection Point ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Proportional Hazards Models ◽

Cox Proportional Hazards Models ◽

Specific Mortality ◽

The Relationship

Abstract Background In addition to the controversy regarding the association of hyperuricemia with mortality, uncertainty also remains regarding the association between low serum uric acid (SUA) and mortality. We aimed to assess the relationship between SUA and all-cause and cause-specific mortality. Methods This cohort study included 9118 US adults from the National Health and Nutrition Examination Survey (1999-2002). Multivariable Cox proportional hazards models were used to evaluate the relationship between SUA and mortality. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and 2-piecewise Cox proportional hazards models, to address the nonlinearity between SUA and mortality. Results During a median follow-up of 5.83 years, 448 all-cause deaths occurred, with 100 cardiovascular disease (CVD) deaths, 118 cancer deaths, and 37 respiratory disease deaths. Compared with the reference group, there was an increased risk of all-cause, CVD, cancer, and respiratory disease mortality for participants in the first and third tertiles of SUA. We further found a nonlinear and U-shaped association between SUA and mortality. The inflection point for the curve was found at a SUA level of 5.7 mg/dL. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.80 (0.65-0.97) and 1.24 (1.10-1.40) to the left and right of the inflection point, respectively. This U-shaped association was observed in both sexes; the inflection point for SUA was 6 mg/dL in males and 4 mg/dL in females. Conclusion Both low and high SUA levels were associated with increased all-cause and cause-specific mortality, supporting a U-shaped association between SUA and mortality.

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Insomnia in the context of short sleep increases suicide risk

SLEEP ◽

10.1093/sleep/zsaa245 ◽

2020 ◽

Author(s):

Hedström Anna Karin ◽

Ola Hössjer ◽

Rino Bellocco ◽

Weimin Ye ◽

Lagerros Ylva Trolle ◽

...

Keyword(s):

Sleep Duration ◽

Suicide Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Total Effect ◽

P Value ◽

Short Sleep ◽

Cox Proportional Hazards Models ◽

The Relationship ◽

Insomnia Symptoms

Abstract Study Objectives The relationship between insomnia and suicide risk is not completely understood. We aimed to investigate the influence of insomnia on suicide risk, taking both sleep duration and depression into consideration. Methods The present study is based on a Swedish prospective cohort study of 38,786 participants with a mean follow-up time of 19.2 years. Cox proportional hazards models with attained age as time-scale were used to estimate hazard ratios (HRs) of death by suicide with 95% confidence intervals (CI) for participants categorized by frequency of insomnia symptoms. Causal mediation analysis was performed to assess to what extent the relationship between insomnia and suicide risk is mediated by depression. Results Insomnia was only associated with suicide risk among short sleepers, whereas no significant association was observed among those who slept 7 h/night or more. The total effect of insomnia in the context of short sleep on suicide risk, expressed on the HR scale, was 2.85 (95% CI 1.42–5.74). The direct effect was 2.25 (95% CI 1.12–4.54) and the indirect effect, mediated by depression, was 1.27 (95% CI 1.05–1.53). Of the total effect, 32% was mediated by depression. The association between insomnia and suicide risk became more pronounced with decreasing depressive symptoms (p value for trend <0.05). Conclusions Insomnia in the context of short sleep increases suicide risk, both directly and indirectly by affecting the risk of depression. Abnormalities of sleep duration and insomnia symptoms should be evaluated when assessing suicide risk.

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Loneliness and Risk of Dementia

The Journals of Gerontology Series B ◽

10.1093/geronb/gby112 ◽

2018 ◽

Vol 75 (7) ◽

pp. 1414-1422 ◽

Cited By ~ 15

Author(s):

Angelina R Sutin ◽

Yannick Stephan ◽

Martina Luchetti ◽

Antonio Terracciano

Keyword(s):

Risk Factors ◽

Social Isolation ◽

Genetic Risk ◽

Proportional Hazards ◽

Genetic Risk Factors ◽

Cognitive Status ◽

Cox Proportional Hazards ◽

Dementia Risk ◽

Increased Risk ◽

Modifiable Factor

Abstract Objective The present study tests whether loneliness is associated with risk of dementia in the largest sample to date and further examines whether the association is independent of social isolation, a related but independent component of social integration, and whether it varies by demographic factors and genetic vulnerability. Method Participants from the Health and Retirement Study (N = 12,030) reported on their loneliness, social isolation, and had information on clinical, behavioral, and genetic risk factors. Cognitive status was assessed at baseline and every 2 years over a 10-year follow-up with the modified Telephone Interview for Cognitive Status (TICSm). A TICSm score of 6 or less was indicative of dementia. Results Cox proportional hazards regression indicated that loneliness was associated with a 40% increased risk of dementia. This association held controlling for social isolation, and clinical, behavioral, and genetic risk factors. The association was similar across gender, race, ethnicity, education, and genetic risk. Discussion Loneliness is associated with increased risk of dementia. It is one modifiable factor that can be intervened on to reduce dementia risk.

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Hypertension and Hypercholesterolemia Modify Dementia Risk in Relation to APOE ɛ4 Status

Journal of Alzheimer s Disease ◽

10.3233/jad-201609 ◽

2021 ◽

pp. 1-12

Author(s):

Jagan A. Pillai ◽

Kou Lei ◽

James Bena ◽

Lisa Penn ◽

James B. Leverenz

Keyword(s):

Risk Factors ◽

Lower Risk ◽

Proportional Hazards ◽

Age Groups ◽

Cox Proportional Hazards ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Cox Proportional Hazards Models ◽

Dementia Risk ◽

Dementia Onset

Background: There is significant interest in understanding the role of modifiable vascular risk factors contributing to dementia risk across age groups. Objective: Risk of dementia onset was assessed in relation to vascular risk factors of hypertension and hypercholesterolemia among cognitively normal APOE ɛ4 carriers and non-carriers. Methods: In a sample of prospectively characterized longitudinal cohort from the National Alzheimer’s Coordinating Center database, 9,349 participants met criteria for normal cognition at baseline, had a CDR-Global (CDR-G) score of zero, and had concomitant data on APOE ɛ4 status and medical co-morbidities including histories of hypertension and hypercholesterolemia. Multivariable Cox proportional hazards models adjusted for well-known potential confounders were used to compare dementia onset among APOE ɛ4 carriers and non-carriers by young (≤65 years) and old (> 65 year) age groups. Results: 519 participants converted to dementia within an average follow up of 5.97 years. Among older APOE ɛ4 carriers, hypercholesterolemia was related to lower risk of dementia (HR (95% CI), 0.68 (0.49–0.94), p = 0.02). Among older APOE ɛ4 non-carriers, hypertension was related to higher risk of dementia (HR (95% CI), 1.44 (1.13–1.82), p = 0.003). These results were corroborated among a subset with autopsy data characterizing underlying neuropathology. Among younger participants, vascular risk factors did not impact dementia risk, likely from a lower frequency of vascular and Alzheimer’s as etiologies of dementia among this cohort. Conclusion: A history of hypercholesterolemia related to a lower risk of dementia among older APOE ɛ4 carriers, while hypertension related to a higher risk of dementia among older APOE ɛ4 non-carriers.

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Faster Transport Status and Mortality in Anuric Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Blood Purification ◽

10.1159/000433416 ◽

2015 ◽

Vol 40 (2) ◽

pp. 160-166 ◽

Cited By ~ 2

Author(s):

Liping Xiong ◽

Li Fan ◽

Qingdong Xu ◽

Qian Zhou ◽

Huiyan Li ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

All Cause Mortality ◽

History Of ◽

The Relationship

Background: There are limited data regarding the relationship between transport status and mortality in anuric continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: According to the dialysate to plasma creatinine ratio (D/P Cr), 292 anuric CAPD patients were stratified to faster (D/P Cr ≥0.65) and slower transport groups (D/P Cr <0.65). The Cox proportional hazards models were used to evaluate the association of transport status with mortality. Results: During a median follow-up of 22.1 months, 24% patients died, 61.4% of them due to cardiovascular disease (CVD). Anuric patients with faster transport were associated with an increased risk of all-cause mortality (HR (95% CI) = 2.16 (1.09-4.26)), but not cardiovascular mortality, after adjustment for confounders. Faster transporters with pre-existing CVD had a greater risk for death compared to those without any history of CVD. Conclusion: Faster transporters were independently associated with high all-cause mortality in anuric CAPD patients. This association was strengthened in patients with pre-existing CVD.

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