Association of β-amyloid level, clinical progression and longitudinal cognitive change in normal older individuals

Objective:To determine the effect of Aβ level on progression risk to MCI or dementia and longitudinal cognitive change in cognitively normal (CN) older individuals.Methods:All CN from the Australian Imaging Biomarkers and Lifestyle study (AIBL) with Aβ PET and ≥3 years follow-up were included (n=534; age 72±6 yrs; 27% Aβ positive; follow-up 5.3±1.7 yrs). Aβ level was divided using the standardised 0-100 Centiloid scale: <15 CL negative, 15-25 CL uncertain, 26-50 CL moderate, 51-100 CL high, >100 CL very high, noting >25 CL approximates a positive scan. Cox proportional hazards analysis and linear mixed effect models were used to assess risk of progression and cognitive decline.Results:Aβ levels in 63% were negative, 10% uncertain, 10% moderate, 14% high and 3% very high. Fifty-seven (11%) progressed to MCI or dementia. Compared to negative Aβ, the hazard ratio for progression for moderate Aβ was 3.2 (95% CI 1.3-7.6; p<0.05), for high was 7.0 (95% CI 3.7-13.3; p<0.001) and for very high was 11.4 (95% CI 5.1-25.8; p<0.001). Decline in cognitive composite score was minimal in the moderate group (-0.02 SD/year, p=0.05) while the high and very high declined substantially (high -0.08 SD/year, p<0.001; very high -0.35 SD/year p<0.001).Conclusion:The risk of MCI or dementia over 5 years in older CN is related to Aβ level on PET, 5% if negative vs 25% if positive but ranging from 12% if 26-50 CL to 28% if 51-100 CL and 50% if >100 CL. This information may be useful for dementia risk counselling and aid design of preclinical AD trials.

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The association between lymphopenia and serious infection risk in rheumatoid arthritis

Rheumatology ◽

10.1093/rheumatology/kez349 ◽

2019 ◽

Vol 59 (4) ◽

pp. 762-766

Author(s):

Sujith Subesinghe ◽

Alexander Kleymann ◽

Andrew Ian Rutherford ◽

Katie Bechman ◽

Sam Norton ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Mixed Effect ◽

Proportional Hazards Regression ◽

Effect Model ◽

Serious Infection ◽

Patients At Risk ◽

Using Data ◽

The Relationship

Abstract Objectives To investigate the relationship between occurrence of serious infection (SI) and lymphocyte counts in patients with RA using data from a single centre. Methods We used routinely captured data from a single tertiary rheumatology centre to explore the relationship between lymphopenia and SI risk. Adult RA patients were included over a 5-year follow-up period. Admissions due to confirmed SI were considered. SI rate with 95% confidence intervals was calculated. The association between SI with baseline lymphocyte counts, time-averaged lymphocyte counts throughout all follow-up, and a nadir lymphocyte count was assessed using Cox proportional hazards regression. The relationship between lymphopenia over time and SI was analysed using a mixed-effect model of lymphocyte counts prior to SI. Results This analysis included 1095 patients with 205 SIs during 2016 person-years of follow-up. The SI rate was 4.61/100 patient-years (95% CI: 3.76, 5.65). Compared with patients with nadir lymphocyte counts >1.5 × 109 cells/l, nadir lymphopenia <1 × 109 cells/l was significantly associated with higher SI risk (HR 3.28; 95% CI: 1.59, 6.76), increasing to HR 8.08 (95% CI: 3.74, 17.44) in patients with lymphopenia <0.5 × 109 cells/l. Lymphocyte counts were observed to be reduced in the 30-day period prior to SI. Conclusion Lymphocyte counts below <1.0 × 109 cells/l were associated with higher SI risk in RA patients; the strongest association between lymphopenia and SI was observed when lymphocyte counts were below <0.5 × 109 cells/l. Lymphopenia may be used as a measure to stratify patients at risk of SI.

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Impact of Comorbidities On Physical Function And Survival of Middle-Aged As Compared To Older, Individuals With Cancer.

10.21203/rs.3.rs-605809/v1 ◽

2021 ◽

Author(s):

Bogda Koczwara ◽

Laura Deckx ◽

Shahid Ullah ◽

Marjan Van den Akker

Keyword(s):

Functional Impairment ◽

Proportional Hazards ◽

Age Groups ◽

Cox Proportional Hazards ◽

Older Individuals ◽

Middle Aged ◽

Binary Logit ◽

Comorbidity Index ◽

Strength Of Association

Abstract Purpose: To investigate if comorbidity predicts mortality and functional impairment in middle-aged individuals with cancer (50-64 years) as compared to older individuals.Methods: A prospective cohort study. Outcomes were mortality and functional impairment at 5 years follow-up. Comorbidity was assessed using adjusted Charlson comorbidity index and polypharmacy (≥5 drugs) as surrogate for comorbidity. Multivariate Cox-proportional hazards and binary logit models were used to assess the risk of 5-year mortality and functional impairment respectively.Results: We included 477 middle-aged (50-64 years) and 563 older (65+ years) individuals with cancer. The prevalence of comorbidity (at least one disease in addition to cancer) was 29% for middle-aged and 45% for older individuals, with polypharmacy observed in 15% and 31% respectively. Presence of ≥3 comorbidities nearly tripled the mortality risk in middle-aged individuals (HR 2.97, 95% CI: 1.43-6.16). In older individuals the HR was 1.7 (95% CI 1.1-2.8). Polypharmacy also significantly increased the risk for mortality in middle-aged (HR 2.35, 95% CI 1.32- 4.16) but not in older individuals (HR 1.2, 95% CI 0.9-1.8). Polypharmacy quadrupled the risk for functional impairment in middle-aged (OR 4.0, 95% CI 1.59-10.06) and older individuals (OR 4.4, 95% CI 1.6-11.7). Conclusion: Comorbidity and polypharmacy are associated with inferior outcomes in younger and older cancer individuals with the strength of association in younger individuals exceeding that of older individuals. Assessment and management of comorbidity should be a priority for cancer care across all age groups.

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Higher risk of dementia in English older individuals who are overweight or obese

International Journal of Epidemiology ◽

10.1093/ije/dyaa099 ◽

2020 ◽

Vol 49 (4) ◽

pp. 1353-1365 ◽

Cited By ~ 3

Author(s):

Yixuan Ma ◽

Olesya Ajnakina ◽

Andrew Steptoe ◽

Dorina Cadar

Keyword(s):

Body Weight ◽

Abdominal Obesity ◽

Central Obesity ◽

Proportional Hazards ◽

Normal Weight ◽

Cox Proportional Hazards ◽

Older Individuals ◽

Obese Women ◽

Dementia Incidence

Abstract Background Several risk factors contribute to dementia, but the role of obesity remains unclear. This study investigated whether increased body weight or central obesity were associated with a higher risk of developing dementia in a representative sample of older English adults. Methods We studied 6582 participants from the English Longitudinal Study of Ageing (ELSA) who were aged ≥50 years and were dementia-free at baseline, that being either wave 1 (2002–2003) for study members who started at wave 1, or at either wave 2 (2004–2005) or 4 (2008–2009) for those who began the study as refreshment samples. Body mass index (BMI) was measured at baseline and categorized into normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (≥30 kg/m2). Central obesity was defined as a waist circumference (WC) >88 cm for women and >102 cm for men. Cumulative incidence of dementia was ascertained based on physician-diagnosed dementia, an overall score >3.38 on the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Hospital Episodes Statistics (HES) data at every ELSA wave from baseline until wave 8 (2016–2017). Cox proportional hazards models were used to assess the association between baseline BMI levels or abdominal obesity in relation to dementia incidence during the mean follow-up period of 11 years. Results From the overall sample, 6.9% (n = 453) of participants developed dementia during the follow-up period of maximum 15 years (2002–2017). Compared with participants with normal weight, those who were obese at baseline had an elevated risk of dementia incidence [hazard ratio (HR) = 1.34, 95% confidence interval (CI) 1.07–1.61] independent of sex, baseline age, apolipoprotein E-ε4 (APOE-ε4), education, physical activity, smoking and marital status. The relationship was slightly accentuated after additionally controlling for hypertension and diabetes (HR = 1.31, 95% CI 1.03–1.59). Women with central obesity had a 39% greater risk of dementia compared with non-central obese women (HR = 1.39, 95% CI 1.12–1.66). When compared with a normal BMI and WC group, the obese and high WC group had 28% (HR = 1.28, 95% CI 1.03–1.53) higher risk of dementia. Conclusions Our results suggest that having an increased body weight or abdominal obesity are associated with increased dementia incidence. These findings have significant implications for dementia prevention and overall public health.

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General thoughts of death and mortality: findings from the Komo-Ise cohort, Japan

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796018000434 ◽

2018 ◽

Vol 28 (6) ◽

pp. 662-669 ◽

Cited By ~ 1

Author(s):

A. Stickley ◽

C. F. S. Ng ◽

C. Watanabe ◽

Y. Inoue ◽

A. Koyanagi ◽

...

Keyword(s):

Mortality Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Older Individuals ◽

Community Based ◽

Wish To Die ◽

Married Individuals ◽

Older Subjects ◽

Older Citizens

AbstractAimsDeath ideation (thinking about/wishing for one's own death, thinking that one would be better off dead) is linked to an increased mortality risk. However, comparatively little is known about more general thoughts of death (GTOD) where no wish to die or life value is expressed. This study examined whether GTOD predicted mortality in a community-based cohort of older adults.MethodsData came from the Komo-Ise cohort study in Gunma prefecture, Japan. The analytic sample comprised 8208 individuals (average age 61.3 (range 47–77)) who were asked in wave 2 of the study in 2000 if they had ‘Thought about death more than usual, either your own, someone else's or death in general?’ in the past 2 weeks. Death data were obtained from the municipal resident registration file. Cox proportional hazards regression analysis was used to examine associations.ResultsDuring the follow-up period (2000–2008), there were 672 deaths. In a model adjusted for baseline covariates, GTOD were significantly associated with all-cause mortality (hazards ratio 1.66, 95% confidence interval 1.20–2.29). Stratified analyses showed an association between GTOD and mortality in men, older subjects (⩾70 years), married individuals and those with higher social support.ConclusionsGTOD are associated with an increased mortality risk among older citizens in Japan. Research is now needed to determine the factors underlying this association and assess the clinical relevance of screening for GTOD in older individuals.

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Associations of Dietary Patterns with Incident Depression: The Maastricht Study

Nutrients ◽

10.3390/nu13031034 ◽

2021 ◽

Vol 13 (3) ◽

pp. 1034

Author(s):

Vincenza Gianfredi ◽

Annemarie Koster ◽

Anna Odone ◽

Andrea Amerio ◽

Carlo Signorelli ◽

...

Keyword(s):

Depressive Symptoms ◽

Dietary Patterns ◽

Proportional Hazards ◽

A Priori ◽

Preventive Measure ◽

Population Based ◽

Cox Proportional Hazards ◽

Healthy Diet ◽

Patient Health

Our aim was to assess the association between a priori defined dietary patterns and incident depressive symptoms. We used data from The Maastricht Study, a population-based cohort study (n = 2646, mean (SD) age 59.9 (8.0) years, 49.5% women; 15,188 person-years of follow-up). Level of adherence to the Dutch Healthy Diet (DHD), Mediterranean Diet, and Dietary Approaches To Stop Hypertension (DASH) were derived from a validated Food Frequency Questionnaire. Depressive symptoms were assessed at baseline and annually over seven-year-follow-up (using the 9-item Patient Health Questionnaire). We used Cox proportional hazards regression analyses to assess the association between dietary patterns and depressive symptoms. One standard deviation (SD) higher adherence in the DHD and DASH was associated with a lower hazard ratio (HR) of depressive symptoms with HRs (95%CI) of 0.78 (0.69–0.89) and 0.87 (0.77–0.98), respectively, after adjustment for sociodemographic and cardiovascular risk factors. After further adjustment for lifestyle factors, the HR per one SD higher DHD was 0.83 (0.73–0.96), whereas adherence to Mediterranean and DASH diets was not associated with incident depressive symptoms. Higher adherence to the DHD lowered risk of incident depressive symptoms. Adherence to healthy diet could be an effective non-pharmacological preventive measure to reduce the incidence of depression.

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Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

BMC Cardiovascular Disorders ◽

10.1186/s12872-020-01834-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maryam Farhadian ◽

Sahar Dehdar Karsidani ◽

Azadeh Mozayanimonfared ◽

Hossein Mahjub

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Coronary Intervention ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Cerebrovascular Events ◽

Long Term Follow Up ◽

Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

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Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa324 ◽

2020 ◽

Author(s):

Yuko Yamaguchi ◽

Marta Zampino ◽

Toshiko Tanaka ◽

Stefania Bandinelli ◽

Yusuke Osawa ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Differentiation Factor ◽

Hazards Model ◽

Increased Risk ◽

The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Influence of Smoking Habits on the Prevalence of Dental Caries: A Register-Based Cohort Study

European Journal of Dentistry ◽

10.1055/s-0041-1729458 ◽

2021 ◽

Author(s):

Miguel A. de Araújo Nobre ◽

Ana M. Sezinando ◽

Inês C. Fernandes ◽

Andreia C. Araújo

Keyword(s):

Dental Caries ◽

Proportional Hazards ◽

Smoking Habit ◽

Cox Proportional Hazards ◽

Radiographic Examination ◽

Rank Test ◽

Significance Level ◽

Cumulative Survival ◽

Caries Lesions

Abstract Objective The study aimed to evaluate the influence of smoking habit on the prevalence of dental caries lesions in a follow-up study. Materials and Methods A total of 3,675 patients (2,186 females and 1,489 males) with an average age of 51.4 years were included. Outcome measures were the incidence of dental caries defined as incipient noncavitated, microcavitated, or cavitated lesions which had been diagnosed through clinical observation with mouth mirror and probe examination evaluating change of texture, translucency, and color; radiographic examination through bitewing radiographs; or secondary caries through placement of a new restoration during the follow-up of the study. Statistical Analysis Cumulative survival (time elapsed with absence of dental caries) was estimated through the Kaplan–Meier product limit estimator with comparison of survival curves (log-rank test). A multivariable Cox proportional hazards regression model was used to evaluate the effect of smoking on the incidence of dental caries lesions when controlled to age, gender, systemic status, frequency of dental hygiene appointments, and socioeconomic status. The significance level was set at 5%. Results Eight hundred sixty-three patients developed caries (23.5% incidence rate). The cumulative survival estimation was 81.8% and 48% survival rate for nonsmokers and smokers, respectively (p < 0.001), with an average of 13.5 months between the healthy and diseased state diagnosis. Smokers registered a hazard ratio for dental caries lesions of 1.32 (p = 0.001) when controlled for the other variables of interest. Conclusion Within the limitations of this study, it was concluded that smoking habit might be a predictor for dental caries.

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Association of Brain Natriuretic Peptide With Mortality in Exceptionally Long-Lived Families

Innovation in Aging ◽

10.1093/geroni/igaa057.681 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 211-211

Author(s):

Allison Kuipers ◽

Robert Boudreau ◽

Mary Feitosa ◽

Angeline Galvin ◽

Bharat Thygarajan ◽

...

Keyword(s):

Older Adults ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Sex Education ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Time To Event ◽

Healthy Older Adults ◽

Secondary Analyses

Abstract Natriuretic peptides are produced within the heart and released in response to increased chamber wall tension and heart failure (HF). N-Terminal prohormone Brain Natriuretic Peptide (NT-proBNP) is a specific natriuretic peptide commonly assayed in persons at risk for HF. In these individuals, NT-proBNP is associated with future disease prognosis and mortality. However, its association with mortality among healthy older adults remains unknown. Therefore, we determined the association of NT-proBNP with all-cause mortality over a median follow-up of 10 years in 3253 individuals free from HF at baseline in the Long Life Family Study, a study of families recruited for exceptional longevity. We performed cox proportional hazards analysis (coxme in R) for time-to event (mortality), adjusted for field center, familial relatedness, age, sex, education, smoking, alcohol, physical activity, BMI, diabetes, hypertension, and cancer. In addition, we performed secondary analyses among individuals (N=2457) within the normal NT-proBNP limits at baseline (<125pg/ml aged <75 years; <450pg/ml aged ≥75 years). Overall, individuals were aged 32-110 years (median 67 years; 44% male), had mean NT-proBNP of 318.5 pg/ml (median 91.0 pg/ml) and 1066 individuals (33%) died over the follow-up period. After adjustment, each 1 SD greater baseline NT-proBNP was associated with a 1.30-times increased hazard of mortality (95% CI: 1.24-1.36; P<0.0001). Results were similar in individuals with normal baseline NT-proBNP (HR: 1.21; 95% CI: 1.11-1.32; P<0.0001). These results suggest that NT-proBNP is a strong and specific biomarker for mortality in older adults independent of current health status, even in those with clinically-defined normal NT-proBNP.

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