Frailty and the risk of dementia: is the association explained by shared environmental and genetic factors?

Abstract Background Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association. Methods The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41–97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment. Results A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age. Conclusions A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia.

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The Prevalence of Frailty in Cancer Patients and Mortality Prediction With a Novel Frailty Index Based Clinical Algorithm-A Multicenter, Prospective, Observational Study

10.21203/rs.3.rs-34820/v1 ◽

2020 ◽

Author(s):

Xi Jin ◽

Yue Ren ◽

Li Shao ◽

Zengqing Guo ◽

Chang Wang ◽

...

Keyword(s):

Cancer Patients ◽

Frailty Index ◽

National Level ◽

Laboratory Data ◽

Mortality Prediction ◽

Prediction Algorithm ◽

Tumor Type ◽

Risk Of Death ◽

Increased Risk ◽

Chinese Cancer Patients

Abstract Purpose To investigate the prediction capacity and status of frailty in Chinese cancer patients in national level, through establishing a novel prediction algorithm. Methods The percentage of frailty in different ages, provinces and tumor type groups of Chinese cancer patients were revealed. The predictioncapacity of frailty on mortality of Chinese cancer patients was analyzed by FI-LAB that is composed of routine laboratory data from accessible blood test and calculated as the ratio of abnormal factors in 22 variables. Establishment of a novel algorithm MCP(mortality of cancer patients)to predict the five-year mortality in Chinese cancer patients was accomplished and its prediction capacity was tested in the training and validation sets using ROC analysis. ResultsWe found that the increased risk of death in cancer patients can be successfully identified through FI-LAB. The univariable and multivariable Cox regression were used to evaluate the effect of frailty on death. In the 5-year follow-up, 20.6% of the 2959 participants (age = 55.8 ± 11.7 years; 43.5% female) were dead while the mean FI-LAB score in baseline was 0.23 (standard deviation = 0.13; range = 0 to 0.73).Frailty (after adjusting for gender, age, and other confounders) could be directly correlated with increased risk of death, with a hazard ratio of 12.67 (95% confidence interval CI: 7.19, 22.31) in comparison with those without frailty. In addition, MCP algorithm presented an area under the ROC (AUC) of 0.691 (95% CI: 0.659-0.684) and 0.648 (95% CI: 0.613-0.684) in the training and validation set, respectively. Conclusion Frailty is common in cancer patients and FI-LAB has high prediction capacity on mortality. The MCP algorithm is a good supplement for frailty evaluation and mortality prediction in cancer patients.

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Acute Coronary Syndrome in Idiopathic Inflammatory Myopathies: A Population-based Study

The Journal of Rheumatology ◽

10.3899/jrheum.181248 ◽

2019 ◽

Vol 46 (11) ◽

pp. 1509-1514 ◽

Cited By ~ 1

Author(s):

Valérie Leclair ◽

John Svensson ◽

Ingrid E. Lundberg ◽

Marie Holmqvist

Keyword(s):

Acute Coronary Syndrome ◽

General Population ◽

Incidence Rate ◽

Competing Risk ◽

First Year ◽

Idiopathic Inflammatory Myopathies ◽

Inflammatory Myopathies ◽

Risk Of Death ◽

Coronary Syndrome ◽

Increased Risk

Objective.Evidence suggests an increased risk of cardiovascular (CV) diseases, including acute coronary syndrome (ACS), in idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the risk of ACS in an incident IIM cohort compared to the general Swedish population.Methods.A cohort of 655 individuals with incident IIM and 6813 general population comparators were identified from national registries. IIM subjects were diagnosed from 2002 to 2011. Followup started at IIM diagnosis and corresponding date in the general population. ACS, CV comorbidities, and CV risk factors were defined using International Classification of Diseases codes. Incidence rates including 95% CI were calculated. Cox proportional hazards models were used to compare the risk of ACS in patients with IIM and the general population. The competing risk of death was accounted for using competing risk regression models.Results.The incidence rate of ACS in IIM was higher than in the general population, particularly within the first year of diagnosis and in older individuals. The overall ACS incidence rate in IIM was 15.6 (95% CI 11.7–20.4) per 1000 person-years, with an HR of 2.4 (95% CI 1.8–3.2) compared with the general population. When accounting for the competing risk of death, the risk of ACS in IIM remained increased with a cumulative incidence of 7% at 5 years compared to 3.3% in the general population.Conclusion.IIM individuals are at higher risk of ACS, particularly within the first year after diagnosis.

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THE EFFECTS OF FRAILTY, POLYPHARMACY, AND COGNITION ON HEALTH OUTCOMES: A STUDY ON INTERRAI RESIDENTIAL CARE DATA

Innovation in Aging ◽

10.1093/geroni/igz038.330 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S86-S86

Author(s):

Macy Zou ◽

Ronald Kelly ◽

Betty Chinda ◽

Mckenzie Braley ◽

Tony Zhang ◽

...

Keyword(s):

Older Adults ◽

Health Outcomes ◽

Residential Care ◽

Frailty Index ◽

Interactive Effects ◽

Deficit Accumulation ◽

Emergency Visits ◽

Ongoing Research ◽

Risk Of Death ◽

Increased Risk

Abstract Frailty Index (FI), polypharmacy and cognition status are significant health concerns in older adults. We conducted this study to investigate the interplay of frailty, polypharmacy, and cognition, in determining health outcomes. InterRAI Residential Care (RAI-RC MDS2.0) data were retrieved from residential care homes in Surrey, BC, Canada. Older residents (65+ years) who had RAI-RC records between 2016 and 2018 were used in the analysis (n=976). A deficit accumulation-based FI was generated using 36 variables. Information on polypharmacy and cognition were obtained by accounting the total number of medications and the cognitive performance scale. Information on falls, emergency visits, and mortality were followed. Multivariate Cox proportional hazard models were used to examine the effects of these variables on different outcomes. The FI showed a near Gaussian distribution (median= 0.370 mean= 0.372 SD= 0.143), and increased linearly with age on a logarithm scale (R=0.75, p<0.001). Residents with cognitive impairment showed a higher level of the FI (KW= 863.3, p<0.001). A higher FI was associated with an increased risk of death (HR=15.2 p=0.006) and emergency visits (HR=2.72 p=0.048), adjusting for age, sex, medications, and education levels. Frailty, polypharmacy, and cognition levels are associated and have interactive effects on health outcomes. Ongoing research is to validate the findings with large samples in different health settings, and to understand the underlying processes of the effect. The close relationships between frailty, polypharmacy, and cognition with health outcomes call for effective integrated strategies for healthcare of older adults with multiple complex health problems.

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Risk Factors for Myocardial Infarction and Stroke Among Sepsis Survivors: A Competing Risks Analysis

Journal of Intensive Care Medicine ◽

10.1177/0885066619844936 ◽

2019 ◽

Vol 35 (1) ◽

pp. 34-41

Author(s):

Yueh-Che Hsieh ◽

Po-Yang Tsou ◽

Yu-Hsun Wang ◽

Christin Chih-Ting Chao ◽

Wan-Chien Lee ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Hospital Discharge ◽

Preventive Measures ◽

Risk Model ◽

Cerebrovascular Diseases ◽

Competing Risk ◽

Research Database ◽

Risk Of Death ◽

Increased Risk

Objectives: Predictors for post-sepsis myocardial infarction (MI) and stroke are yet to be identified due to the competing risk of death. Methods: This study included all hospitalized patients with sepsis from National Health Insurance Research Database of Taiwan between 2000 and 2011. The primary outcome was the first occurrence of MI and stroke requiring hospitalization within 180 days following hospital discharge from the index sepsis episode. The association between predictors and post-sepsis MI and stroke were analyzed using cumulative incidence competing risk model that controlled for the competing risk of death. Results: Among 42 316 patients with sepsis, 1012 (2.4%) patients developed MI and stroke within 180 days of hospital discharge. The leading 5 predictors for post-sepsis MI and stroke are prior cerebrovascular diseases (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.74-2.32), intra-abdominal infection (HR: 1.94, 95% CI: 1.71-2.20), previous MI (HR: 1.81, 95% CI: 1.53-2.15), lower respiratory tract infection (HR: 1.62, 95% CI: 1.43-1.85), and septic encephalopathy (HR: 1.61, 95% CI: 1.26-2.06). Conclusions: Baseline comorbidities and sources of infection were associated with an increased risk of post-sepsis MI and stroke. The identified risk factors may help physicians select a group of patients with sepsis who may benefit from preventive measures, antiplatelet treatment, and other preventive measures for post-sepsis MI and stroke.

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Respiratory-related death in individuals with incident asthma and COPD: a competing risk analysis

BMC Pulmonary Medicine ◽

10.1186/s12890-022-01823-4 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Alicia V. Gayle ◽

Cosetta Minelli ◽

Jennifer K. Quint

Keyword(s):

Causes Of Death ◽

Smoking Status ◽

Excess Risk ◽

Competing Risk ◽

Practice Research ◽

Mortality Data ◽

Clinical Practice Research Datalink ◽

Risk Of Death ◽

Increased Risk ◽

Competing Risk Models

Abstract Background Distinguishing between mortality attributed to respiratory causes and other causes among people with asthma, COPD, and asthma-COPD overlap (ACO) is important. This study used electronic health records in England to estimate excess risk of death from respiratory-related causes after accounting for other causes of death. Methods We used linked Clinical Practice Research Datalink (CPRD) primary care and Office for National Statistics mortality data to identify adults with asthma and COPD from 2005 to 2015. Causes of death were ascertained using death certificates. Hazard ratios (HR) and excess risk of death were estimated using Fine-Gray competing risk models and adjusting for age, sex, smoking status, body mass index and socioeconomic status. Results 65,021 people with asthma and 45,649 with COPD in the CPRD dataset were frequency matched 5:1 with people without the disease on age, sex and general practice. Only 14 in 100,000 people with asthma are predicted to experience a respiratory-related death up to 10 years post-diagnosis, whereas in COPD this is 98 in 100,000. Asthma is associated with an 0.01% excess incidence of respiratory related mortality whereas COPD is associated with an 0.07% excess. Among people with asthma-COPD overlap (N = 22,145) we observed an increased risk of respiratory-related death compared to those with asthma alone (HR = 1.30; 95% CI 1.21–1.40) but not COPD alone (HR = 0.89; 95% CI 0.83–0.94). Conclusions Asthma and COPD are associated with an increased risk of respiratory-related death after accounting for other causes; however, diagnosis of COPD carries a much higher probability. ACO is associated with a lower risk compared to COPD alone but higher risk compared to asthma alone.

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More random motor activity fluctuations predict incident frailty, disability, and mortality

Science Translational Medicine ◽

10.1126/scitranslmed.aax1977 ◽

2019 ◽

Vol 11 (516) ◽

pp. eaax1977 ◽

Cited By ~ 4

Author(s):

Peng Li ◽

Andrew S. P. Lim ◽

Lei Gao ◽

Chelsea Hu ◽

Lei Yu ◽

...

Keyword(s):

Motor Activity ◽

Sex Education ◽

The Elderly ◽

Prognostic Information ◽

Risk Of Death ◽

Temporal Correlations ◽

Increased Risk ◽

Temporal Structures ◽

Elderly Cohort

Mobile healthcare increasingly relies on analytical tools that can extract meaningful information from ambulatory physiological recordings. We tested whether a nonlinear tool of fractal physiology could predict long-term health consequences in a large, elderly cohort. Fractal physiology is an emerging field that aims to study how fractal temporal structures in physiological fluctuations generated by complex physiological networks can provide important information about system adaptability. We assessed fractal temporal correlations in the spontaneous fluctuations of ambulatory motor activity of 1275 older participants at baseline, with a follow-up period of up to 13 years. We found that people with reduced temporal correlations (more random activity fluctuations) at baseline had increased risk of frailty, disability, and all-cause death during follow-up. Specifically, for 1-SD decrease in the temporal activity correlations of this studied cohort, the risk of frailty increased by 31%, the risk of disability increased by 15 to 25%, and the risk of death increased by 26%. These incidences occurred on average 4.7 years (frailty), 3 to 4.2 years (disability), and 5.8 years (death) after baseline. These observations were independent of age, sex, education, chronic health conditions, depressive symptoms, cognition, motor function, and total daily activity. The temporal structures in daily motor activity fluctuations may contain unique prognostic information regarding wellness and health in the elderly population.

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Excess mortality in Italy: Should we care about low influenza vaccine uptake?

Scandinavian Journal of Public Health ◽

10.1177/1403494817720102 ◽

2017 ◽

Vol 46 (2) ◽

pp. 170-174 ◽

Cited By ~ 3

Author(s):

Francia Fausto ◽

Pandolfi Paolo ◽

Odone Anna ◽

Signorelli Carlo

Keyword(s):

Excess Mortality ◽

Local Level ◽

Frailty Index ◽

Age Distribution ◽

The Elderly ◽

Vaccine Uptake ◽

Elderly Subjects ◽

Mortality Data ◽

Risk Of Death ◽

Increased Risk

Aims: The aims of this study were to explore 2015 mortality data further and to assess excess deaths’ determinants. Methods: We analysed data from a large metropolitan area in the north of Italy, the city of Bologna. We took advantage of a comprehensive local-level database and merged three different data sources to analitically explore reported 2014–2015 excess mortality and its determinants. Effect estimates were derived from multivariable Poisson regression analysis, according to vaccination status and frailty index. Results: We report 9.8% excess mortality in 2015 compared to 2014, with seasonal and age distribution patterns in line with national figures. All-cause mortality in the elderly population is 36% higher (risk ratio [RR]=1.36, 95% confidence interval [CI] 1.27–1.45) in subjects not vaccinated against seasonal flu compared to vaccinated subjects, with risk of death for influenza or pneumonia being 43% higher (RR=1.43, 95% CI 1.02–2.00) in unvaccinated subjects. Conclusions: Reported excess mortality’s determinants in Italy should be further explored. Elderly subjects not vaccinated against the flu appear to have increased risk of all-cause and cause-specific mortality compared to vaccinated subjects after accounting for possible confounders. Our findings raise awareness of the need to promote immunisation against the flu among elder populations and offer insights to plan and implement effective public-health interventions.

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Retinal Vascular Measures from Diabetes Retinal Screening Photographs and Risk of Incident Dementia in Type 2 Diabetes: A GoDARTS Study

10.1101/2020.11.15.20230490 ◽

2020 ◽

Author(s):

Alexander SF Doney ◽

Aditya Nar ◽

Yu Huang ◽

Emanuele Trucco ◽

Tom MacGillivray ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fractal Dimension ◽

Competing Risk ◽

Imaging Biomarkers ◽

Prevention Strategies ◽

Risk Of Death ◽

Increased Risk ◽

Patients With Diabetes ◽

Reduced Risk

AbstractObjectivePatients with diabetes have an increased risk of dementia. Improved prediction of dementia is an important goal in developing future prevention strategies. Diabetic retinopathy screening (DRS) photographs may be a convenient source of imaging biomarkers of brain health. We therefore investigated the association of retinal vascular measures (RVMs) from DRS photographs in patients with type 2 diabetes with dementia risk.Research Design and MethodsRVMs were obtained from 6,111 patients in the GoDARTS bioresource using VAMPIRE software. Their association, independent of Apo E4 genotype and clinical parameters, was determined for incident all cause dementia (ACD) and separately Alzheimer’s dementia (AD) and vascular dementia (VD). We used Cox’s proportional hazards with competing risk of death without dementia. The potential value of RVMs to increase the accuracy of risk prediction was evaluated.ResultsIncreased retinal arteriolar fractal dimension associated with increased risk of ACD (csHR 1.17; 1.08-1.26) and AD (HR 1.33; 1.16-1.52), whereas increased venular fractal dimension (FDV) was associated with reduced risk of AD (csHR 0.85; 0.74-0.96). Conversely, FDV was associated with increased risk of VD (csHR 1.22; 1.07-1.40). Wider arteriolar calibre was associated with a reduced risk of ACD (csHR 0.9; 0.83-0.98) and wider venular calibre was associated with a reduced risk of AD (csHR 0.87; 0.78-0.97). Accounting for competing risk did not substantially alter these findings. RVMs significantly increased the accuracy of prediction.ConclusionsConventional DRS photographs could enhance stratifying patients with diabetes at increased risk of dementia facilitating the development of future prevention strategies.

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Association Between Excess Leisure Sedentary Time and Risk of Stroke in Young Individuals

Stroke ◽

10.1161/strokeaha.121.034985 ◽

2021 ◽

Author(s):

Raed A. Joundi ◽

Scott B. Patten ◽

Jeanne V.A. Williams ◽

Eric E. Smith

Keyword(s):

Sedentary Time ◽

Cox Regression ◽

Canadian Community Health Survey ◽

Competing Risk ◽

Sensitivity Analyses ◽

Risk Of Death ◽

Increased Risk ◽

Community Health Survey

Background and Purpose: The association between physical activity (PA) and lower risk of stroke is well established, but the relationship between leisure sedentary time and stroke is less well studied. Methods: We used 9 years of the Canadian Community Health Survey between 2000 and 2012 to create a cohort of healthy individuals without prior stroke, heart disease, or cancer. We linked to hospital records to determine subsequent hospitalization or emergency department visit for stroke until December 31, 2017. We quantified the association between self-reported leisure sedentary time (categorized as <4, 4 to <6, 6 to <8, and 8+ hours/day) and risk of stroke using Cox regression models and competing risk regression, assessing for modification by PA, age, and sex and adjusting for demographic, vascular, and social factors. Results: There were 143 180 people in our cohort and 2965 stroke events in follow-up. Median time from survey response to stroke was 5.6 years. There was a 3-way interaction between leisure sedentary time, PA, and age. The risk of stroke with 8+ hours of sedentary time was significantly elevated only among individuals <60 years of age who were in the lowest PA quartile (fully adjusted hazard ratio, 4.50 [95% CI, 1.64–12.3]). The association was significant across multiple sensitivity analyses, including adjustment for mood disorders and when accounting for the competing risk of death. Conclusions: Excess leisure sedentary time of 8+ hours/day is associated with increased risk of long-term stroke among individuals <60 years of age with low PA. These findings support efforts to enhance PA and reduce sedentary time in younger individuals.

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Associations of Chronic Kidney Disease With Dementia Before and After Transient Ischemic Attack and Stroke: Population-Based Cohort Study

Neurology ◽

10.1212/wnl.0000000000013205 ◽

2022 ◽

pp. 10.1212/WNL.0000000000013205

Author(s):

Dearbhla M. Kelly ◽

Sarah T. Pendlebury ◽

peter M. rothwell

Keyword(s):

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Sex Education ◽

Population Based ◽

Competing Risk ◽

Minor Stroke ◽

Stroke Severity ◽

Increased Risk ◽

Before And After

Objective:Individuals with chronic kidney disease (CKD) appear to be at increased risk of cognitive impairment, with both vascular and neurodegenerative mechanisms postulated. To explore the vascular hypothesis, we studied the association between CKD and dementia before and after transient ischaemic attack (TIA) and stroke.Methods:In a prospective, population-based cohort study of TIA and stroke (Oxford Vascular Study; 2002-2012), pre-event and new post-event dementia were ascertained through direct patient assessment and follow-up for 5 years, supplemented by review of hospital/primary care records. Associations between pre-event dementia and CKD (defined as an estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73m2) were examined using logistic regression, and between post-event dementia and CKD using Cox and competing risk regression models, adjusted for age, sex, education, stroke severity, prior stroke, white matter disease, diabetes mellitus, and dysphasia.Results:Among 2305 TIA/stroke patients (median [IQR] age, 77 [67-84] years, 1133 [49%] male, 688 [30%] TIA), 1174 (50.9%) had CKD. CKD was associated with both pre-event (odds ratio [OR], 2.04 [95% CI, 1.52–2.72]; P<0.001) and post-event dementia (hazard ratio [HR], 2.01 [95% CI, 1.65–2.44]; P<0.001), but these associations attenuated after adjustment for covariates (OR=0.92 [0.65-1.31]; p=0.65 and HR=1.09 [0.85-1.39]; p=0.50). The results were similar when a competing risk model was used (subdistribution HR [SHR] =1.74 [1.43-2.12; p<0.001, attenuating to 1.01 [0.78-1.33]; p=0.92 with adjustment). CKD was more strongly associated with late (>1 year) post-event dementia (SHR=2.32, 1.70-3.17; p<0.001), particularly after TIA and minor stroke (SHR=3.08, 2.05-4.64; p<0.001), but not significantly so after adjustment (SHR=1.53, 0.90-2.60; p=0.12).Conclusions:In patients with TIA and stroke, CKD was not independently associated with either pre- or post-event dementia, suggesting that renal-specific mechanisms are unlikely to play an important role in aetiology.

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