Characterizing the Individuals Who Regain or Maintain Walking Ability after a Hip Fracture: Insights Into Physical Resilience.

OBJECTIVES: Maintaining walking ability is key to healthy aging. Hip fractures often lead to declined walking ability. This study investigated characteristics of individuals who regained walking ability after a hip fracture, an expression of physical resilience. DESIGN: Register-based cohort study. SETTING AND PARTICIPANTS: A total of 55,467 Swedish residents aged ≥60 years with a first hip fracture (71% women, mean age = 82.3 ± 8) included in the Swedish Hip Fracture Register. METHODS: Information about diseases, medications, and socioeconomic (SES) factors came from registers. Individuals were classified by prefracture walking ability (independent or assisted walking) and whether their walking ability 4 months post-fracture was maintained (physical resilience or nonresilience). Cluster analyses were conducted among individuals who maintained their walking ability to assess different physical resilience profiles. RESULTS: At baseline, 38,493 individuals walked independently (69%), and 16,982 were assisted walkers. Half of the independent walkers maintained their walking ability 4 months post-fracture. Among them, 3 clusters were identified: a "Low SES, Low Disease" cluster (n = 8580, mean age 81.1 ± 7.5); a "High SES, Low Disease" cluster (n = 7778, mean age 76.7 ± 7.4); and a third "High SES, High Disease" cluster (n = 4320, mean age 77.7 ± 7.4). Sixty percent of the pre-assisted walkers maintained their level of assisted walking ability. Also among them, 3 clusters were identified: a "Low SES-Independent Living" cluster (n = 3077, mean age 85.5 ± 7.1); a second "Care Home" cluster (n = 2912, mean age 87.0 ± 6.5) with a high proportion with dementia diagnosis; and a last "High SES" cluster (n = 4044, mean age 83.0 ± 7.0) with the largest proportion of men. CONCLUSIONS AND IMPLICATIONS: Physical resilience is not characterized by one typical healthy profile, and it is possible to regain walking ability after a hip fracture despite unfavorable prerequisites in 1 domain. A favorable status in one domain may compensate for an unfavorable status in another, for example, a high disease burden in combination with high SES.

Risk of All-Cause Dementia, Alzheimer Disease, and Vascular Dementia in Breast Cancer Survivors: A Longitudinal Register-Based Study.

Background and Objectives: Now more than two-thirds of cancer survivors are aged 65 years or older, but evidence about their long-term health is thin. Cancer and its treatments have been linked to accelerated aging, so there is a concern that aging cancer survivors have an increased risk of age-related diseases, including dementia. Methods: We examined the risk of dementia among 5-year breast cancer survivors using a matched cohort study design. We included breast cancer survivors aged 50 years and older at diagnosis (n = 26,741) and cancer-free comparison participants (n = 249,540). Women eligible for inclusion in the study were those born 1935-1975 and registered in the Swedish Total Population Register between January 1, 1991, and December 31, 2015. We defined breast cancer survivors as women with an initial breast cancer diagnosis between 1991 and 2005 who survived 5 or more years after their first diagnosis. We assessed all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) using International Classification of Diseases codes. Survival analyses were conducted using age-adjusted subdistribution hazard models accounting for competing risk of death. Results: We did not observe an association between breast cancer survivorship and risk of all-cause dementia, AD, or VaD. However, in models stratified by age at cancer diagnosis, women diagnosed with cancer after age 65 years had a higher risk of all-cause dementia (subdistribution hazard ratio [SHR] = 1.30, 95% CI 1.07-1.58), AD (SHR = 1.35, 95% CI 1.05-1.75), and VaD (SHR = 1.64, 95% CI 1.11-2.43) in models adjusted for age, education, and country of origin. Discussion: Older breast cancer survivors who survive cancer have a higher risk for dementia than their peers without a cancer diagnosis, in contrast to earlier studies showing that prevalent or incident cancer is associated with a lower risk of dementia. With the older adult population growing rapidly and because cancer and dementia are 2 of the most common and debilitating diseases among older adults, it is critical that we understand the link between the 2.

Time trends in atrial fibrillation-related stroke during 2001-2020 in Sweden: a nationwide, observational study.

Background: Great efforts have been made to improve stroke prevention in atrial fibrillation (AF) patients. Meanwhile, incidence of AF is increasing, which may affect the share of AF-related stroke on all strokes. We aimed to examine the temporal trends in the incidence of AF-related ischemic stroke between 2001 and 2020, if it varied by use of novel oral anticoagulant drugs (NOAC), and if the relative risk of ischemic stroke associated with AF changed over time. Methods: Data from the total Swedish population aged ≥70 years during the period 2001-2020 were used. Annual incidence rate (IR) was calculated for overall and AF-related ischemic stroke which was defined as first-ever ischemic stroke with AF diagnosed up to 5 years before, on the same day, or within 2 months after the stroke event. Cox regression models were performed to examine if the hazard ratio (HR) between AF and stroke changed over time. Findings: While IR of ischemic strokes declined during 2001-2020, IR of AF-related ischemic stroke remained stable between 2001 and 2010 but showed a consistent decline between 2010 and 2020. The HR of ischemic stroke within 3 years from an AF diagnosis came down from 2.39 (95% confidence interval: 2.31-2.48) to 1.54 (1.48-1.61) over the study period, which was largely explained by a substantial increase in the use of NOAC among AF patients after 2012. Yet, by the end of 2020, 24% of all ischemic strokes had a preceding or concurrent AF diagnosis, which is slightly higher than in 2001. Interpretation: Even though both the absolute and relative risk of AF-related ischemic stroke declined over the past 20 years, every fourth ischemic stroke in 2020 still had a preceding or concurrent AF diagnosis. This represents a great potential for future gains in stroke prevention among AF patients. Funding: Swedish Research Council and Loo and Hans Osterman Foundation for Medical Research.

Elevated Uric Acid Is Associated With New-Onset Atrial Fibrillation: Results From the Swedish AMORIS Cohort.

Background The role of uric acid is gaining increasing importance in the evaluation of cardiovascular disease, but its relationship with atrial fibrillation (AF) is unclear. This study aims to investigate the association between uric acid levels and risk of new-onset AF. Methods and Results A total of 339 604 individuals 30 to 60 years of age and free from cardiovascular disease at baseline (1985-1996) in the Swedish AMORIS (Apolipoprotein-Mortality Risk) cohort were followed until December 31, 2019 for incident AF. Cox regression models were used to examine the association between uric acid and AF, adjusting for potential confounders and stratifying by incident cardiovascular disease. Over a mean follow-up of 25.9 years, 46 516 incident AF cases occurred. Compared with the lowest uric acid quartile, each of the upper 3 quartiles were associated with an increased risk of AF in a dose-response manner. Adjusted hazard ratios were 1.09 (95% CI, 1.06-1.12) for second quartile, 1.19 (95% CI, 1.16-1.23) for third quartile, and 1.45 (95% CI, 1.41-1.49) for fourth quartile. The association was similar among individuals with and without incident hypertension, diabetes, heart failure, or coronary heart disease. The dose-response pattern was further supported in a subsample of individuals with repeated measurements of uric acid. Conclusions Elevated uric acid was associated with an increased risk of AF, not only among people with cardiovascular disease and cardiovascular risk factors but also among those without. Future investigations are needed to examine whether lowering uric acid is relevant for AF prevention.

Trends in Frailty Between 1990 and 2020 in Sweden Among 75-, 85-, and 95-Year-Old Women and Men: A Nationwide Study from Sweden.

BACKGROUND: Aging is the primary risk factor for frailty, which is defined as an inability to respond to acute or chronic stressors. Individuals are living longer with greater multimorbidity, but there is a paucity of evidence examining frailty across birth cohorts and ages. METHODS: We investigated frailty prevalence and its association with mortality at ages 75, 85, and 95 in the 1895-1945 birth cohorts in Sweden with data from population registries. Frailty was assessed with the Hospital Frailty Risk Score (HFRS). RESULTS: We observed that frailty increased with increasing age and that it has become more common in more recent birth cohorts. At age 75, the percent frail in the Total Population Register increased from 1.1% to 4.6% from birth cohorts 1915-1945, corresponding to calendar years 1990-2020. At age 85, the percentage of frail increased from 3.5% to 11.5% from birth cohorts 1905-1935, and at age 95 from birth cohorts 1895-1925, from 4.7% to 18.7%. Our results show that the increase was primarily driven by an increase in the distribution of individuals with scores in the highest quartile of HFRS, while the bottom 3 quartiles remained relatively stable across birth cohorts. Women accounted for a greater distribution of the overall population and frail population, though these disparities decreased over time. Despite increasing levels of frailty, the relationship between frailty and mortality did not change over time, nor did it differ by sex. CONCLUSION: Increased frailty with improved survival points to a chronic condition that could be intervened upon.

Lipid levels in midlife and risk of atrial fibrillation over 3 decades-Experience from the Swedish AMORIS cohort: A cohort study.

BACKGROUND: The role of cholesterol levels in the development of atrial fibrillation (AF) is still controversial. In addition, whether and to what extent apolipoproteins are associated with the risk of AF is rarely studied. In this study, we aimed to investigate the association between blood lipid levels in midlife and subsequent risk of new-onset AF. METHODS AND FINDINGS: This population-based study included 65,136 individuals aged 45 to 60 years without overt cardiovascular diseases (CVDs) from the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort. Lipids were measured in 1985 to 1996, and individuals were followed until December 31, 2019 for incident AF (i.e., study outcome). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age, sex, and socioeconomic status. Over a mean follow-up of 24.2 years (standard deviation 7.5, range 0.2 to 35.9), 13,871 (21.3%) incident AF cases occurred. Higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were statistically significantly associated with a lower risk of AF during the first 5 years of follow-up (HR = 0.61, 95% CI: 0.41 to 0.99, p = 0.013; HR = 0.64, 95% CI: 0.45 to 0.92, p = 0.016), but not thereafter (HR ranging from 0.94 [95% CI: 0.89 to 1.00, p = 0.038] to 0.96 [95% CI: 0.77 to 1.19, p > 0.05]). Lower levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) and higher triglycerides (TG)/HDL-C ratio were statistically significantly associated with a higher risk of AF during the entire follow-up (HR ranging from 1.13 [95% CI: 1.07 to 1.19, p < 0.001] to 1.53 [95% CI: 1.12 to 2.00, p = 0.007]). Apolipoprotein B (ApoB)/ApoA-I ratio was not associated with AF risk. The observed associations were similar among those who developed incident heart failure (HF)/coronary heart disease (CHD) and those who did not. The main limitations of this study include lack of adjustments for lifestyle factors and high blood pressure leading to potential residual confounding. CONCLUSIONS: High TC and LDL-C in midlife was associated with a lower risk of AF, but this association was present only within 5 years from lipid measurement and not thereafter. On the contrary, low HDL-C and ApoA-I and high TG/HDL-C ratio were associated with an increased risk of AF over almost 35 years of follow-up. ApoB/ApoA-I ratio was not associated with AF risk.

The association of apolipoproteins with later-life all-cause and cardiovascular mortality: a population-based study stratified by age.

Midlife lipid levels are important predictors of cardiovascular diseases, yet their association with mortality in older adults is less clear. We aimed to (1) identify lipid profiles based on cholesterol, triglycerides, and apolipoproteins using cluster analysis, and (2) investigate how lipid profiles and lipid levels at different ages are associated with later-life all-cause and cardiovascular mortality. We used data from 98,270 individuals in the Swedish AMORIS cohort who had blood measurements between 1985-1996 and were followed until 2012. Over the follow-up (mean 18.0 years), 30,730 (31.3%) individuals died. Three lipid profiles were identified. Compared with reference profile, a high lipid profile (low ApoA-I and high total cholesterol (TC), triglycerides, ApoB, and ApoB/ApoA-I ratio) at ages 39-59 or 60-79 was associated with higher all-cause mortality. A high lipid profile at ≥ 80 years, however, did not confer higher mortality. For the specific markers, high TC (≥ 7.25 mmol/L) was associated with higher all-cause mortality in ages 39-59 but lower mortality in ages 60-79 and ≥ 80. Low ApoA-I (< 1.28 g/L) and high ApoB/ApoA-I ratio (≥ 1.18), on the other hand, were associated with higher cardiovascular mortality regardless of age at lipid measurement, highlighting their potential relevance for survival in both young and older individuals.

From Normal Cognition to Cognitive Impairment and Dementia: Impact of Orthostatic Hypotension.

[Figure: see text].

Cerebral Small Vessel Disease Associated With Atrial Fibrillation Among Older Adults: A Population-Based Study.

Background and Purpose: Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults. Methods: Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001­2004) and follow-ups (2004­2007 and 2007­2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models. Results: At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (ß coefficient=0.45 [95% CI, 0.04­0.86]) and lateral ventricular volume (0.58 [0.13­1.02]). There was no significant association of AF with annual changes in perivascular spaces number (ß coefficient=0.53 [95% CI, −0.27 to 1.34]) or lacune number (−0.01 [−0.07 to 0.05]). Conclusions: Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.

Blood-Based Biomarkers and Long-term Risk of Frailty-Experience From the Swedish AMORIS Cohort.

BACKGROUND: Frailty is associated with reduced quality of life, poor health outcomes, and death. Past studies have investigated how specific biomarkers are associated with frailty but understanding biomarkers in concert with each other and the associated risk of frailty is critical for clinical application. METHODS: Using a sample aged ≥59 years at baseline from the Swedish AMORIS (Apolipoprotein MOrtality RISk) cohort (n = 19 341), with biomarkers measured at baseline (1985-1996), we conducted latent class analysis with 18 biomarkers and used Cox models to determine the association between class and frailty and all-cause mortality. RESULTS: Four classes were identified. Compared to the largest class, the Reference class (81.7%), all other classes were associated with increased risk of both frailty and mortality. The Anemia class (5.8%), characterized by comparatively lower iron markers and higher inflammatory markers, had hazard ratio (HR) = 1.54, 95% confidence interval (CI) 1.38, 1.73 for frailty and HR = 1.76, 95% CI 1.65, 1.87 for mortality. The Diabetes class (6.5%) was characterized by higher glucose and fructosamine, and had HR = 1.59, 95% CI 1.43, 1.77 for frailty and HR = 1.74, 95% CI 1.64, 1.85 for mortality. Finally, the Liver class (6.0%), characterized by higher liver enzyme levels, had HR = 1.15, 95% CI 1.01, 1.30 for frailty and HR = 1.40, 95% CI 1.31, 1.50 for mortality. Sex-stratified analyses did not show any substantial differences between men and women. CONCLUSIONS: Distinct sets of commonly available biomarkers were associated with development of frailty and monitoring these biomarkers in patients may allow for earlier detection and possible prevention of frailty, with the potential for improved quality of life.

Tracing temporal trends in dementia incidence over 25 years in central Stockholm, Sweden.

INTRODUCTION: Recent reports from high-income countries have suggested a declining incidence of dementia. METHODS: Trends in dementia incidence over 25 years among people ≥75 years of age were examined using two population-based cohort studies: the Kungsholmen Project (KP, n = 1473, 1987-1998) and the Swedish National study on Aging and Care in Kungsholmen (SNAC-K, n = 1746, 2001-2013). RESULTS: We identified 440 (29.9%) and 388 (22.2%) incident dementia cases in the KP and SNAC-K cohorts, respectively. The incidence of dementia declined by 30% (hazard ratio [HR] = 0.70; 95% confidence interval [CI] 0.61-0.80) during the second decade. Adjustment of education, psychosocial working conditions, lifestyle, and vascular diseases did not substantially change the results (HR = 0.77, 95% CI 0.65-0.90). This decline was observed particularly in women and people with elementary education. DISCUSSION: Our study provides direct evidence of a declining trend in dementia incidence. Improved cognitive reserve and cardiovascular health could partially explain the decline.

Atrial fibrillation, antithrombotic treatment, and cognitive aging: A population-based study.

OBJECTIVE: To examine the association of atrial fibrillation (AF) with cognitive decline and dementia in old age, and to explore the cognitive benefit of antithrombotic treatment in patients with AF. METHODS: This population-based cohort study included 2,685 dementia-free participants from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001-2004 to 2010-2013. AF was ascertained from clinical examination, ECG, and patient registry. Global cognitive function was assessed using the Mini-Mental State Examination. We followed the DSM-IV criteria for the diagnosis of dementia, the NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences) criteria for vascular dementia, and the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer disease. Data were analyzed using multiple linear mixed-effects and Cox regression models. RESULTS: We identified 243 participants (9.1%) with AF at baseline. During the 9-year follow-up period, 279 participants (11.4%) developed AF and 399 (14.9%) developed dementia. As a time-varying variable, AF was significantly associated with a faster annual Mini-Mental State Examination decline (ß coefficient = -0.24, 95% confidence interval [CI]: -0.31 to -0.16) and an increased hazard ratio (HR) of all-cause dementia (HR = 1.40, 95% CI: 1.11-1.77) and vascular and mixed dementia (HR = 1.88, 95% CI: 1.09-3.23), but not Alzheimer disease (HR = 1.33, 95% CI: 0.92-1.94). Among people with either prevalent or incident AF, use of anticoagulant drugs, but not antiplatelet treatment, was associated with a 60% decreased risk of dementia (HR = 0.40, 95% CI: 0.18-0.92). CONCLUSION: AF is associated with a faster global cognitive decline and an increased risk of dementia in older people. Use of anticoagulant drugs may reduce dementia risk in patients with AF.

Atrial Fibrillation, Cognitive Decline, and Dementia: an Epidemiologic Review.

PURPOSE OF REVIEW: Atrial fibrillation (AF) and dementia are both prevalent diseases in aging societies, which exert a great economic burden worldwide. Although a handful of epidemiologic studies have indicated that AF is independently associated with faster cognitive decline and a higher risk of dementia, there is still a lack of comprehensive understanding of the observed association. In this review, we summarize evidence from major epidemiologic studies concerning AF-related cognitive decline and dementia, the potential mechanisms underlying their association, and the cognitive benefits of treatment options. RECENT FINDINGS: A large majority of population-based longitudinal studies have consistently shown an independent association of AF with cognitive decline and dementia with varying effect sizes, depending on the age of the study population and the presence of clinical stroke. The underlying pathways linking AF to cognitive phenotypes may involve systemic inflammation, cerebral hypoperfusion, and cerebral small vessel disease and microemboli. However, current evidence is insufficient to support the potential benefits of AF treatment in reducing risk of cognitive decline and dementia. SUMMARY: Current epidemiologic research suggests that AF contributes to cognitive decline and dementia, independent of a history of stroke. Further work is warranted to elucidate the potential mechanisms underlying this association, and more well-designed studies are needed to explore the possible cognitive benefits of different therapeutic options in patients with AF.

Atrial fibrillation and use of antithrombotic medications in older people: A population-based study.

BACKGROUND: Trends in the use of antithrombotic drugs in elderly patients with atrial fibrillation (AF) are largely unknown. We estimated the prevalence of AF in an older population, and examined whether use of anticoagulant and antiplatelet drugs in older AF patients has changed over time. METHODS: Data from the population-based Swedish National study on Aging and Care in Kungsholmen (n=3363, age≥60years, 64.9% women) were used (2001-2004 and 2007-2010). AF cases were identified through 12-lead electrocardiogram, physician examinations, and patient register records (ICD-10 code I48). We used the CHADS2 and CHA2DS2-VASc scores to estimate stroke risk, and an incomplete HAS-BLED score to estimate bleeding risk. RESULTS: At baseline (2001-2004), 328 persons (9.8%) were ascertained to have AF. The prevalence of AF increased significantly with age from 2.8% in people aged 60-66years to 21.2% in those ≥90years, and was more common in men than in women (11.2% vs. 9.0%). Among AF patients with CHADS2 score ≥2 at baseline, 25% were taking anticoagulant drugs and 54% were taking antiplatelet drugs. High bleeding risk was significantly associated with not using anticoagulant drugs in AF patients (multi-adjusted OR=2.50, p=0.015). Between 2001-2004 and 2007-2010, use of anticoagulant drugs increased significantly, especially in AF patients with CHA2DS2-VASc score ≥2 (23% vs. 33%, p=0.008) and in those with HAS-BLED score <3 (32% vs. 53%, p=0.004). CONCLUSION: AF is common among old people. The use of anticoagulant drugs increased over time in AF patients, yet still two-thirds of those with high stroke risk remained untreated.

Characterization of a bifunctional xylanase/endoglucanase from yak rumen microorganisms.

A new gene, RuCelA, encoding a bifunctional xylanase/endoglucanase, was cloned from a metagenomic library of yak rumen microorganisms. RuCelA showed activity against xylan and carboxymethylcellulose (CMC), suggesting bifunctional xylanase/endoglucanase activity. The optimal conditions for xylanase and endoglucanase activities were 65°C, pH 7.0 and 50°C, pH 5.0, respectively. In addition, the presence of Co(+) and Co(2+) can greatly improve RuCelA's endoglucanase activity, while inhibits its xylanase activity. Further examination of substrate preference showed a higher activity against barley glucan and lichenin than against xylan and CMC. Using xylan and barley glucan as substrates, RuCelA displayed obvious synergistic effects with ß-1,4-xylosidase and ß-1,4-glucosidase. Generation of soluble oligosaccharides from lignocellulose is the key step in bioethanol production, and it is greatly notable that RuCelA can produce xylo-oligosaccharides and cello-oligosaccharides in the continuous saccharification of pretreated rice straw, which can be further degraded into fermentable sugars. Therefore, the bifunctional RuCelA distinguishes itself as an ideal candidate for industrial applications.