A subset of older adults present post mortem with Alzheimer disease (AD) pathologic features but without any significant clinical manifestation of dementia. Vascular endothelial growth factor (VEGF) ...has been implicated in staving off AD-related neurodegeneration.
To evaluate whether VEGF levels are associated with brain aging outcomes (hippocampal volume and cognition) and to further evaluate whether VEGF modifies relations between AD biomarkers and brain aging outcomes.
Biomarker analysis using neuroimaging and neuropsychological outcomes from the Alzheimer's Disease Neuroimaging Initiative. This prospective longitudinal study across North America included individuals with normal cognition (n = 90), mild cognitive impairment (n = 130), and AD (n = 59) and began in October 2004, with follow-up ongoing.
Cerebrospinal fluid VEGF was cross-sectionally related to brain aging outcomes (hippocampal volume, episodic memory, and executive function) using a general linear model and longitudinally using mixed-effects regression. Alzheimer disease biomarker (cerebrospinal fluid β-amyloid 42 and total tau)-by-VEGF interactions evaluated the effect of VEGF on brain aging outcomes in the presence of enhanced AD biomarkers.
Vascular endothelial growth factor was associated with baseline hippocampal volume (t277 = 2.62; P = .009), longitudinal hippocampal atrophy (t858 = 2.48; P = .01), and longitudinal decline in memory (t1629 = 4.09; P < .001) and executive function (t1616 = 3.00; P = .003). Vascular endothelial growth factor interacted with tau in predicting longitudinal hippocampal atrophy (t845 = 4.17; P < .001), memory decline (t1610 = 2.49; P = .01), and executive function decline (t1597 = 3.71; P < .001). Vascular endothelial growth factor interacted with β-amyloid 42 in predicting longitudinal memory decline (t1618 = -2.53; P = .01).
Elevated cerebrospinal fluid VEGF was associated with more optimal brain aging in vivo. The neuroprotective effect appeared strongest in the presence of enhanced AD biomarkers, suggesting that VEGF may be particularly beneficial in individuals showing early hallmarks of the AD cascade. Future work should evaluate the interaction between VEGF expression in vitro and pathologic burden to address potential mechanisms.
Multimorbidity occurs in adults of all ages, but the number and complexity of comorbid conditions commonly increase with advancing age such that cardiovascular disease (CVD) in older adults typically ...occurs in a context of multimorbidity. Current clinical practice and research mainly target single disease-specific care that does not embrace the complexities imposed by concurrent conditions. In this paper, emerging concepts regarding CVD in combination with multimorbidity are reviewed, including recommendations for incorporating multimorbidity into clinical decision making, critical knowledge gaps, and research priorities to optimize care of complex older patients.
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The prevalence of frailty (diminished physiologic reserve) and its effect on outcomes for those aged 18 years and older with critical illness is unclear.
We hypothesized greater frailty would be ...associated with subsequent mortality, disability, and cognitive impairment, regardless of age.
At enrollment, we measured frailty using the Clinical Frailty Scale (range, 1 very fit to 7 severely frail). At 3 and 12 months post-discharge, we assessed vital status, instrumental activities of daily living, basic activities of daily living, and cognition. We used multivariable regression to analyze associations between Clinical Frailty Scale scores and outcomes, adjusting for age, sex, education, comorbidities, baseline disability, baseline cognition, severity of illness, delirium, coma, sepsis, mechanical ventilation, and sedatives/opiates.
We enrolled 1,040 patients who were a median (interquartile range) of 62 (53-72) years old and who had a median Clinical Frailty Scale score of 3 (3-5). Half of those with clinical frailty (i.e., Clinical Frailty Scale score ≥5) were younger than 65 years old. Greater Clinical Frailty Scale scores were independently associated with greater mortality (P = 0.01 at 3 mo and P < 0.001 at 12 mo) and with greater odds of disability in instrumental activities of daily living (P = 0.04 at 3 mo and P = 0.002 at 12 mo). Clinical Frailty Scale scores were not associated with disability in basic activities of daily living or with cognition.
Frailty is common in critically ill adults aged 18 years and older and is independently associated with increased mortality and greater disability. Future studies should explore routine screening for clinical frailty in critically ill patients of all ages. Interventions to reduce mortality and disability among patients with heightened vulnerability should be developed and tested. Clinical trial registered with www.clinicaltrials.gov (NCT 00392795 and NCT 00400062).
Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how ...aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults.
Vanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (n=155; age, 72±7 years; 59% male) or mild cognitive impairment (n=115; age, 73±7 years; 57% male). Aortic pulse wave velocity (PWV; meters per second) was quantified from cardiac magnetic resonance. Resting CBF (milliliters per 100 g per minute) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudocontinuous arterial spin labeling magnetic resonance imaging. Linear regression models related aortic PWV to regional CBF, adjusting for age, race/ethnicity, education, Framingham Stroke Risk Profile (diabetes mellitus, smoking, left ventricular hypertrophy, prevalent cardiovascular disease, atrial fibrillation), hypertension, body mass index, apolipoprotein E4 ( APOE ε4) status, and regional tissue volume. Models were repeated testing PWV× APOE ε4 interactions. Sensitivity analyses excluded participants with prevalent cardiovascular disease and atrial fibrillation.
Among participants with normal cognition, higher aortic PWV related to lower frontal lobe CBF (β=-0.43; P=0.04) and higher CVR in the whole brain (β=0.11; P=0.02), frontal lobes (β=0.12; P<0.05), temporal lobes (β=0.11; P=0.02), and occipital lobes (β=0.14; P=0.01). Among APOE ε4 carriers with normal cognition, findings were more pronounced with higher PWV relating to lower whole-brain CBF (β=-1.16; P=0.047), lower temporal lobe CBF (β=-1.81; P=0.004), and higher temporal lobe CVR (β=0.26; P=0.08), although the last result did not meet the a priori significance threshold. Results were similar in sensitivity models. Among participants with mild cognitive impairment, higher aortic PWV related to lower CBF in the occipital lobe (β=-0.70; P=0.02), but this finding was attenuated when participants with prevalent cardiovascular disease and atrial fibrillation were excluded. Among APOE ε4 carriers with mild cognitive impairment, findings were more pronounced with higher PWV relating to lower temporal lobe CBF (β=-1.20; P=0.02).
Greater aortic stiffening relates to lower regional CBF and higher CVR in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer's disease. Central arterial stiffening may contribute to reductions in regional CBF despite preserved cerebrovascular reserve capacity.
Multimorbidity is the most significant condition affecting older adults, and it impacts every component of health care management and delivery. Multimorbidity significantly increases with age. For ...individuals with a diagnosis of cardiovascular disease, multimorbidity has a significant effect on the presentation of the disease and the diagnosis, management, and patient-centered preferences in care. Evidence-based therapeutics have focused on cardiovascular focused morbidity. Over the next 25 years, the proportion of adults aged 65 and older is estimated to increase three-fold. The needs of these patients require a fundamental shift in care from single disease practices to a more patient-centered framework.
It is well known that cardiovascular disease manifests differently in women and men. The underlying causes of these differences during the aging lifespan are less well understood. Sex differences in ...cardiac and vascular phenotypes are seen in childhood and tend to track along distinct trajectories related to dimorphism in genetic factors as well as response to risk exposures and hormonal changes during the life course. These differences underlie sex-specific variation in cardiovascular events later in life, including myocardial infarction, heart failure, ischemic stroke, and peripheral vascular disease. With respect to cardiac phenotypes, females have intrinsically smaller body size-adjusted cardiac volumes and they tend to experience greater age-related wall thickening and myocardial stiffening with aging. With respect to vascular phenotypes, sexual dimorphism in both physiology and pathophysiology are also seen, including overt differences in blood pressure trajectories. The majority of sex differences in myocardial and vascular alterations that manifest with aging seem to follow relatively consistent trajectories from the very early to the very later stages of life. This review aims to synthesize recent cardiovascular aging-related research to highlight clinically relevant studies in diverse female and male populations that can inform approaches to improving the diagnosis, management, and prognosis of cardiovascular disease risks in the aging population at large.
Abstract The population of older adults is expanding rapidly, and aging predisposes to cardiovascular disease. The principle of patient-centered care must respond to the preponderance of cardiac ...disease that now occurs in combination with the complexities of old age. Geriatric cardiology melds cardiovascular perspectives with multimorbidity, polypharmacy, frailty, cognitive decline, and other clinical, social, financial, and psychological dimensions of aging. Although some assume that a cardiologist may instinctively cultivate some of these skills over the course of a career, we assert that the volume and complexity of older cardiovascular patients in contemporary practice warrants a more direct approach to achieve suitable training and a more reliable process of care. We present a rationale and vision for geriatric cardiology as a melding of primary cardiovascular and geriatrics skills, thereby infusing cardiology practice with expanded proficiencies in diagnosis, risks, care coordination, communications, end-of-life, and other competences required to best manage older cardiovascular patients.
ECFS best practice guidelines: the 2018 revision Castellani, Carlo; Duff, Alistair J.A.; Bell, Scott C. ...
Journal of cystic fibrosis,
March 2018, 2018-03-00, 20180301, Letnik:
17, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Developments in managing CF continue to drive dramatic improvements in survival. As newborn screening rolls-out across Europe, CF centres are increasingly caring for cohorts of patients who have ...minimal lung disease on diagnosis. With the introduction of mutation-specific therapies and the prospect of truly personalised medicine, patients have the potential to enjoy good quality of life in adulthood with ever-increasing life expectancy. The landmark Standards of Care published in 2005 set out what high quality CF care is and how it can be delivered throughout Europe. This underwent a fundamental re-write in 2014, resulting in three documents; center framework, quality management and best practice guidelines. This document is a revision of the latter, updating standards for best practice in key aspects of CF care, in the context of a fast-moving and dynamic field.
In continuing to give a broad overview of the standards expected for newborn screening, diagnosis, preventative treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support, this consensus on best practice is expected to prove useful to clinical teams both in countries where CF care is developing and those with established CF centres. The document is an ECFS product and endorsed by the CF Network in ERN LUNG and CF Europe.
Objectives
To determine the prevalence, recognition, co‐occurrence, and recent onset of geriatric syndromes in individuals transferred from the hospital to a skilled nursing facility (SNF).
Design
...Quality improvement project.
Setting
Acute care academic medical center and 23 regional partner SNFs.
Participants
Medicare beneficiaries hospitalized between January 2013 and April 2014 and referred to SNFs (N = 686).
Measurements
Project staff measured nine geriatric syndromes: weight loss, lack of appetite, incontinence, and pain (standardized interview); depression (Geriatric Depression Scale); delirium (Brief Confusion Assessment Method); cognitive impairment (Brief Interview for Mental Status); and falls and pressure ulcers (hospital medical record using hospital‐implemented screening tools). Estimated prevalence, new‐onset prevalence, and common coexisting clusters were determined. The extent to which treating physicians commonly recognized syndromes and communicated them to SNFs in hospital discharge documentation was evaluated.
Results
Geriatric syndromes were prevalent in more than 90% of hospitalized adults referred to SNFs; 55% met criteria for three or more coexisting syndromes. The most‐prevalent syndromes were falls (39%), incontinence (39%), loss of appetite (37%), and weight loss (33%). In individuals who met criteria for three or more syndromes, the most common triad clusters were nutritional syndromes (weight loss, loss of appetite), incontinence, and depression. Treating hospital physicians commonly did not recognize and document geriatric syndromes in discharge summaries, missing 33% to 95% of syndromes present according to research personnel.
Conclusion
Geriatric syndromes in hospitalized older adults transferred to SNFs are prevalent and commonly coexist, with the most frequent clusters including nutritional syndromes, depression, and incontinence. Despite the high prevalence, this clinical information is rarely communicated to SNFs on discharge.
Cerebrospinal fluid (CSF) neurofilament light (NFL) is a protein biomarker of axonal injury. To study whether NFL is associated with diffusion tensor imaging (DTI) measurements of white matter (WM) ...microstructure, Vanderbilt Memory & Aging Project participants with normal cognition (n = 77), early mild cognitive impairment (n = 15), and MCI (n = 55) underwent lumbar puncture to obtain CSF and 3T brain MRI. Voxel-wise analyses cross-sectionally related NFL to DTI metrics, adjusting for demographic and vascular risk factors. Increased NFL correlated with multiple DTI metrics (p-values < 0.05). An NFL × diagnosis interaction (excluding early mild cognitive impairment) on WM microstructure (p-values < 0.05) was detected, with associations strongest among MCI. Multiple NFL × CSF biomarker interactions were detected. Associations between NFL and worse WM metrics were strongest among amyloid-β42–negative, tau-positive, and suspected nonamyloid pathology participants. Findings suggest increased NFL, a biomarker of axonal injury, is correlated with compromised WM microstructure. Results highlight the role of elevated NFL in predicting WM damage in cognitively impaired older adults who are amyloid-negative, tau-positive, or meet suspected nonamyloid pathology criteria.
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