Linda P Fried

Linda P Fried
Columbia University | CU · Mailman School of Public Health

M.D., M.P.H.

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643
Publications
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Publications

Publications (643)
Article
Full-text available
Background We have previously developed and validated a biomarker-based metric of overall health status using Mahalanobis distance (DM) to measure how far from the norm of a reference population (RP) an individual’s biomarker profile is. DM is not particularly sensitive to the choice of biomarkers; however, this makes comparison across studies diff...
Article
Full-text available
Despite its widespread presence in older adults, frailty etiology is still unclear, being associated with dysregulation in diverse physiological systems. Here, we show evidence that frailty emerges from broad loss of homeostasis integrated through complex systems dynamics. Using the NuAge and WHAS cohorts, we calculated Mahalanobis distance-based p...
Preprint
Full-text available
Background: Generalized, biomarker-based metrics of health status have numerous applications in fields ranging from sociology and economics to clinical research. We recently proposed a novel metric of health status based on physiological dysregulation measured as a Mahalanobis distance (DM) among clinical biomarkers. While DM was not particularly s...
Article
Full-text available
Background Gender differences in life expectancy and societal roles have implications for a country's capacity to support its older population. Specifically, the longevity risk associated with longer life expectancy of women, with greater risk of morbidity entails different needs between genders in older age. We aimed to quantify gender differences...
Article
Objectives Public health education must respond to 21st-century public health challenges in an ever-evolving landscape. We describe implementation and educational outcomes of the Columbia University Master of Public Health (MPH) Core (hereinafter, Core) curriculum since its inception. Methods This retrospective evaluation combined 6 years (2013-20...
Article
Full-text available
Frailty is a clinical syndrome often present in older adults and characterized by a heightened vulnerability to stressors. The biological antecedents and etiology of frailty are unclear despite decades of research: frailty is associated with dysregulation in a wide range of physiological systems, but no specific cause has been identified. Here, we...
Article
Frailty in aging marks a state of decreased reserves resulting in increased vulnerability to adverse outcomes when exposed to stressors. This Perspective synthesizes the evidence on the aging-related pathophysiology underpinning the clinical presentation of physical frailty as a phenotype of a clinical syndrome that is distinct from the cumulative-...
Article
Objectives: To investigate the rate and patterns of accumulation of frailty manifestations in relationship to all-cause mortality and whether there is a point in the progression of frailty beyond which the process becomes irreversible and death becomes imminent (a.k.a. point of no return). Design: Longitudinal observational study. Setting: Com...
Article
Audio Interview Interview with Dr. Linda Fried on advances in research on aging and ongoing efforts to provide older Americans with high-quality prevention and care. (12:33)Download Increases in life expectancy necessitate new scientific understanding of how to both extend and enhance health over the course of our longer lives. Accumulated evidence...
Article
With increasing effectiveness of antiretroviral therapy, people with HIV (PWH) are living longer and the prevalence of older PWH continues to increase. Accordingly, PWH are experiencing an increased burden of age-related comorbidities. With this shifting demographic, clinicians and researchers face additional challenges in how to identify, address,...
Article
Background Alcohol consumption causes greater harm in older than younger adults. As the population ages, understanding cross-country and time-varying drinking patterns of older adults is of critical importance. Available evidence relies primarily on ecological data. Methods We harmonized survey data for 179,881 adults age 50+ observed repeatedly b...
Article
Full-text available
Objective The purpose of this consensus statement is to determine the state of the field of loneliness among older people, highlighting key issues for researchers, policymakers and those designing services and interventions. Methods In December 2018, an international meeting on loneliness was held in Belfast with leaders from across the USA and Eu...
Preprint
Full-text available
Frailty is a clinical syndrome often present in older adults and characterized by a heightened vulnerability to stressors. The biological antecedents and etiology of frailty are unclear despite decades of research: frailty is associated with dysregulation in a wide range of physiological systems, but no specific cause has been identified. Here, we...
Article
Background The response to adrenocorticotropic hormone (ACTH) is poorly characterized in old-old adults and may provide insight into the physiologic response to stress. Methods We performed a standard 250 mcg ACTH stimulation test in a home-based substudy of 51 women aged 85-96 years enrolled in the Women’s Health and Aging Study II who were not t...
Article
Full-text available
Objective The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. Methods These recommendations were formed using the GRADE approach, w...
Article
The scientific questions we pursue are shaped by our cultural assumptions and biases, often in ways we are unaware. Here, we argue that modern biases against older adults (ageism) have unconsciously led aging biologists to assume that traits of older individuals are negative and those of younger individuals positive. We illustrate this bias with th...
Article
Frailty is an emerging global health burden, with major implications for clinical practice and public health. The prevalence of frailty is expected to rise alongside rapid growth in the ageing population. The course of frailty is characterised by a decline in functioning across multiple physiological systems, accompanied by an increased vulnerabili...
Article
Frailty syndrome is hypothesized to arise from malfunction in feedback mechanisms among interacting physiological systems. However, empirical evidence to support this hypothesis is not yet available. We present evidence of a feed-forward loop relationship between certain components of the frailty syndrome: body composition, strength and physical pe...
Article
Background: Alcohol consumption in later life has increased in the past decade, and the relationship between alcohol consumption and mortality is controversial. Recent studies suggest little, if any, health benefit to alcohol. Yet most rely on single-time point consumption assessments and minimal confounder adjustments. Methods: We report on 16...
Article
Frailty has long been an important concept in the practice of geriatric medicine and in gerontological research, but integration and implementation of frailty concepts into clinical practice in the United States has been slow. The National Institute on Aging (NIA) Intramural Research Program and the Johns Hopkins Older Americans Independence Center...
Article
Human enhancement technologies are opening tremendous opportunities but also challenges to the core of what it means to be human. We argue that the goal of human enhancement should be to enhance quality of life and well-being not only of individuals but also of the communities they inhabit.
Article
This article reports on the impact of the Experience Corps® (EC) Baltimore program, an intergenerational, school-based program aimed at improving academic achievement and reducing disruptive school behavior in urban, elementary school students in Kindergarten through third grade (K-3). Teams of adult volunteers aged 60 and older were placed in publ...
Article
Background: Physical frailty is a clinical syndrome associated with aging and manifesting as slowness, weakness, reduced physical activity, weight loss, and/or exhaustion. Frail older adults often report that their major problem is "low energy", and there is indirect evidence to support the hypothesis that frailty is a syndrome of dysregulated ene...
Article
Full-text available
Changes in both swallowing and taste commonly occur in advanced age, though the relationship between the two is unknown. This study examined the association between a water swallow screen test and taste identification and intensity rating. Participants included 47 community-dwelling women aged 85–94 years. Participants completed three trials of a w...
Article
Previous studies suggest significant age-associated phenotypic remodeling of circulating immune cells (T and B clymphocytes and monocytes) in older adults, a key feature of immunosenescence. However, longitudinal evidence supporting such remodeling for older individuals is scarce. This study aimed to investigate longitudinal trajectories of circula...
Chapter
Individual biomarkers are often studied as indicators of abnormality, but a complex systems perspective suggests that further insight may be gained by considering biomarker values in the context of others. The concept of homeostasis implies that normal levels of a biomarker may be abnormal in relation to the levels of other biomarkers, and vice ver...
Article
Background: Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult...
Article
Reports on the association between multiple clinical and behavioral health indicators and major health outcomes among older adults are scarce. We prospectively examined concordance with American Cancer Society and American Heart Association disease prevention guidelines in relation to cancer, cardiovascular disease (CVD) and mortality among Cardiov...
Article
The aging process differs in important ways between the sexes, with women living longer but at higher risk for frailty (the male-female health-survival paradox). The underlying biological mechanisms remain poorly understood, but may relate to sex differences in physiological dysregulation patterns. Here, using biomarkers from two longitudinal cohor...
Article
Background Disruption of insulin-like growth factor-I (IGF-I) increases health and lifespan in animal models, though this is unconfirmed in humans. If IGF-I stability indicates homeostasis, the absolute level of IGF-I may be less clinically relevant than maintaining an IGF-I setpoint. Methods Participants were 945 US community-dwelling individuals...
Article
Full-text available
Objective To develop Clinical Practice Guidelines for the screening, assessment and management of the geriatric condition of frailty. Methods An adapted Grading of Recommendations, Assessment, Development, and Evaluation approach was used to develop the guidelines. This process involved detailed evaluation of the current scientific evidence paired...
Article
China has the world’s largest aging population that grows at a staggering rate. For example, the number of adults aged 80 years and over, the oldest and frail subset of the aging population currently grows at 1 million per year. Thus, the need for quality geriatrics and innovative care model development is unprecedented. Initially funded by the Chi...
Article
Increasing availability of large clinical datasets including laboratory results raises the prospect of studying aging through these rich sources of biomarker data. However, substantial caution is warranted: most individual biomarkers fluctuate for many different reasons, and changes can have different interpretations in different contexts. This pro...
Article
Recent studies have shown contradictory associations between calcium levels and health outcomes. We suspected these conflicting results were the consequence of more general issues with how biomarkers are analyzed in epidemiological studies, particularly in the context of aging. To demonstrate the risks of typical analyses, we used three longitudina...
Article
Full-text available
OBJECTIVES: Evidence suggests vitamin D deficiency is associated with developing frailty. However, cardiometabolic factors are related to both conditions and may confound and/or mediate the vitamin D–frailty association. We aimed to determine the association of vitamin D concentration with incidence of frailty, and the role of cardiometabolic disea...
Article
CKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum solu...
Chapter
Societies exert profound influences on the developmental paths of their citizens. Whether engaged or disengaged, satisfied or dissatisfied, socially embedded or lonely, healthy or disabled; whether people feel in control of their lives or view themselves as victims of circumstance, all are intrinsically tied to broad sociocultural contexts in which...
Article
The author reports no relationships that could be construed as a conflict of interest.
Article
Corresponding Author: John W. Rowe, MD, Robert N. Butler Columbia Aging Center, Columbia University Mailman School of Public Health, 722 W 168th St, New York, NY 10032 (jwr2108@columbia.edu). Published Online: September 26, 2016. doi:10.1001/jama.2016.12335 Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form fo...
Article
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Putin et al. [1] just published an excellent article showing how machine learning methods (specifically deep neural networks, DNNs) can be used to quantify the aging process using a set of 41 standard clinical biomarkers, most of which are not specifically recognized as biomarkers of aging. DNNs provide a method to obtain a predictive algorithm fro...
Article
Different phenotypes have increasingly been used as tools for clinical characterization of frailty among older adults. Although there have been studies about the comparability and effectiveness of various simplifications and approximations of existing frailty phenotypes for risk prediction, there have been no studies in which investigators evaluate...
Article
In the last 100 years, populations in developed countries have experienced an unprecedented addition of 30 years to life expectancy. Developing countries are now experiencing this same phenomenon, but over a shorter time frame. With this success comes the challenge of maximizing health and vitality across these added years. The compression of morbi...
Article
Objectives: To examine the relationship between herpesvirus infections and mortality and incident frailty risks in community-dwelling older women. Design: Nested prospective cohort study. Setting: Women's Health and Aging Studies I and II. Participants: Community-dwelling older women aged 70 to 79 (n = 633). Measurements: Baseline serum an...
Article
Background: Clinical cognitive impairment and physical frailty often co-occur. However, it is unclear whether preclinical impairment or decline in cognitive domains are associated with onset of physical frailty. We tested this hypothesis and further hypothesized that preclinical impairment and decline in executive functioning are more strongly ass...
Article
The world is aging as a result of unprecedented successes worldwide adding 30 years of life expectancy and presenting great opportunities for all of society, but only if we invest effectively. This article, written as a requested background article for the World Health Organization 2015 World Report on Aging, proposes that creating health into the...
Article
Background: Pentraxin 3 (PTX3) is an inflammatory biomarker primarily reflecting vascular damage. PTX3 is associated with cardiovascular disease (CVD); however, associations with frailty, another inflammation-related disease of aging, are unknown. Methods: At baseline, we examined these associations in 1,948 white and black men and women (mean age...
Chapter
Over the last decades epidemiological studies identified major risk factors for chronic diseases and these led to preventive interventions that reduced the burden of cardiovascular diseases and mortality and contributed to increased longevity in the population. In the epidemiological context, aging was considered as an important “confounder”, somet...
Data
Table S1 Results from structural equations models showing lagged effects of dysregulation across systems. Appendix S1 Additional details on data sets, health outcomes measures, and structural equations models.
Data
Fig. S1 Correlations among dysregulation scores of the a priori systems. The only difference from Fig. 1 in the main text is we did not adjust for age.
Article
Full-text available
We evaluated a transformed core curriculum for the Columbia University, Mailman School of Public Health (New York, New York) master of public health (MPH) degree. The curriculum, launched in 2012, aims to teach public health as it is practiced: in interdisciplinary teams, drawing on expertise from multiple domains to address complex health challeng...
Article
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An increasing number of aging researchers believes that multi-system physiological dysregulation may be a key biological mechanism of aging, but evidence of this has been sparse. Here, we used biomarker data on nearly 33 000 individuals from four large datasets to test for the presence of multi-system dysregulation. We grouped 37 biomarkers into si...
Article
Older adults with a high number of chronic conditions and who live in environments that do not promote physical activity have great difficulty initiating and adhering to exercise programs. Novel lifestyle activity interventions that can effectively increase physical activity may address disparities in health in these populations. This study evaluat...
Article
Full-text available
Physiological dysregulation may underlie aging and many chronic diseases, but is challenging to quantify because of the complexity of the underlying systems. Recently, we described a measure of physiological dysregulation, DM, that uses statistical distance to assess the degree to which an individual ' s biomarker profile is normal versus aberrant....
Article
Volunteering in late life is associated with health benefits such as reduced risk of hypertension, improved self-related health and well-being, delayed physical disability, enhanced cognition, and lower mortality. Although the mechanisms of these correlations are not clear, increases in physical activity, cognitive engagement, and social interactio...
Article
There is a substantial interest in identifying interventions that can protect and buffer older adults from atrophy in the cortex and particularly, the hippocampus, a region important to memory. We report the 2-year effects of a randomized controlled trial of an intergenerational social health promotion program on older men's and women's brain volum...
Article
Full-text available
Elevated oxidative stress levels may be one mechanism contributing to poor health outcomes. Financial strain and oxidative stress are each predictors of morbidity and mortality, but little research has investigated their relationship. Community-dwelling older adults (n = 728) from the Women's Health and Aging Studies I and II were included in this...
Article
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Many studies of aging examine biomarkers one at a time, but complex systems theory and network theory suggest that interpretations of individual markers may be context-dependent. Here, we attempted to detect underlying processes governing the levels of many biomarkers simultaneously by applying principal components analysis to 43 common clinical bi...
Article
Curricular change is essential for maintaining vibrant, timely, and relevant educational programming. However, major renewal of a long-standing curriculum at an established university presents many challenges for leaders, faculty, staff, and students. We present a case study of a dramatic curriculum renewal of one of the nation's largest Master of...
Article
Full-text available
Being and feeling generative, defined as exhibiting concern and behavior to benefit others, is an important developmental goal of midlife and beyond. Although a growing body of evidence suggests mental and physical health benefits of feeling generative in later life, little information exists as to the modifiability of generativity perceptions. The...
Article
Full-text available
We examined the impact of the Experience Corps(®) (EC) program on school climate within Baltimore City public elementary schools. In this program, teams of older adult volunteers were placed in high intensity (>15 h per week), meaningful roles in public elementary schools, to improve the educational outcomes of children as well as the health and we...
Article
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Objective: Previous studies exploring the relationship of neighborhood characteristics with metabolic conditions have focused on middle-aged adults but none have comprehensively investigated associations in older adults, a potentially vulnerable population. The aim was to explore the relationship of neighborhood characteristics with metabolic cond...
Article
Full-text available
Experience Corps® (EC) was designed to simultaneously increase cognitive, social, and physical activity through high-intensity volunteerism in elementary school classrooms. It is, therefore, highly likely that EC participation may alter pre-existing patterns of lifestyle activity. This study examined the impact of "real-world" volunteer engagement...
Article
We present evidence of feed-forward loop relationships and positive association between physical activity and performance levels, which are components of frailty, using measures from 431 high functioning women initially aged 70-79 years followed over 7 visits. Physical activity levels were assessed using a questionnaire. Grip strength was measured...
Article
Objective Previous studies exploring the relationship of neighborhood characteristics with metabolic conditions have focused on middle-aged adults but none have comprehensively investigated associations in older adults, a potentially vulnerable population. The aim was to explore the relationship of neighborhood characteristics with metabolic condit...