Research Agenda for Frailty in Older Adults: Toward a Better Understanding of Physiology and Etiology: Summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Journal of the American Geriatrics Society (Impact Factor: 4.57). 07/2006; 54(6):991-1001. DOI: 10.1111/j.1532-5415.2006.00745.x
Source: PubMed


Evolving definitions of frailty, and improved understanding of molecular and physiological declines in multiple systems that may increase vulnerability in frail, older adults has encouraged investigators from many disciplines to contribute to this emerging field of research. This article reports on the results of the 2004 American Geriatrics Society/National Institute on Aging conference on a Research Agenda on Frailty in Older Adults, which brought together a diverse group of clinical and basic scientists to encourage further investigation in this area. This conference was primarily focused on physical and physiological aspects of frailty. Although social and psychological aspects of frailty are critically important and merit future research, these topics were largely beyond the scope of this meeting. Included in this article are sections on the evolving conceptualization and definitions of frailty; physiological underpinnings of frailty, including the potential contributions of inflammatory, endocrine, skeletal muscle, and neurologic system changes; potential molecular and genetic contributors; proposed animal models; and integrative, system biology approaches that may help to facilitate future frailty research. In addition, several specific recommendations as to future directions were developed from suggestions put forth by participants, including recommendations on definition and phenotype development, methodological development to perform clinical studies of individual-system and multiple-system vulnerability to stressors, development of animal and cellular models, application of population-based studies to frailty research, and the development of large collaborative networks in which populations and resources can be shared. This meeting and subsequent article were not meant to be a comprehensive review of frailty research; instead, they were and are meant to provide a more-targeted research agenda-setting process.

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Available from: Linda P Fried, Mar 08, 2015
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    • "It is well-known that the phenotype of the frailty syndrome in the elderly is identified according to the presence of at least three of the following criteria: self-reported unintentional weight loss, self-reported fatigue, directly measured low grip strength, self-reported low physical activity, and directly measured low gait speed [12]. Such patients are more vulnerable to adverse clinical outcomes such as falls, the risk of hospitalization, and death [13]. "
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    ABSTRACT: This paper presents an algorithm that applies metrics derived from automatic QRS detection and segmentation in electrocardiogram signals for analyzing Heart Rate Variability to study the evolution of metrics in the frequency domain of a clinical procedure. The analysis was performed on three sets of elderly people, who are categorized according to frailty phenotype. The first set was comprised of frail elderly, the second pre-frail elderly, and the third robust elderly. Investigators from many disciplines have been encouraged to contribute to the understanding of molecular and physiological changes in multiple systems that may increase the vulnerability of frail elderly. In this work, the frailty phenotype can be characterized by unintentional weight loss, as self-reported, fatigue assessed by self-report, grip strength (measured directly), physical activity level assessed by self-report and gait speed (measured). The results obtained demonstrate the existence of significant differences between Heart Rate Variability metrics for the three groups, especially considering a higher preponderance for sympathetic nervous system for the group of robust patients in response to postural maneuver.
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    • "In recent years, frailty has not only been considered a biological or physiological state, but also a multidimensional concept [4], demanding therefore a multidisciplinary approach. In a systematic review that evaluated clinimetric properties, at least twenty frailty instruments have been described [9], and cognition was present in only 40% of them [13]. "
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    ABSTRACT: Late-life cognitive disorders may be prevented by influencing age-related conditions such as frailty, characterized by decreased resistance to stressors and increased risk for adverse health outcomes. In the present review article, we examined clinical and epidemiological studies investigating the possible role of different frailty models in modulating the risk of Alzheimer's disease (AD), dementia, vascular dementia (VaD), mild cognitive impairment (MCI), and late-life cognitive impairment/decline that have been published over the past 3 years. Both deficit accumulation and physical frailty models were associated with late-life cognitive impairment/decline, incident dementia, AD, MCI, VaD, non-AD dementias, and AD pathology, proposing cognitive frailty as a new clinical construct with coexisting physical frailty and cognitive impairment in nondemented older subjects. Two subtypes of this new clinical condition have been recently proposed: " potentially reversible " cognitive frailty and " reversible " cognitive frailty. The physical factors should be physical prefrailty and frailty, while the cognitive impairment of potentially reversible cognitive frailty should be MCI (Clinical Dementia rating Scale = 0.5), while the cognitive impairment of reversible cognitive frailty should be pre-MCI Subjective Cognitive Decline (SCD), as recently proposed by the SCD Initiative Working Group. The mechanisms underlying the cognitive-frailty link are multifactorial and vascular, inflammatory, nutritional, and metabolic influences may be of major relevance. Considering both physical frailty and cognition as a single complex phenotype may be crucial in the prevention of dementia and its subtypes with secondary preventive trials on cognitive frail older subjects.
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    • "Frailty is easily assessed as weight loss, muscle weakness, exhaustion, low physical ability and activity (see Fried et al., 2001, 2004; Walston, 2005; Walston et al., 2006). So measured, frailty predicts losses of abilities to complete daily activities, hospitalization and death (Walston et al., 2006). Additionally, some measures used to calculate AL are implicated in Syndrome X. "
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    ABSTRACT: Lifelong exposure to stressors promotes physiological dysregulation and produces an allostatic load (AL). In European-derived samples, AL associates significantly with sex, age and health. To assess associations of AL with age, sex, socio-demographic differences and self-reports of diet and ability to complete activities of daily living in older Japanese residing in rural Nagasaki Prefecture. In 2011, 96 older residents of Nagasaki Prefecture, Japan, were assessed for components of AL. They also self-reported their age, principal life-long occupational activity, educational attainments, marital status, dietary choices and abilities to complete daily living activities. Average age was 67.9 years (range = 55-89; SD = 8.65). Among these 48 men and 48 women, AL was not related significantly to age, although women showed lower AL than men. AL did not differ significantly between respondents by occupation, marital status, education or abilities to complete daily activities. Women who reported eating more green/yellow vegetables or consuming more meat had lower AL than their counterparts. Men who reported drinking more alcohol spirits had higher AL. Among older Japanese residing outside a major urban area, AL varies significantly by sex, but not age, while being associated with dietary choices. Although lack of association with life ways was not expected, AL apparently assesses physiological dysregulation cross-culturally.
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