Kenneth Rockwood

Frailty in elderly people

Frailty is the most problematic expression of population ageing. It is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. In landmark studies, investigators have developed valid models of frailty and these models have allowed epidemiological investigations that show the association between frailty and adverse health outcomes. We need to develop more efficient methods to detect frailty and measure its severity in routine clinical practice, especially methods that are useful for primary care. Such progress would greatly inform the appropriate selection of elderly people for invasive procedures or drug treatments and would be the basis for a shift in the care of frail elderly people towards more appropriate goal-directed care.

A global clinical measure of fitness and frailty in elderly people

Background: There is no single generally accepted clinical definition of frailty. Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians. We aimed to develop a tool that would be both predictive and easy to use. Methods: We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging (CSHA). We followed this cohort prospectively; after 5 years, we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care, and correlated the results with those obtained from other established tools. Results: The CSHA Clinical Frailty Scale was highly correlated (r = 0.80) with the Frailty Index. Each 1-category increment of our scale significantly increased the medium-term risks of death (21.2% within about 70 mo, 95% confidence interval [CI] 12.5%–30.6%) and entry into an institution (23.9%, 95% CI 8.8%–41.2%) in multivariable models that adjusted for age, sex and education. Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition, function or comorbidity in assessing risk for death (area under the curve 0.77 for 18-month and 0.70 for 70-month mortality). Interpretation: Frailty is a valid and clinically important construct that is recognizable by physicians. Clinical judgments about frailty can yield useful predictive information.

Vascular cognitive impairment

Cerebrovascular disease is increasingly recognized as a common cause of cognitive impairment and dementia in later life either alone or in conjunction with other pathologies, most often Alzheimer disease (AD). Progress in the field has been limited by difficulties in terminology; for example, use of the term dementia necessitates the presence of memory impairment, which is the norm in AD, but not in cognitive disorders associated with cerebrovascular disease. The term vascular cognitive impairment (VCI) has been proposed as an umbrella term to recognize the broad spectrum of cognitive, and indeed behavioral, changes associated with vascular pathology. It is characterized by a specific cognitive profile with predominantly attentional and executive impairments together with particular noncognitive features (especially depression) and a relatively stable course, at least in clinical trial populations. Subtypes of VCI have been proposed based on clinical and pathologic differences, including cortical, subcortical, strategic infarct, hypoperfusion, hemorrhagic, and mixed (with AD) type. Diagnostic criteria are emerging but require refinement and validation, especially for mixed dementias. There remain fundamental gaps in our understanding of pathophysiology, predicting prognosis and outcome, and in therapeutics. Clinical trials to date, mainly in populations selected using currently accepted criteria for vascular dementia, have generally been disappointing. A relatively modest cognitive benefit of agents such as nimodipine, memantine, and cholinesterase inhibitors has been reported, although the clinical significance of these improvements remains to be established. Further studies, focusing on particular subtypes of VCI and involving subjects at earlier stages of the disease, are required. The aim of this article is to review the concept of VCI in terms of the evidence base surrounding diagnosis, clinical features, pathophysiology, and management and to make some recommendations regarding further research in the area. It begins with a discussion on the historical background, which is important to understand the different and somewhat confusing terminology that currently exists in the field.

A standard procedure for creating a frailty index.

BackgroundFrailty can be measured in relation to the accumulation of deficits using a frailty index. A frailty index can be developed from most ageing databases. Our objective is to systematically describe a standard procedure for constructing a frailty index.MethodsThis is a secondary analysis of the Yale Precipitating Events Project cohort study, based in New Haven CT. Non-disabled people aged 70 years or older (n = 754) were enrolled and re-contacted every 18 months. The database includes variables on function, cognition, co-morbidity, health attitudes and practices and physical performance measures. Data came from the baseline cohort and those available at the first 18-month follow-up assessment.ResultsProcedures for selecting health variables as candidate deficits were applied to yield 40 deficits. Recoding procedures were applied for categorical, ordinal and interval variables such that they could be mapped to the interval 0–1, where 0 = absence of a deficit, and 1= full expression of the deficit. These individual deficit scores were combined in an index, where 0= no deficit present, and 1= all 40 deficits present. The values of the index were well fit by a gamma distribution. Between the baseline and follow-up cohorts, the age-related slope of deficit accumulation increased from 0.020 (95% confidence interval, 0.014–0.026) to 0.026 (0.020–0.032). The 99% limit to deficit accumulation was 0.6 in the baseline cohort and 0.7 in the follow-up cohort. Multivariate Cox analysis showed the frailty index, age and sex to be significant predictors of mortality.ConclusionA systematic process for creating a frailty index, which relates deficit accumulation to the individual risk of death, showed reproducible properties in the Yale Precipitating Events Project cohort study. This method of quantifying frailty can aid our understanding of frailty-related health characteristics in older adults.

Accumulation of deficits as a proxy measure of aging.

This paper develops a method for appraising health status in elderly people. A frailty index was defined as the proportion of accumulated deficits (symptoms, signs, functional impairments, and laboratory abnormalities). It serves as an individual state variable, reflecting severity of illness and proximity to death. In a representative database of elderly Canadians we found that deficits accumulated at 3% per year, and show a gamma distribution, typical for systems with redundant components that can be used in case of failure of a given subsystem. Of note, the slope of the index is insensitive to the individual nature of the deficits, and serves as an important prognostic factor for life expectancy. The formula for estimating an individuals life span given the frailty index value is presented. For different patterns of cognitive impairments the average within-group index value increases with the severity of the cognitive impairment, and the relative variability of the index is significantly reduced. Finally, the statistical distribution of the frailty index sharply differs between well groups (gamma distribution) and morbid groups (normal distribution). This pattern reflects an increase in uncompensated deficits in impaired organisms, which would lead to illness of various etiologies, and ultimately to increased mortality. The accumulation of deficits is as an example of a macroscopic variable, i.e., one that reflects general properties of aging at the level of the whole organism rather than any given functional deficiency. In consequence, we propose that it may be used as a proxy measure of aging.

A reevaluation of the duration of survival after the onset of dementia.

BACKGROUND Dementia shortens life expectancy; estimates of median survival after the onset of dementia have ranged from 5 to 9.3 years. Previous studies of people with existing dementia, however, may have underestimated the deleterious effects of dementia on survival by failing to consider persons with rapidly progressive illness who died before they could be included in a study (referred to as length bias). METHODS We used data from the Canadian Study of Health and Aging to estimate survival from the onset of symptoms of dementia; the estimate was adjusted for length bias. A random sample of 10,263 subjects 65 years old or older from throughout Canada was screened for cognitive impairment. For those with dementia, we ascertained the date of onset and conducted follow-up for five years. RESULTS We analyzed data on 821 subjects, of whom 396 had probable Alzheimers disease, 252 had possible Alzheimers disease, and 173 had vascular dementia. For the group as a whole, the unadjusted median survival was 6.6 years (95 percent confidence interval, 6.2 to 7.1). After adjustment for length bias, the estimated median survival was 3.3 years (95 percent confidence interval, 2.7 to 4.0). The median survival was 3.1 years for subjects with probable Alzheimers disease, 3.5 years for subjects with possible Alzheimers disease, and 3.3 years for subjects with vascular dementia. CONCLUSIONS Median survival after the onset of dementia is much shorter than has previously been estimated.

Searching for an Operational Definition of Frailty: A Delphi Method Based Consensus Statement. The Frailty Operative Definition-Consensus Conference Project

BACKGROUND There is no consensus regarding the definition of frailty for clinical uses. METHODS A modified Delphi process was used to attempt to achieve consensus definition. Experts were selected from different fields and organized into five Focus Groups. A questionnaire was developed and sent to experts in the area of frailty. Responses and comments were analyzed using a pre-established strategy. Statements with an agreement more than or equal to 80% were accepted. RESULTS Overall, 44% of the statements regarding the concept of frailty and 18% of the statements regarding diagnostic criteria were accepted. There was consensus on the value of screening for frailty and about the identification of six domains of frailty for inclusion in a clinical definition, but no agreement was reached concerning a specific set of clinical/laboratory biomarkers useful for diagnosis. CONCLUSIONS There is agreement on the usefulness of defining frailty in clinical settings as well as on its main dimensions. However, additional research is needed before an operative definition of frailty can be established.

Validity and reliability of the Edmonton Frail Scale

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Frailty Defined by Deficit Accumulation and Geriatric Medicine Defined by Frailty

As nonreplicative cells age, they commonly accumulate subcellular deficits that can compromise function. As people age, they too experience problems that can accumulate. As deficits (symptoms, signs, illnesses, disabilities) accumulate, people become more susceptible to adverse health outcomes, including worse health and even death. This state of increased risk of adverse health outcomes is indistinguishable from the idea of frailty, so deficit accumulation represents another way to define frailty. Counting deficits not only allows grades of frailty to be discerned but also provides insights into the complex problems of older adults. This process is potentially useful to geriatricians who need to be experts in managing complexity. A key to managing complexity is through instruments such as a comprehensive geriatric assessment, which can serve as the basis for routine clinical estimation of an individuals degree of frailty. Understanding people and their needs as deficits accumulate is an exciting challenge for clinical research on frailty and its management by geriatricians.

Frailty, fitness and late-life mortality in relation to chronological and biological age

BackgroundPeople age at remarkably different rates, but how to estimate trajectories of senescence is controversial.MethodsIn a secondary analysis of a representative cohort of Canadians aged 65 and over (n = 2914) we estimated a frailty index based on the proportion of 20 deficits observed in a structured clinical examination. The construct validity of the index was examined through its relationship to chronological age (CA). The criterion validity was examined in its ability to predict mortality, and in relation to other predictions about aging. From the frailty index, relative (to CA) fitness and frailty were estimated, as was an individuals biological age.ResultsThe average value of the frailty index increased with age in a log-linear relationship (r = 0.91; p < 0.001). In a Cox regression analysis, biological age was significantly more highly associated with death than chronological age. The average increase in the frailty index (i.e. the average accumulation of deficits) amongst those with no cognitive impairment was 3 per cent per year.ConclusionsThe frailty index is a sensitive predictor of survival. As the index includes items not traditionally related to adverse health outcomes, the finding is compatible with a view of frailty as the failure to integrate the complex responses required to maintain function.