The questions patients are asked about their preferences with regard to life-sustaining treatment usually focus on specific interventions, but the outcomes of treatment and their likelihood affect patients' preferences. We administered a questionnaire about treatment preferences to 226 persons who were 60 years of age or older and who had a limited life expectancy due to cancer, congestive heart failure, or chronic obstructive pulmonary disease. The study participants were asked whether they would want to receive a given treatment, first when the outcome was known with certainty and then with different likelihoods of an adverse outcome. The outcome without treatment was specified as death from the underlying disease. The burden of treatment (i.e., the length of the hospital stay, extent of testing, and invasiveness of interventions), the outcome, and the likelihood of the outcome all influenced treatment preferences. For a low-burden treatment with the restoration of current health, 98.7 percent of participants said they would choose to receive the treatment (rather than not receive it and die), but 11.2 percent of these participants would not choose the treatment if it had a high burden. If the outcome was survival but with severe functional impairment or cognitive impairment, 74.4 percent and 88.8 percent of these participants, respectively, would not choose treatment. The number of participants who said they would choose treatment declined as the likelihood of an adverse outcome increased, with fewer participants choosing treatment when the possible outcome was functional or cognitive impairment than when it was death. Preferences did not differ according to the primary diagnosis. Advance care planning should take into account patients' attitudes toward the burden of treatment, the possible outcomes, and their likelihood. The likelihood of adverse functional and cognitive outcomes of treatment requires explicit consideration.

Despite the importance of functional status to older persons and their families, little is known about the course of disability at the end of life. We evaluated data on 383 decedents from a longitudinal study involving 754 community-dwelling older persons. None of the subjects had disability in essential activities of daily living at the beginning of the study, and the level of disability was ascertained during monthly interviews for more than 10 years. Information on the conditions leading to death was obtained from death certificates and comprehensive assessments that were completed at 18-month intervals after the baseline assessment. In the last year of life, five distinct trajectories were identified, from no disability to the most severe disability: 65 subjects had no disability (17.0%), 76 had catastrophic disability (19.8%), 67 had accelerated disability (17.5%), 91 had progressive disability (23.8%), and 84 had persistently severe disability (21.9%). The most common condition leading to death was frailty (in 107 subjects [27.9%]), followed by organ failure (in 82 subjects [21.4%]), cancer (in 74 subjects [19.3%]), other causes (in 57 subjects [14.9%]), advanced dementia (in 53 subjects [13.8%]), and sudden death (in 10 subjects [2.6%]). When the distribution of the disability trajectories was evaluated according to the conditions leading to death, a predominant trajectory was observed only for subjects who died from advanced dementia (67.9% of these subjects had a trajectory of persistently severe disability) and sudden death (50.0% of these subjects had no disability). For the four other conditions leading to death, no more than 34% of the subjects had any of the disability trajectories. The distribution of disability trajectories was particularly heterogeneous among the subjects with organ failure (from 12.2 to 32.9% of the subjects followed a specific trajectory) and frailty (from 14.0 to 27.1% of the subjects followed a specific trajectory). In most of the decedents, the course of disability in the last year of life did not follow a predictable pattern based on the condition leading to death.

Functional decline in physically frail, elderly persons is associated with substantial morbidity. It is uncertain whether such functional decline can be prevented.

Research from JAMA — Hospitalization, Restricted Activity, and the Development of Disability Among Older Persons — ContextPreventing the development of disability in activities of daily living is an important goal in older adults, yet relatively little is known about the disabling process.ObjectivesTo evaluate the relationship between 2 types of intervening events (hospitalization and restricted activity) and the development of disability and to determine whether this relationship is modified by the presence of physical frailty.Design, Setting, and ParticipantsProspective cohort study, conducted in the general community in greater New Haven, Conn, from March 1998 to March 2003, of 754 persons aged 70 years or older, who were not disabled (ie, required no personal assistance) in 4 essential activities of daily living: bathing, dressing, walking inside the house, and transferring from a chair. Participants were categorized into 2 groups according to the presence of physical frailty (defined on the basis of slow gait speed) and were followed up with monthly telephone interviews for up to 5 years to ascertain exposure to intervening events and determine the occurrence of disability.Main Outcome MeasureDisability, defined as the need for personal assistance in bathing, dressing, walking inside the house, or transferring from a chair.ResultsDuring the 5-year follow-up period, disability developed among 417 (55.3%) participants, 372 (49.3%) were hospitalized and 600 (79.6%) had at least 1 episode of restricted activity. The multivariable hazard ratios for the development of disability were 61.8 (95% confidence interval [CI], 49.0-78.0) within a month of hospitalization and 5.54 (95% CI, 4.27-7.19) within a month of restricted activity. Strong associations were observed for participants who were physically frail and those who were not physically frail. Hospital admissions for falls were most likely to lead to disability. Intervening events occurring more than a month prior to disability onset were not associated with the development of disability. The population-attributable fractions associated with new exposure to hospitalization and restricted activity, respectively, were 0.48 and 0.19; 0.40 and 0.20, respectively, for frail participants and 0.61 and 0.16, respectively, for nonfrail participants.ConclusionsIllnesses and injuries leading to either hospitalization or restricted activity represent important sources of disability for older persons living in the community, regardless of the presence of physical frailty. These intervening events may be suitable targets for the prevention of disability.

We evaluated TLR function in primary human dendritic cells (DCs) from 104 young (age 21–30 y) and older (≥65 y) individuals. We used multicolor flow cytometry and intracellular cytokine staining of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) and found substantial decreases in older compared with young individuals in TNF-α, IL-6, and/or IL-12 (p40) production in mDCs and in TNF-α and IFN-α production in pDCs in response to TLR1/2, TLR2/6, TLR3, TLR5, and TLR8 engagement in mDCs and TLR7 and TLR9 in pDCs. These differences were highly significant after adjustment for heterogeneity between young and older groups (e.g., gender, race, body mass index, number of comorbid medical conditions) using mixed-effect statistical modeling. Studies of surface and intracellular expression of TLR proteins and of TLR gene expression in purified mDCs and pDCs revealed potential contributions for both transcriptional and posttranscriptional mechanisms in these age-associated effects. Moreover, intracellular cytokine production in the absence of TLR ligand stimulation was elevated in cells from older compared with young individuals, suggesting a dysregulation of cytokine production that may limit further activation by TLR engagement. Our results provide evidence for immunosenescence in DCs; notably, defects in cytokine production were strongly associated with poor Ab response to influenza immunization, a functional consequence of impaired TLR function in the aging innate immune response.

Among older persons, disability in essential activities of daily living, such as bathing, dressing, walking, and transferring, is common and associated with increased mortality, institutionalization, and greater use of formal and informal home services.¹ Active life expectancy, a metric that is often used by policy makers to forecast the functional health of older persons, is based on disability.^2,3