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.

Background 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. Methods 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. Results 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). Conclusions 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.

A home-based program targeting underlying impairments in physical abilities can reduce the progression of functional decline among physically frail, elderly persons who live at home.

Context Preventing 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. Objectives To 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 Participants Prospective 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 Measure Disability, defined as the need for personal assistance in bathing, dressing, walking inside the house, or transferring from a chair. Results During 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 populationattributable 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. Conclusions Illnesses 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 Toll-like receptor (TLR) function in primary human dendritic cells from 104 young (age 21–30) and older (≥ 65 years) individuals. We used multicolor flow cytometry and intracellular cytokine staining of myeloid (mDC) and plasmacytoid (pDC) DCs and found substantial decreases in older, compared to 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 [BMI], 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 post-transcriptional mechanisms in these age-associated effects. Moreover, intracellular cytokine production in the absence of TLR ligand stimulation was elevated in cells from older, compared to young individuals, suggesting a dysregulation of cytokine production that may limit further activation by TLR engagement. Our results provide evidence for immunosenescence in dendritic cells; notably, defects in cytokine production were strongly associated with poor antibody response to influenza immunization, a functional consequence of impaired TLR function in the aging innate immune response.