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Importance: Given the critical role of neurocognitive development in early life, understanding the association between early-life circumstances and racial disparities in cognition has important implications., Objective: To assess whether racial differences in early-life circumstances are collectively and individually associated with racial disparities in late-life cognition among older adults in the US., Design, Setting, and Participants: This cross-sectional study used comprehensive life history data from the Health and Retirement Study, a nationally representative survey of US adults 50 years or older. Data analyses were performed from August 9, 2022, to January 20, 2024., Main Outcomes and Measures: Racial differences in early-life circumstances and racial disparities in late-life cognition were investigated using a Blinder-Oaxaca decomposition regression model. Cognitive outcomes, including cognitive score and cognitive impairment, were evaluated using the Telephone Interview for Cognitive Status. Early-life educational experiences were primary explanatory variables; early-life cohort, regional, financial, health, trauma, family relationship factors, and educational attainment were additional explanatory variables; demographic and genetic factors were covariates., Results: The study sample comprised 9015 participants; 1634 non-Hispanic Black (hereafter, Black) individuals (18.1%) and 7381 non-Hispanic White (hereafter, White) individuals (81.9%). Among Black participants, the mean (SD) age was 69.2 (9.2) years and 1094 (67.0%) were women. Among White participants, the mean (SD) age was 73.2 (10.1) years and 4410 (59.7%) were women. Cognitive scores (scale, 0-27) were significantly lower among Black participants (13.5 [95% CI, 13.3-13.7] points) than among White participants (15.8 [95% CI, 15.7-15.9] points), while the prevalence of cognitive impairment (cognitive score <12) was significantly higher among Black participants (33.6 [95% CI, 31.3-35.9] percentage points [ppt]) than among White participants (16.4 [95% CI, 15.6-17.2] ppt). Substantial racial differences were observed in early-life circumstances. Overall, differences in early-life circumstances were associated with 61.5% of the racial disparities in cognitive score (1.4 [95% CI, 0.88-2.0] points), and 82.3% of the racial disparities in cognitive impairment (14.2 [95% CI, 8.8-19.5] ppt), respectively. In multivariable analyses, early-life educational experiences were associated with 35.2% of the disparities in cognitive score and 48.6% in cognitive impairment. Notably, school racial segregation (all segregated schooling before college) was associated with 28.8% to 39.7% of the racial disparities in cognition. These findings were consistent in a series of sensitivity analyses., Conclusions and Relevance: The findings of this cross-sectional study suggest that less favorable early-life circumstances are associated with clinically meaningful racial disparities in late-life cognition. Policies that improve educational equity have the potential to reduce racial disparities in cognition in older ages. Clinicians may leverage early-life circumstances to promote the screening, prevention, and interventions of cognitive impairment more efficiently, thereby promoting health equity.

Importance: Older adults who are hospitalized for COVID-19 are at risk of delirium. Little is known about the association of in-hospital delirium with functional and cognitive outcomes among older adults who have survived a COVID-19 hospitalization., Objective: To evaluate the association of delirium with functional disability and cognitive impairment over the 6 months after discharge among older adults hospitalized with COVID-19., Design, Setting, and Participants: This prospective cohort study involved patients aged 60 years or older who were hospitalized with COVID-19 between June 18, 2020, and June 30, 2021, at 5 hospitals in a major tertiary care system in the US. Follow-up occurred through January 11, 2022. Data analysis was performed from December 2022 to February 2024., Exposure: Delirium during the COVID-19 hospitalization was assessed using the Chart-based Delirium Identification Instrument (CHART-DEL) and CHART-DEL-ICU., Main Outcomes and Measures: Primary outcomes were disability in 15 functional activities and the presence of cognitive impairment (defined as Montreal Cognitive Assessment score <22) at 1, 3, and 6 months after hospital discharge. The associations of in-hospital delirium with functional disability and cognitive impairment were evaluated using zero-inflated negative binominal and logistic regression models, respectively, with adjustment for age, month of follow-up, and baseline (before COVID-19) measures of the respective outcome., Results: The cohort included 311 older adults (mean [SD] age, 71.3 [8.5] years; 163 female [52.4%]) who survived COVID-19 hospitalization. In the functional disability sample of 311 participants, 49 participants (15.8%) experienced in-hospital delirium. In the cognition sample of 271 participants, 31 (11.4%) experienced in-hospital delirium. In-hospital delirium was associated with both increased functional disability (rate ratio, 1.32; 95% CI, 1.05-1.66) and increased cognitive impairment (odds ratio, 2.48; 95% CI, 1.38-4.82) over the 6 months after discharge from the COVID-19 hospitalization., Conclusions and Relevance: In this cohort study of 311 hospitalized older adults with COVID-19, in-hospital delirium was associated with increased functional disability and cognitive impairment over the 6 months following discharge. Older survivors of a COVID-19 hospitalization who experience in-hospital delirium should be assessed for disability and cognitive impairment during postdischarge follow-up.

Importance: Aortic stenosis (AS) is a major public health challenge with a growing therapeutic landscape, but current biomarkers do not inform personalized screening and follow-up. A video-based artificial intelligence (AI) biomarker (Digital AS Severity index [DASSi]) can detect severe AS using single-view long-axis echocardiography without Doppler characterization., Objective: To deploy DASSi to patients with no AS or with mild or moderate AS at baseline to identify AS development and progression., Design, Setting, and Participants: This is a cohort study that examined 2 cohorts of patients without severe AS undergoing echocardiography in the Yale New Haven Health System (YNHHS; 2015-2021) and Cedars-Sinai Medical Center (CSMC; 2018-2019). A novel computational pipeline for the cross-modal translation of DASSi into cardiac magnetic resonance (CMR) imaging was further developed in the UK Biobank. Analyses were performed between August 2023 and February 2024., Exposure: DASSi (range, 0-1) derived from AI applied to echocardiography and CMR videos., Main Outcomes and Measures: Annualized change in peak aortic valve velocity (AV-Vmax) and late (>6 months) aortic valve replacement (AVR)., Results: A total of 12 599 participants were included in the echocardiographic study (YNHHS: n = 8798; median [IQR] age, 71 [60-80] years; 4250 [48.3%] women; median [IQR] follow-up, 4.1 [2.4-5.4] years; and CSMC: n = 3801; median [IQR] age, 67 [54-78] years; 1685 [44.3%] women; median [IQR] follow-up, 3.4 [2.8-3.9] years). Higher baseline DASSi was associated with faster progression in AV-Vmax (per 0.1 DASSi increment: YNHHS, 0.033 m/s per year [95% CI, 0.028-0.038] among 5483 participants; CSMC, 0.082 m/s per year [95% CI, 0.053-0.111] among 1292 participants), with values of 0.2 or greater associated with a 4- to 5-fold higher AVR risk than values less than 0.2 (YNHHS: 715 events; adjusted hazard ratio [HR], 4.97 [95% CI, 2.71-5.82]; CSMC: 56 events; adjusted HR, 4.04 [95% CI, 0.92-17.70]), independent of age, sex, race, ethnicity, ejection fraction, and AV-Vmax. This was reproduced across 45 474 participants (median [IQR] age, 65 [59-71] years; 23 559 [51.8%] women; median [IQR] follow-up, 2.5 [1.6-3.9] years) undergoing CMR imaging in the UK Biobank (for participants with DASSi ≥0.2 vs those with DASSi <.02, adjusted HR, 11.38 [95% CI, 2.56-50.57]). Saliency maps and phenome-wide association studies supported associations with cardiac structure and function and traditional cardiovascular risk factors., Conclusions and Relevance: In this cohort study of patients without severe AS undergoing echocardiography or CMR imaging, a new AI-based video biomarker was independently associated with AS development and progression, enabling opportunistic risk stratification across cardiovascular imaging modalities as well as potential application on handheld devices.

Importance: Older adults with socioeconomic disadvantage develop a greater burden of disability after critical illness than those without socioeconomic disadvantage. The delivery of in-hospital rehabilitation that can mitigate functional decline may be influenced by social determinants of health (SDOH). Whether rehabilitation delivery differs by SDOH during critical illness hospitalization is not known., Objective: To evaluate whether SDOH are associated with the delivery of skilled rehabilitation during critical illness hospitalization among older adults., Design, Setting, and Participants: This cohort study used data from the National Health and Aging Trends Study linked with Medicare claims (2011-2018). Participants included older adults hospitalized with a stay in the intensive care unit (ICU). Data were analyzed from August 2022 to September 2023., Exposures: Dual eligibility for Medicare and Medicaid, education, income, limited English proficiency (LEP), and rural residence., Main Outcome and Measures: The primary outcome was delivery of physical therapy (PT) and/or occupational therapy (OT) during ICU hospitalization, characterized as any in-hospital PT or OT and rate of in-hospital PT or OT, calculated as total number of units divided by length of stay., Results: In the sample of 1618 ICU hospitalizations (median [IQR] patient age, 81.0 [75.0-86.0] years; 842 [52.0%] female), 371 hospitalizations (22.9%) were among patients with dual Medicare and Medicaid eligibility, 523 hospitalizations (32.6%) were among patients with less than high school education, 320 hospitalizations (19.8%) were for patients with rural residence, and 56 hospitalizations (3.5%) were among patients with LEP. A total of 1076 hospitalized patients (68.5%) received any PT or OT, with a mean rate of 0.94 (95% CI, 0.86-1.02) units/d. After adjustment for age, sex, prehospitalization disability, mechanical ventilation, and organ dysfunction, factors associated with lower odds of receipt of PT or OT included dual Medicare and Medicaid eligibility (adjusted odds ratio, 0.70 [95% CI, 0.50-0.97]) and rural residence (adjusted odds ratio, 0.65 [95% CI, 0.48-0.87]). LEP was associated with a lower rate of PT or OT (adjusted rate ratio, 0.55 [95% CI, 0.32-0.94])., Conclusions and Relevance: These findings highlight the need to consider SDOH in efforts to promote rehabilitation delivery during ICU hospitalization and to investigate factors underlying inequities in this practice.

Importance: Nationally representative estimates of hospital readmissions within 30 and 180 days after major surgery, including both fee-for-service and Medicare Advantage beneficiaries, are lacking., Objectives: To provide population-based estimates of hospital readmission within 30 and 180 days after major surgery in community-living older US residents and examine whether these estimates differ according to key demographic, surgical, and geriatric characteristics., Design, Setting, and Participants: A prospective longitudinal cohort study of National Health and Aging Trends Study data (calendar years 2011-2018), linked to records from the Centers for Medicare & Medicaid Services (CMS). Data analysis was conducted from April to August 2023. Participants included community-living US residents of the contiguous US aged 65 years or older who had at least 1 major surgery from 2011 to 2018. Data analysis was conducted from April 10 to August 28, 2023., Main Outcomes and Measures: Major operations and hospital readmissions within 30 and 180 days were identified through data linkages with CMS files that included both fee-for-service and Medicare Advantage beneficiaries. Data on frailty and dementia were obtained from the annual National Health and Aging Trends Study assessments., Results: A total of 1780 major operations (representing 9 556 171 survey-weighted operations nationally) were identified from 1477 community-living participants; mean (SD) age was 79.5 (7.0) years, with 56% being female. The weighted rates of hospital readmission were 11.6% (95% CI, 9.8%-13.6%) for 30 days and 27.6% (95% CI, 24.7%-30.7%) for 180 days. The highest readmission rates within 180 days were observed among participants aged 90 years or older (36.8%; 95% CI, 28.3%-46.3%), those undergoing vascular surgery (45.8%; 95% CI, 37.7%-54.1%), and persons with frailty (36.9%; 95% CI, 30.8%-43.5%) or probable dementia (39.0%; 95% CI, 30.7%-48.1%). In age- and sex-adjusted models with death as a competing risk, the hazard ratios for hospital readmission within 180 days were 2.29 (95% CI, 1.70-3.09) for frailty and 1.58 (95% CI, 1.15-2.18) for probable dementia., Conclusions and Relevance: In this nationally representative cohort study of community-living older US residents, the likelihood of hospital readmissions within 180 days after major surgery was increased among older persons who were frail or had probable dementia, highlighting the potential value of these geriatric conditions in identifying those at increased risk.

Importance: It is uncertain whether emergency preparedness and regulatory oversight for US nursing homes are aligned with local wildfire risk., Objective: To evaluate the likelihood that nursing homes at elevated risk of wildfire exposure meet US Centers for Medicare & Medicaid Services (CMS) emergency preparedness standards and to compare the time to reinspection by exposure status., Design, Setting, and Participants: This cross-sectional study of nursing homes in the continental western US from January 1, 2017, through December 31, 2019, was conducted using cross-sectional and survival analyses. The prevalence of high-risk facilities within 5 km of areas at or exceeding the 85th percentile of nationalized wildfire risk across areas overseen by 4 CMS regional offices (New Mexico, Mountain West, Pacific/Southwest, and Pacific Northwest) was determined. Critical emergency preparedness deficiencies cited during CMS Life Safety Code Inspections were identified. Data analysis was performed from October 10 to December 12, 2022., Main Outcomes and Measures: The primary outcome classified whether facilities were cited for at least 1 critical emergency preparedness deficiency during the observation window. Regionally stratified generalized estimating equations were used to evaluate associations between risk status and the presence and number of deficiencies, adjusted for nursing home characteristics. For the subset of facilities with deficiencies, differences in restricted mean survival time to reinspection were evaluated., Results: Of the 2218 nursing homes in this study, 1219 (55.0%) were exposed to elevated wildfire risk. The Pacific/Southwest had the highest percentage of both exposed (680 of 870 [78.2%]) and unexposed (359 of 486 [73.9%]) facilities with 1 or more deficiencies. The Mountain West had the largest difference in the percentage of exposed (87 of 215 [40.5%]) vs unexposed (47 of 193 [24.4%]) facilities with 1 or more deficiencies. Exposed facilities in the Pacific Northwest had the greatest mean (SD) number of deficiencies (4.3 [5.4]). Exposure was associated with the presence of deficiencies in the Mountain West (odds ratio [OR], 2.12 [95% CI, 1.50-3.01]) and the presence (OR, 1.84 [95% CI, 1.55-2.18]) and number (rate ratio, 1.39 [95% CI, 1.06-1.83]) of deficiencies in the Pacific Northwest. Exposed Mountain West facilities with deficiencies were reinspected later, on average, than unexposed facilities (adjusted restricted mean survival time difference, 91.2 days [95% CI, 30.6-151.8 days])., Conclusions and Relevance: In this cross-sectional study, regional heterogeneity in nursing home emergency preparedness for and regulatory responsiveness to local wildfire risk was observed. These findings suggest that there may be opportunities to improve the responsiveness of nursing homes to and regulatory oversight of surrounding wildfire risk.

Importance: Whether US nursing homes are well prepared for exposure to hurricane-related inundation is uncertain., Objectives: To estimate the prevalence of nursing homes exposed to hurricane-related inundation and evaluate whether exposed facilities are more likely to meet Centers for Medicare & Medicaid Services (CMS) emergency preparedness standards., Design, Setting, and Participants: This cross-sectional study included CMS-certified nursing homes in Coastal Atlantic and Gulf Coast states from January 1, 2017, to December 31, 2019. The prevalence of facilities exposed to at least 2 feet of hurricane-related inundation used models from the National Hurricane Center across coastal areas overseen by 5 CMS regional offices: New England, New York metropolitan area, Mid-Atlantic region, Southeast and Eastern Gulf Coast, and Western Gulf Coast. Critical emergency preparedness deficiencies cited during CMS life safety code inspections were identified., Main Outcomes and Measures: The analysis used generalized estimating equations with binomial and negative binomial distributions to evaluate associations between exposure status and the presence and number of critical emergency preparedness deficiencies. Regionally stratified associations (odds ratios [ORs]) and rate ratios [RRs]) with 95% CIs, adjusted for state-level fixed effects and nursing home characteristics, were reported., Results: Of 5914 nursing homes, 617 (10.4%) were at risk of inundation exposure, and 1763 (29.8%) had a critical emergency preparedness deficiency. Exposed facilities were less likely to be rural, were larger, and had similar CMS health inspection, quality, and staffing ratings compared with unexposed facilities. Exposure was positively associated with the presence and number of emergency preparedness deficiencies for the nursing homes within the Mid-Atlantic region (adjusted OR, 1.91 [95% CI, 1.15-3.20]; adjusted RR, 2.51 [95% CI, 1.41-4.47]). Conversely, exposure was negatively associated with the number of emergency preparedness deficiencies among facilities within the Western Gulf Coast (aRR, 0.55 [95% CI, 0.36-0.86]). The associations for the number of emergency preparedness deficiencies remained after correction for multiple comparisons., Conclusions and Relevance: The findings of this cross-sectional study suggest that the association between exposure to hurricane-related inundation and nursing home emergency preparedness differs considerably across the Coastal Atlantic and Gulf regulatory regions. These findings further suggest that there may be opportunities to reduce regional heterogeneity and improve the alignment of nursing home emergency preparedness with surrounding environmental risks.

Importance: Despite their importance to guiding public health decision-making and policies and to establishing programs aimed at improving surgical care, contemporary nationally representative mortality data for geriatric surgery are lacking., Objective: To calculate population-based estimates of mortality after major surgery in community-living older US adults and to determine how these estimates differ according to key demographic, surgical, and geriatric characteristics., Design, Setting, and Participants: Prospective longitudinal cohort study with 1 year of follow-up in the continental US from 2011 to 2018. Participants included 5590 community-living fee-for-service Medicare beneficiaries, aged 65 years or older, from the National Health and Aging Trends Study (NHATS). Data analysis was conducted from February 22, 2021, to March 16, 2022., Main Outcomes and Measures: Major surgeries and mortality over 1 year were identified through linkages with data from the Centers for Medicare & Medicaid Services. Data on frailty and dementia were obtained from the annual NHATS assessments., Results: From 2011 to 2017, of the 1193 major surgeries (from 992 community-living participants), the mean (SD) age was 79.2 (7.1) years; 665 were women (55.7%), and 30 were Hispanic (2.5%), 198 non-Hispanic Black (16.6%), and 915 non-Hispanic White (76.7%). Over the 1-year follow-up period, there were 206 deaths representing 872 096 survey-weighted deaths and 13.4% (95% CI, 10.9%-15.9%) mortality. Mortality rates were 7.4% (95% CI, 4.9%-9.9%) for elective surgeries and 22.3% (95% CI, 17.4%-27.1%) for nonelective surgeries. For geriatric subgroups, 1-year mortality was 6.0% (95% CI, 2.6%-9.4%) for persons who were nonfrail, 27.8% (95% CI, 21.2%-34.3%) for those who were frail, 11.6% (95% CI, 8.8%-14.4%) for persons without dementia, and 32.7% (95% CI, 24.3%-41.0%) for those with probable dementia. The age- and sex-adjusted hazard ratios for 1-year mortality were 4.41 (95% CI, 2.53-7.69) for frailty with a reduction in restricted mean survival time of 48.8 days and 2.18 (95% CI, 1.40-3.40) for probable dementia with a reduction in restricted mean survival time of 44.9 days., Conclusions and Relevance: In this study, the population-based estimate of 1-year mortality after major surgery among community-living older adults in the US was 13.4% but was 3-fold higher for nonelective than elective procedures. Mortality was considerably elevated among older persons who were frail or who had probable dementia, highlighting the potential prognostic value of geriatric conditions after major surgery.

Importance: The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases., Objective: To determine whether there is an association between CKD and ICH risk., Design, Setting, and Participants: A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022., Exposures: CKD stages 1 to 5., Main Outcomes and Measures: The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes., Results: In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P < .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007)., Conclusions and Relevance: In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Importance: Accelerated aging makes adults more vulnerable to chronic diseases and death. Whether childhood adversity is associated with accelerated aging processes, and to what extent lifestyle mediates the association, remain unknown., Objective: To examine the associations of childhood adversity with a phenotypic aging measure and the role of unhealthy lifestyle in mediating these associations., Design, Setting, and Participants: A retrospective cohort analysis was conducted using data from adult participants in the UK Biobank baseline survey (2006-2010) and online mental health survey (2016). Data analysis was performed from September 1, 2021, to February 28, 2022., Exposures: Childhood adversity, including physical neglect, emotional neglect, sexual abuse, physical abuse, and emotional abuse, was assessed retrospectively through the online mental health survey (2016)., Main Outcomes and Measures: A phenotypic aging measure, phenotypic age acceleration, was calculated, with higher values indicating accelerated aging. Body mass index, smoking status, alcohol consumption, physical activity, and diet were combined to construct an unhealthy lifestyle score (range, 0-5, with higher scores denoting a more unhealthy lifestyle)., Results: A total of 127 495 participants aged 40 to 69 years (mean [SD] chronological age at baseline, 56.4 [7.7] years; 70 979 women [55.7%]; 123 987 White participants [97.2%]) were included. Each individual type of childhood adversity and cumulative childhood adversity score were associated with phenotypic age acceleration. For instance, compared with participants who did not experience childhood adversity, those who experienced 4 (β = 0.296, 95% CI, 0.130-0.462) or 5 (β = 0.833; 95% CI, 0.537-1.129) childhood adversities had higher phenotypic age acceleration in fully adjusted models. The formal mediation analysis revealed that unhealthy lifestyle partially mediated the associations of childhood adversity with phenotypic age acceleration by 11.8% to 42.1%., Conclusions and Relevance: In this retrospective cohort study, childhood adversity was significantly associated with acceleration of aging and, more importantly, unhealthy lifestyle partially mediated these associations. These findings reveal a pathway from childhood adversity to health in middle and early older adulthood through lifestyle and underscore the potential of more psychological strategies beyond lifestyle interventions to promote healthy aging.

Importance: The American Heart Association (AHA) Life's Simple 7 (LS7) score captures 7 biological and lifestyle factors associated with promoting cardiovascular health., Objectives: To test whether healthier LS7 profiles are associated with significant brain health benefits in persons without stroke or dementia, and to evaluate whether genomic information can recapitulate the observed LS7., Design, Setting, and Participants: This genetic association study was a nested neuroimaging study within the UK Biobank, a large population-based cohort study in the United Kingdom. Between March 2006 and October 2010, the UK Biobank enrolled 502 480 community-dwelling persons aged 40 to 69 years at recruitment. This study focused on a subset of 35 914 participants without stroke or dementia who completed research brain magnetic resonance imaging (MRI) and had available genome-wide data. All analyses were conducted between March 2021 and March 2022., Exposures: The LS7 (blood pressure, low-density lipoprotein cholesterol, hemoglobin A1c, smoking, exercise, diet, and body mass index) profiles were ascertained clinically and genomically. Independent genetic variants known to influence each of the traits included in the LS7 were assessed. The total LS7 score ranges from 0 (worst) to 14 (best) and was categorized as poor (≤4), average (>4 to 9) and optimal (>9)., Main Outcomes and Measures: The outcomes of interest were 2 neuroimaging markers of brain health: white matter hyperintensity (WMH) volume and brain volume (BV)., Results: The final analytical sample included 35 914 participants (mean [SD] age 64.1 [7.6] years; 18 830 [52.4%] women). For WMH, compared with persons with poor observed LS7 profiles, those with average profiles had 16% (β = -0.18; SE, 0.03; P < .001) lower mean volume and those with optimal profiles had 39% (β = -0.39; SE, 0.03; P < .001) lower mean volume. Similar results were obtained using the genomic LS7 for WMH (average LS7 profile: β = -0.06; SE, 0.014; P < .001; optimal LS7 profile: β = -0.08; SE, 0.018; P < .001). For BV, compared with persons with poor observed LS7 profiles, those with average LS7 profiles had 0.55% (β = 0.09; SE, 0.02; P < .001) higher volume, and those with optimal LS7 profiles had 1.9% (β = 0.14; SE, 0.02; P < .001) higher volume. The genomic LS7 profiles were not associated with BV., Conclusions and Relevance: These findings suggest that healthier LS7 profiles were associated with better profiles of 2 neuroimaging markers of brain health in persons without stroke or dementia, indicating that cardiovascular health optimization was associated with improved brain health in asymptomatic persons. Genomic information appropriately recapitulated 1 of these associations, confirming the feasibility of modeling the LS7 genomically and pointing to an important role of genetic predisposition in the observed association among cardiometabolic and lifestyle factors and brain health.

Importance: Neighborhood disadvantage is a novel social determinant of health that could adversely affect the functional well-being of older persons. Deficiencies in resource-poor environments can potentially be addressed through social and public health interventions., Objective: To evaluate whether estimates of active and disabled life expectancy differ on the basis of neighborhood disadvantage after accounting for individual-level socioeconomic characteristics and other prognostic factors., Design, Setting, and Participants: This prospective longitudinal cohort study included 754 nondisabled community-living persons, aged 70 years or older, who were members of the Precipitating Events Project in south central Connecticut from March 1998 to June 2020., Main Outcomes and Measures: Disability in 4 essential activities of daily living (bathing, dressing, walking, and transferring) was assessed each month. Scores on the Area Deprivation Index, a census-based socioeconomic measure with 17 education, employment, housing quality, and poverty indicators, were obtained through linkages with the 2000 Neighborhood Atlas. Area Deprivation Index scores were dichotomized at the 80th state percentile to distinguish neighborhoods that were disadvantaged (81-100) from those that were not (1-80)., Results: Among the 754 participants, the mean (SD) age was 78.4 (5.3) years, and 487 (64.6%) were female. Within 5-year age increments from 70 to 90, active life expectancy was consistently lower in participants from neighborhoods that were disadvantaged vs not disadvantaged, and these differences persisted and remained statistically significant after adjustment for individual-level race and ethnicity, education, income, and other prognostic factors. At age 70 years, adjusted estimates (95% CI) for active life expectancy (in years) were 12.3 (11.5-13.1) in the disadvantaged group and 14.2 (13.5-14.7) in the nondisadvantaged group. At each age, participants from disadvantaged neighborhoods spent a greater percentage of their projected remaining life disabled, relative to those from nondisadvantaged neighborhoods, with adjusted values (SE) ranging from 17.7 (0.8) vs 15.3 (0.5) at age 70 years to 55.0 (1.7) vs 48.1 (1.3) at age 90 years., Conclusions and Relevance: In this prospective longitudinal cohort study, living in a disadvantaged neighborhood was associated with lower active life expectancy and a greater percentage of projected remaining life with disability. By addressing deficiencies in resource-poor environments, new or expanded social and public health initiatives have the potential to improve the functional well-being of community-living older persons and, in turn, reduce health disparities in the US.

Importance: Severe disability greatly diminishes quality of life and often leads to a protracted period of long-term care or death, yet the processes underlying severe disability have not been fully evaluated., Objective: To evaluate potential risk factors and precipitants associated with severe disability that develops progressively (during ≥2 months) vs catastrophically (from 1 month to the next)., Design, Setting, and Participants: Prospective cohort study conducted in greater New Haven, Connecticut, from March 1998 to December 2016, with 754 nondisabled community-living persons aged 70 years or older. Data analysis was conducted from November 2018 to May 2019., Main Outcomes and Measures: Candidate risk factors were assessed every 18 months. Functional status and potential precipitants, including illnesses or injuries leading to hospitalization, emergency department visit, or restricted activity, were assessed each month. Severe disability was defined as the need for personal assistance with at least 3 of 4 essential activities of daily living. The analysis was based on person-months within 18-month intervals., Results: The mean (SD) age for the 754 participants was 78.4 (5.3) years, 487 (64.6%) were women, and 683 (90.5%) were non-Hispanic white participants. The incidence of progressive and catastrophic severe disability was 3.5% and 9.7%, respectively, based on 3550 intervals. In multivariable analysis, 6 risk factors were independently associated with progressive disability (≥85 years: hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; hearing impairment: HR, 1.7; 95% CI, 1.0-2.8; frailty: HR, 2.4; 95% CI, 1.6-3.7; cognitive impairment: HR, 2.0; 95% CI, 1.3-3.1; low functional self-efficacy: HR, 1.8; 95% CI, 1.2-2.8; low peak flow: HR, 1.7; 95% CI, 1.2-2.4), and 4 were independently associated with catastrophic disability (visual impairment: HR, 1.4; 95% CI, 1.1-1.8; hearing impairment: HR, 1.3; 95% CI, 1.0-1.7; poor physical performance: HR, 1.8; 95% CI, 1.3-2.5; low peak flow: HR, 1.3; 95% CI, 1.0-1.7). The associations of the precipitants were much more pronounced than those of the risk factors, with HRs as high as 321.4 (95% CI, 194.5-531.0) for hospitalization and catastrophic disability and 48.3 (95% CI, 31.0%-75.4%) for hospitalization and progressive disability. Elimination of an intervening hospitalization was associated with a decrease in the risk of progressive and catastrophic severe disability of 3.0% (95% CI, 3.0%-3.1%) and 12.3% (95% CI, 12.1%-12.5%), respectively. Risk differences were 0.6% (95% CI, 0.6%-0.6%) and 1.3% (95% CI, 1.3%-1.4%) for emergency department visit and 0.1% (95% CI, 0.1%-0.2%) and 0.4% (95% CI, 0.4%-0.4%) for restricted activity, and ranged from 0.1% (95% CI, 0.1%-0.1%) to 0.3% (95% CI, 0.3%-0.3%) for the independent risk factors, for progressive and catastrophic disability, respectively., Conclusions and Relevance: The findings of this study suggest that whether it develops progressively or catastrophically, severe disability among older community-living adults arises most commonly in the setting of an intervening illness or injury. To reduce the burden of severe disability, more aggressive efforts will be needed to prevent and manage intervening illnesses or injuries and to facilitate recovery after these debilitating events.

Importance: Many older survivors of acute myocardial infarction (AMI) experience functional decline, an outcome of primary importance to older adults. Mobility impairment has been proposed as a risk factor for functional decline but has not been evaluated to date in older patients hospitalized for AMI., Objective: To examine the association of mobility impairment, measured during hospitalization, as a risk marker for functional decline among older patients with AMI., Design, Setting, and Participants: Prospective cohort study among 94 academic and community hospitals in the United States. Participants were 2587 hospitalized patients with AMI who were 75 years or older. The study dates were January 2013 to June 2017., Main Outcomes and Measures: Mobility was evaluated during AMI hospitalization using the Timed "Up and Go," with scores categorized as preserved mobility (≤15 seconds to complete), mild impairment (>15 to ≤25 seconds to complete), moderate impairment (>25 seconds to complete), and severe impairment (unable to complete). Self-reported function in activities of daily living (ADLs) (bathing, dressing, transferring, and walking around the home) and walking 0.4 km (one-quarter mile) was assessed at baseline and 6 months after discharge. The primary outcomes were worsening of 1 or more ADLs and loss of ability to walk 0.4 km from baseline to 6 months after discharge. The association between mobility impairment and risk of functional decline was evaluated with multivariable-adjusted logistic regression., Results: Among 2587 hospitalized patients with AMI, the mean (SD) age was 81.4 (4.8) years, and 1462 (56.5%) were male. More than half of the cohort exhibited mobility impairment during AMI hospitalization (21.8% [564 of 2587] had mild impairment, 16.0% [414 of 2587] had moderate impairment, and 15.2% [391 of 2587] had severe impairment); 12.8% (332 of 2587) reported ADL decline, and 16.7% (431 of 2587) reported decline in 0.4-km mobility. Only 3.8% (30 of 800) of participants with preserved mobility experienced any ADL decline compared with 6.9% (39 of 564) of participants with mild impairment (adjusted odds ratio [aOR], 1.24; 95% CI, 0.74-2.09), 18.6% (77 of 414) of participants with moderate impairment (aOR, 2.67; 95% CI, 1.67-4.27), and 34.7% (136 of 391) of participants with severe impairment (aOR, 5.45; 95% CI, 3.29-9.01). Eleven percent (90 of 800) of participants with preserved mobility declined in ability to walk 0.4 km compared with 15.2% (85 of 558) of participants with mild impairment (aOR, 1.51; 95% CI, 1.04-2.20), 19.0% (78 of 411) of participants with moderate impairment (aOR, 2.03; 95% CI, 1.37-3.02), and 24.6% (95 of 386) of participants with severe impairment (aOR, 3.25; 95% CI, 2.02-5.23)., Conclusions and Relevance: This study's findings suggest that mobility impairment assessed during hospitalization may be a potent risk marker for functional decline in older survivors of AMI. These findings also suggest that brief, validated assessments of mobility should be part of the care of older hospitalized patients with AMI to identify those at risk for this important patient-centered outcome.

Importance: In one-third of older men with anemia, no recognized cause can be found., Objective: To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration., Design, Setting, and Participants: A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≤12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014., Interventions: Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months., Main Outcomes and Measures: The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors., Results: The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline., Conclusions and Relevance: Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels., Trial Registration: clinicaltrials.gov Identifier: NCT00799617.

Importance: As men age, they experience decreased serum testosterone concentrations, decreased bone mineral density (BMD), and increased risk of fracture., Objective: To determine whether testosterone treatment of older men with low testosterone increases volumetric BMD (vBMD) and estimated bone strength., Design, Setting, and Participants: Placebo-controlled, double-blind trial with treatment allocation by minimization at 9 US academic medical centers of men 65 years or older with 2 testosterone concentrations averaging less than 275 ng/L participating in the Testosterone Trials from December 2011 to June 2014. The analysis was a modified intent-to-treat comparison of treatment groups by multivariable linear regression adjusted for balancing factors as required by minimization., Interventions: Testosterone gel, adjusted to maintain the testosterone level within the normal range for young men, or placebo gel for 1 year., Main Outcomes and Measures: Spine and hip vBMD was determined by quantitative computed tomography at baseline and 12 months. Bone strength was estimated by finite element analysis of quantitative computed tomography data. Areal BMD was assessed by dual energy x-ray absorptiometry at baseline and 12 months., Results: There were 211 participants (mean [SD] age, 72.3 [5.9] years; 86% white; mean [SD] body mass index, 31.2 [3.4]). Testosterone treatment was associated with significantly greater increases than placebo in mean spine trabecular vBMD (7.5%; 95% CI, 4.8% to 10.3% vs 0.8%; 95% CI, -1.9% to 3.4%; treatment effect, 6.8%; 95% CI, 4.8%-8.7%; P < .001), spine peripheral vBMD, hip trabecular and peripheral vBMD, and mean estimated strength of spine trabecular bone (10.8%; 95% CI, 7.4% to 14.3% vs 2.4%; 95% CI, -1.0% to 5.7%; treatment effect, 8.5%; 95% CI, 6.0%-10.9%; P < .001), spine peripheral bone, and hip trabecular and peripheral bone. The estimated strength increases were greater in trabecular than peripheral bone and greater in the spine than hip. Testosterone treatment increased spine areal BMD but less than vBMD., Conclusions and Relevance: Testosterone treatment for 1 year of older men with low testosterone significantly increased vBMD and estimated bone strength, more in trabecular than peripheral bone and more in the spine than hip. A larger, longer trial could determine whether this treatment also reduces fracture risk., Trial Registration: clinicaltrials.gov Identifier: NCT00799617.

Importance: Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions., Objective: To determine if testosterone treatment compared with placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI)., Design, Setting, and Participants: The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014., Interventions: Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year., Main Outcomes and Measures: The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to -26), executive function (Trail-Making Test B minus A; range, -290 to 290), and spatial ability (Card Rotation Test; score range, -80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months., Results: Among the 493 men with AAMI (mean age, 72.3 years [SD, 5.8]; mean baseline testosterone, 234 ng/dL [SD, 65.1]), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the testosterone group and 245 men in the placebo completed the memory study. There was no significant mean change from baseline to 6 and 12 months in delayed paragraph recall score among men with AAMI in the testosterone and placebo groups (adjusted estimated difference, -0.07 [95% CI, -0.92 to 0.79]; P = .88). Mean scores for delayed paragraph recall were 14.0 at baseline, 16.0 at 6 months, and 16.2 at 12 months in the testosterone group and 14.4 at baseline, 16.0 at 6 months, and 16.5 at 12 months in the placebo group. Testosterone was also not associated with significant differences in visual memory (-0.28 [95% CI, -0.76 to 0.19]; P = .24), executive function (-5.51 [95% CI, -12.91 to 1.88]; P = .14), or spatial ability (-0.12 [95% CI, -1.89 to 1.65]; P = .89)., Conclusions and Relevance: Among older men with low testosterone and age-associated memory impairment, treatment with testosterone for 1 year compared with placebo was not associated with improved memory or other cognitive functions., Trial Registration: clinicaltrials.gov Identifier: NCT00799617.

Importance: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk., Objective: To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume., Design, Setting, and Participants: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014., Intervention: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months., Main Outcomes and Measures: The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis)., Results: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95% CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group., Conclusions and Relevance: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding., Trial Registration: clinicaltrials.gov Identifier: NCT00799617.

Importance: Little is known about functional trajectories of older persons in the year before and after admission to the intensive care unit (ICU) or how pre-ICU functional trajectories affect post-ICU functional trajectories and death., Objectives: To characterize functional trajectories in the year before and after ICU admission and to evaluate the associations among pre-ICU functional trajectories and post-ICU functional trajectories, short-term mortality, and long-term mortality., Design, Setting, and Participants: Prospective cohort study of 754 community-dwelling persons 70 years or older, conducted between March 23, 1998, and December 31, 2012, in greater New Haven, Connecticut. The analytic sample included 291 participants who had at least 1 admission to an ICU through December 2011., Main Outcomes and Measures: Functional trajectories in the year before and after an ICU admission based on 13 basic, instrumental, and mobility activities. Additional outcomes included short-term (30 day) and long-term (1 year) mortality., Results: The mean (SD) age of participants was 83.7 (5.5) years. Three distinct pre-ICU functional trajectories identified were minimal disability (29.6%), mild to moderate disability (44.0%), and severe disability (26.5%). Seventy participants (24.1%) experienced early death, defined as death in the hospital (50 participants [17.2%]) or death after hospital discharge but within 30 days of admission (20 participants [6.9%]). Among the remaining 221 participants, 3 distinct post-ICU functional trajectories identified were minimal disability (20.8%), mild to moderate disability (28.1%), and severe disability (51.1%). More than half of the participants (53.4%) experienced functional decline or early death after critical illness. The pre-ICU functional trajectories of mild to moderate disability and severe disability were associated with more than double (adjusted hazard ratio [HR], 2.41; 95% CI, 1.29-4.50) and triple (adjusted HR, 3.84; 95% CI, 1.84-8.03) the risk of death within 1 year of ICU admission, respectively. Other factors associated with 1-year mortality included ICU length of stay (adjusted HR, 1.03; 95% CI, 1.00-1.05), mechanical ventilation (adjusted HR, 2.89; 95% CI, 1.91-4.37), and shock (adjusted HR, 2.68; 95% CI, 1.63-4.38)., Conclusions and Relevance: Among older persons with critical illness, more than half died within 1 month or experienced significant functional decline over the following year, with particularly poor outcomes in those who had high levels of premorbid disability. These results may help to inform discussions about prognosis and goals of care before and during critical illness.

Importance: The increasing intensity of diabetes mellitus management over the past decade may have resulted in lower rates of hyperglycemic emergencies but higher rates of hospital admissions for hypoglycemia among older adults. Trends in these hospitalizations and subsequent outcomes are not known., Objective: To characterize changes in hyperglycemia and hypoglycemia hospitalization rates and subsequent mortality and readmission rates among older adults in the United States over a 12-year period, and to compare these results according to age, sex, and race., Design, Setting, and Patients: Retrospective observational study using data from 33,952,331 Medicare fee-for-service beneficiaries 65 years or older from 1999 to 2011., Main Outcomes and Measures: Hospitalization rates for hyperglycemia and hypoglycemia, 30-day and 1-year mortality rates, and 30-day readmission rates., Results: A total of 279,937 patients experienced 302,095 hospitalizations for hyperglycemia, and 404,467 patients experienced 429,850 hospitalizations for hypoglycemia between 1999 and 2011. During this time, rates of admissions for hyperglycemia declined by 38.6% (from 114 to 70 admissions per 100,000 person-years), while admissions for hypoglycemia increased by 11.7% (from 94 to 105 admissions per 100,000 person-years). In analyses designed to account for changing diabetes mellitus prevalence, admissions for hyperglycemia and hypoglycemia declined by 55.2% and 9.5%, respectively. Trends were similar across age, sex, and racial subgroups, but hypoglycemia rates were 2-fold higher for older patients (≥75 years) when compared with younger patients (65-74 years), and admission rates for both hyperglycemia and hypoglycemia were 4-fold higher for black patients compared with white patients. The 30-day and 1-year mortality and 30-day readmission rates improved during the study period and were similar after an index hospitalization for either hyperglycemia or hypoglycemia (5.4%, 17.1%, and 15.3%, respectively, after hyperglycemia hospitalizations in 2010; 4.4%, 19.9%, and 16.3% after hypoglycemia hospitalizations)., Conclusions and Relevance: Hospital admission rates for hypoglycemia now exceed those for hyperglycemia among older adults. Although admissions for hypoglycemia have declined modestly since 2007, rates among black Medicare beneficiaries and those older than 75 years remain high. Hospital admissions for severe hypoglycemia seem to pose a greater health threat than those for hyperglycemia, suggesting new opportunities for improvement in care of persons with diabetes mellitus.

Importance: In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability., Objective: To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability., Design, Setting, and Participants: The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban, and rural communities at 8 centers throughout the United States. We randomized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m., Interventions: Participants were randomized to a structured, moderate-intensity physical activity program (n = 818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included aerobic, resistance, and flexibility training activities or to a health education program (n = 817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises., Main Outcomes and Measures: The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m., Results: Incident major mobility disability occurred in 30.1% (246 participants) of the physical activity group and 35.5% (290 participants) of the health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P = .03).Persistent mobility disability was experienced by 120 participants (14.7%) in the physical activity group and 162 participants (19.8%) in the health education group (HR, 0.72 [95% CI, 0.57-0.91]; P = .006). Serious adverse events were reported by 404 participants (49.4%) in the physical activity group and 373 participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI, 0.98-1.20])., Conclusions and Relevance: A structured, moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability. These findings suggest mobility benefit from such a program in vulnerable older adults., Trial Registration: clinicaltrials.gov Identifier: NCT01072500.

Importance: Although a serious fall injury is often a devastating event, little is known about the course of disability (ie, functional trajectories) before a serious fall injury or the relationship between these trajectories and those that follow the fall., Objectives: To identify distinct sets of functional trajectories in the year immediately before and after a serious fall injury, to evaluate the relationship between the prefall and postfall trajectories, and to determine whether these results differed based on the type of injury., Design, Setting, and Participants: Prospective cohort study conducted in greater New Haven, Connecticut, from March 16, 1998, to June 30, 2012, in 754 community-living persons aged 70 years or older who were initially nondisabled in their basic activities of daily living. Of the 130 participants who subsequently sustained a serious fall injury, 62 had a hip fracture and 68 had another fall-related injury leading to hospitalization., Main Outcomes and Measures: Functional trajectories, based on 13 basic, instrumental, and mobility activities assessed during monthly interviews, were identified in the year before and the year after the serious fall injury., Results: Before the fall, 5 distinct trajectories were identified: no disability in 16 participants (12.3%), mild disability in 34 (26.2%), moderate disability in 34 (26.2%), progressive disability in 23 (17.7%), and severe disability in 23 (17.7%). After the fall, 4 distinct trajectories were identified: rapid recovery in 12 participants (9.2%), gradual recovery in 35 (26.9%), little recovery in 26 (20.0%), and no recovery in 57 (43.8%). For both hip fractures and other serious fall injuries, the probabilities of the postfall trajectories were greatly influenced by the prefall trajectories, such that rapid recovery was observed only among persons who had no disability or mild disability, and a substantive recovery, defined as rapid or gradual, was highly unlikely among those who had progressive or severe disability. The postfall trajectories were consistently worse for hip fractures than for the other serious injuries., Conclusions and Relevance: The functional trajectories before and after a serious fall injury are quite varied but highly interconnected, suggesting that the likelihood of recovery is greatly constrained by the prefall trajectory.

Importance: Freedom from symptoms is an important determinant of a good death, but little is known about symptom occurrence during the last year of life., Objective: To evaluate the monthly occurrence of physical and psychological symptoms leading to restrictions in daily activities (ie, restricting symptoms) among older persons during the last year of life and to determine the associations of demographic and clinical factors with symptom occurrence., Design, Setting, and Participants: Prospective cohort study. Comprehensive assessments were completed every 18 months, and monthly interviews were conducted to assess the presence of restricting symptoms. Of 1002 nondisabled community-dwelling individuals 70 years or older in greater New Haven, Connecticut, eligible to participate, 754 agreed and were enrolled between 1998 and 1999., Main Outcomes and Measures: The primary outcome was the monthly occurrence of restricting symptoms as a dichotomous outcome. The monthly mean count of restricting symptoms was a secondary outcome., Results: Among the 491 participants who died after their first interview and before June 30, 2011, mean age at death was 85.8 years, 61.9% were women, and 9.0% were nonwhite. The mean number of comorbid conditions was 2.4, and 73.1% had multimorbidity. The monthly occurrence of restricting symptoms was fairly constant from 12 months before death (20.4%) until 5 months before death (27.4%), when it began to increase rapidly, reaching 57.2% in the month before death. In multivariable analysis, age younger than 85 years (odds ratio [OR], 1.30 [95% CI, 1.07-1.57]), multimorbidity (OR, 1.38 [95% CI, 1.09-1.75]), and proximity to time of death (OR, 1.14 per month [95% CI, 1.11-1.16]) were significantly associated with the monthly occurrence of restricting symptoms. Participants who died of cancer had higher monthly symptom occurrence (OR, 1.80 [95% CI, 1.03-3.14]) than participants who died of sudden death, although this difference was only marginally significant (P = .04). Symptom burden did not otherwise differ substantially according to condition leading to death., Conclusions and Relevance: Restricting symptoms are common during the last year of life, increasing substantially approximately 5 months before death. Our results highlight the importance of assessing and managing symptoms in older patients, particularly those with multimorbidity.

Context: Disability among older persons is a complex and highly dynamic process, with high rates of recovery and frequent transitions between states of disability. The role of intervening illnesses and injuries (ie, events) on these transitions is uncertain., Objectives: To evaluate the relationship between intervening events and transitions among states of no disability, mild disability, severe disability, and death and to determine the association of physical frailty with these transitions., Design, Setting, and Participants: Prospective cohort study conducted in greater New Haven, Connecticut, from March 1998 to December 2008 of 754 community-living persons aged 70 years or older who were nondisabled at baseline in 4 essential activities of daily living: bathing, dressing, walking, and transferring. Telephone interviews were completed monthly for more than 10 years to assess disability and ascertain exposure to intervening events, which included illnesses and injuries leading to either hospitalization or restricted activity. Physical frailty (defined as gait speed >10 seconds on the rapid gait test) was assessed every 18 months through 108 months., Main Outcome Measure: Transitions between no disability, mild disability, and severe disability and 3 transitions from each of these states to death, evaluated each month., Results: Hospitalization was strongly associated with 8 of the 9 possible transitions, with increased multivariable hazard ratios (HRs) as high as 168 (95% confidence interval [CI], 118-239) for the transition from no disability to severe disability and decreased HRs as low as 0.41 (95% CI, 0.30-0.54) for the transition from mild disability to no disability. Restricted activity also increased the likelihood of transitioning from no disability to both mild and severe disability (HR, 2.59; 95% CI, 2.23-3.02; and HR, 8.03; 95% CI, 5.28-12.21), respectively, and from mild disability to severe disability (HR, 1.45; 95% CI, 1.14-1.84), but was not associated with recovery from mild or severe disability. For all 9 transitions, the presence of physical frailty accentuated the associations of the intervening events. For example, the absolute risk of transitioning from no disability to mild disability within 1 month after hospitalization for frail individuals was 34.9% (95% CI, 34.5%-35.3%) vs 4.9% (95% CI, 4.7%-5.1%) for nonfrail individuals. Among the possible reasons for hospitalization, fall-related injury conferred the highest likelihood of developing new or worsening disability., Conclusions: Among older persons, particularly those who were physically frail, intervening illnesses and injuries greatly increased the likelihood of developing new or worsening disability. Only the most potent events, ie, those leading to hospitalization, reduced the likelihood of recovery from disability.

Context: Maintaining independence of older persons is a public health priority, and identifying the factors that contribute to decline in physical function is needed to prevent or postpone the disablement process. The potential deleterious effect of poor nutrition on decline in physical function in older persons is unclear., Objective: To determine whether a low serum concentration of micronutrients is associated with subsequent decline in physical function among older men and women living in the community., Design, Setting, and Participants: Longitudinal study of 698 community-living persons 65 years or older who were randomly selected from a population registry in Tuscany, Italy. Participants completed the baseline examination from November 1, 1998, through May 28, 2000, and the 3-year follow-up assessments from November 1, 2001, through March 30, 2003., Main Outcome Measure: Decline in physical function was defined as a loss of at least 1 point in the Short Physical Performance Battery during the 3-year follow-up. Odds ratios (ORs) were calculated for the lowest quartile of each nutrient using the other 3 quartiles combined as the reference group. Two additional and complementary analytical approaches were used to confirm the validity of the results., Results: The mean decline in the Short Physical Performance Battery score was 1.1 point. In a logistic regression analysis that was adjusted for potential confounders, only a low concentration of vitamin E (<1.1 microg/mL [<24.9 micromol/L]) was significantly associated with subsequent decline in physical function (OR, 1.62; 95% confidence interval, 1.11-2.36; P = .01 for association of lowest alpha-tocopherol quartile with at least a 1-point decline in physical function). In a general linear model, the concentration of vitamin E at baseline, when analyzed as a continuous measure, was significantly associated with the Short Physical Performance Battery score at follow-up after adjustment for potential confounders and Short Physical Performance Battery score at baseline (beta = .023; P = .01). In a classification and regression tree analysis, age older than 81 years and vitamin E (in participants aged 70-80 years) were identified as the strongest determinants of decline in physical function (physical decline in 84% and 60%, respectively; misclassification error rate, 0.33)., Conclusions: These results provide empirical evidence that a low serum concentration of vitamin E is associated with subsequent decline in physical function among community-living older adults. Clinical trials may be warranted to determine whether an optimal concentration of vitamin E reduces functional decline and the onset of disability in older persons.

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 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., 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.

Context: Previous studies have found that a sizeable minority of newly disabled older persons recover independent function; however, long intervals between assessments have led to difficulty in determining the true incidence and duration of disability, and therefore in accurately characterizing the probability and course of recovery., Objectives: To determine the rate of and time to recovery of independent function in community-dwelling older persons who become newly disabled in their activities of daily living (ADLs), to determine the duration of recovery, and to compare the likelihood of recovery among pertinent subgroups of older persons., Design, Setting, and Participants: Prospective cohort study, with monthly assessments of ADL function, for 754 initially nondisabled, community-dwelling persons aged 70 years or older, performed in a small urban area from March 1998 to May 2003., Main Outcome Measures: Demographic features, chronic conditions, cognitive function, and physical frailty were determined during comprehensive assessments at 18-month intervals. Disability, defined as needing personal assistance with 1 or more key ADLs (bathing, dressing, walking, and transferring), was assessed during monthly telephone interviews., Results: A total of 420 participants (56%) experienced disability during a median follow-up of 51 months. Of these participants, 399 (81%) recovered (ie, regained independence in all 4 ADLs) within 12 months of their initial disability episode, and a majority (57%) of these maintained independence for at least 6 months. Among participants who experienced 3 or more consecutive months of disability, a majority (60%) recovered, but only a third of these maintained independence for at least 6 months. Persons who were cognitively impaired, physically frail, or severely disabled (ie, in 3-4 ADLs) at onset were less likely to recover than those who were cognitively intact, nonfrail, or mildly disabled, respectively. Nonetheless, a majority of participants within each subgroup recovered., Conclusions: Newly disabled older persons recover independent ADL function at rates far exceeding those that have been previously reported. Recovery from disability, however, is often short-lasting, suggesting that additional efforts are warranted to maintain independence in this high-risk group.

While the benefits of physical activity and exercise among older persons are becoming increasingly clear, the role of exercise stress testing and safety monitoring for older persons who want to start an exercise program is unclear. Current guidelines regarding exercise stress testing likely are not applicable to the majority of persons aged 75 years or older who are interested in restoring or enhancing their physical function through a program of physical activity and exercise. In addition to being expensive and of unproven benefit, the current policy of routine exercise stress testing potentially could deter many older persons from participating in an exercise program. Research is needed to investigate current physician practices, evaluate the risk of adverse cardiac events, determine the role of pharmacological stress testing, and measure and compare absolute and relative exercise intensities. To assist clinicians, we offer a set of recommendations regarding precautions that can be taken to minimize the risk of adverse cardiac events among previously sedentary older persons who do not have symptomatic cardiovascular disease and are interested in starting an exercise program. JAMA. 2000;284:342-349

A prospective study of persons older than 70 years provided evidence to contest the association between blood cholesterol level and incidence of CHD or death due to CHD. Drug treatment for mild to moderate hypertension substantially reduced morbidity and mortality from stroke and from CHD.

Objective: To evaluate how well quality of life is being measured in the medical literature and to offer a new approach to the measurement., Data Sources: Original English-language articles having the term "quality of life" in their titles were identified from a recent Quality-of-Life Bibliography and from two MEDLINE searches. Articles were eligible for review only if they described or used one or more "quality-of-life" instruments., Study Selection: Twenty-five articles were randomly selected from each of the three data sources., Data Extraction: Each article was reviewed for its compliance with two sets of criteria having several components, which are cited under "Data Synthesis.", Data Synthesis: (1) Investigators conceptually defined quality of life in only 11 (15%) of the 75 articles; identified the targeted domains in only 35 (47%); gave reasons for selecting the chosen quality-of-life instruments in only 27 (36%); and aggregated their results into a composite quality-of-life score in only 27 (38%) of 71 eligible articles. (2) No article distinguished "overall" quality of life from health-related quality of life; patients were invited to give their own separate rating for quality of life in only 13 articles (17%); and among 71 eligible articles, patients were asked to supplement the stipulated items with personal responses in only nine (13%) and to rate the importance of individual items in only six (8.5%)., Conclusions: Because quality of life is a uniquely personal perception, denoting the way that individual patients feel about their health status and/or nonmedical aspects of their lives, most measurements of quality of life in the medical literature seem to aim at the wrong target. Quality of life can be suitably measured only by determining the opinions of patients and by supplementing (or replacing) the instruments developed by "experts."