Deficit Accumulation Approach Research Articles

Social Vulnerability and Mental Health Among People with HIV and Substance Use: The Role of Race.

Poor mental health significantly impacts people with HIV (PWH) and those who drink alcohol. Limited data exist on the combined effects of social determinants of health (social vulnerability) on mental health in PWH with unhealthy substance use. We investigated the relationship between social vulnerability and poor mental health in PWH and whether this relationship differed by race/ethnicity. We conducted a cross-sectional analysis using data from the Boston ARCH Cohort among PWH with current or past unhealthy substance use. We created a 23-item social vulnerability index (SVI) using a deficit accumulation approach comprised of social determinants of health indicators. We estimated whether higher SVI score is associated with anxiety and depressive symptoms using logistic regression analysis. Among 251 participants with a mean age of 52 (SD = 10) years, 67.3% were male, 52% Black, 21% Hispanic, 19% White, and 73% unemployed. The SVI had a mean of 9.30 (SD = 3.4) with a 1.5-18 range. Nearly two in five persons reported past month heavy alcohol use and 35% illicit drug use. The prevalence of anxiety and depressive symptoms was 34.4% and 54.2% respectively. Higher SVI score was associated with anxiety symptoms (adjusted odds ratio [aOR] = 2.01, 95% confidence interval [CI] 1.46, 2.76, p ≤ 0.001), and depressive symptoms (aOR = 2.42, 95% CI 1.74, 3.36, p ≤ 0.001). Race/ethnicity did not moderate the relationship between SVI and each mental health outcome. SVI was significantly associated with poor mental health across racial/ethnicity groups in this cohort. Interventions that address social vulnerability may improve well-being and quality of life for PWH.

Implications of frailty before and after intensive care unit admission.

In the decade since the first publications related to frailty in those with critical illness, the study of frailty has rapidly increased. The purpose of this review is to update the reader on recent advances across several important areas of frailty research: how best to identify frailty in those with critical illness, studies describing the relationship between frailty and delirium, and how frailty affects outcomes for those with coronavirus disease 2019 (COVID-19), which, despite rates and severity of acute infection declining, still tremendously impacts patients long after the acute infection, resulting in symptoms of long COVID-19. A number of frailty assessment tools exist, to date, the Clinical Frailty Scale based on the deficit accumulation approach to defining frailty, is the most commonly used in ICU studies. Several novel frailty instruments for the ICU are being developed. Because tools assessing frailty by the phenotypic and deficit accumulation approaches identify different populations, careful choice of a frailty assessment tool is warranted.Frailty and delirium are hypothesized to represent different clinical expressions of a similar underlying vulnerability, thus identifying frailty may be a useful means by which to identify patients at high risk of becoming delirious. Recent studies show that frailty at ICU admission is a predictor of the development of delirium.Finally, frailty and its outcomes were studied in patients with COVID-19. As with other causes of critical illness, frailty was highly prevalent in those admitted to the ICU and is associated with greater mortality. Frailty was also associated with increased decisions to limit life support treatments, but these decisions were not different among those admitted with COVID-19 or for other reasons. Frailty in those with critical illness is an emerging field of study. Future work to define the optimal means by which to identify this syndrome and how best to manage critically ill patients with frailty are needed.

The Healthy Ageing/Vulnerable Environment (HAVEN) Index: Measuring neighbourhood age‐friendliness

AbstractThis study describes the development and testing of the Healthy Ageing/Vulnerable Environment (HAVEN) Index, a prototype composite spatial index for South Australia that reflects an area’s age‐friendliness. The index incorporates over 40 indicator variables across six variable themes: income and employment; education; health and housing; social connectedness; geographic access; and physical environment. Based on the deficit accumulation approach, the modelling uses area‐level rather than individual‐level data and is compiled through quantitative geospatial methods. Analysis using the HAVEN Index of state‐wide mortality data and hospital emergency department (ED) presentations for Central Adelaide found that vulnerable areas were associated with a higher risk of mortality and ED presentation. Comparisons between the HAVEN Index and a widely used national area‐level measure of socio‐economic differences found that the HAVEN Index compares favourably and provides additional information about local areas, which can inform needs‐based approaches to support the reduction of spatial inequalities and the development of age‐friendly neighbourhoods.

Claims-based Frailty Index in Japanese Older Adults: A Cohort Study Using LIFE Study Data.

We aimed to assess whether the United States-developed Claims-based Frailty Index (CFI) can be implemented in Japanese older adults using claims data. We used the monthly claims data and certification of long-term care (LTC) insurance data of residents from 12 municipalities from April 2014 to March 2019. The 12 months from first recording was defined as the "baseline period," and the time thereafter as the "follow-up period". Participants aged ≥65 years were included, and those with no certified LTC insurance or who died at baseline were excluded. New certification of LTC insurance and all-cause mortality during the follow-up period were defined as outcome events. CFI categorization consisted of three steps including: 1) using 12 months deficit-accumulation approach that assigned different weights to each of the 52 items; 2) the accumulated score to derive the CFI; and 3) categorizing the CFI as "robust" (<0.15), "prefrail" (0.15-0.24), and "frail" (≥0.25). Kaplan-Meier survival curves and Cox proportional hazard models were used to determine the association between CFI and outcomes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. There were 519,941 participants in total. After adjusting for covariates, the severe CFI category had a high risk of certification of LTC insurance (prefrail: HR 1.33; 95% CI, 1.27-1.39 and frail: HR 1.60; 95% CI, 1.53-1.68) and all-cause mortality (prefrail: HR 1.44; 95% CI, 1.29-1.60 and frail: HR 1.84; 95% CI, 1.66-2.05). This study suggests that CFI can be implemented in Japanese claims data to predict the certification of LTC insurance and mortality.

Prognostic accuracy of 70 individual frailty biomarkers in predicting mortality in the Canadian Longitudinal Study on Aging

The frailty index (FI) uses a deficit accumulation approach to derive a single, comprehensive, and replicable indicator of age-related health status. Yet, many researchers continue to seek a single “frailty biomarker” to facilitate clinical screening. We investigated the prognostic accuracy of 70 individual biomarkers in predicting mortality, comparing each with a composite FI. A total of 29,341 individuals from the comprehensive cohort of the Canadian Longitudinal Study on Aging were included (mean, 59.4 ± 9.9 years; 50.3% female). Twenty-three blood-based biomarkers and 47 test-based biomarkers (e.g., physical, cardiac, cardiology) were examined. Two composite FIs were derived: FI-Blood and FI-Examination. Mortality status was ascertained using provincial vital statistics linkages and contact with next of kin. Areas under the curve were calculated to compare prognostic accuracy across models (i.e., age, sex, biomarker, FI) in predicting mortality. Compared to an age-sex only model, the addition of individual biomarkers demonstrated improved model fit for 24/70 biomarkers (11 blood, 13 test-based). Inclusion of FI-Blood or FI-Examination improved mortality prediction when compared to any of the 70 biomarker-age-sex models. Individual addition of seven biomarkers (walking speed, chair rise, time up and go, pulse, red blood cell distribution width, C-reactive protein, white blood cells) demonstrated an improved fit when added to the age-sex-FI model. FI scores had better mortality risk prediction than any biomarker. Although seven biomarkers demonstrated improved prognostic accuracy when considered alongside an FI score, all biomarkers had worse prognostic accuracy on their own. Rather than a single biomarker test, implementation of routine FI assessment in clinical settings may provide a more accurate and reliable screening tool to identify those at increased risk of adverse outcomes.

EARLY-LIFE WAR EXPOSURE AND LATER-LIFE FRAILTY AMONG OLDER ADULTS IN VIETNAM: DOES WAR HASTEN AGING?

Abstract We aimed to assess the nature and degree of association between exposure to potentially traumatic wartime experiences in early life and later-life frailty. The Vietnam Health and Aging Study included war survivors in Vietnam, age 60+. Latent class analysis (LCA) is used to construct classes exposed to similar numbers and types of wartime experiences. Frailty is measured using a deficit accumulation approach that approximates biological aging. LCA yields 9 unique wartime exposure classes, ranging from extreme exposure to non-exposed. Higher frailty levels among those with heavy/severe exposures certain combinations of experiences, including intense bombing, witnessing death firsthand, having experienced sleep disruptions during wartime, and having feared for one’s life during war. The difference in frailty-associated aging between the most and least affected individuals is more than 18 years. War trauma hastens aging and warrants greater attention toward long-term implications of war on health among vast post-conflict populations across the globe.

Social Vulnerability and Frailty in Hospitalized Older Adults.

Social vulnerability is the accumulation of disadvantageous social circumstances resulting in susceptibility to adverse health outcomes. Associated with increased mortality, cognitive decline, and disability, social vulnerability has primarily been studied in large population databases rather than frail hospitalized individuals. We examined how social vulnerability contributes to hospital outcomes and use of hospital resources for older adults presenting to the Emergency Department. We analyzed patients 65 years of age or older admitted through the Emergency Department and consulted to internal medicine or geriatrics at a Canadian tertiary care hospital from July 2009 to September 2020. A 20-item social vulnerability index (SVI) and a 57-item frailty index (FI) were calculated, using a deficit accumulation approach. Outcomes were length of stay (LOS), extended hospital LOS designation, alternative level of care (ALC) designation, in-hospital mortality, and discharge to long-term care (LTC). In 1,146 patients (mean age 80.5±8.3, 54.0% female), mean SVI was 0.40±0.16 and FI was 0.44±0.14. The SVI scores were not associated with admission to hospital. Amongst those admitted, for every 0.1 unit increase in SVI, LOS increased by 1.15 days (p<.001) after adjusting for age, sex and FI. SVI was associated with staying over the expected LOS (aOR: 1.19, 1.05-1.34, p=.009) and ALC status (aOR 1.39, 1.12-1.74, p<.004). SVI was not associated with in-hospital mortality, but was associated with incident discharge to LTC (aOR 1.03, 1.02-1.04, p<.001). Independent of frailty, being socially vulnerable was associated with increased LOS, designation as ALC, and being discharged to LTC from hospital. Consideration of social vulnerability's influence on prolonged hospitalization and long-term care needs has implications for screening and hospital resources.

Development and validation of a hospital frailty risk measure using Canadian clinical administrative data.

Accessible measures specific to the Canadian context are needed to support health system planning for older adults living with frailty. We sought to develop and validate the Canadian Institute for Health Information (CIHI) Hospital Frailty Risk Measure (HFRM). Using CIHI administrative data, we conducted a retrospective cohort study involving patients aged 65 years and older who were discharged from Canadian hospitals from Apr. 1, 2018, to Mar. 31, 2019. We used a 2-phase approach to develop and validate the CIHI HFRM. The first phase, construction of the measure, was based on the deficit accumulation approach (identification of age-related conditions using a 2-year look-back). The second phase involved refinement into 3 formats (continuous risk score, 8 risk groups and binary risk measure), with assessment of their predictive validity for several frailty-related adverse outcomes using data to 2019/20. We assessed convergent validity with the United Kingdom Hospital Frailty Risk Score. The cohort consisted of 788 701 patients. The CIHI HFRM included 36 deficit categories and 595 diagnosis codes that cover morbidity, function, sensory loss, cognition and mood. The median continuous risk score was 0.111 (interquartile range 0.056-0.194, equivalent to 2-7 deficits); 35.1% (n = 277 000) of the cohort were found at risk of frailty (≥ 6 deficits). The CIHI HFRM showed satisfactory predictive validity and reasonable goodness-of-fit. For the continuous risk score format (unit = 0.1), the hazard ratio (HR) for 1-year risk of death was 1.39 (95% confidence interval [CI] 1.38-1.41), with a C-statistic of 0.717 (95% CI 0.715-0.720); the odds ratio for high users of hospital beds was 1.85 (95% CI 1.82-1.88), with a C-statistic of 0.709 (95% CI 0.704-0.714), and the HR of 90-day admission to long-term care was 1.91 (95% CI 1.88-1.93), with a C-statistic of 0.810 (95% CI 0.808-0.813). Compared with the continuous risk score, using a format of 8 risk groups had similar discriminatory ability and the binary risk measure had slightly weaker performance. The CIHI HFRM is a valid tool showing good discriminatory power for several adverse outcomes. The tool can be used by decision-makers and researchers by providing information on hospital-level prevalence of frailty to support system-level capacity planning for Canada's aging population.

FRAILTY AND AGE-RELATED CONDITIONS AMONG WORLD TRADE CENTER GENERAL RESPONDERS

Abstract As WTC exposure may precipitate frailty, we examined patterns of frailty in the general responders cohort. We used two methods to assess frailty: a Clinical Frailty Index (FI) developed using a deficit accumulation approach utilizing clinical assessments performed during routine annual visits to a WTC clinical program in New York City; and a frailty questionnaire (5-point FRAIL scale) collected from a subsample of responders. Using a Clinical FI cutoff score of 0.25, over 25% of the 7,679 participants, median age 58.3 years (IQR 9.3), who had any visit to the WTC clinical program from 2017 to 2019, were frail. In a subsample of 100 participants with additional frailty assessment (FRAIL scale), we found that 27% were pre-frail, 5% were frail, 14% had recent falls, 9% had ADL dependencies; 34% had mild cognitive impairment. These data suggest that frailty and its related conditions are prevalent among the cohort despite younger age.

Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation.

Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d=18), a frailty index (FI, d=66) and a lifestyle/social vulnerability index (LSVI, d=10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.

Frailty indices based on self-report, blood-based biomarkers and examination-based data in the Canadian Longitudinal Study on Aging.

Frailty can be operationalised using the deficit accumulation approach, which considers health deficits across multiple domains. We aimed to develop, validate and compare three different frailty indices (FI) constructed from self-reported health measures (FI-Self Report), blood-based biomarkers (FI-Blood) and examination-based assessments (FI-Examination). Up to 30,027 participants aged 45-85years from the baseline (2011-2015) comprehensive cohort of the Canadian Longitudinal Study on Aging were included in the analyses. Following standard criteria, three FIs were created: a 48-item FI-Self Report, a 23-item FI-Blood and a 47-item FI-Examination. In addition a 118-item FI-Combined was constructed. Mortality status was ascertained in July 2019. FI-Blood and FI-Examination demonstrated broader distributions than FI-Self Report. FI-Self Report and FI-Blood scores were higher in females, whereas FI-Examination scores were higher in males. All FI scores increased nonlinearly with age and were highest at lower education levels. In sex and age-adjusted models, a 0.01 increase in FI score was associated with a 1.08 [95% confidence interval (CI): 1.07,1.10], 1.05 (1.04,1.06), 1.07 (1.05,1.08) and a 1.13 (1.11,1.16) increased odds of mortality for FI-Self Report, FI-Blood, FI-Examination and FI-Combined, respectively. Inclusion of the three distinct FI types in a single model yielded the best prognostic accuracy and model fit, even compared to the FI-Combined, with all FIs remaining independently associated with mortality. Characteristics of all FIs were largely consistent with previously established FIs. To adequately capture frailty levels and to improve our understanding of the heterogeneity of ageing, FIs should consider multiple types of deficits including self-reported, blood and examination-based measures.

Impact of Polypharmacy and Potentially Inappropriate Medications Among Older Adults with Blood Cancers

Impact of Polypharmacy and Potentially Inappropriate Medications Among Older Adults with Blood Cancers

Early-Life War Exposure and Later-Life Frailty Among Older Adults in Vietnam: Does War Hasten Aging?

This study aimed to assess the nature and degree of association between exposure to potentially traumatic wartime experiences in early life, such as living in a heavily bombed region or witnessing death firsthand, and later-life frailty. The Vietnam Health and Aging Study included war survivors in Vietnam, 60+, who completed a survey and health exam between May and August 2018. Latent class analysis (LCA) is used to construct classes exposed to similar numbers and types of wartime experiences. Frailty is measured using a deficit accumulation approach that proxies biological aging. Fractional logit regression associates latent classes with frailty scores. Coefficients are used to calculate predicted frailty scores and expected age at which specific levels of frailty are reached across wartime exposure classes. LCA yields 9 unique wartime exposure classes, ranging from extreme exposure to nonexposed. Higher frailty is found among those with more heavy/severe exposures with a combination of certain types of experiences, including intense bombing, witnessing death firsthand, having experienced sleep disruptions during wartime, and having feared for one's life during war. The difference in frailty-associated aging between the most and least affected individuals is more than 18 years. War trauma hastens aging and warrants greater attention toward long-term implications of war on health among vast postconflict populations across the globe.

Association Between Chronologic Age and Geriatric Assessment-Identified Impairments: Findings From the CARE Registry.

The NCCN Guidelines for Older Adult Oncology recommend that, when possible, older adults with cancer undergo a geriatric assessment (GA) to provide a comprehensive health appraisal to guide interventions and appropriate treatment selection. However, the association of age with GA-identified impairments (GA impairments) remains understudied and the appropriate age cutoff for using the GA remains unknown. We designed a cross-sectional study using the Cancer and Aging Resilience Evaluation (CARE) registry of older adults with cancer. We included adults aged ≥60 years diagnosed with gastrointestinal malignancy who underwent a patient-reported GA prior to their initial consultation at the gastrointestinal oncology clinic. We noted the presence of GA impairments and frailty using Rockwood's deficit accumulation approach. We studied the relation between chronologic age and GA impairments/frailty using Spearman rank correlation and chi-square tests of trend. We identified 455 eligible older adults aged ≥60 years with gastrointestinal malignancies; the median age was 68 years (range, 64-74 years) and colorectal (33%) and pancreatic (24%) cancers were the most common cancer type. The correlation between chronologic age and number of geriatric impairments was weak and did not reach statistical significance (Spearman ρ, 0.07; P=.16). Furthermore, the prevalence of domain-specific impairments or frailty was comparable across the 3 age groups (60-64 years, 65-74 years, ≥75 years) with the exception of comorbidity burden. Notably, 61% of patients aged 60 to 64 years had ≥2 GA impairments and 35% had evidence of frailty, which was comparable to patients aged 65 to 74 years (66% and 36%, respectively) and ≥75 years (70% and 40%, respectively). Using chronologic age alone to identify which patients may benefit from GA is problematic. Future studies should identify screening tools that may identify patients at high risk of frailty and GA impairments.

Impact of geriatric assessment (GA) based frailty index (CARE-Frailty Index) on mortality and treatment-related toxicity among older adults with gastrointestinal (GI) malignancies.

12046 Background: Older adults with cancer are at increased risk of treatment-related toxicity and mortality. A comprehensive geriatric assessment (GA) may uncover aging associated vulnerability and identify those at greatest risk of adverse outcomes. We studied the association between a novel frailty index and treatment-related morbidity and mortality among older adults with GI malignancies. Methods: Older adults (≥60y) referred for initial consultation at the UAB GI oncology clinic between 9/2017 to 12/2020 were enrolled in a prospective Cancer and Aging Resilience Evaluation (CARE) registry. All participants underwent a patient-reported GA at baseline as previously described (Williams et al J Geriat Oncol 2020). Using this information, we constructed a 44-item frailty index using a deficit accumulation approach. Vital status was acquired by linking with death records and chart review. In a subgroup of patients continuing care at UAB, we collected information on toxicity for the first 6 months of treatment via chart review using CTCAE v5.0. We used Kaplan Meier Methods and log-rank test to compare survival distributions, and a multivariate cox regression to adjust for potential confounders. We compared the toxicity rates across frailty subgroups using risk ratio (RR) calculated from general linear models. Results: Of 765 consecutive older adults referred to GI oncology clinic, 590 (77%) had available data to measure frailty index. Median age at enrollment was 68y; with 59% males and 72% White. Common cancer types included colorectal (30%) and pancreatic cancer (26%); mostly with advanced stage disease (stage III 28%; IV 46%). Overall, 168 (28%) were characterized as pre-frail and 230 (39.3%) as frail. As compared to non-frail, those who were frail were more likely to be Black (33% vs 20%; p &lt; 0.01) and have pancreatic cancer (33.6% vs 21.8%; p &lt; 0.01). Over a median follow up of 22 months, 212 (36%) patients had died. The 2y overall survival among non-frail, pre-frail and frail patients was 71%, 63% and 51%, respectively (log rank p value &lt; 0.001). In a multivariate cox regression, as compared to non-frail patients, frailty was associated with worse OS (HR 1.75; 95% CI 1.13-2.70; p = 0.01) after adjusting for age, sex, race, cancer stage, cancer type, line of therapy and performance status. In a subset of 168 patients with available data, baseline frailty was associated with increased risk of ≥grade 3 non-hematologic toxicity (RR 2.23; 95% CI 1.27-3.92; p &lt; 0.01) but not ≥grade 3 hematologic toxicity (RR 1.03; 95% CI 0.67-1.58; p = 0.90) as compared to non-frail patients Conclusions: The CARE-Frailty Index is a novel frailty index built on the principle of deficit accumulation using a patient-reported GA, and appears to be a robust predictor of survival and may predict treatment related toxicity among older adults with GI malignancies.

Inequalities in Frailty Among Older Turkish and Moroccan Immigrants and Native Dutch: Data from the Longitudinal Aging Study Amsterdam

Very few studies have investigated frailty among older immigrants in Europe. The aim of the current study was to investigate inequalities in frailty in young-olds related to gender, educational level and country of origin, as well as intersections between these characteristics. Cross-sectional data were used from older Turkish and Moroccan immigrants (n = 466) and native Dutch (n = 1,020), all aged 55–65 years and participating in the Longitudinal Aging Study Amsterdam. Frailty was assessed with a 30-item frailty index, based on the deficit accumulation approach. Frailty was higher among women, lower educated, and people with a migration background. Of all groups considered, frailty levels were the highest among Turkish immigrants. No statistically significant interaction effects between gender, educational level and country of origin were found. When targeting frailty interventions, special attention should be devoted to older immigrants, as they are the most vulnerable group with the highest frailty levels.

Changes in the severity and lethality of age-related health deficit accumulation in the USA between 1999 and 2018: a population-based cohort study

With an ageing population, the number of people with frailty is increasing. Despite this trend, the extent to which the severity and lethality of frailty have changed over time is not well understood. We aimed to investigate how frailty severity and lethality have changed over an 18-year period in the USA. In this population-based observational study, we used data from the National Health and Nutrition Examination Survey (NHANES) to identify community-dwelling individuals (aged ≥20 years) in the USA between 1999 and 2018. We analysed data from a series of ten 2-year, nationally representative, cross-sectional, prospective studies (from 1999-2000 to 2017-18) from the NHANES. Frailty was measured by use of the deficit accumulation approach (ie, a 46-item frailty index). The proportion of individuals categorised as non-frail, or living with very mild frailty, mild frailty, moderate frailty, and severe frailty were compared across cohorts. Random-effects models were used to examine the association between frailty index score and sex, age, and cohort. Mortality status as of Dec 31, 2015, was ascertained by use of National Death Index data, and 5-year mortality was available in the first six cohorts (1999-2010). Cox regression models and Kaplan-Meier curves were used to estimate the association between frailty index scores and mortality. In total, 49 004 individuals were included in our study. Associations were mainly non-linear (quadratic), with frailty increasing at a faster rate in more recent cohorts. Between 1999 and 2018, the proportion of non-frail individuals decreased by 10·4% (from 2747 [63·8%; 95% CI 61·9-65·6] of 4307 to 2884 [53·4%; 51·3-55·5] of 5399), whereas the proportion of individuals with very mild frailty increased by 2·4% (from 987 [22·9%; 21·3-24·6] to 1365 [25·3%; 23·5-27·2]), by 2·7% (from 370 [8·6%; 7·7-9·6] to 609 [11·3%; 10·1-12·5]) in those with mild frailty, by 3·1% (from 140 [3·3%; 2·7-3·9] to 347 [6·4%; 5·6-7·4]) in those with moderate frailty, and by 2·1% (from 63 [1·5%; 1·1-1·9] to 195 [3·6%; 3·0-4·3]) in those with severe frailty. Being a woman, older, and from a more recent cohort were associated with higher frailty index scores (all p<0·0001). In more recent cohorts, mean frailty index scores increased more quickly with age (p<0·0001), and sex differences in mean frailty index scores decreased (p<0·0001). In men of all ages and in women aged 35 years or older, mean frailty index scores were higher in more recent cohorts, with larger increases in frailty in older age groups. In 28 692 individuals from the first six cohorts (1999-2000 to 2009-10) with linked mortality data, frailty index scores were significantly associated with mortality (hazard ratio 1·053 [95% CI 1·050-1·057] per 0·01 increase in frailty index score). The absence of an interaction between cohort and frailty index score (p=0·58) suggested that the association between frailty and mortality was similar for all cohorts. Increasing frailty levels in more recent cohorts of middle-aged and older adults combined with stable frailty lethality between 1999 and 2018, suggest a challenge to healthy longevity, with the proportion of individuals with a high degree of frailty continuing to increase. Supported in part by the Canadian Institutes of Health Research.

Low TSH Is Associated With Frailty in an Older Veteran Population Independent of Other Thyroid Function Tests

Low TSH is associated with frailty in the older adult. We studied whether low TSH is an independent marker of frailty or is an indicator of subclinical hyperthyroidism, which in turn predicts frailty. Of outpatient veterans seen between January 2005 and December 2016, we identified 100 patients aged ≥60 years with two low TSH (<0.5 µIU/ml) and one fT3 measurement and 50 matched controls (TSH 0.5–5.0 µIU/ml). We used a deficit accumulation approach to create a frailty index (FI). The higher the FI, the more likely (p<0.001) that patients had expired. Patients with low (0.31 ± 0.11 µIU/mL) versus normal (1.84 ± 0.84 µIU/mL) TSH had higher mean FI compared to controls (0.25 ± 0.12 vs. 0.15 ± 0.07, p < .001). Low TSH was significantly associated with frailty (p < .001), independent of age. However, lower TSH was not associated with higher fT3 or fT4 levels. There was a nonsignificant inverse association of fT3 levels with FI (p = .13), which disappeared when adjusted for age. Similar to prior studies, low TSH was associated with frailty. However, neither fT3 nor fT4 predicted low TSH or FI, suggesting that the association of low TSH with frailty is not due to subclinical hyperthyroidism, but perhaps to effects of comorbidities on TSH secretion.

Association between a Deficit Accumulation Frailty Index and Mobility Outcomes in Older Adults: Secondary Analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study.

Frailty is a geriatric syndrome represented by susceptibility to precipitating health events and reduced functional reserve. Frailty can be difficult to measure in clinical practice and research. One approach to approximate frailty is based on a deficit accumulation approach, which assesses a larger number of less specific measures such as the presence of comorbidities, physical or cognitive assessments, and lab tests, and summarizes these as a frailty index. The objective of this study was to develop such an index using the Lifestyle Interventions and Independence for Elders (LIFE) Study and evaluate the validity of the frailty measure derived based on baseline information via its association with the primary outcomes of the trial, namely major mobility disability (MMD) and persistent MMD (pMMD). Further, this study aimed to evaluate the effectiveness of the physical activity intervention among participants based on their baseline frailty score. Subjects in the LIFE Study were evaluated at baseline for demographics, clinical history, and a battery of physical and cognitive functioning assessments. In total, 75 possible deficits were scored either as present (yes/no) or based on each score’s quintiles for score-based assessments. The frailty index was measured as the total sum of deficits divided by the total number of possible deficits on a continuous scale between 0 and 100 (i.e., percent of deficits present). The frailty index was further divided into quintiles for comparison. A proportional hazards model was estimated for the MMD outcome controlling for other baseline information. A data driven approach was also used to determine relevant cut-offs in the frailty index where the trial intervention appeared to be modified. Among 1635 trial participants, the mean frailty index was 30.4 ± 6.6 and normally distributed. Over 2.5 years of average follow-up, 14.6%, 16.5%, 18.6%, 22.6%, and 27.6% of participants experienced MMD in quintiles 1–5, respectively. Each 1-unit increase in the frailty index increased the hazard of MMD by 4% (2–5%), and there was a nearly 2-fold increase in MMD between the highest and lowest frailty quintiles. Using log-rank criteria, a cut-point at the median was identified. Further, iterations tested for a frailty cut-off and indicated a subgroup beyond the 85th percentile wherein the physical activity intervention appeared to be no longer be effective. This internally derived deficit accumulation frailty index was uniquely able to identify individuals at higher risk of MMD and pMMD and showed that along the spectrum of frailty, the physical activity intervention remained effective for the majority of participants.

Cumulative health deficits, APOE genotype, and risk for later-life mild cognitive impairment and dementia

ObjectiveTo determine whether health-deficit accumulation is associated with the risks of mild cognitive impairment (MCI) and dementia independently of APOE genotype.MethodsA frailty index was calculated using the deficit-accumulation approach in...