Precipitating Events Project Research Articles

Insomnia Severity and Daytime Sleepiness in Caregivers of Advanced Age.

Aging-related changes and caregiver burden may increase the risk for sleep disturbances among older caregivers, yet few studies have examined the prevalence of insomnia and daytime sleepiness in this group. We examined the relationship of caregiver status with insomnia and daytime sleepiness among persons of advanced age (>75 years of age). Cross-sectional. Community. Yale Precipitating Events Project participants (n=383, mean age 84.4 years, 67% female, 12% African American, 25% caregivers). Caregivers were persons who reported caring for another person in the past week or caring for/helping a friend or relative >4 times in the past month. We examined the correlates of caregiver status, including demographic (age, sex, race/ethnicity, education, marital status), psychosocial (living alone, Medicaid eligibility, depressive symptoms, social support, hours volunteered), and physical (obesity, chronic conditions, medication use, self-rated health status, physical activity, functional disability, cognitive impairment) factors. We used the Insomnia Severity Index (ISI) to establish insomnia severity (ISI score 0-28) or clinically significant insomnia symptoms (ISI ≥8). We used the Epworth Sleepiness Scale to establish daytime sleepiness (ESS score 0-24) or hypersomnia (ESS ≥10). In nonparametric multivariable regression analyses, we examined the relationship of caregiver status with insomnia or daytime sleepiness. Compared to non-caregivers, caregivers were younger, more educated, less likely to be Medicaid eligible and had lower rates of depression, obesity, poor self-rated health, low physical activity, functional disability, and cognitive impairment. Mean ISI and ESS scores were in the normal range and similar among non-caregivers and caregivers (ISI scores of 6.9±5.6 and 6.9±5.4, and ESS scores of 6.4±4.7 and 6.1±4.3, in non-caregivers and caregivers, respectively). Multivariable-adjusted models demonstrated no significant differences in ISI and ESS scores between non-caregivers and caregivers (regression coefficients for ISI and ESS scores of -0.01 [95% CI= -1.58, 1.21] and -0.10 [-1.05, 1.21], respectively). When compared to older non-caregivers, older caregivers had more advantageous demographic, psychosocial, and physical profiles and had similar levels of insomnia and daytime sleepiness on standardized questionnaires. Future research is needed to elucidate contextual factors (e.g., caregiving intensity and care partner disease) that may increase the risk of sleep disturbances among caregivers of advanced age.

Association Between Neighborhood Disadvantage and Functional Well-being in Community-Living Older Persons

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. 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. 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. 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). 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. 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.

Spliceosome Mutations Are Associated with Frailty in Older Patients with Myeloid Malignancies

Background: Frailty is a state of depleted physiologic reserve that is common in older patients with myeloid malignancies. While it is associated with chemotherapy-related toxicity, poor response to therapy, and higher mortality (Sherman, 2013; Fega, 2015), little is known about its causes. Moreover, there are increasing data demonstrating that clonal somatic mutations may be related to atherosclerotic disease (Jaiswal, 2017), which is an important driver of frailty. In this context, we sought to determine whether there is an association between hematopoietic DNA mutations and frailty in patients with overt myeloid neoplasms, hypothesizing that both RAS/MAPK and spliceosome mutations would be associated with the frailty phenotype.Methods: Starting in February of 2015,all patients aged 75 and older who presented for initial consultation to the DFCI Adult Leukemia Clinic were approached for evaluation by a trained research assistant. In a 15-minute interview, the assistant used two methods to characterize the patient as frail, pre-frail, or robust. The first employs a cumulative deficit approach (Rockwood, 2007) including 26 questions adapted from the Yale Precipitating Events Project (Searle, 2008), as well as the delayed recall section of the Montreal Cognitive Assessment (Nasreddine, 2005), a clock-in-the-box test (Chester, 2011), a grip strength test (Gill, 2006), and a gait speed test (Studenski, 2011). The second is a phenotype approach (Fried, 2001), which gives equal weight to performance on the gait speed and grip strength tests, as well as three questions about weight loss, energy expenditure and self-reported exhaustion. Patients were assigned frailty designations using the worse of the two scores. 85% of patients approached agreed to participate. Routine assessment of recurrent genetic alterations was performed using the Rapid Heme Panel (RHP), a gene panel sequencing test that evaluates 95 genes recurrently mutated in hematologic malignancies (Kluk, 2016). Associations between mutations and frailty were assessed via tests for trend across frailty status categories as well as a Fisher's exact test comparing the proportion of patients with robust status (versus frail/pre-frail combined).Results: As of July 2017, 93 patients with MDS (n=39), MPN (n=18), MDS/MPN (n=18), or AML (n=18) had completed frailty assessment and disease genetic characterization. Patients were majority male (n=70, 75%) with median age of 78 years (range, 75-89). Hypertension (65%) and hyperlipidemia (42%) were common. 59% (n=55) of patients in the cohort were pre-frail, 23% were frail (n=21), and 18% (n=17) were robust. There were no significant differences in frailty status between AML patients and those with chronic myeloid disorders (MDS, MPN, MDS/MPN). Gene mutations present in at least 5% of the cohort included SRSF2 (25%), SF3B1 (12%) , U2AF1 (8%), TET2 (44%), ASXL1 (26%), DNMT3A (8%), JAK2 (24%), RUNX1 (19%), TP53 (13%), STAG2 (9%), IDH2 (8%), EZH2 (8%) , and CBL (6%). 47% of patients had one of 4 non-co-occurring splicing mutations (SRSF2, SF3B1, U2AF1, ZRSR2). 18% of patients had one or more mutations that cause aberrant activation of RAS/MAPK signaling (NRAS, KRAS, CBL, PTPN11, RIT1, FLT3, KIT) and are associated with leukemic transformation of MDS (Lindsley, 2015). Patient with any splicing mutations were less likely to be robust (5% robust, 73% pre-frail, 23% frail) compared to those without (31% robust, 47% pre-frail, 22% frail; P for trend = 0.05; P -exact for robust versus pre-frail/frail = 0.001). Patients with an SF3B1 mutation specifically were also less likely to be robust then patients without an SF3B1 mutation (P for trend=0.02, Figure). The association between presence of a splicing mutation and frailty persisted within subgroups of patients with chronic myeloid malignancies and patients with AML, although the latter did not reach statistical significance (p=0.10) in that small dataset. No other single mutation, number of mutations present, or presence of a mutation in the RAS/MAPK pathway was significantly associated with frailty.Conclusion: In our cohort, patients with splicing mutations were less likely to be robust than patients without splicing mutations. These findings suggest that molecular characterization of myeloid disease may identify patients at higher risk for frailty and complications associated with treatment. [Display omitted] DisclosuresDeAngelo:Glycomimetics: Research Funding; Amgen: Consultancy, Research Funding; BMS: Consultancy; Blueprint Medicines: Honoraria, Research Funding; Immunogen: Honoraria, Research Funding; Shire: Honoraria; Takeda Pharmaceuticals U.S.A., Inc.: Honoraria; Celgene: Research Funding; Incyte: Consultancy, Honoraria; Pfizer Inc.: Consultancy, Honoraria, Research Funding; ARIAD: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding. Steensma:Celgene: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Janssen: Consultancy, Research Funding; H3 Biosciences: Consultancy; Incyte: Equity Ownership; Onconova: Consultancy; Takeda: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lane:Stemline Therapeutics: Research Funding; N-of-one: Consultancy. Lindsley:MedImmune: Research Funding; Jazz Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy.

Cohort Profile: The Precipitating Events Project (PEP Study).

The Precipitating Events Project (PEP Study) is an ongoing longitudinal study of 754 nondisabled community-living persons age 70 years or older who were members of a large health plan in greater New Haven, Connecticut, USA. The study was established to rigorously evaluate the epidemiology of disability in older persons and to elucidate the role of intervening illnesses and injuries on the disabling process. Of the eligible members, 75.2% agreed to participate and were enrolled between March 1998 and October 1999. Participants have completed comprehensive home-based assessments at 18-month intervals and have been interviewed monthly over the phone with a completion rate of 99%. Detailed participant-level data on health care utilization are obtained annually through linkages with Medicare claims. Through June 2019, 702 (93.1%) participants have died after a median of 109 months, while 43 (5.7%) have dropped out of the study after a median of 27 months. Death certificates are available for all decedents. To date, 117 original reports have been published using data from the PEP Study, including many focusing on other high priority areas such as end of life, frailty, depressive symptoms, aging stereotypes, pain, sleep, and methodologic research. The PEP Study welcomes proposals to access data for meritorious analyses from qualified investigators.

Spousal Influences on Monthly Disability in Late-Life Marriage in the Precipitating Events Project.

Few studies have examined spousal influences on disability in late-life marriage, and no prior study has examined these associations using monthly data. Drawing from interdependence theory, we hypothesized that one spouse currently having higher disability would be positively associated with their partner having higher disability in the next month. We also examined whether participants were at risk for increased disability when both spouses had higher prior disability. In addition, we examined gender differences in spousal associations. Data were from 37 married couples in the Precipitating Events Project, an ongoing longitudinal study of 754 initially nondisabled adults aged 70 years and older. Assessments included monthly disability (13 basic, instrumental, and mobility activities of daily living) and demographics. As hypothesized, higher disability in one spouse was positively associated with higher subsequent disability in their partner. Also, wives with higher disability were especially vulnerable to subsequent increased disability when husbands had higher disability. Incorporating a spouse's current disability level in modeling older adults' subsequent disability provides additional predictive information. Wives with greater disability may be at a particularly high risk of accelerated decline when their husbands have greater disability.

SPOUSAL ASSOCIATIONS IN MONTHLY REPORTS OF DISABILITY IN THE PRECIPITATING EVENTS PROJECT

While many prior studies have evaluated the antecedents and consequences of changes in disability, few have considered the social context. As nearly 60% of older adults currently live with a spouse or intimate partner, it is important to examine spousal influences on disability. This study examined spousal associations in self-reported disability using data from the Precipitating Events Project, an ongoing longitudinal study of 754 initially nondisabled community living adults age 70 and over who have had monthly assessments of functional status since 1999. We hypothesized that one spouse’s level of disability would be associated with increases in the other spouse’s subsequent disability. We used the Actor Partner Interdependence Model (APIM), a statistical modeling framework that accounts for the interdependence in two-person data and tests the associations of both self (actor) and partner influences on outcomes. We used multilevel, longitudinal APIMs to examine lagged associations in spouses’ monthly reports of disability in 13 activities of daily living (e.g., walking a quarter mile, bathing) in the 37 married couples. As hypothesized, one partner’s prior disability level was significantly associated with the other partner’s (the actor’s) subsequent disability level (B = .674, SE = .012, p < .001) after controlling for the actor’s prior disability level. Also, when both couple members had higher levels of prior disability, they were particularly at risk of subsequent increases in disability (B = .016, SE = .003, p < .001). Incorporating partner disability level in modeling individuals’ outcomes provides greater precision in predicting future disability levels.

The Epidemiology of Patient-Reported Hypersomnia in Persons With Advanced Age.

To examine the epidemiology and key demographic and clinical correlates of patient-reported hypersomnia in persons with advanced age. Cross-sectional design. Community. A total of 357 community-dwelling persons from the Yale Precipitating Events Project with a mean age of 84.2 years (range = 78-102 years). We studied patient-reported hypersomnia, defined categorically by an Epworth Sleepiness Scale (ESS) score of 10 or greater; as well as the severity of hypersomnia symptoms, defined continuously by an ESS score range of 0 to 24 (higher scores denote greater sleepiness). In multivariable regression models, we examined cross-sectional associations between key correlates and ESS score, expressed as categorical and continuous variables. Key correlates included: demographics, education, smoking status, body mass index, self-reported medical conditions, Center for Epidemiologic Studies Depression score, Mini-Mental State Examination score, Physical Activity Scale for the Elderly, restless legs syndrome (RLS), self-reported sleep-disordered breathing (SDB), medications, and Insomnia Severity Index. Mean ESS score for all participants was 6.4. Patient-reported hypersomnia (ESS score ≥10) was established in 82 participants (23.0%)-their mean ESS score was 13.0. In multivariable models, male sex, nonwhite race, arthritis, depressive symptoms, low physical activity, RLS, SDB, central nervous system depressant medications, and insomnia severity were cross-sectionally associated with patient-reported hypersomnia (higher adjusted odds ratios, ranging from 1.93-2.86) and/or with the severity of hypersomnia symptoms (higher ESS scores, ranging from 0.11-2.86 points). Patient-reported hypersomnia was prevalent in a sample of community-dwelling persons with advanced age. In addition, based on cross-sectional associations with the ESS score, key demographic and clinical characteristics were identified that may inform screening strategies for hypersomnia in advanced age. J Am Geriatr Soc 67:2545-2552, 2019.

Short-Term Disability Fluctuations in Late Life.

Late-life disability is highly dynamic but within-person short-term fluctuations have not been assessed previously. We analyze how substantial such late-life disability fluctuations are and whether they are associated with time-to-death, long-term disability trajectories, frailty, and sociodemographics. Monthly survey data (Precipitating Events Project Study) on activities of daily living/instrumental activities of daily living (ADL/IADL) disability (0-9) in the last years of life from 642 deceased respondents providing 56,308 observations were analyzed with a two-step approach. Observation-level residuals extracted from a Poisson mixed regression model (first step), which depict vertical short-term fluctuations from individual long-term trajectories, were analyzed with a linear mixed regression model (second step). Short-term disability fluctuations amounted to about one ADL/IADL limitation, increased in the last 4 years of life, and were closely associated with disability increases. Associations with frailty or sociodemographics characteristics were absent except for living alone. Short-term disability fluctuations in late life were substantial, were linked to mortality-related processes, and represent a concomitant feature of disability increases in late life.

NATURAL HISTORY OF FRAILTY AND COGNITIVE IMPAIRMENT: LONGITUDINAL EVIDENCE FROM THREE POPULATION STUDIES

Physical frailty and cognitive impairment are associated and often coexist in older adults. What is unknown is: (1) whether there are sentinel patterns in the temporal development of physical frailty and cognitive impairment; (2) whether these patterns reflect different etiologies; and (3) whether health of older adults is deferentially impacted depending on their order and rate of occurrence. To begin to address these questions, the studies present longitudinal evidence from three prospective epidemiological cohorts: the National Health and Aging Trends Study (NHAT; n=7,439), the Women’s Health and Aging Study II (WHAS; n=436), and the Yale Precipitating Events Project (PEP; n=754). Talk 1 discusses temporal orders in the development of frailty and cognitive impairment in the NHATS, and their relationship with multimorbidity and onset of dementia. Talk 2 uses data from WHAS to examine the role of dysregulation across multiple physiological systems involving stress response and energy metabolism in the onset of cognitive impairment and frailty. Talk 3 assesses the associations of frailty and cognitive impairment separately versus jointly with cumulative 5-year incidence of ADL disability in NHATS, while accounting for competing risk of mortality. Talk 4 analyzed patterns of joint trajectories of cognition and frailty and their associations with patient-reported health outcomes in PEP. Taken together, findings from these studies provide preliminary evidence supporting the hypothesis that cognitive impairment and physical frailty result in part from distinct physiological processes; and the varying patterns of symptom emergence may signal different etiologic pathways, which would require different interventions.

Measurement and Prevalence of Cognitive Impairment in Older Patients with Hematologic Malignancies

Background:Little is known about the frequency of cognitive impairment in older patients with blood cancers, nor how such impairment may contribute to their overall frailty. Understanding the prevalence of impairment is specifically important for this population, because intact cognition is needed to make complex medical decisions, including whether to pursue intensive treatments versus supportive care. We report data from the Older Adult Hematologic Malignancy (OHM) clinic at the Dana-Farber Cancer Institute, which routinely screens patients 75 or older for frailty using tools that incorporate subjective and objective measures of cognition.Methods: Since February of 2015,all patients aged 75 and older who present for initial consultation for hematologic malignancy have been approached for evaluation by a trained clinic assistant. In a 15-minute interview, the assistant uses two parallel methods of screening to characterize the patient as frail, pre-frail or robust. The first employs a "cumulative deficit" approach (Rockwood, 2007) including a 26-item questionnaire adapted from theYale Precipitating Events Project (Searle, 2008), a grip strength test (Gill, 2006), gait speed test (Studenski, 2011), delayed recall section of the Montreal Cognitive Assessment (MOCA; Nasreddine, 2005) and the Clock In Box test, a cognitive impairment screening tool (CIB; Chester, 2011). The second uses a "phenotypic" approach (Fried, 2001), which gives equal weight to the gait speed and grip strength tests, plus three questions about weight loss, energy expenditure and self-reported exhaustion. We also assess two subjective measures of cognition: (1) whether the patient knows why s/he is presenting to the hospital and (2) whether s/he needs help filling out the questionnaire.Results: As of July 1, 2016, 235 of 275 patients approached (85%) agreed to be assessed. Median age was 78 years and 37% were female; 32% were seen in the leukemia clinic, 37% in the lymphoma clinic and 31% in the myeloma clinic. More patients were determined to be definitively frail or robust by the cumulative deficit approach compared with the phenotypic approach, which categorized the majority of patients as pre-frail (Table 1). With respect to cognition, 35.4% of the cohort was found to have probable impairment and 27.3% possible impairment by CIB (Table 2). Fewer patients were found to have probable impairment (18.0%) and possible impairment (19.8%) by MOCA delayed recall. Overall, 18.5% of robust patients had possible or probable cognitive impairment by CIB, and 9.5% by MOCA delayed recall. Nearly 7% of the patients could not explain why they were presenting to the hospital; all of these patients also had probable cognitive impairment and were pre-frail or frail. Moreover, 17% of the total cohort needed assistance completing the questionnaire; half of these had probable cognitive impairment, 43% had possible impairment, and most (92.5%) were pre-frail or frail. The odds of being pre-frail or frail (phenotypic) if cognitively impaired per CIB was 1.89 (95% CI 1.073.34; p=0.03). The odds of being pre-frail or frail (phenotypic) if cognitively impaired per MOCA delayed recall was 1.86 (95% CI 1.02-3.40; p=0.04).Conclusions: Cognitive impairment was prevalent in this cohort of older patients with blood cancers, with between one- to two-thirds of patients testing as probably or possibly impaired using standard measures.A portion of patients who were robust per the brief phenotypic frailty screen were also cognitively impaired, which suggests routinely performing comprehensive frailty screening (cumulative deficit) or adding a cognitive measure such as the CIB. Compared to the phenotypic approach, the cumulative deficit approach, which incorporates specific measurement of cognitive impairment, seemed to result in further discriminaton between patients who were frail versus robust. The CIB test detected more cognitive impairment than the MOCA delayed recall, likely because it assesses both executive function and working memory, whereas the MOCA delayed recall only tests the latter. Taken together, our data suggest that cognitive impairment likely contributes significantly to overall frailty for older patients with blood cancers, and argue for routine testing for such impairment in this patient population. [Display omitted] [Display omitted] DisclosuresStone:Amgen: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jansen: Consultancy; Seattle Genetics: Consultancy; Celator: Consultancy; Agios: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; ONO: Consultancy; Juno Therapeutics: Consultancy; Merck: Consultancy; Roche: Consultancy; Sunesis Pharmaceuticals: Consultancy; Xenetic Biosciences: Consultancy. Soiffer:Kiadis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees.

Feasibility of Routine Frailty Screening Assessment for Patients in a Hematologic Oncology Clinic: Results from a Pilot Study

Background: Although frailty is felt to influence outcomes in hematologic oncology, formal frailty assessment is rarely performed in this patient population. We report preliminary data from a pilot study initiated with the goal of identifying patients who would benefit from comprehensive geriatric assessment (CGA) by an embedded geriatrician at the Dana-Farber Cancer Institute (DFCI).Methods: Starting in February of 2015,all patients aged 75 and older who present for an initial consultation for hematologic malignancy at DFCI have been approached for evaluation by a trained clinic assistant. In a 15-minute interview that occurs before they see the oncologist, the assistant uses two parallel methods of screening to characterize the patient as frail, pre-frail, or robust. The first employs a "cumulative deficit" approach (Rockwood, 2007) including 26 questions adapted from the Yale Precipitating Events Project (Searle, 2008), as well as the delayed recall section of the Montreal Cognitive Assessment (Nasreddine, 2005), a clock-in-the-box test (Chester, 2011), a grip strength test (Gill, 2006), and a gait speed test (Studenski, 2011). The second is a "phenotype" approach (Fried, 2001), which gives equal weight to performance on the gait speed and grip strength tests, as well as three questions about weight loss, energy expenditure and self-reported exhaustion. Patients are assigned frailty designations with each method, and a combined designation (the worse of the two if they do not match). Frail and pre-frail patients on the combined assignment are randomized to see an embedded geriatrician for CGA at a subsequent visit. For patients with cancers that typically require intervention (eg, we excluded cancers such as low-risk MDS and indolent CLL), we assessed whether frailty category correlated with subsequent treatment choice (chemotherapy vs supportive care) within two months of assessment.Results: As of August 1, 2015, 105 patients aged 75 or older have been approached; 86 (82%) have agreed to be assessed. The most common reasons for refusal were (categories not mutually exclusive): anxiety about potential results (50%), patient not planning to return to DFCI (39%), and patient feeling s/he was not in need of geriatric services (22%). The median age of those assessed was 78 years; 41% were female, and 33% were seen at the leukemia clinic, 31% at the lymphoma clinic, and 36% at the myeloma clinic. Overall, on the combined measure, 15% of patients were frail, 54% pre-frail, and 31% robust. Agreement between the cumulative deficit and phenotype methods was moderate (weighted kappa = .65). For those patients with cancers that typically require intervention (n=57), treatment status at two months by the different assessments systems is shown below:Conclusion: Routine screening frailty assessment of older blood cancer patients by a non-MD clinic assistant is feasible and informative. So far, well over half of the patients in this pilot have been found to be frail or pre-frail, and would likely benefit from CGA and follow-up. Regardless of frailty designation, most patients with cancers that typically require intervention were treated with chemotherapy rather than supportive care. Moreover, for those patients, the cumulative deficit technique was better at predicting subsequent treatment status. [Display omitted] DisclosuresSteensma:Incyte: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Onconova: Consultancy. Laubach:Novartis: Research Funding; Onyx: Research Funding; Celgene: Research Funding; Millennium: Research Funding. Stone:Celator: Consultancy; Merck: Consultancy; Amgen: Consultancy; Abbvie: Consultancy; Roche/Genetech: Consultancy; AROG: Consultancy; Novartis: Research Funding; Sunesis: Consultancy, Other: DSMB for clinical trial; Agios: Consultancy; Juno: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Pfizer: Consultancy.

Cognitive Aging Trajectories and Burdens of Disability, Hospitalization and Nursing Home Admission Among Community-living Older Persons.

The course of cognitive aging has demonstrated substantial heterogeneity. This study attempted to identify distinctive cognitive trajectories and examine their relationship with burdens of disability, hospitalization, and nursing home admission. Seven hundred and fifty-four community-living persons aged 70 years or older in the Yale Precipitating Events Project were assessed with the Mini-Mental State Examination every 18 months for up to 108 months. A group-based trajectory model was used to determine cognitive aging trajectories while adjusting for age, sex, and education. Cumulative burden of disabilities, hospitalizations, and nursing home admissions over 141 months associated with the cognitive trajectories were evaluated using a generalized estimating equation Poisson model. Five distinct cognitive trajectories were identified, with about a third of participants starting with high baseline cognitive function and demonstrating No decline during the follow-up period. The remaining participants diverged with Minimal (prevalence 41%), Moderate (16%), Progressive (8%), and Rapid (3%) cognitive decline. Participants with No decline incurred the lowest incidence rates (per 1,000 person-months) of disability in activities of daily living (ADL; 75, 95% confidence intervals: 60-95) and instrumental ADL (492, 453-535), hospitalization (29, 26-33) and nursing home admission (18, 12-27), whereas participants on the Rapid trajectory experienced the greatest burden of ADL disability (612, 595-758) and those on the Progressive trajectory had the highest nursing home admission (363, 292-451). Community-living older persons follow distinct cognitive aging trajectories and experience increasing burdens of disability, hospitalization, and nursing home placement as they age, with greater burdens for those on a declining cognitive trajectory.

Disentangling the disabling process: insights from the precipitating events project.

Among older persons, disability in activities of daily living is common and highly morbid. The Precipitating Events Project (PEP Study), an ongoing longitudinal study of 754 initially nondisabled, community-living persons, aged 70 or older, was designed to further elucidate the epidemiology of disability, with the goal of informing the development of effective interventions to maintain and restore independent function. Over the past 16 years, participants have completed comprehensive, home-based assessments at 18-month intervals and have been interviewed monthly to reassess their functional status and ascertain intervening events, other health care utilization, and deaths. Findings from the PEP Study have demonstrated that the disabling process for many older persons is characterized by multiple and possibly interrelated disability episodes, even over relatively short periods of time, and that disability often results when an intervening event is superimposed upon a vulnerable host. Given the frequency of assessments, long duration of follow-up, and recent linkage to Medicare data, the PEP Study will continue to be an outstanding platform for disability research in older persons. In addition, as the number of decedents accrues, the PEP Study will increasingly become a valuable resource for investigating symptoms, function, and health care utilization at the end of life.

Comparison of alternate scoring of variables on the performance of the frailty index

BackgroundThe frailty index (FI) is used to measure the health status of ageing individuals. An FI is constructed as the proportion of deficits present in an individual out of the total number of age-related health variables considered. The purpose of this study was to systematically assess whether dichotomizing deficits included in an FI affects the information value of the whole index.MethodsSecondary analysis of three population-based longitudinal studies of community dwelling individuals: Nova Scotia Health Survey (NSHS, n = 3227 aged 18+), Survey of Health, Ageing and Retirement in Europe (SHARE, n = 37546 aged 50+), and Yale Precipitating Events Project (Yale-PEP, n = 754 aged 70+). For each dataset, we constructed two FIs from baseline data using the deficit accumulation approach. In each dataset, both FIs included the same variables (23 in NSHS, 70 in SHARE, 33 in Yale-PEP). One FI was constructed with only dichotomous values (marking presence or absence of a deficit); in the other FI, as many variables as possible were coded as ordinal (graded severity of a deficit). Participants in each study were followed for different durations (NSHS: 10 years, SHARE: 5 years, Yale PEP: 12 years).ResultsWithin each dataset, the difference in mean scores between the ordinal and dichotomous-only FIs ranged from 0 to 1.5 deficits. Their ability to predict mortality was identical; their absolute difference in area under the ROC curve ranged from 0.00 to 0.02, and their absolute difference between Cox Hazard Ratios ranged from 0.001 to 0.009.ConclusionsAnalyses from three diverse datasets suggest that variables included in an FI can be coded either as dichotomous or ordinal, with negligible impact on the performance of the index in predicting mortality.

Epidemiology of Restricting Fatigue in Older Adults: The Precipitating Events Project

To estimate the rate of restricting fatigue in community-living older adults and to determine whether the rates differ according to age, sex, race, physical frailty, and depression. Prospective cohort study. Greater New Haven, Connecticut. Nondisabled community-living older men and women aged 70 and older (N = 754). Restricting fatigue was defined as staying in bed for at least half the day and/or cutting down on one's usual activities because of fatigue for 3 consecutive months or longer. Physical frailty was defined on the basis of slow gait speed, and depression was assessed using the Center for Epidemiologic Studies Depression Scale. During a median follow-up of 111 months, the cumulative incidence of restricting fatigue was 31.1% for men and 42.1% for women. The overall incidence rate of restricting fatigue was 6.7 per 1,000 person-months (7.8 for women and 4.4 for men, P < .001), which did not differ according to race. Rates were higher in persons who were physically frail than those who were not (P < .001), in those who were depressed than those who were not (P < .001), and in persons aged 75 to 79 and 80 to 84 than those aged 70 to 74 (both P < .01) but not in those aged 85 and older. Of the 459 episodes of restricting fatigue, the median duration was 3 months, which did not differ according to age, sex, race, physical frailty, or depression. Restricting fatigue is common in community-living older adults. Women, individuals aged 75 to 84, and individuals with physical frailty or depression had higher rates of restricting fatigue than their respective counterparts.

A dynamic trajectory class model for intensive longitudinal categorical outcome.

This paper presents a novel dynamic latent class model for a longitudinal response that is frequently measured as in our prospective study of older adults with monthly data on activities of daily living for more than 10 years. The proposed method is especially useful when the longitudinal response is measured much more frequently than other relevant covariates. The trajectory classes are latent classes that represent distinct temporal patterns of the longitudinal response wherein an individual may remain in a trajectory class or switch to another as the class membership predictors are updated periodically over time. The identification of a common set of trajectory classes allows changes among the temporal patterns to be distinguished from local fluctuations in the response. Within a trajectory class, the longitudinal response is modeled by a class-specific generalized linear mixed model. An informative event such as death is jointly modeled by class-specific probability of the event through shared random effects with that for the longitudinal response. We do not impose the conditional independence assumption given the classes. We illustrate the method by analyzing the change over time in activities of daily living trajectory class among 754 older adults with 70,500 person-months of follow-up in the Precipitating Events Project. We also investigate the impact of jointly modeling the class-specific probability of the event on the parameter estimates in a simulation study. The primary contribution of our paper is the periodic updating of trajectory classes for a longitudinal categorical response without assuming conditional independence.

Long-Term Trajectories of Lower Extremity Function in Older Adults: Estimating Gender Differences While Accounting for Potential Mortality Bias

Gender-specific trajectories of lower extremity function (LEF) and the potential for bias in LEF estimation due to differences in survival have been understudied. We evaluated longitudinal data from 690 initially nondisabled adults age 70 or older from the Precipitating Events Project. LEF was assessed every 18 months for 12 years using a modified Short Physical Performance Battery (mSPPB). Hierarchical linear models with adjustments for length-of-survival estimated the intraindividual trajectory of LEF and differences in trajectory intercept and slope between men and women. LEF declined following a nonlinear trajectory. In the full sample, and among participants with high (mSPPB 10-12) and intermediate (mSPPB 7-9) baseline LEF, the rate-of-decline in mSPPB was slower in women than in men, with no gender differences in baseline mSPPB scores. Among participants with low baseline LEF (mSPPB ≤6), men had a higher starting mSPPB score, whereas women experienced a deceleration in the rate-of-decline over time. In all groups, participants who survived longer had higher starting mSPPB scores and slower rates-of-decline compared with those who died sooner. Over the course of 12 years, older women preserve LEF better than men. Nonadjustment for differences in survival results in overestimating the level and underestimating the rate-of-decline in LEF over time.

A Method for Partitioning the Attributable Fraction of Multiple Time-Dependent Coexisting Risk Factors for an Adverse Health Outcome

We decomposed the total effect of coexisting diseases on a timed occurrence of an adverse outcome into additive effects from individual diseases. In a cohort of older adults enrolled in the Precipitating Events Project in New Haven County, Connecticut, we assessed a longitudinal extension of the average attributable fraction method (LE-AAF) to estimate the additive and order-free contributions of multiple diseases to the timed occurrence of a health outcome, with right censoring, which may be useful when relationships among diseases are complex. We partitioned the contribution to death into additive LE-AAFs for multiple diseases. The onset of heart failure and acute episodes of pneumonia during follow-up contributed the most to death, with the overall LE-AAFs equal to 13.0% and 12.1%, respectively. The contribution of preexisting diseases decreased over the years, with a trend of increasing contribution from new onset of diseases. LE-AAF can be useful for determining the additive and order-free contribution of individual time-varying diseases to a time-to-event outcome.

Mixed Methods for the Interpretation of Longitudinal Gerontologic Data

This article's main objective is to demonstrate that data analysis, including quantitative data analysis, is a process of interpretation involving basic hermeneutic principles that philosophers have identified in the interpretive process as applied to other, mainly literary, creations. Such principles include a version of the hermeneutic circle, an insistence on interpretive presuppositions, and a resistance to reducing the discovery of truth to the application of inductive methods. The importance of interpretation becomes especially evident when qualitative and quantitative methods are combined in a single clinical research project and when the data being analyzed are longitudinal. Study objectives will be accomplished by showing that three major hermeneutic principles make practical methodological contributions to an insightful, illustrative mixed methods analysis of a qualitative study of changes in functional disability over time embedded in the Precipitating Events Project-a major longitudinal, quantitative study of functional disability among older persons. Mixed methods, especially as shaped by hermeneutic insights such as the importance of empathetic understanding, are potentially valuable resources for scientific investigations of the experience of aging: a practical aim of this article is to articulate and demonstrate this contention.

Transitions in frailty status in older adults in relation to mobility: a multistate modeling approach employing a deficit count.

To investigate how changes in frailty status and mortality risk relate to baseline frailty state, mobility performance, age, and sex. Cohort study. The Yale Precipitating Events Project, New Haven, Connecticut. Seven hundred fifty-four community-dwelling people aged 70 and older at baseline followed up at 18, 36, and 54 months. Frailty status, assessed at 18-month intervals, was defined using a frailty index (FI) as the number of deficits in 36 health variables. Mobility was defined as time in seconds on the rapid gait test, in which participants walked back and forth over a 20-foot course as quickly as possible. Multistate transition probabilities were calculated with baseline frailty, mobility, age, and sex estimated using Poisson and logistic regressions in survivors and those who died, respectively. In multivariable analyses, baseline frailty status and age were significantly associated with changes in frailty status and risk of death, whereas mobility was significantly associated with the frailty but not with mortality. At all values of the FI, participants with better mobility were more likely than those with poor mobility to remain stable or to improve. For example, at 54 months, 20.6% (95% confidence interval (CI)=16-25.2) of participants with poor mobility had the same or fewer deficits, compared with 32.4% (95% CI=27.9-36.9) of those with better mobility. A multistate transition model effectively measured the probability of change in frailty status and risk of death. Mobility, age, and baseline frailty were significant factors in frailty state transitions.