Trajectory Of Functional Decline Research Articles

Exploring trajectories of functional decline and recovery among older adults: a data-driven approach

Independently performing activities of daily living (ADLs) is vital for maintaining one’s quality of life. Losing this ability can significantly impact an individual’s overall health status, including their mental health and social well-being. Aging is an important factor contributing to the loss of ADL abilities, and our study focuses on investigating the trajectories of functional decline and recovery in older adults. Employing trajectory analytics methodologies, this research delves into the intricate dynamics of ADL pathways, unveiling their complexity, diversity, and inherent characteristics. The study leverages a substantial dataset encompassing ADL assessments of nursing home residents with diverse disability profiles in the United States. The investigation begins by transforming these assessments into sequences of disability combinations, followed by applying various statistical measures, indicators, and visual analytics. Valuable insights are gained into the typical disability states, transitions, and patterns over time. The results also indicate that while predicting the progression of ADL disabilities presents manageable challenges, the duration of these states proves more complicated. Our findings hold significant potential for improving healthcare decision-making by enabling clinicians to anticipate possible patterns, develop targeted and effective interventions that support older patients in preserving their independence, and enhance overall care quality.

Trajectories of walking speed in older adults with atrial fibrillation: a 15 year-follow-up population-based study

Abstract Background Atrial fibrillation (AF), the most common arrhythmia in older adults, has been associated with frailty. However, the role exerted by AF in the long-term trajectories of functional decline still needs to be elucidated. Purpose The aim of the present study was to evaluate AF clinical impact on functional decline by tracing the evolution of the walking speed (WS) over 15 years of follow-up in a population-based cohort of older individuals. Methods This population-based cohort study included 3141 non-institutionalized participants (age ≥60 years; 63.6% women) from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) carried out in Stockholm, who were regularly examined from 2001–2004 to 2016-2019. AF was ascertained from clinical examination, electrocardiogram, and the Swedish National Patient Registry. Physical decline was assessed measuring participants mobility through the WS test (m/s). Participants WS was evaluated at baseline, and then followed up every 6 years (those aged <78 years) or every 3 years (those aged ≥78 years). Incident heart failure, stroke and dementia were also recorded during the follow-up visits. The association between AF and WS trajectories was tested by multivariable joint models accounting for the longitudinal dropouts due to death. Analyses were also stratified by relevant individual characteristics after adjustment for clinically relevant covariates. Results At baseline, 285 (9.1%) participants were ascertained to have prevalent AF. Upon accounting for several potential confounders, we observed a faster annual WS decline in AF participants than in non-AF peers (β coefficient per year = −0.013, 95% confidence interval [CI]: −0.017 to −0.007) after multivariable adjustment for age, sex, education, dementia, COPD, diabetes, hypertension, heart failure, stroke, physical activity levels and BMI. The association was stronger in individuals 78+ than those younger than 78 years and in those without stroke, heart failure and higher engagement in physical activity (p per interaction <0.05). In a secondary analysis carried out among participants who were free of heart failure, stroke, and dementia at baseline, controlling by incident heart failure, incident stroke, and incident dementia did not attenuate the association between AF and WS change. Conclusion AF is independently associated with a faster physical performance decline in older individuals Incident stroke, heart failure or dementia don’t seem to mediate the relationship between AF and mobility decline over time.

Specific neuropsychiatric symptoms are associated with functional decline trajectories in Alzheimer's disease and Lewy body dementia: a five-year follow-up study.

Neuropsychiatric symptoms (NPS) are often overlooked and under-identified symptoms associated with dementia, despite their significant impact on the prognosis of individuals living with the disease. The specific role of certain NPS in functional prognosis remains unclear. To determine the association of different NPS with functional decline in people living with Alzheimer's disease (AD) or Lewy body dementia (LBD). This is an analysis of data from the Dementia Study of Western Norway (DemVest) with 196 patients included of which 111 had AD and 85 LBD. The Neuropsychiatric Inventory (NPI) and the Rapid Disability Rating Scale (RDRS-2) for activities of daily living were administered annually for 5 years. NPI total score and individual items with RDRS-2 trajectories were analyzed with linear mixed models. The LBD group exhibited higher levels of functional impairment and a greater burden of NPS at baseline. Over the 5-year follow-up, hallucinations, aggression, depression, anxiety, apathy, disinhibition, aberrant motor behavior, nighttime behavior disturbances, and abnormal eating patterns were significantly associated with the decline in functional abilities in individuals with AD, as well as irritability and aberrant motor behavior in those with LBD. These results highlight the relevance of early detection and intervention of these particularly relevant NPS, due to its potential of also impacting physical function. Better detection and management of these NPS could improve functional prognosis in people living with dementia. Specific NPS demonstrate relevant distinct associations with Longitudinal trajectories of functional decline in AD and LBD.

Trajectories of Functional Decline in Older Adults: A Latent Class Growth Curve Analysis.

There have been few studies examining trajectories of functional decline among older adults in the United States using large representative databases. The purpose of this study was to describe the mean trajectory of functional decline for a representative sample of US older adults, to determine the optimal number of latent classes within that sample, and to identify key differences between the classes on select variables. Through the use of link functions, non-linear trajectories can be modeled. Three classes were identified and were named Rapid Decline, Late Decline, and High Baseline. The Late Decline Group was the most numerous and was characterized by low initial functional disability with a steep rise starting around age 85. The Rapid Decline Group also had low initial functional disability, but decline started around age 80. The High Baseline Group had high initial functional disability and less steep trajectory. Age and comorbidity were the most influential factors in functional decline. Race was statistically significant but the difference disappeared when controlling for other covariates. Sex did not significantly influence the trajectory. There were significant differences among the classes for mortality during study, initial age, initial functional status, and for several specific comorbidities: arthritis, diabetes, lung disease, and stroke.

SIOG2022-0108* - Trajectory of functional decline and loss of independence in activities of daily living (ADL) in older adults with advanced cancer receiving treatment

SIOG2022-0108* - Trajectory of functional decline and loss of independence in activities of daily living (ADL) in older adults with advanced cancer receiving treatment

Optimising function and well-being in older adults: protocol for an integrated research programme in Aotearoa/New Zealand

BackgroundMaintaining independence is of key importance to older people. Ways to enable health strategies, strengthen and support whanāu (family) at the community level are needed. The Ageing Well through Eating, Sleeping, Socialising and Mobility (AWESSOM) programme in Aotearoa/New Zealand (NZ) delivers five integrated studies across different ethnicities and ages to optimise well-being and to reverse the trajectory of functional decline and dependence associated with ageing.MethodsWell-being, independence and the trajectory of dependence are constructs viewed differently according to ethnicity, age, and socio-cultural circumstance. For each AWESSoM study these constructs are defined and guide study development through collaboration with a wide range of stakeholders, and with reference to current evidence. The Compression of Functional Decline model (CFD) underpins aspects of the programme. Interventions vary to optimise engagement and include a co-developed whānau (family) centred initiative (Ngā Pou o Rongo), the use of a novel LifeCurve™App to support behavioural change, development of health and social initiatives to support Pacific elders, and the use of a comprehensive oral health and cognitive stimulation programme for cohorts in aged residential care. Running parallel to these interventions is analysis of large data sets from primary care providers and national health databases to understand complex multi-morbidities and identify those at risk of adverse outcomes. Themes or target areas of sleep, physical activity, oral health, and social connectedness complement social capital and community integration in a balanced programme involving older people across the ability spectrum.DiscussionAWESSoM delivers a programme of bespoke yet integrated studies. Outcomes and process analysis from this research will inform about novel approaches to implement relevant, socio-cultural interventions to optimise well-being and health, and to reverse the trajectory of decline experienced with age.Trial registrationThe At-risk cohort study was registered by the Australian New Zealand Clinical Trials registry on 08/12/2021 (Registration number ACTRN 12621001679875).

The Differential Impact of Multimorbidity Patterns and Subsequent Accumulation on Longitudinal Trajectories of Physical Function Decline in a Population-Based Cohort of Older People.

Although both the patterns and accumulation of multimorbidity are important for predicting physical function, studies have not simultaneously examined their impact on functional decline. This study aimed to associate multimorbidity patterns and subsequently developed conditions with longitudinal trajectories of functional decline, and it tested whether the effects of newly developed conditions on functional decline varied across distinct multimorbidity patterns. We included 6 634 participants aged at least 60 years from the China Health and Retirement Longitudinal Survey. Latent class analysis identified multimorbidity patterns from 14 chronic conditions. Mixed negative binomial models estimated the changes in physical function measured across 4 waves as a function of multimorbidity patterns, subsequently developed conditions, and their interactions. Five distinct patterns were identified 3 years before Wave 1: stomach/arthritis (15.7%), cardiometabolic (6.7%), arthritis/hypertension (47.9%), hepatorenal/multisystem (18.3%), and lung/asthma (11.4%). The hepatorenal/multisystem and the lung/asthma pattern were associated with worse baseline physical function, and the hypertension/arthritis pattern was associated with greater decline of physical function. The effect of developing new conditions on decline of physical function over time was most evident for individuals from the cardiometabolic pattern. Considering both the combinations and progressive nature of multimorbidity is important for identifying individuals at greater risk of disability. Future studies are warranted to differentiate the factors responsible for the progression of chronic conditions in distinct multimorbidity patterns and investigate the potential implications for improved prediction of functional decline.

Identifying and characterizing patterns of functional decline in memory clinic patients

AbstractBackgroundAlzheimer’s disease and related disorders (ADRD) are characterized by progressive cognitive and functional decline. To improve prognosis, it is important to predict the expected rate of functional decline. In the current study, we sought to uncover patterns of changes in everyday functioning among memory clinic patients, and to explore factors associated with said groups.MethodMemory clinic patients (N=573, 64.7±7.9 years old, 39% female) underwent extensive dementia screening at baseline, and were followed over time (median 1.0 years, range 0.3–6.2 years, N observations=1632). Diagnoses included subjective cognitive decline, mild cognitive impairment, and dementia with varying etiologies. We measured everyday functioning with the Amsterdam Instrumental Activities of Daily Living Questionnaire (A‐IADL‐Q). Longitudinal latent class analysis (LLCA) was used to identify groups of patients based on their rate of change in IADL, including non‐linear trajectories. We subsequently used random forests to explore the associations between the LLCA groups and demographics, neuropsychological test performance, and magnetic resonance imaging rating scales for medial temporal and global atrophy.ResultWe identified six groups: two stable (high and average), three declining (slow, moderate, and fast), and one improving group (see Table 1, Figure 1). All groups differed in baseline A‐IADL‐Q scores, with the declining groups having lower scores. The fast declining group consisted mostly of dementia patients, whereas the high stable group consisted mostly of patients with subjective cognitive decline. The area under the curve of the random forest classification was .95, thus accurately assigning patients to the correct group based on baseline characteristics. The following variables contributed most to the classification of the groups: baseline A‐IADL‐Q score (mean decrease accuracy [MDA]=200.5), a visuospatial task (copy of Rey Complex Figure, MDA=36.6) and a processing speed task (Letter Digit Substitution Task, MDA=18.5). Atrophy rating scales contributed less.ConclusionDifferent trajectories of functional decline were distinguished, and associated with baseline levels of cognitive and daily functioning. Our findings suggest that neuropsychological assessment may provide additional information on future changes in daily functioning. These findings may contribute to a more accurate prognosis of future functional decline, and by extension, future care needs.

Functional decline among older cancer survivors in the Baltimore longitudinal study of aging.

Evidence has begun to emerge indicating that cancer survivors experience accelerated aging. This study examines this phenomenon by evaluating trajectories of functional decline in older adults with a history of a cancer diagnosis relative to those without a history of cancer. Community dwelling healthy volunteers in the Baltimore Longitudinal Study of Aging were evaluated in the Clinical Research Unit of the National Institute on Aging Intramural Research Program. Between 2006 and 2019, 1728 men and women (aged 22-100) underwent clinical evaluation of functional status; 359 reported having a history of cancer. Longitudinal associations between self-reported cancer history and measures of functional decline were examined using generalized estimating equations. Additionally, time-to-event and Cox proportional hazards models were used to examine trajectories of decline. Where appropriate, age-stratified associations were examined, and models were adjusted for sex, body mass index, race, smoking status, education, and number of comorbid conditions. Among all participants, a history of cancer was associated with 1.42 (95% CI 1.11-1.81) greater odds of weak grip strength. Among older participants (>65 years of age), those with a history of cancer had 1.61 (95% CI 1.28, 2.02) greater odds of slow gait speed and a 0.11 unit (95% CI 0.19-0.03) lower physical performance score than those with no cancer history. Time-to-event analysis showed that older individuals with a history of cancer experienced steeper decline in grip strength and gait speed than older adults with no history of cancer (p < 0.01). Cancer survivors, especially older individuals, demonstrate greater odds of and accelerated functional decline, suggesting that cancer and/or its treatment may alter aging trajectories. Observational and intervention studies are needed for prevention, mitigation, and/or reversal of aging-related effects of cancer and its treatment.

Long-term Visual Outcomes after Release from Protocol in Patients who Participated in the Inhibition of VEGF in Age-related Choroidal Neovascularisation (IVAN) Trial

PurposeTo describe visual outcomes, frequency of treatment and monitoring visits, and anti–vascular endothelial growth factor drugs used in usual care in participants who exited a trial in which treatment for neovascular age-related macular degeneration (nAMD) was initiated with bevacizumab or ranibizumab.DesignMulticenter cohort study up to 7 years after trial exit.ParticipantsPatients enrolled in the Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial; after excluding participants from 2 sites and who died or withdrew during the trial, 537 were included in this follow-up cohort.MethodsData were collected between May 26, 2016, and August 24, 2017. Distance visual acuity (DVA) (letters read) in both eyes and treatments for nAMD administered to either eye at all usual care visits were extracted from medical records of all participants until the point of data collection (duration of study eye monitoring).Main Outcome MeasuresRate of change of DVA during active surveillance of the study eye (study eye monitoring), estimated using a multivariable linear random effects model. Other outcome measures were visit and treatment frequency and switches in anti–vascular endothelial growth factor (VEGF) drug.ResultsData were obtained for 99% (532/537) of eligible participants. The median duration of study eye monitoring after IVAN exit was 3.3 years (interquartile range [IQR], 1.3–4.7), and median DVA was 58.0 letters (IQR, 34.0–73.0). Study eye DVA deteriorated by 4.3 (95% confidence interval [CI], 3.7–4.9) letters per year. Injection rate did not influence the rate of change in DVA after adjusting for key covariates. After IVAN exit, 174 participants (32%) received no treatment; 332 of 358 (93%) were treated first with ranibizumab, 78 (23%) of whom switched to aflibercept. The DVA was similar among participants who switched or did not switch at the end of study monitoring.ConclusionsApproximately 5 years after the IVAN study finished, with unprecedented completeness of follow-up for such a trial, the trajectory of functional decline in the study eye was shown to be greater than that previously reported for incomplete trial cohorts. Anti-VEGF injection rates and treatment switches were not important factors in determining visual acuity outcomes.

Burden and Impact of Geriatric Syndromes in 2-Year, Progression-Free Survivors of Older Allogeneic Hematopoietic Cell Transplant Recipients – a Landmark Analysis

<h3>Introduction/Methods</h3> The trajectory of functional decline and the prevalence of geriatric syndromes have not been examined among long-term survivors of older allo-HCT recipients. We previously described significant burden and adverse impact of post-transplant geriatric syndromes, delirium and fall, among older allogeneic recipients. We report here theprevalence and impact of geriatric syndromes in 2-year, progression-free survivors among this cohort of patients using our institutional database. Baseline characteristics, transplant outcomes, geriatric assessment domains, and geriatric syndromes were obtained and analyzed as previously described. <h3>Results</h3> We identified 199 2-year, progression-free survivors of patients allografted at age ≥60 years from 2001 to 2016, including 111 out of 241 patients on the CD34+ selection platform (46%), and 88 out of 231 T-cell replete patients (38%). The median age at allo-HCT was 65.4 years (range 60 – 78.7); 73% had myeloid malignancies; 69% had high/very high risk HCT-CI/age; 14% had a mismatched donor; and 56% had a CD34+ selected graft. With a median follow-up of 5.7 years for survivors, the 3-yr OS and RFS from the 2-year landmark was 86% (95% CI, 80 – 91) and 83% (95% CI, 78 – 89). Thirty-three patients died, including 8 from relapse/disease progression, and 25 from non-relapse mortality (6 each from secondary neoplasm, organ failure, and infections). The 3-year cumulative incidence of new functional impairment (FI), defined as new admission to skilled nursing facility, fall, or assisted walking device from the 2-year landmark, was 20% (95% CI, 15 – 27). In addition, the 3-year cumulative incidence of new psychiatric illness and cognitive decline was 6% (95% CI, 3 – 11) and 5% (95% CI, 3 – 10), respectively (Figure 1). We examined factors associated with new FI and found that, among others, patients who were transplanted with a CD34+ selected graft had lower incidence of new FI in univariate (hazard ratio [HR]=0.49, 95% CI 0.28 – 0.86, P=0.014) and multivariate analysis with borderline significance (HR=0.53, 95% CI 0.27 – 1.02, P=0.056). In 2-year landmark analyses, both high/very high HCT-CI/age index and mismatched donor were significantly associated with inferior OS and RFS (Table 1). <h3>Conclusion</h3> While limited by the single institution, retrospective design, heterogenous transplant approach, and likely under-reporting, our findings nevertheless illustrate the high prevalence of FI among older allo-HCT survivors, which maybe attenuated by the CD34+ selection platform. In addition, the impact of graft-versus-host disease on the development of geriatric syndromes merits closer examination. While requiring prospective confirmation, long-term functional impairment should be considered as an important secondary outcome when comparing curative strategies to other less intense approaches in older patients with hematologic malignancies.

The trajectory of functional decline over the last 4 months of life in a palliative care population: A prospective, consecutive cohort study.

Understanding current patterns of functional decline will inform patient care and has health service and resource implications. This prospective consecutive cohort study aims to map the shape of functional decline trajectories at the end of life by diagnosis. Changes in functional status were measured using the Australia-modified Karnofsky Performance Status Scale. Segmented regression was used to identify time points prior to death associated with significant changes in the slope of functional decline for each diagnostic cohort. Sensitivity analyses explored the impact of severe symptoms and late referrals, age and sex. In all, 115 specialist palliative care services submit prospectively collected patient data to the national Palliative Care Outcomes Collaboration across Australia. Data on 55,954 patients who died in the care of these services between 1 January 2013 and 31 December 2015 were included. Two simplified functional decline trajectories were identified in the last 4 months of life. Trajectory 1 has an almost uniform slow decline until the last 14 days of life when function declines more rapidly. Trajectory 2 has a flatter more stable trajectory with greater functional impairment at 120 days before death, followed by a more rapid decline in the last 2 weeks of life. The most rapid rate of decline occurs in the last 2 weeks of life for all cohorts. Two simplified trajectories of functional decline in the last 4 months of life were identified for five patient cohorts. Both trajectories present opportunities to plan for responsive healthcare that will support patients and families.

Exploring 2.5-Year Trajectories of Functional Decline in Older Adults by Applying a Growth Mixture Model and Frequency of Outings as a Predictor: A 2010-2013 JAGES Longitudinal Study.

BackgroundWe explored the distinct trajectories of functional decline among older adults in Japan, and evaluated whether the frequency of outings, an important indicator of social activity, predicts the identified trajectories.MethodsWe analyzed data on 2,364 adults aged 65 years or older from the Japan Aichi Gerontological Evaluation Study. Participants were initially independent and later developed functional disability during a 31-month follow-up period. We used the level of long-term care needs certified in the public health insurance system as a proxy of functional ability and linked the fully tracked data of changes in the care levels to the baseline data. A low frequency of outings was defined as leaving one’s home less than once per week at baseline. We applied a growth mixture model to identify trajectories in functional decline by sex and then examined the association between the frequency of outings and the identified trajectories using multinomial logistic regression analysis.ResultsThree distinct trajectories were identified: “slowly declining” (64.3% of men and 79.7% of women), “persistently disabled” (4.5% and 3.7%, respectively), and “rapidly declining” (31.3% and 16.6%, respectively). Men with fewer outings had 2.14 times greater odds (95% confidence interval, 1.03–4.41) of being persistently disabled. The association between outing frequency and functional decline trajectory was less clear statistically among women.ConclusionsWhile the majority of older adults showed a slow functional decline, some showed persistent moderate disability. Providing more opportunities to go out or assistance in that regard may be important for preventing persistent disability, and such needs might be greater among men.

A single systemic inflammatory insult causes acute motor deficits and accelerates disease progression in a mouse model of human tauopathy

IntroductionNeuroinflammation, which contributes to neurodegeneration, is a consistent hallmark of dementia. Emerging evidence suggests that systemic inflammation also contributes to disease progression. MethodsThe ability of systemically administered lipopolysaccharide (LPS - 500 μg/kg) to effect acute and chronic behavioural changes in C57BL/6 and P301S tauopathy mice was assessed. Markers of pathology were assessed in the brain and spinal cord. ResultsP301S mice display regional microgliosis. Systemic LPS treatment induced exaggerated acute sickness behaviour and motor dysfunction in P301S mice compared with wild-type controls and advanced the onset and accelerated chronic decline. LPS treatment was associated with increased tau pathology 24 hours after LPS injection and spinal cord microgliosis at the end stage. DiscussionThis is the first demonstration that a single systemic inflammatory episode causes exaggerated acute functional impairments and accelerates the long-term trajectory of functional decline associated with neurodegeneration in a mouse model of human tauopathy. The findings have relevance to management of human dementias.

Trajectories of functional decline in older adults with neuropsychiatric and cardiovascular multimorbidity: A Swedish cohort study.

BackgroundFunctional decline is a strong health determinant in older adults, and chronic diseases play a major role in this age-related phenomenon. In this study, we explored possible clinical pathways underlying functional heterogeneity in older adults by quantifying the impact of cardiovascular (CV) and neuropsychiatric (NP) chronic diseases and their co-occurrence on trajectories of functional decline.Methods and findingsWe studied 2,385 people ≥60 years (range 60–101 years) participating in the Swedish National study of Aging and Care in Kungsholmen (SNAC-K). Participants underwent clinical examination at baseline (2001–2004) and every 3 or 6 years for up to 9 years. We grouped participants on the basis of 7 mutually exclusive clinical patterns of 0, 1, or more CV and NP diseases and their co-occurrence, from a group without any CV and NP disease to a group characterised by the presence of CV or NP multimorbidity, accompanied by at least 1 other CV or NP disorder. The group with no CV and/or NP diseases served as the reference group. Functional decline was estimated over 9 years of follow-up by measuring mobility (walking speed, m/s) and independence (ability to carry out six activities of daily living [ADL]). Mixed-effect linear regression models were used (1) to explore the individual-level prognostic predictivity of the different CV and NP clinical patterns at baseline and (2) to quantify the association between the clinical patterns and functional decline at the group level by entering the clinical patterns as time-varying measures. During the 9-year follow-up, participants with multiple CV and NP diseases had the steepest decline in walking speed (up to 0.7 m/s; p < 0.001) and ADL independence (up to three impairments in ADL, p < 0.001) (reference group: participants without any CV and NP disease). When the clinical patterns were analyzed as time varying, isolated CV multimorbidity impacted only walking speed (β −0.1; p < 0.001). Conversely, all the clinical patterns that included at least 1 NP disease were significantly associated with decline in both walking speed (β −0.21–−0.08; p < 0.001) and ADL independence (β −0.27–−0.06; p < 0.05). Groups with the most complex clinical patterns had 5%–20% lower functioning at follow-up than the reference group. Key limitations of the study include that we did not take into account the specific weight of single diseases and their severity and that the exclusion of participants with less than 2 assessments may have led to an underestimation of the tested associations.ConclusionsIn older adults, different patterns of CV and NP morbidity lead to different trajectories of functional decline over time, a finding that explains part of the heterogeneity observed in older adults’ functionality. NP diseases, alone or in association, are prevalent and major determinants of functional decline, whereas isolated CV multimorbidity is associated only with declines in mobility.

Longitudinal Modeling of Functional Decline Associated with Pathologic Alzheimer's Disease in Older Persons without Cognitive Impairment.

Therapeutic research on Alzheimer's disease (AD) has moved to intercepting the disease at the preclinical phase. Most drugs in late development have focused on the amyloid hypothesis. To understand the magnitude of amyloid-related functional decline and to identify the functional domains sensitive to decline in a preclinical AD population. Data were from the Religious Orders Study and the Rush Memory and Aging Project. Cognitive decline was measured by a modified version of the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite. The trajectories of functional decline, as measured by the instrumental and basic activities of daily living, were longitudinally modeled in 484 participants without cognitive impairment at baseline and having both a final clinical and a postmortem neuropathology assessment of AD. Individuals with different final clinical diagnoses had different trajectories of cognitive and functional decline. Individuals with AD dementia, minor cognitive impairment, and no cognitive impairment had the most, intermediate, and least declines. While individuals with pathologic AD had significantly more cognitive decline over time than those without, the magnitude of difference in functional decline between these two groups was small. Functional domains such as handling finance and handling medications were more sensitive to decline. Demonstrating the functional benefit of an amyloid-targeting drug represents a significant challenge as elderly people experience functional decline due to a wide range of reasons with limited manifestation attributable to AD neuropathology. More sensitive functional scales focusing on the functional domains sensitive to decline in preclinical AD are needed.

The impact of menopause on functional status in women with rheumatoid arthritis.

The aim of this study was to investigate the association of menopause with functional status outcomes in women with RA. Participants were women in a US-wide observational cohort who developed RA before menopause. The HAQ measured functional status. We controlled for confounding variables and used univariate and multivariable generalized estimating equation methods with the sandwich estimator of variance. Best models were selected using the quasi-likelihood under the independence model criterion. A sensitivity analysis was performed using linear mixed effects regression models. A total of 8189 women were eligible. Of these, 2005 (24.5%) were pre-menopausal, 611 (7.5%) transitioned through menopause during the study, and 5573 (68.1%) were post-menopausal. Within each respective group, the mean (s.d.) ages were 39.7 (7.8), 50.7 (3.4) and 62.3 (9.3) years. Our results showed that women who were pre-menopausal had less functional decline as measured by the HAQ compared with women who were post-menopausal; these results were robust and strong even after adjustment for other significant factors. The ever-use of hormonal replacement therapy, ever having a pregnancy, and longer length of reproductive life were associated with less functional decline. After menopause, the trajectory of functional decline worsened and accelerated in women with RA. The results suggest that menopausal status is associated with functional decline in women with RA. Furthermore, menopause is associated with a worsening progression of functional decline. These data indicate that menopause has a significant impact on the level and rate of functional decline in women with RA.

Predicting Trajectories of Functional Decline in 60- to 70-Year-Old People

Background: Early identification of people at risk of functional decline is essential for delivering targeted preventive interventions. Objective: The aim of this study is to identify and predict trajectories of functional decline over 9 years in males and females aged 60-70 years. Methods: We included 403 community-dwelling participants from the InCHIANTI study and 395 from the LASA study aged 60-70 years at baseline, of whom the majority reported no functional decline at baseline (median 0, interquartile range 0-1). Participants were included if they reported data on ≥2 measurements of functional ability during a 9-year follow-up. Functional ability was scored with 6 self-reported items on activities of daily living. We performed latent class growth analysis to identify trajectories of functional decline and applied multinomial regression models to develop prediction models of identified trajectories. Analyses were stratified for sex. Results: Three distinct trajectories were identified: no/little decline (219 males, 241 females), intermediate decline (114 males, 158 females), and severe decline (36 males, 30 females). Higher gait speed showed decreased risk of functional limitations in males (intermediate limitations, odds ratio [OR] 0.74, 95% CI 0.57-0.97; severe limitations, OR 0.42, 95% CI 0.26-0.66). The final model in males further included the predictors fear of falling and alcohol intake (no/little decline, area under the receiver operating curve [AUC] 0.68, 95% CI 0.62-0.73; intermediate decline, AUC 0.63, 95% CI 0.56-0.69; severe decline, AUC 0.79, 95% CI 0.71-0.87). In females, higher gait speed showed a decreased risk of intermediate limitations (OR 0.51, 95% CI 0.38-0.68) and severe limitations (OR 0.18, 95% CI 0.07-0.44). Other predictors in females were age, living alone, economic satisfaction, balance, physical activity, BMI, and cardiovascular disease (no/little decline, AUC 0.80, 95% CI 0.75-0.85; intermediate decline, AUC 0.74, 95% CI 0.69-0.79; severe decline, AUC 0.95, 95% CI 0.91-0.99). Conclusion: Already in people aged 60-70 years, 3 distinct trajectories of functional decline were identified in these cohorts over a 9-year follow-up. Predictors of trajectories differed between males and females, except for gait speed. Identification of people at risk is the basis for targeting interventions.

End of life care trajectories – hospital inpatient care in last two years of life

Introduction : End of life (EOL) care trajectories have been found to differ by cause of death categories representing different trajectories of functional decline (Fassbender et al. 2009). The aim of our study is to use the same categorisation of causes of death (terminal illness, organ failure, frailty, sudden deaths, other) to investigate hospital inpatient care utilisation patterns in the last two years of life in Norway. Methods : Data on cause of death, place of death, age and gender for all decedents in 2011 from the Norwegian cause of deaths registry were linked by unique person identifier with data from Norwegian Patient register on inpatient hospital utilisation in the last 730 days before death. Statistical analysis of differences in care utilisation in different time periods before death, as well as graphical analysis of time pattern in service use were performed. Results : The highest median number of inpatient days over the last two years before death was found for terminal illness, more than double compared to organ failure, which in turn was the double of frailty and sudden death. For all trajectory groups the proportion being in hospital on a particular day before death increases steeply in the last months of life, starting earlier for terminal illness than for organ failure, which in turn started earlier than for frailty and sudden death. Nearly 70 percent of decedents dying of terminal illness had hospital stay within the last 30 days of life. The corresponding proportions was 50% for organ failure, and about 1/3 for frailty and sudden death. Differences in utilisation as well as time pattern within trajectory groups varied with age as well as place of death. Typically, the highest number of hospital days was found for hospital deaths and lowest for home deaths, and the number of days in hospital decreased with higher age among the elderly decedents. Discussions : The overall results are in line with the findings in Fassbender et al. (2009) which found the same ranking of cost for inpatient care between terminal illness, organ failure and frailty. Conclusions : Cause of death trajectories categories help to differentiate patterns of hospital utilisation before death. Lessons learned : Care trajectories differ by place of death already several month or even years before death, which could reflect that place of death is an indication of differences in functional decline of decedents within the cause of death trajectory categories. Care trajectories should also be studied separately for different age groups. Limitations : The study only looks at inpatient hospital use, other health and care services could serve as alternatives to hospital admission. Suggestions for future research : In our future research, we will include other health and care services. References : 1- Fassbender K, Fainsinger RL, Carson M and Finegan BA. Cost trajectories at the end of life: the Canadian experience. J Pain Symptom Manag. 2009; 38: 75-80.

Identification of the trajectory of functional decline for advance care planning in a nursing home population.

To identify diagnostic groups and the form of the trajectory of functional decline that has the potential to enhance advance care planning (ACP) in a nursing home (NH) population. Retrospective, longitudinal study with dependent variable (function) derived from the Resident Classification Scale (RCS), 1997-2008. Trajectory modelling used linear and curvilinear terms. The organ failure or other residents have a linear average functional decline. The organ failure residents had an average decline of 6.5 points per year and average function score at death of 68.6, CI [62.4, 74.8]. The cancer and frailty residents had significant curvilinear terms. The frailty residents had a slower rate of decline at 9.54 points per year and were most care dependent at death, with an average function score of 77.1, CI [73.8, 80.9]. Functional change is a measurable variable for a predictive tool to enhance ACP for NH residents based on their diagnosis.