Disability trajectories by progression independent of relapse activity status differ in pediatric, adult and late-onset multiple sclerosis.

BACKGROUND: To compare Expanded Disability Status Scale (EDSS) trajectories over time between Multiple Sclerosis (MS) groups with pediatric (POMS), adult (AOMS) and late (LOMS) onset, and between patients with and without progression independent of relapse activity (PIRA). METHODS: Patients with a first visit within 1 year from onset, ≥ 5-year follow-up and ≥ 1 visit every 6 months were selected from the Italian MS Register. Adjusted disability trajectories were assessed by longitudinal models for repeated measures. Comparisons between groups and between patients with and without PIRA in subgroups were performed by evaluating the yearly differences of mean EDSS score changes versus baseline (delta-EDSS). A first CDA event was defined as a 6-months confirmed disability increase from study baseline, measured by EDSS (increase ≥ 1.5 points with baseline EDSS = 0; ≥ 1.0 with baseline EDSS score ≤ 5.0 and ≥ 0.5 point with baseline EDSS > 5.5). PIRA was defined as a CDA event occurring more than 90 days after and more than 30 days before the onset of a relapse. RESULTS: 3777 MS patients (268 POMS, 3282 AOMS, 227 LOMS) were included. The slope of disability trajectories significantly diverged in AOMS vs POMS starting from the second year of follow-up (Year 2: delta2-EDSS 0.18 (0.05; 0.31), p = 0.0054) and then mean delta2-EDSS gradually increased up to 0.23 (0.07; 0.39, p = 0.004) at year 5. Patients with PIRA had significant (p < 0.0001) steeper increase in EDSS scores than those without PIRA in all groups, although in POMS, the disability trajectories began to diverge later and at a lesser extent with delta-EDSS score of 0.48 vs 0.83 in AOMS and 1.57 in LOMS, at 3 years after the first PIRA. CONCLUSIONS: Age is relevant in determining disability progression in MS. POMS shows a less steep increase in EDSS scores over time than older patients. The effect of PIRA in accelerating EDSS progression is less pronounced in POMS than in AOMS and LOMS.

Late-onset multiple sclerosis: disability trajectories in relapsing-remitting patients of the Italian MS Registry.

BACKGROUND: Generally infrequent, multiple sclerosis (MS) with late onset (LOMS) is characterized by an onset over the age of 50 and a mainly progressive course, while relapsing-remitting (RR) forms are less frequently observed and explored. This study aimed to characterize a large cohort of MS patients with RRMS at onset to assess the baseline factors related to the worst disability trajectories and explore the role of LOMS. METHODS: The data were extracted from the Italian MS Register (IMSR). Disability trajectories, defined using at least two and up to twenty expanded disability status scale (EDSS) assessments annually performed, were implemented using group-based trajectory models (GBTMs) to identify different groups with the same trajectories over time. MS profiles were explored using multinomial logistic regression. RESULTS: A total of 16,159 RR patients [1012 (6.26%) presented with LOMS] were analyzed. The GBTM identified four disability trajectories. The group with the most severe EDSS trend included 12.3% of the patients with a mean EDSS score > 4, which increased over time and exceeded 6 score. The group with medium severity EDSS trend comprised 21.9% of the patients and showed a change in EDSS > 3 scores over time. The largest group with 50.8% of patients reported a constant EDSS of 2 score. Finally, the benign group comprised 14.9% of the patients with a low and constant EDSS of 1 score over time. The probability of being in the worst groups increased if the patient was male; had LOMS or experienced brainstem, spinal, or supratentorial symptoms. CONCLUSIONS: Four MS severity profiles among RRMS patients in the IMSR have been reported, with LOMS being associated with a rapid worsening of EDSS scores. These findings have important implications for recognizing and managing how older age, aging, and age-related factors interact with MS and its evolution.

Adverse Childhood Experiences and Trajectories of ADL Disability among Middle-Aged and Older Adults in China: Findings from the CHARLS Cohort Study.

OBJECTIVES: There is little evidence on the association between adverse childhood experiences (ACEs) and disability trajectories among middle-aged and older adults. This study aimed to investigate the association between ACEs and activities of daily living (ADL) trajectories over eight years of follow-up and the mediation role of different chronic diseases on this relationship. DESIGN: Prospective cohort study, eight-year follow-up. SETTING: China Health and Retirement Longitudinal Study(CHARLS). PARTICIPANTS: A total of 10651 participants age 45 and over from CHARLS 2011 to 2018 were included in this study. MEASUREMENTS: Five ACEs exposure groups were formed based on the cumulative ACE scores. A 6-item ADL score was used, including bathing, dressing, eating, getting in/out of bed, using the toilet, and controlling urination, to measure the ADL disability, and the group-based trajectory model (GBTM) was used to identify the ADL disability trajectories. Multinomial logistic regression was performed to investigate the association between ACEs and ADL disability trajectory memberships, and KHB-method was used to estimate the contribution of different chronic diseases on this relationship. RESULTS: Of the 10651 participants, 9.64% showed a mild-increasing trajectory in terms of change in ADL score during follow-up, followed by the low-mild trajectory (32.00%) and low-low trajectory (58.36%). Compared with those without ACEs exposure, participants who had ≥4 ACEs were associated with an increased risk of being on low-mild trajectory (OR 1.32, 95%CI:1.11-1.57) and mild-increasing trajectory (OR 1.41, 95%CI: 1.06-1.89), respectively. Besides, mediation analysis revealed chronic diseases had a mediation effect in this association, with the largest effect from arthritis or rheumatism (over 60%), followed by digestive system disease (around 14%), respiratory disease (around 12%), and cardio-metabolic disease (around 5%). CONCLUSION: This study suggested that exposure to ACEs was associated with a higher risk of being worse ADL disability trajectories. Moreover, chronic disease accounts for a meaningful proportion of this association. Further studies are needed to clarify how chronic diseases mediate the association between ACEs and ADL disability trajectories.

Hierarchical structure in the activities of daily living and trajectories of disability prior to death in elderly Chinese individuals.

BACKGROUND: The global burden of disability continues to increase. Understanding the hierarchical structure of activities of daily living (ADL) and the trajectories of disability of elderly individuals is pivotal to developing early interventions. PURPOSE: To determine the hierarchical structure of the ability of Chinese elderly individuals to perform ADL and further describe the trajectories of disability prior to death. METHODS: Longitudinal item response theory model (LIRT) was constructed for 28,345 elderly participants in the Chinese Longitudinal Healthy Longevity Survey, in which ADL were measured using the Katz scale from 1998 to 2018, until the participants' death. Two difficulty parameters (κ-partial and κ-total) were used in the LIRT defining the thresholds for hierarchical structure in ADL (κ-partial: no limitation to partial limitation, κ-total: partial limitation to totally limited). Disability values estimated from the LIRT were fitted to a mixed-effects model to examine the manner in which the trajectories of disability varied with different subject characteristics. RESULTS: The findings confirmed the earliest loss in the capability to perform ADL (bathing(κ-partial = - 1.396), toileting(κ-partial = - 0.904)) at the level of partial limitation, with an overlap of partial and totally limited (total bathing, partial dressing, partial transferring, total dressing, partial feeding, partial continence), and finally a total loss of capability for toileting, feeding, transferring, and continence (κ-total = 3.647). Disability trajectories varied with sex (ß = 0.041, SE = 0.001), place of residence (ß = 0.010, SE = 0.001), and marital status (ß = 0.144, SE = 0.001). Females, individuals living in urban areas, and those who lived without a spouse had a poorer disability status. CONCLUSION: The loss in the ability to perform ADL has a hierarchical structure. Subject characteristics affect trajectories of disability in the elderly Chinese population.

Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies.

BACKGROUND AND AIMS: No consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC). METHODS: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups. RESULTS: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5-11.7) years. Mean annual delta-EDSS values were all significantly (p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01-0.19, p = 0.03) at 1 year to 0.30 (0.07-0.53, p = 0.009) at 5 years and to 0.67 (0.31-1.03, p = 0.0003) at 10 years. CONCLUSION: Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time.

Definitions of primary-progressive multiple sclerosis trajectories by rate of clinical disability progression.

BACKGROUND: Patients with primary progressive multiple sclerosis (PPMS) vary in the rate of disability progression. OBJECTIVE: To classify clinical disability trajectories by rate of disability progression and evaluate predictive variables in PPMS patients. METHODS: We analyzed the cumulative incidence of progression to disability and in accordance defined clinical PPMS disability trajectories. Correlation was performed with age, gender and disability at first presentation. Estimated onset was calculated and validated by the mathematical slope of disability progression. RESULTS: The cohort included 304 PPMS patients, 146 (48%) were females, the mean age at first visit was 41.1 years, and the median follow up was 18.9 years. Median time to reach moderate and severe disability was 4.5 years (95%CI 3.8-5.2) and 12.6 years (95%CI 10.1-14.2), respectively. Extremely fast patients (3.3%) progressed to severe disability within 2-years, while very slow patients (4.7%) did not progress to moderate disability even 20 years after first presentation. Age and gender were not associated with progression. Moderate disability at first visit was associated with faster progression to severe disability. Mean estimated range of disease onset was between 4.3 to 9.9 years prior to first presentation. CONCLUSIONS: Majority of PPMS patients progressed to moderate disability within 5-years and to severe disability within 15-years from first presentation. Clinical disability progression trajectories can help treatment-related decisions.

Trajectories of Late-Life Disability Vary by the Condition Leading to Death.

BACKGROUND: Previous research suggested that there might be distinct patterns of functional decline in the last years of life depending on the condition leading to death, but the validity of these results and hence the explanatory value of the condition leading to death for late-life disability are uncertain. METHODS: A total of 636 decedents from a cohort of 754 community-living persons, 70+ years of age (Yale PEP Study) provided 33 700 monthly observations of self-/proxy-reported disability during the last 5 years of life. Nonlinear trajectories and short-term fluctuations of late-life disability by condition leading to death (cancer, organ failure, frailty, severe dementia, sudden death, other) were estimated with flexible mixed spline regression models. RESULTS: Disability trajectories at the end of life varied distinctively by the condition leading to death. Estimated disability trajectories among cancer deaths increased gradually up until about 6 months before death, after which a steep terminal decline set in. Among those with organ failure, frailty, and dementia, in contrast, disability was higher, increased more gradually, and there was no clear-cut terminal phase. Adding the condition leading to death to other known risk factors increased the amount of explained between-person variation in late-life disability from R2 = 0.35 to 0.49. Short-term fluctuations in disability were not specific for decedents with organ failure. CONCLUSIONS: The condition leading to death is an important determinant of trajectories of late-life disability. These trajectories follow distinct patterns partially resembling a previously outlined theoretical typology.

Predictors for functional decline after an injurious fall: a population-based cohort study.

BACKGROUND: The functional consequences of injurious falls are well known. However, studies of the factors that can modify trajectories of disability after an injury from a fall are scarce. AIMS: We aimed to investigate whether sociodemographic and health-related factors may impact this association. METHODS: The study population consisted of 1426 community-dwelling older adults (≥ 60 years) from the SNAC-K cohort study in Stockholm, Sweden. Functional status over 12 years of follow-up was assessed using the number of limitations in basic and instrumental activities of daily living. Sex, cohabitation status, physical activity, and self-rated health were assessed at baseline. Injurious falls were defined as falls requiring healthcare and were assessed over 3 years starting at baseline. Data were analyzed using linear-mixed effects models. RESULTS: The fastest increase in the number of disabilities was observed in those who had endured an injurious fall and were living alone (ß coefficient = 0.408; p < 0.001), been physically inactive (ß coefficient = 0.587; p < 0.001), and had poor self-rated health (ß coefficient = 0.514; p < 0.001). The negative impact of these factors was more pronounced among fallers compared to non-fallers. DISCUSSION: Living alone, being physically inactive, and having poor self-rated health magnifies the negative effect of an injurious fall on functional status. Among individuals who endure an injurious fall, the heterogeneity in long-term functional status is substantial, depending on the individuals' characteristics and behaviors. CONCLUSIONS: These findings emphasize the need for a person-centered approach in care provision and can guide secondary prevention within health care.

Trajectories of Work Disability and Economic Insecurity Approaching Retirement.

OBJECTIVES: In this article, we examine the connection between trajectories of work disability and economic precarity in late midlife. We conceptualize work disability as a possible mechanism linking early and later life economic disadvantage. METHODS: We model trajectories of work disability characterized by timing and stability for a cohort of Baby Boomers (22-32 in 1981) using 32 years of data from the Panel Study of Income Dynamics and latent class analysis. Measures of childhood disadvantage are included as predictors of work disability trajectories, which are subsequently included in logistic regression models predicting four economic outcomes (poverty, asset poverty, home ownership, and pension ownership) at ages 54-64. RESULTS: Childhood disadvantage selected individuals into five distinct classes of work disability that differed in timing and stability. All of the disability trajectories were associated with an increased risk of economic insecurity in late midlife compared to the never work disabled. DISCUSSION: This study contributes to the aging literature through its incorporation of the early life origins of pathways of disability and their links to economic outcomes approaching retirement. Findings suggest work disability is anchored in early life disadvantage and is associated with economic insecurity later in life.

The Heterogeneity of Disability Trajectories in Later Life: Dynamics of Activities of Daily Living Performance Among Nursing Home Residents.

Objective: This study investigated the variability in activities of daily living (ADL) trajectories among 6,155 nursing home residents using unique and rich observational data. Method: The impairment in ADL performance was considered as a dynamic process in a multi-state framework. Using an innovative mixture model, such states were not defined a priori but inferred from the data. Results: The process of change in functional health differed among residents. We identified four latent regimes: stability or slight deterioration, relevant change, variability, and recovery. Impaired body functions and poor physical performance were main risk factors associated with degradation in functional health. Discussion: The evolution of disability in later life is not completely gradual or homogeneous. Steep deterioration in functional health can be followed by periods of stability or even recovery. The current condition can be used to successfully predict the evolution of ADL allowing to set and target different care priorities and practices.

Disability trajectories and associated disablement process factors among older adults in Taiwan.

OBJECTIVES: We aimed to identify disability trajectories and examine whether the predisposing, intra-individual, and extra-individual factors in the disablement process predicted different disability trajectories among older adults in Taiwan. METHODS: Data were from the Taiwan Longitudinal Study on Aging (TLSA) Survey in 1996-2007 (n=3186). Disability trajectories for activities of daily living (ADLs) and instrumental activities of daily living (IADLs) were identified by using latent class growth curves modeling. Factors including demographics, health conditions, health behaviors, social relations, and use of assistive devices were significantly predicted different disability trajectories of older adults over the following 11 years by applying hierarchical logistic regression. RESULTS: Three disability trajectories--maintained function, progressive disability, and consistent disability--were identified. Predisposing factors such as younger age, more educational attainment, and better health conditions had protective effects of leading to a later healthier maintained function trajectory. Intra-individual factors such as engaging in leisure time activities (LTAs) were positively related to the maintained function trajectory but negatively related to the consistent disability trajectory; decreasing social networks was common to those on consistent disability trajectory; dissatisfaction with social support was noted in maintained function trajectory group. An extra-individual factor, using assistive devices, was significantly related to maintaining older adults' disability levels, even for those who started disabled. CONCLUSIONS: The findings suggested that predisposing, intra-individual, and extra-individual factors play different roles in the development of later disability trajectories. More educational attainment, better health conditions, active in LTAs, and using assistive devices might benefit the maintenance of functioning in Taiwanese older adults.