Early Functional Decline Research Articles

Movement-related Activity of Patients with Rheumatoid Arthritis in Physical Rehabilitation

The article explains the main issues of health and social problems of rheumatoid arthritis. It was established that the urgency of rheumatoid arthritis is caused by progressive disease, severity of the musculoskeletal system. It is noted that there is a high incidence of lesions of working age in which there are early functional abilities decline, loss of professional and social skills, the difficulties of physical and psychological adjustment of patients to violations of motor functions. There was accent an attention that the disease causes significant morbidity, decreased quality of life and high economic expenses. According to modern standards of rheumatoid arthritis treatment, the treatment goal is achieving state of prolonged remission, in addition is decreasing of pain in joints, improvement of its movement, improvement the general patient’s stage, high temperature decreasing. There were established that carefully chosen exercises, physical activity and other renewable contribute help to stop further progression of the disease, restoring function of the affected joints and improve physical and mental condition of the patient and their quality of life. There was proved the necessity to develop a theoretical justification and comprehensive rehabilitation program for early treatment of rheumatoid arthritis, which is aimed to improve the efficiency of rehabilitation, improve ability to work, physical stage and life quality.

Cued memory decline in biomarker-defined preclinical Alzheimer disease.

To determine whether a decline in cued recall is observable in the preclinical stage of Alzheimer disease (AD) in clinically normal older adults with elevated β-amyloid (Aβ) burden on PET imaging. Clinically normal older adults underwent baseline neuroimaging (PET to assess Aβ+/- status and MRI) and annual neuropsychological testing. Cox proportional hazards models were used to assess the relative risk of cued memory decline (drop of 1, 2, 3, or 4 points on the total score of the Free and Cued Selective Reminding Test) in relation to neuroimaging measures, functional status, age, sex, and education. A total of 276 older adults (Clinical Dementia Rating = 0, mean Mini-Mental State Examination score = 29 ± 1.06) were followed up for a mean of 3.6 ± 1.2 years. Despite the infrequency of cued memory decline (only 19% of participants scored ≤46/48 in total recall by year 3), Aβ+ participants were 3.55 times (95% confidence interval = 1.77-7.12) more likely to exhibit decline in total recall (≤46/48) compared with their Aβ- peers. Furthermore, Aβ+ participants who scored ≤46/48 had smaller hippocampal volumes (t = 3.37, p = 0.001) and evidence of early functional decline, i.e., greater risk of progression to global Clinical Dementia Rating of 0.5 (χ2 = 14.30, p < 0.001), compared with their Aβ+ peers with intact total recall. Cued memory decline in healthy older adults may be particularly indicative of Aβ-related decline during the preclinical stage of AD and useful for identifying Aβ+ clinically normal individuals at greatest risk of short-term clinical progression.

Early Age-Related Functional Connectivity Decline in High-Order Cognitive Networks.

As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established. Here, an extensive cross-sectional sample (21–85 years old, N = 887) from a public fcMRI database was used to characterize adult lifespan connectivity dynamics within and between seven brain networks: the default mode, salience, dorsal attention, fronto-parietal control, auditory, visual and motor networks. The entire cohort was divided into young (21–40 years, mean ± SD: 25.5 ± 4.8, n = 543); middle-aged (41–60 years, 50.6 ± 5.4, n = 238); and old (61 years and above, 69.0 ± 6.3, n = 106) subgroups. Correlation matrices as well as a mixed model analysis of covariance indicated that within high-order cognitive networks a considerable connectivity decline is already evident by middle adulthood. In contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline. Additionally, alterations in inter-network interactions are noticeable primarily in the transition between young and middle adulthood. These results provide evidence that aging-related neural changes start early in adult life.

Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.

Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group and sex (with P<0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non-human primate model. Further studies across the life span will determine progression of cardiac dysfunction.

Is the Australian 75+ Health Assessment person-centred? A qualitative descriptive study of older people's perceptions.

Objective The aim of the present study was to explore the perspectives of older people following their recent participation in a 75+ Health Assessment (75+HA) and interrogate these perspectives using a person-centred lens. Methods A qualitative descriptive study design was used within a larger study funded by the Australian Primary Health Care Research Institute. Nineteen participants from four different general practices in one Australian state described their perceptions of the 75+HA in a face-to-face interview. Data were then analysed using a qualitative content analysis approach. Results The purpose of the 75+HA was not well understood by participants. Participant responses reveal that where, when, who and how a primary health professional conducted the 75+HA affected what older people talked about, the guidance they sought to deal with issues and, in turn, the actioning of issues that were discussed during the 75+HA. Conclusion To enable older people to make informed decisions about and successfully manage their own health and well being, and to choose when to invite others to act on their behalf, primary health professionals need to ask questions in the 75+HA within a person-centred mindset. The 75+HA is an opportunity to ensure older people know why they need support, which ones, and agree to, supports and services they require. What is known about the topic? The Australian Medicare Benefits Schedule includes the 75+HA, developed as a proactive primary care opportunity for general practitioners and practice nurses to identify issues affecting community-dwelling older people's health and well being. The aim of the 75+HA is to consider a broad range of factors that could affect physical, psychological and social functioning, which, in turn, affects overall health, and the capacity of older people to live independently in the community. Underlying the 75+HA is the importance of detecting early functional decline to enable healthy aging. What does this paper add? There is scant, if any, attention in the literature to the views of consumers who have completed a 75+HA, especially with regard to whether this opportunity is conducted with a person-centred mindset. This paper addresses this gap. Even after participating in the 75+HA, most participants were unclear as to the purpose of the assessment, what information had been recorded and what would happen from any concerns identified in the assessment. Comments about the 75+HA included that it did not ask people about their goals and what comprised their functionality to ensure their independent living. What are the implications for practitioners? A person-centred approach requires active collaboration between primary health professionals and older people who are living the process of, and planning for, aging-in-place. Assessments like the 75+HA can assist in identifying whether older people may be experiencing early signs of functional decline, even if older people self-report living without problems in their home. Practitioners need to ask questions of older people and respond to what they say with a person-centred mindset.

Depression is often undiagnosed in older people with cancer.

Depression is commonly associated with cancer, either as a pre-existing condition or as a consequence of the illness. Depression is also associated with adverse outcomes such as poor treatment compliance, short survival, long hospital stays, early functional decline, impaired quality of life and increased healthcare costs.

CORR Insights(®): implant design variations in reverse total shoulder arthroplasty influence the required deltoid force and resultant joint load.

R everse shoulder arthroplasty has become an important and powerful tool in the treatment of a variety of severe shoulder pathologies, including rotator cuff arthropathy, complex proximal humeral fractures, and failed anatomic arthroplasties. With increased widespread use, numerous studies have been performed on how changes in its basic components affect the biomechanics and function of the implant. It is clear from several biomechanical studies [2–6] that placement of a reverse total shoulder arthroplasty lowers and medializes the center of rotation of the glenohumeral joint in comparision to the normal anatomic center of rotation. This effectively improves the deltoid moment arm reducing the overall loads to abduct the arm. It also reduces the rotator cuff moment arms, placing the posterior rotator cuff at a disadvantage and subsequently limiting some of the ability for external rotation. With any new technology, however, there exists complications, and the reverse shoulder arthroplasty is not free from this issue. Complications of particular concern include scapular notching, limited ROM, acromial stress fractures, deltoid overtensioning, and dislocation. Several techniques that have been used to reduce common complications associated with reverse shoulder arthroplasty (instability, scapular notching and reduced external rotation motion and strength) include glenosphere lateralization, humeral lateralization, and humeral lengthening. It is currently unclear which of these options is the best strategy to limit these problems without incurring further negative consequences like increased deltoid force for abduction. Excessive deltoid loads can lead to deltoid related pain, acromial stress fractures, and potentially early functional decline due to deltoid senescence. The current study by Giles and colleagues further defines the overall effects of changes in implant variables This CORR Insights is a commentary on the article ‘‘Implant Design Variations in Reverse Total Shoulder Arthroplasty Influence the Required Deltoid Force and Resultant Joint Load’’ by Giles and colleagues available at: DOI: 10.1007/ s11999-015-4526-0. The author certifies that he, or any member of his immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/ licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR or The Association of Bone and Joint Surgeons. This CORR Insights comment refers to the article available at DOI: 10.1007/s11999015-4526-0.

Dental Apical Papilla as Therapy for Spinal Cord Injury

Stem cells of the apical papilla (SCAP) represent great promise regarding treatment of neural tissue damage, such as spinal cord injury (SCI). They derive from the neural crest, express numerous neurogenic markers, and mediate neurite outgrowth and axonal targeting. The goal of the present work was to investigate for the first time their potential to promote motor recovery after SCI in a rat hemisection model when delivered in their original stem cell niche—that is, by transplantation of the human apical papilla tissue itself into the lesion. Control groups consisted of animals subjected to laminectomy only (shams) and to lesion either untreated or injected with a fibrin hydrogel with or without human SCAP. Basso-Beattie-Bresnahan locomotor scores at 1 and 3 d postsurgery confirmed early functional decline in all SCI groups. This significant impairment was reversed, as seen in CatWalk analyses, after transplantation of apical papilla into the injured spinal cord wound, whereas the other groups demonstrated persistent functional impairment. Moreover, tactile allodynia did not develop as an unwanted side effect in any of the groups, even though the SCAP hydrogel group showed higher expression of the microglial marker Iba-1, which has been frequently associated with allodynia. Notably, the apical papilla transplant group presented with reduced Iba-1 expression level. Masson trichrome and human mitochondria staining showed the preservation of the apical papilla integrity and the presence of numerous human cells, while human cells could no longer be detected in the SCAP hydrogel group at the 6-wk postsurgery time point. Altogether, our data suggest that the transplantation of a human apical papilla at the lesion site improves gait in spinally injured rats and reduces glial reactivity. It also underlines the potential interest for the application of delivering SCAP in their original niche, as compared with use of a fibrin hydrogel.

The Australian 75+ Health Assessment: could it detect early functional decline better?

The aim of the present study was to identify opportunities to improve the reach and impact of the Australian Medicare 75+ Health Assessment (75+HA) to detect early functional decline (FD). A comparison of two published review articles produced two outputs: (1) assessments identified in the systematic review that underpinned the 75+HA items were ranked for evidence of effectiveness and compared with the volume of research into assessment areas identified by a recent review on indicators of early FD; and (2) items in the 75+HA were compared with those in the recent review. The review underpinning the 75+HA found 19 assessment areas, with strongest evidence of effectiveness for vision/hearing, teeth/oral, balance/gait, cognitive and service use. The more recent review reported on six domains (eight subdomains) of FD assessment: physical and cognitive elements of the performance capacity domain were the least well assessed, whereas the most comprehensively assessed domains were health service use, performance capacity (mental subdomain), participation (motivation/volition subdomain) and demographics. The 75+HA addresses only some items related to early FD as identified by the recent literature. Reassessment of the 75+HA with a view to including current evidence-based assessments for early FD is recommended. Updating the 75+HA items with ways to detect FD earlier may increase its relevance to Australia's ageing population.

Associations between difficulty in 6 basic activities of daily living and cognitive and lower extremity physical functions in older adults

Background: It is important for older adults to maintain independence in activities of daily living (ADL) to have optimal quality of life. Many factors including the biological, psychological, and social factors have been linked to disability in basic ADL (BADL). Previous studies have investigated the relationship between BADL dependence and functions in older adults. However, the relationship between BADL difficulty and functions has not been well examined. Selfreported BADL difficulty reflects an individual’s awareness, and may serve the researcher better when the interest is about the disease consequences and the objective is to evaluate intervention effectiveness. Purpose:Unlikemuchof the previous research examining the BADL dependence, the purpose of the study is to investigate the relationship between BADL difficulty and cognitive and physical functions in community-dwelling older adults. Self-reported difficulty is believed to precede dependence. Identifying older adults with BADL difficulties may help clinicians to detect early functional decline. Methods: In the cross-sectional study, a convenience sample of 51 community-dwelling older adults was recruited. Interviews were conducted to collect data on self-reported difficulty in six BADLs (bathing, dressing, eating, transfer: getting in/out of bed/chairs, walking, using toilet), clock drawing tests (CLOX1&CLOX2),Mini-Mental State Exam (MMSE), and 5 physical function tests including Short Physical Performance Battery (SPPB), Berg Balance Scale (BBS), gait speed, 5 times sit-to-stand test, and Timed Up & Go Test (TUG). For each BADL task, the student’s t test and Mann–Whitney testwere use to compare differences between older adults with and without difficulty. Results: Among the six BADLs, walking, toileting and transfer are associated with poor cognitive or lower extremity physical functions. Compared to older adults who reported walking difficulty (n= 8, CLOX1= 5.71 ± 4.31, CLOX2 = 8.71 ± 2.29, BBS = 40.38 ± 7.27, SPPB = 4.25 ± 2.49, gait speed = 0.41 ± 0.15 m/sec, TUG = 26.16 ± 6.69 sec), older adults without walking difficulty performed better in cognitive and physical function tests (n = 43, CLOX1 = 9.80 ± 3.31, CLOX2 = 11.64± 2.53, BBS = 49.24± 7.03, SPPB = 7.45± 2.46, gait speed = 0.73± 0.28 m/sec, TUG = 15.90 ± 6.12 sec). Difficulty in toileting is associated with lower SPPB score (2.50 ± 0.71) and longer TUG time (30.27 ± 4.59 sec) (p < .05). Difficulty in transfer is associated with lowerMMSE (17.00± 0.00) andCLOX2 score (5.00± 0.00) (p< .05). Conclusion(s): In older adults, difficulty in walking and toileting is associated with poor lower extremity physical function. Difficulty in walking and transfer is associated with lower cognitive function. Implications: Self-reported difficulty in BADL, such as walking,may suggest the need for further cognitive and physical function screening. Screening older adults with BADL difficulty would allow clinicians to identify high-risk individuals and provide early interventions to prevent or delay onset of future BADL dependence.

Early indications that low mental quality of life scores in recently unwell older people predict downstream functional decline.

BackgroundAccurately detecting markers of early functional decline (FD) are essential to support older people to successfully age in place; however, these markers are poorly understood. We tested the hypothesis that compromised mental quality of life after a minor health crisis could be an early predictor of FD.MethodsThis longitudinal observational cohort study was conducted in the emergency department (ED) of a large Australian hospital and in the community. Data were collected from 148 community-dwelling people aged 65+ years, who provided data at recruitment (baseline), and at 1 month and 3 months post discharge from the ED. Short Form-12 mental quality of life component scores (MCS) were regressed with patient descriptors taken at baseline (age, sex, socioeconomic status, education, Mini-Mental State Examination, and primary language), and over-time estimates of FD taken at baseline, and at 1 and 3 months post discharge (instrumental activities of daily living, frequency of falls and hospitalizations, use of gait aids, receipt of community services, living status, and requiring a carer).ResultsMCS at 1 month (MCS1) post ED discharge was significantly associated with instrumental activities of daily living at 1 (r=0.45, P<0.001) and 3 months (r=0.401, P=0.001) post ED discharge, but not at baseline (r=0.010, P>0.05). Subjects with lower than the population median MCS showed a significant linear decline in total instrumental activities of daily living scores over 3 months (P=0.025). There was no linear trend over time in the relationship between MCS1 with frequency of falls (P=0.20) or hospitalizations (P=0.42); however, there was a significant difference at 3 months post ED discharge for falls (P=0.036) and hospitalizations (P=0.039) between low and high MCS1 groups. There were no significant confounders.ConclusionLow MCS scores 1 month after a minor health crisis appear to significantly predict downstream FD. This finding needs to be tested in a larger sample.

Factors affecting longitudinal functional decline and survival in amyotrophic lateral sclerosis patients

Our objective was to elucidate the clinical factors affecting functional decline and survival in Japanese amyotrophic lateral sclerosis (ALS) patients. We constructed a multicenter prospective ALS cohort that included 451 sporadic ALS patients in the analysis. We longitudinally utilized the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) as the functional scale, and determined the timing of introduction of a tracheostomy for positive-pressure ventilation and death. A joint modelling approach was employed to identify prognostic factors for functional decline and survival. Age at onset was a common prognostic factor for both functional decline and survival (p < 0.001, p < 0.001, respectively). Female gender (p = 0.019) and initial symptoms, including upper limb weakness (p = 0.010), lower limb weakness (p = 0.008) or bulbar symptoms (p = 0.005), were related to early functional decline, whereas neck weakness as an initial symptom (p = 0.018), non-use of riluzole (p = 0.030) and proximal dominant muscle weakness in the upper extremities (p = 0.01) were related to a shorter survival time. A decline in the ALSFRS-R score was correlated with a shortened survival time (p < 0.001). In conclusion, the factors affecting functional decline and survival in ALS were common in part but different to some extent. This difference has not been previously well recognized but is informative in clinical practice and for conducting trials.

Identifying indicators of early functional decline in community-dwelling older people: a review.

Functional decline is an insidious-onset manifestation of aging, which can be overlooked in its early stages. Current screening measures for incipient functional decline are generally applied at one point-in-time, in hospital wards or emergency departments when older people are in health crisis. This potentially provides an imprecise estimate of the situation. In line with internationally recognized challenges of dealing with the needs of aging populations, it is essential that sensitive screening for incipient functional decline occurs much earlier, in familiar community settings. The present review presents an evidence-based synthesis of features, measures and/or manifestations of early functional decline in community-dwelling older individuals. A systematic search was carried out to collate indicators of early functional decline. These were then organized into constructs, which reflected the principal measurement intent as identified by the author of each article. A total of 146 articles (reporting 195 psychometrically sound measurement tools, representing 107 constructs) were included in the review. The constructs were then clustered into six broad health domains: medical status, performance capacity, participation, demographics, anthropometry and relationships with health providers. These domains were developed after consultation with a range of allied health professionals and a consumer representative. The present review provides the first known evidence-based synthesis of indicators of early functional decline in older community-dwelling people, and shows the range of constructs that need to be considered in assessment for early functional decline.

Sarcopenia according to the european working group on sarcopenia in older people (EWGSOP) versus Dynapenia as a risk factor for disability in the elderly.

Sarcopenia, defined as low muscle mass (LMM), and dynapenia have been associated with adverse outcomes in elderly. Contrast the association of sarcopenia versus dynapenia with incidence of disability. A four-year prospective study (2006-2010). São Paulo, Brazil. 478 individuals aged 60 and older from the Saúde, Bem-Estar e Envelhecimento (SABE) study who were non-disabled at baseline. Sarcopenia, measured according to the European Working Group on Sarcopenia in Older People (EWGSOP), includes: LMM assessed by skeletal muscle mass index ≤8.90kg/m2 (men) and ≤6.37kg/m2 (women); low muscle strength (LMS) assessed by handgrip strength <30kg (men) and <20kg (women); and low physical performance (LPP) assessed by gait speed ≤0.8m/s. Diagnosis of sarcopenia required LMM plus LMS or LPP. Dynapenia was defined as handgrip strength <30kg (men) and <20kg (women). Covariates included socio-demographic and behavioral variables, medical conditions, hospitalization, depressive symptoms, cognition, perception of vision, hearing and body mass index. Disability in mobility or instrumental activities of daily living (IADL) or disability in activities of daily living (ADL) and IADL. The incidence density of mobility or IADL disability was 43.4/1000 person/year and 22.6/1000 person/year for IADL and ADL disability. There was no significant difference in incidence density according sarcopenia or dynapenia status. After controlling for all covariates, sarcopenia was associated with mobility or IADL disability (relative risk ratio = 2.23, 95%Confidence Interval: 1.03-4.85). Dynapenia was not associated with disability. Sarcopenia according to the EWGSOP definition can be used in clinical practice as a screening tool for early functional decline (mobility or IADL disability).

Understanding the Complexities of Functional Ability in Alzheimer's Disease: More Than Just Basic and Instrumental Factors

Background: Dementia of the Alzheimer’s type (AD) is defined by both cognitive and functional decline; new criteria allow for identification of milder, non-functionally impaired patients. Understanding loss of autonomy in AD is essential, as later stages represent a significant burden and cost to patients, their families, and society. The purpose of the present analyses was to determine the factor structure of the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale (ADCS-ADL) in a cohort of AD patients. Methods: Baseline ADCS-ADL assessments of 734 AD patients from the PLASA study were included in an exploratory factor analysis (EFA). Because the ADCS-ADL was designed to assess change over time, change from baseline scores over 2 years were also analyzed using an EFA. Factorial solutions were evaluated based on cross-loading, non-loadings, and number of items per factor. Results: Mean age at baseline was 79.3, mean MMSE was 19.8 and 73.3‰ of participants were female. Baseline data suggested a 4-factor solution that included factors for basic ADLs (BADLs), domestic/household activities, communication/engagement with the environment, and outside activities. The change scores EFA suggested a 2-factor solution of BADLs and instrumental ADLs (IADLs). Conclusions: Distinct factors of IADLs should be considered for further validation as areas of attention to catch early functional decline.

PC-FACS

PC-FACS

Functional Decline in Older Patients With Cancer Receiving First-Line Chemotherapy

To determine factors associated with early functional decline during first-line chemotherapy in older patients. Patients age ≥ 70 years receiving first-line chemotherapy for cancer were prospectively considered for inclusion across 12 centers in France. Functional decline was defined as a decrease of ≥ 0.5 points on the Activities of Daily Living (ADL) scale between the beginning of chemotherapy and the second cycle. Factors associated with functional decline were sought from pretreatment abbreviated comprehensive geriatric assessment, including ADL, Instrumental ADL (IADL), Mini-Nutritional Assessment (MNA), Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS15), and Timed Get Up and Go (GUG) test, and from comorbidities (Cumulative Illness Rating Scale-Geriatrics), MAX2 index, and baseline biologic and clinical information. Of 364 included patients, 50 experienced functional decline (16.7%; median, 0.5 points). Abnormal preadmission performance status, IADL, GDS15, MMSE, GUG, and MNA were associated with increased likelihood of functional decline (univariate analysis). In the multivariate model adjusted for baseline ADL and MAX2 index, high baseline GDS (odds ratio [OR], 2.16; 95% CI, 1.09 to 4.30; P = .03) and low IADL scores (OR, 2.87; 95% CI, 1.06 to 7.79; P = .04) were independently associated with increased risk of functional decline. Our results outline associations between baseline depression, instrumental dependencies, and early functional decline during chemotherapy for older patients. ADL should be sequentially evaluated early during treatment. Baseline evaluation of GDS15 and IADL may be proposed to anticipate this event.

Serum Interleukin 6 Is Predictive of Early Functional Decline and Mortality in Interstitial Lung Disease Associated with Systemic Sclerosis

Biomarkers of progression of interstitial lung disease (ILD) are needed to allow early therapeutic intervention in patients with scleroderma-associated disease (SSc-ILD). A panel of 8 serum cytokines [interleukin 6 (IL-6), IL-8, IL-10, CCL2, CXCL10, vascular endothelial growth factor, fibroblast growth factor 2, and CX3CL1] was assessed by Luminex bead technology in exploratory cohorts of 74 patients with SSc and 58 patients with idiopathic pulmonary fibrosis (IPF). Mortality and significant lung function decline [forced vital capacity (FVC) ≥ 10%; DLCO ≥ 15%] from date of serum collection were evaluated by proportional hazards analysis. Based on these findings, the prognostic value of serum IL-6, evaluated by ELISA, was assessed in a larger test cohort of 212 patients with SSc-ILD. In the exploratory cohort, only serum IL-6 was an independent predictor of DLCO decline in both IPF and SSc-ILD. The IL-6 threshold level most predictive of DLCO decline within a year was 7.67 pg/ml. In the larger test cohort, serum IL-6 > 7.67 pg/ml was predictive of decline in FVC (HR 2.58 ± 0.98, p = 0.01) and in DLCO (HR 3.2 ± 1.7, p = 0.02) within the first year, and predictive of death within the first 30 months (HR 2.69 ± 0.96, p = 0.005). When stratified according to severity (FVC < 70%), serum IL-6 > 7.67 pg/ml was predictive of functional decline or death within the first year in patients with milder disease (OR 3.1, 95% CI 1.4-7.2, p = 0.007), but not in those with severe ILD. In SSc-ILD, serum IL-6 levels appear to be predictive of early disease progression in patients with mild ILD, and could be used to target treatment in this group, if confirmed by prospective studies.

From Genetics to Dietetics: The Contribution of Epidemiology to Understanding Alzheimer's Disease

Late-life dementia results from non-modifiable risk factors such as age and genetics, modulated by deleterious and protective environmental factors among which nutrition may play a major role. This paper highlights five major recent contributions of the French Three-City (3C) and PAQUID epidemiological studies to Alzheimer's disease (AD) knowledge, targeting genetic and dietary risk factors, and the impact of cognitive decline in daily living. The 3C study contributed to a large genome-wide association study to identify new genetic risk factors for AD. In addition to apolipoprotein E (APOE), two loci gave replicated evidence of association: one within CLU, encoding clusterin or apolipoprotein J, and the other within CR1, encoding the complement component receptor 1. Although the attributable fraction of risk for these polymorphisms is moderate, genetic studies provide significant insights into the molecular bases of AD. Regarding dietary data, findings from 3C suggest that healthy diets associating sources of both omega 3 fatty acids (fish) and antioxidants (fruits and vegetables) such as the Mediterranean diet, and caffeine could be associated with decreased risk for AD. However, the protective effect of omega3 fatty acids might be limited to APOE4 non-carriers. Future research should focus on gene-nutrient interactions. Regarding the functional impact of prodromal AD, the PAQUID study showed that taking into account mild functional limitations considerably increases the predictive value of neuropsychological tests for conversion to dementia. Research should focus on sensitive instruments to capture early functional decline to improve the identification of elderly patients at high risk of conversion to dementia.

Performance Measures Predict Onset of Activity of Daily Living Difficulty in Community‐Dwelling Older Adults

To assess the predictive value of five performance-based measures for the onset of difficulty in activities of daily living (ADLs). A prospective cohort study; home visits every 6 months for 18 months. Community-based. Community-dwelling older adults, n=110, (mean age 80.3+/-7.0; range 67-98) who reported no difficulty in basic ADLs. The Short Physical Performance Battery (SPPB), gait speed, Berg Balance Scale (BBS), grip strength, and Timed Up and Go Test (TUG) were evaluated at baseline. Seven ADL items were assessed at baseline and 6, 12, and 18 months. The onset of ADL disability was self-report of difficulty in any of the seven ADL items. Logistic regression models were fitted for each of the physical performance measures to predict onset of ADL difficulty at 6, 12, and 18 months. After controlling for age, comorbid conditions, and sex, the BBS was the most consistent and best predictor for the onset of ADL difficulty over an 18-month period (6 months, c-statistic=0.725, (95% confidence interval (CI)=0.60-0.85; 12 months, c-statistic=0.840 95% CI=0.75, 0.93; 18 months, c-statistic=0.821, 95% CI=0.71, 0.93). The SPPB showed excellent predictive value for the onset of difficulty at 12 months. Ninety-five, 89, and 75 older adults completed the 6, 12, and 18-month follow-up visits, respectively. BBS, followed by SPPB, TUG, gait speed, and grip strength, were predictive of the onset of ADL difficulty over an 18-month period in community-dwelling older adults. Screening nondisabled older adults with simple performance tests could allow clinicians to identify those at risk for ADL difficulty and may help to detect early functional decline.