Predictors Of Decline Research Articles

Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies

BackgroundConverging evidence suggests that markers of Alzheimer’s disease (AD) pathology in cognitively unimpaired older individuals are associated with high risk of cognitive decline and progression to functional impairment. The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) and Longitudinal Evaluation of Amyloid and Neurodegeneration Risk (LEARN) Studies enrolled a large cohort of cognitively normal older individuals across a range of baseline amyloid PET levels. Recent advances in AD blood-based biomarkers further enable the comparison of baseline markers in the prediction of longitudinal clinical outcomes.ObjectivesWe sought to evaluate whether biomarker indicators of higher levels of AD pathology at baseline predicted greater cognitive and functional decline, and to compare the relative predictive power of amyloid PET imaging, tau PET imaging, and a plasma P-tau217 assay.DesignAll participants underwent baseline amyloid PET scan, plasma P-tau217; longitudinal cognitive testing with the Primary Alzheimer Cognitive Composite (PACC) every 6 months; and annual functional assessments with the clinical dementia rating (CDR), cognitive functional index (CFI), and activities of daily living (ADL) scales. Baseline tau PET scans were obtained in a subset of participants. Participants with elevated amyloid (Aβ+) on screening PET who met inclusion/exclusion criteria were randomized to receive placebo or solanezumab in a double-blind phase of the A4 Study over 240+ weeks. Participants who did not have elevated amyloid (Aβ−) but were otherwise eligible for the A4 Study were referred to the companion observational LEARN Study with the same outcome assessments over 240+ weeks.SettingThe A4 and LEARN Studies were conducted at 67 clinical trial sites in the United States, Canada, Japan and Australia.ParticipantsOlder participants (ages 65–85) who were cognitively unimpaired at baseline (CDR-GS=0, MMSE 25–30 with educational adjustment, and Logical Memory scores within the normal range LMIIa 6–18) were eligible to continue in screening. Aβ+ participants were randomized to either placebo (n=583) or solanezumab (n=564) in the A4 Study. A subset of Aβ+ underwent tau PET imaging in A4 (n=350). Aβ− were enrolled into the LEARN Study (n=553).MeasurementsBaseline 18-F Florbetapir amyloid PET, 18-F Flortaucipir tau PET in a subset and plasma P-tau217 with an electrochemiluminescence (ECL) immunoassay were evaluated as predictors of cognitive (PACC), and functional (CDR, CFI and ADL) change. Models were evaluated to explore the impact of baseline tertiles of amyloid PET and tertiles of plasma P-tau217 on cognitive and functional outcomes in the A4 Study compared to LEARN. Multivariable models were used to evaluate the unique and common variance explained in longitudinal outcomes based on baseline predictors, including effects for age, gender, education, race/ethnic group, APOEε4 carrier status, baseline PACC performance and treatment assignment in A4 participants (solanezumab vs placebo).ResultsHigher baseline amyloid PET CL and P-tau217 levels were associated with faster rates of PACC decline, and increased likelihood of progression to functional impairment (CDR 0.5 or higher on two consecutive measurements), both across LEARN Aβ− and A4 Aβ+ (solanezumab and placebo arms). In analyses considering all baseline predictor variables, P-tau217 was the strongest predictor of PACC decline. Among participants in the highest tertiles of amyloid PET or P-tau217, >50% progressed to CDR 0.5 or greater. In the tau PET substudy, neocortical tau was the strongest predictor of PACC decline, but plasma P-tau217 contributed additional independent predictive variance in commonality variance models.ConclusionsIn a large cohort of cognitively unimpaired individuals enrolled in a Phase 3 clinical trial and companion observational study, these findings confirm that higher baseline levels of amyloid and tau markers are associated with increased rates of cognitive decline and progression to functional impairment. Interestingly, plasma P-tau217 was the best predictor of decline in the overall sample, superior to baseline amyloid PET. Neocortical tau was the strongest predictor of cognitive decline in the subgroup with tau PET, suggesting that tau deposition is most closely linked to clinical decline. These findings indicate that biomarkers of AD pathology are useful to predict decline in an older asymptomatic population and may prove valuable in the selection of individuals for disease-modifying treatments.

Linking Dementia Pathology and Alteration in Brain Activation to Complex Daily Functional Decline During the Preclinical Dementia Stages: Protocol for a Prospective Observational Cohort Study.

Progressive difficulty in performing everyday functional activities is a key diagnostic feature of dementia syndromes. However, not much is known about the neural signature of functional decline, particularly during the very early stages of dementia. Early intervention before overt impairment is observed offers the best hope of reducing the burdens of Alzheimer disease (AD) and other dementias. However, to justify early intervention, those at risk need to be detected earlier and more accurately. The decline in complex daily function (CdF) such as managing medications has been reported to precede impairment in basic activities of daily living (eg, eating and dressing). Our goal is to establish the neural signature of decline in CdF during the preclinical dementia period. Gait is central to many CdF and community-based activities. Hence, to elucidate the neural signature of CdF, we validated a novel electroencephalographic approach to measuring gait-related brain activation while participants perform complex gait-based functional tasks. We hypothesize that dementia-related pathology during the preclinical period activates a unique gait-related electroencephalographic (grEEG) pattern that predicts a subsequent decline in CdF. We provide preliminary findings showing that older adults reporting CdF limitations can be characterized by a unique gait-related neural signature: weaker sensorimotor and stronger motor control activation. This subsample also had smaller brain volume and white matter hyperintensities in regions affected early by dementia and engaged in less physical exercise. We propose a prospective observational cohort study in cognitively unimpaired older adults with and without subclinical AD (plasma amyloid-β) and vascular (white matter hyperintensities) pathologies. We aim to (1) establish the unique grEEG activation as the neural signature and predictor of decline in CdF during the preclinical dementia period; (2) determine associations between dementia-related pathologies and incidence of the neural signature of CdF; and (3) establish associations between a dementia risk factor, physical inactivity, and the neural signature of CdF. By establishing the clinical relevance and biological basis of the neural signature of CdF decline, we aim to improve prediction during the preclinical stages of ADs and other dementias. Our approach has important research and translational implications because grEEG protocols are relatively inexpensive and portable, and predicting CdF decline may have real-world benefits. DERR1-10.2196/56726.

Neurocognitive Changes in Patients with Post-COVID Depression.

Background: Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD, n = 25) patients using neuropsychological testing. Methods: The study involved 71 post-COVID patients with matched control groups: recovered COVID-19 individuals without complications (n = 18) and individuals without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, and a comparison group (noPCD, n = 46) included participants with neurological COVID-19 complications, excluding clinical depression. Results: The PCD patients showed gender-dependent significant cognitive impairment in the MoCA, Word Memory Test (WMT), Stroop task (SCWT), and Trail Making Test (TMT) compared to the controls and noPCD patients. Men with PCD showed worse performances on the SCWT, in MoCA attention score, and on the WMT (immediate and delayed word recall), while women with PCD showed a decline in MoCA total score, an increased processing time with less errors on the TMT, and worse immediate recall. No differences between groups in Sniffin's stick test were found. Conclusions: COVID-related direct (post-COVID symptoms) and depression-mediated (depression itself, male sex, and severity of COVID-19) predictors of decline in memory and information processing speed were identified. Our findings may help to personalize the treatment of depression, taking a patient's gender and severity of previous COVID-19 disease into account.

Geriatric Nutritional Risk Index as a Possible Predictor of Decline in Kidney Function in Older People.

The Geriatric Nutritional Risk Index (GNRI) is associated with morbidity and mortality in older individuals. Our study explored the relationship between GNRI, decline in kidney function, and all-cause mortality in older individuals. This retrospective cohort study analyzed data from participants aged ≥60 years who underwent a general health checkup between 2002 and 2018. The primary exposure was the GNRI, divided into quartiles. The primary and secondary outcomes were a decline in kidney function assessed using the 5-year estimated glomerular filtration rate (eGFR) and all-cause mortality, respectively. The analysis included a total of 1,599 participants (median age, 63 years; interquartile range [IQR], 61-67; 54% males). The mean±standard deviation of GNRI was 114±7. Compared with the highest GNRI quartile, the lower GNRI quartiles were associated with steeper 5-year slopes in eGFR, with a fully adjusted beta coefficient and 95% confidence intervals (CIs) of -0.50 (-0.86, -0.14), -0.29 (-0.63, 0.05), and -0.19 (-0.53, 0.14) for the first, second, and third GNRI quartiles, respectively. The median follow-up duration was 7.4 years (IQR, 4.6-12.4). During this period, we identified 108 deaths (7.8 per 1,000 person-years). The first GNRI quartile was associated with all-cause mortality compared to the highest GNRI quartile (hazard ratio of 2.20; 95% CI 1.23, 3.95). Nutritional status, as evaluated using the GNRI, was associated with 5-year changes in kidney function and all-cause mortality in older individuals.

10 Semantic Memory as a Predictor of Future Memory Decline

Objective:To determine if the degree of split between phonemic verbal fluency and semantic verbal fluency at initial visit is predictive of decline in memory performance between initial evaluation and follow-up.Participants and Methods:Data from a retrospective multidisciplinary memory clinic database at Spectrum Health was utilized. We examined data from 90 participants who had both an initial and follow-up evaluation completed (initial age = 77.1±4.7 years, follow-up age = 78.4±4.7 years, education = 13.9±3.1 years, race = 91% White, 7% Black, & 2% Hispanic, sex = 61% female, time between evaluations = 15.2±9.9 months). Patients who returned for follow-up did not meet criteria for dementia at time one. Split between phonemic and semantic fluency, termed the semantic-phonological delta (SPD) was measured at the initial evaluation by subtracting the Controlled Oral Word Association Test (COWAT; FAS) T-score from the Animal Naming Test (ANT) T-score. Change in memory score was defined in two ways: 1) subtracting the follow-up evaluation Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) List Recognition Score (RBANS percentiles were converted to a scaled score) from the initial evaluation List Recognition Score (List Recognition Delta), and 2) computing the difference in the RBANS Delayed Memory Index Standard Score between the initial evaluation and the follow-up evaluation (RBANS Memory Delta).Results:Average semantic fluency T scores were (M = 40.3, SD = 12.3) and phonemic fluency T scores were (M = 42.7, SD = 10.3) at initial evaluation. Bivariate correlations were used to determine the relationship between the clinical variables. SPD was significantly correlated with List Recognition Delta, r(88) = .23, p = .026, with greater discrepancies in verbal fluency scores associated with higher level of decline in List Recognition at follow-up. By comparison, Semantic Fluency performance itself at initial evaluation was not significantly correlated with List Recognition Delta, r(88) = .17, p = .097. The correlation between SPD and the RBANS Memory Delta was also not significant, r(88) = .14, p = .166. At follow-up evaluation, 39% of the sample received a diagnosis of Alzheimer’s disease. Of those diagnosed with Alzheimer’s disease, 66% had a negative SPD split at time one, performing worse on semantic fluency compared to phonemic fluency.Conclusions:SPD is a better predictor of decline in RBANS List Recognition performance between evaluations than semantic fluency alone, with a larger negative SPD score (worse semantic fluency performance compared to phonemic fluency) at initial evaluation predicting decline in List Recognition performance at follow-up evaluation. SPD at initial evaluation was not significantly correlated with change in RBANS Delayed Memory Index score between evaluations. This may be because there are some patients who are similarly impaired in both semantic and phonemic verbal fluency at initial evaluation who later demonstrate progressive decline in memory retrieval due to hippocampal-sparing etiologies (e.g., vascular dementia). Overall, these findings are consistent with previous work suggesting that declines in the semantic memory system precede declines in episodic memory retention in conditions such as Alzheimer’s disease.

Neuroimaging biomarkers of glial activation for predicting the annual cognitive function decline in patients with Alzheimer’s disease

BackgroundGlial activation is central to the pathogenesis of Alzheimer’s disease (AD). However, researchers have not demonstrated its relationship to longitudinal cognitive deterioration. We aimed to compare the prognostic effects of baseline positron emission tomography (PET) imaging of glial activation and amyloid/tau pathology on the successive annual cognitive decline in patients with AD. MethodsWe selected 17 patients diagnosed with mild cognitive impairment or AD. We assessed the annual changes in global cognition and memory. Furthermore, we assessed the predictive effects of baseline amyloid and tau pathology indicated by cerebrospinal fluid (CSF) concentrations and PET imaging of glial activation (11C-DPA-713-binding potential in the area of Braak 1–3 [11C-DPA-713-BPND]) on global cognition and memory using a stepwise regression analysis. ResultsThe final multiple regression model of annual changes in global cognition and memory scores included 11C-DPA-713-BPND as the predictor. The CSF Aβ42/40 ratios and p-tau concentrations were removed from the final model. In stepwise Bayesian regression analysis, the Bayes factor-based model comparison suggested that the best model included 11C-DPA-713-BPND as the predictor of decline in global cognition and memory. ConclusionsTranslocator protein–PET imaging of glial activation is a stronger predictor of AD clinical progression than the amount of amyloid/tau pathology measured using CSF concentrations. Glial activation is the primary cause of tau-induced neuronal toxicity and cognitive deterioration, thereby highlighting the potential of blocking maladaptive microglial responses as a therapeutic strategy for AD treatment.

SABR for Early Non-Small Cell Lung Cancer: Changes in Pulmonary Function, Dyspnea, and Quality of Life

The aim of this study is to report pulmonary function tests (PFTs), clinician-reported and patient-reported QoL outcomes on a cohort of NSCLC patients treated with SABR. 119 patients with NSCLC were treated with SABR in the prospective cohort SSBROC study of patients with T1-T2N0M0 NSCLC. PFTs and quality of life measures were obtained at baseline pre-treatment and 6 monthly. Here we report on the 6- to 18-month time points. ANCOVA methods adjusting for baseline analysed potential predictors on outcomes of PFT and patient-reported dyspnoea at 18 months. The only statistically significant decline in PFTs was seen in FEV1 at 18 months post-SABR with a decline of -0.11L (p = 0.0087, 95% CI -0.18 to -0.02). Of potential predictors of decline, only a 1 unit increase in smoking pack years resulted in a -0.12 change in DLCO (p = 0.026, 95% CI -0.02 to -0.23) and a 0.003 decrease in FEV1 (p = 0.026, 95% CI -0.006 to -0.0004). For patient reported outcomes, statistically significant worsening in both QLQC30 and QLQLC13 dyspnoea scores occurred at the 18-month time point, but not earlier. No potential predictors of worsening dyspnoea were statistically significant. There was no statistically significant decline in clinician-reported outcomes or global QoL scores. We found a statistically significant decline in FEV1 at 18 months post-treatment. Smoking pack years was a predictor for decline in DLCO and FEV1 at 18 months. Worsening of patient-reported dyspnoea scores was observed, consistent with the expected progression of lung co-morbid disease.

Fear of falling is associated with gait parameters during obstacle avoidance with different physical characteristics in older adults

BACKGROUND: Fear of falling (FOF) is related to worse locomotor performance, is a predictor of decline in functionality, and predisposes falls in older adults. It is necessary to investigate how FOF influences locomotor parameters during walking and in obstacle avoidance in older adults. AIM: To investigate the relationship between FOF and the locomotor variables during walking through and obstacle avoidance with different physical characteristics. METHOD: 22 older adults participated in this study and were invited to perform three tasks: 1) Walking Through; 2) Walking with a solid obstacle and 3) Walking with a fragile obstacle. RESULTS: Correlations were found between FOF and following variables: 1) Walking Through: step velocity (r=-0.640, p=0.003), width (r=0.641, p=0.003), double support time (r=0.523, p=0.022); 2) Solid obstacle: step velocity (r=-0.666, p=0.002), length (r=-0.758, p<0.001), foot-obstacle horizontal distance (r=-0.479, p=0.038), right stride velocity (r=-0.534, p=0.019), length (r=-0.522, p=0.022), left stride velocity (r=-0.551, p=0.014), left stride duration (r=0.561, p=0.012); 3) Fragilid obstacle: step velocity (r=-0.629, p=0.004), length (r=-0.556, p=0.014), foot-obstacle distance (r=-0.540, p=0.017), obstacle-foot distance (r=-0.492, p=0.032), right stride velocity (r=-0.583, p=0.009), length (r=-0.498, p=0.030), left stride velocity (r=-0.574, p=0.010), length (r=-0.462, p=0.047), width (r=-0.514, p=0.024), right stride duration (r=0.479, p=0.038), left stride duration (r=0.646, p=0.003). CONCLUSION: The characteristics of the obstacle did not influence the older adults FOF during walking through and obstacle avoidance. Although they adopt predictive and reactive compensatory adaptations in an attempt to make the task safer, these adaptations actually make the task more dangerous and increase the risk of stumbling and falling.

Predictors of decline in kidney function in the general population: a decade of follow-up from the Tehran Lipid and Glucose Study

Background and aims We aimed to assess the potential socio-demographic, clinical, and lifestyle-related risk factors for kidney function decline (KFD), defined as ≥30% estimated glomerular filtration rate (eGFR) decline, in an Iranian cohort study. Methods 7190 participants (4049 women) aged 20–90 years with 2–5 eGFR data from examinations (2001–2005 to 2015–2018) were included. Cox proportional hazard models were used to examine the association between potential risk factors and eGFR decline. Results During 11.5 years of follow-up, 1471 (889 women) participants had incident KFD with a crude incidence rate of 192.1 (182.6–202.2) per 10,000 person-year. Among the total population, older age, female gender, prehypertension, hypertension, diabetes, widowed/divorced states, higher triglycerides (TG), prevalent cardiovascular diseases (CVD), and higher baseline eGFR were significantly associated with higher, while moderate physical activity and a positive family history of diabetes were associated with lower risk of KFD (all p values <.05). Prevalent CVD in women but not men, diabetes, and hypertension among postmenopausal than premenopausal women were significant risk factors of KFD. According to the presence of chronic kidney disease (CKD) at baseline, higher eGFR decreased the risk of KFD in patients with CKD and increased KFD risk in those without CKD (all p for interactions <.05). Conclusion KFD is associated with multiple modifiable risk factors among the Iranian urban population that is affected by gender, menopausal status, and initial kidney function. Interventions targeting these factors might potentially help reduce the burden of KFD. Key messages: Menopausal status may influence the relationship between cardiometabolic risk factors and KFD; The impact of higher baseline eGFR on the risk of KFD differed between subjects with preserved kidney function and CKD patients. The interaction between gender, menopausal status, and baseline kidney function with different risk factors on KFD may help to make renal risk prediction scores to identify those in the general population at risk who may benefit from early prevention.

Perceptions of fatigue and neuromuscular measures of performance fatigability during prolonged low-intensity elbow flexions.

What is the central question of this study? What is the predictive relationship between self-reported scales to quantify perceptions of fatigue during exercise and gold standard measures used to quantify the development of neuromuscular fatigue? What is the main finding and its importance? No scale was determined to be substantively more effective than another. However, the number of ongoing contractions performed was shown to be a better predictor of fatigue in the motor system than any of the subjective scales. The purpose of this study was to determine the relationship between transcranial magnetic stimulation (TMS) measures of performance fatigability and commonly used scales that quantify perceptions of fatigue during exercise. Twenty healthy participants (age 23±3years, 10 female) performed 10 submaximal isometric elbow flexions at 20% maximal voluntary contraction (MVC) for 2min, separated by 45s of rest. Biceps brachii muscle electromyography and elbow flexion torque responses to single-pulse TMS were obtained at the end of each contraction to assess central factors of performance fatigability. A rating of perceived exertion (RPE) scale, Omnibus Resistance scale, Likert scale, Rating of Fatigue scale and a visual analogue scale (VAS) were used to assess perceptions of fatigue at the end of each contraction. The RPE (root mean square error (RMSE)=0.144) and Rating of Fatigue (RMSE=0.145) scales were the best predictors of decline in MVC torque, whereas the Likert (RMSE=0.266) and RPE (RMSE=0.268) scales were the best predictors of electromyographic amplitude. Although the Likert (RMSE=7.6) and Rating of Fatigue (RMSE=7.6) scales were the best predictors of voluntary muscle activation of any scale, the number of contractions performed during the protocol was a better predictor (RMSE=7.3). The ability of the scales to predict TMS measures of performance fatigability were in general similar. Interestingly, the number of contractions performed was a better predictor of TMS measures than the scales themselves.

Mothers' sense of coherence and oral health-related quality of life of preschoolers: a 3-year cohort study.

The aim of the present study was to assess whether mothers' sense of coherence (SOC) was a predictor of decline in oral health-related quality of life (OHRQoL) of preschoolers. A 3-year cohort study was conducted in Diamantina, Brazil. At baseline, 162 preschoolers aged one to three years were randomly selected from among children registered in local Primary Healthcare Units. In the first stage, mothers completed a sociodemographic questionnaire, the Brazilian version of the Early Childhood Oral Health Impact Scale (B-ECOHIS), and the Brazilian short version of the Sense of Coherence Scale (SOC-13). The total score obtained from the SOC-13 was used to select exposed and unexposed children. Clinical examinations were performed to detect the presence of dental caries, traumatic dental injury, and malocclusion. At follow-up, mothers completed the sociodemographic questionnaire and the B-ECOHIS again. The incidence of severe dental caries and adherence to the proposed treatment at baseline were evaluated. A decline in OHRQoL was considered if there was an increase in the B-ECOHIS score of at least one unit. The chi-square test and Poisson regression were performed. A total of 151 preschoolers participated in the study, among whom 37.7% showed a decline in OHRQoL. Mothers' SOC was not associated with a negative impact on OHRQoL (RR = 1.24; 95%CI = 0.81-1.88), while the incidence of severe dental caries had a greater impact on the decline in OHRQoL (RR = 2.02; 95%CI = 1.29-3.16). Mothers' low SOC was not a predictor of decline in the OHRQoL of preschoolers after a 3-year follow-up period.

Elevation of hemoglobin A1c increases the risk of decline in left ventricular systolic function among patients with coronary artery disease

AimsThe aim of this study was to investigate the association of HbA1c and left ventricular (LV) systolic function among patients with coronary artery disease (CAD). MethodsCAD patients from the Cardiorenal ImprovemeNt II (CIN-II, NCT05050877) registry were included in the study. They were separated into four groups based on HbA1c levels (Q1: HbA1c<5.7%; Q2: 5.7% ≤ HbA1c < 6.1%; Q3: 6.1% ≤ HbA1c < 6.9%; Q4: HbA1c ≥ 6.9%). The endpoint was decline in LV systolic function, defined as an absolute decrease in LV ejection fraction (LVEF) ≥10% from baseline to follow-up with 3–12 months. The association of HbA1c and LVEF was assessed by logistics regression models. ResultsCAD patients (n = 3,994) (age 62.9 ± 10.6 years; 22.2% female) were included in the final analysis. A decline in LV systolic function was recorded in 429 (11%) patients during follow-up. After fully adjusting for confounders, HbA1c was significantly associated with the high risk of decline in LV systolic function (OR 1.12 [95%CI 1.05-1.20] P = 0.001). By stratifying HbA1c as four groups, there is a significantly increased risk of decline in LV systolic function when HbA1c ≥6.1% (Q2, Q3 and Q4 vs Q1, with OR 1.22 [0.88–1.68] P = 0.235; OR 1.48 [1.07–2.05] P = 0.019; OR 1.60 [1.160–2.22] P = 0.004, respectively). Meanwhile, patients with decline in LV systolic function had a higher risk of cardiovascular death. ConclusionsElevated HbA1c is a predictor of decline in LV systolic function in CAD patients. Clinicians should be aware of the risk of decline in LV systolic function in CAD patients with elevated HbA1c, and take measures as soon as possible.

Abstract 13448: Time Course and Predictors of Renal Function Decline After Pediatric Heart Transplantation: A PHTS Multi-Institutional Analysis

Introduction: Decline in renal function can impact both the management and outcomes of pediatric heart transplantation (HTx). Initial renal function decline may be subclinical and underappreciated. We sought to identify the time course and predictors of decline in renal function and the impact of these changes on HTx outcomes. Methods: The Pediatric Heart Transplant Society (PHTS) database was queried to identify HTx recipients at participating centers from 1996 to 2019 with at least 1 year of follow-up. Patients with simultaneous or previous kidney transplant were excluded. Renal function was measured by modified Schwartz formula eGFR on annual follow-up forms and stratified into eGFR groups by National Kidney Foundation chronic kidney disease staging guidelines. “Initial renal function decline” was defined as the initial drop by at least one eGFR group relative to stage at 1 year post transplant (“baseline”). Results: Of the 5,250 patients who met inclusion criteria, initial renal function decline occurred, relative to baseline, in 7.4%, 18.7%, and 55.7%, by 1, 5, and 10 years of follow up, respectively (Figure A). eGFR group distribution for the cohort progressively worsened over the follow up period (Figure B). On multivariate Cox modeling, risk factors for renal function decline were increased BSA at 1 year post-transplant (HR 1.24 [1.02, 1.52]), acute rejection with hemodynamic compromise (HR 1.24 [1.10, 1.39]), and Black race (HR 1.21 [1.08, 1.36]) with the use of tacrolimus (vs cyclosporine) being protective (HR 0.77 [0.69, 0.85]). Patients whose eGFR was &lt; 30 mL/min at 1 year follow up had an increased risk of graft loss (P &lt; 0.0001 compared to all other groups). Conclusions: Decline in renal function occurs progressively, affecting over 50% of HTx recipients in long term follow up, independent of renal condition at the time of HTx. Avoidance of potentially nephrotoxic events and medications must be considered at all times in the long term management of pediatric HTx.

Establishment of Clinical Construct of Intrinsic Capacity in Older Adults and Its Prediction of Functional Decline.

BackgroundThe World Health Organization has conceptualised the health and healthcare of older adults around the concept of healthy ageing. Healthy ageing is defined as “the process of developing and maintaining the functional ability that enables well-being in older age”. This functional ability is the sum of two key factors: intrinsic capacity and interacting environment. This concept of intrinsic capacity encompasses a wide spectrum of health characteristics including the physiological and psychological changes associated with the ageing process. In general, IC declines from a high and stable state to an impaired status as people age. Monitoring individuals for changes in intrinsic capacity in the context of their environment will provide a holistic method of tracking the functioning of older adults at both a population and individual level, providing an opportunity to address any reversible factors of decline. However, this would require a clear and objective conceptualisation of the concept of intrinsic capacity.MethodologyOne hundred subjects were recruited via invitation by advertisement on the institute campus. Study participants underwent detailed physical examination and measurement of various physical and chemical biomarkers which were likely to represent intrinsic capacity as evidenced by the literature review. Outcomes measured were a decline in ADL, IADL, mortality and hospitalisation over a follow-up period of six months. Exploratory factor analysis (EFA) was done to obtain a clinical construct of the proposed entity of intrinsic capacity. Unpaired t-test and univariate logistic regression were used to check for the association between the composite score (IC) and its domains with the decline in ADL, IADL, mortality and hospitalisation.ResultsOne composite score (composite IC score) and eight subfactors emerged. The composite score and subfactor domains showed good construct validity. Composite intrinsic capacity score and subdomains of strength and cognition were significantly different among subjects with and without ADL and IADL decline. Univariate logistic regression showed that composite intrinsic capacity score was a predictor of decline in ADL and IADL even after adjusting for age, sex, comorbidity status and education level of the subject with an adjusted odds ratio of 0.99 and 0.98, respectively. Subdomains of strength and cognition also predicted a decline in ADL and IADL independently.ConclusionThe development of an objective construct of the concept of intrinsic capacity, using commonly measured clinical and biochemical parameters, is feasible and predictive of the subsequent functionality of an individual.

Depressive symptoms predict memory decline in Essential Tremor

IntroductionEssential tremor (ET), a common movement disorder, is characterized by motor, cognitive and psychiatric symptoms. Depressed mood, a symptom of ET, has historically been viewed as a psychological response to disability. However, depressive symptoms are emerging as a predictor of cognitive decline across several clinical populations. We examined if depressive symptoms predict decline in global cognition, memory, and executive functioning among older adults with ET. Methods125 cognitively normal participants with ET completed three in-person assessments of cognition, mood, and motor symptoms at baseline, 18 months, and 36 months; baseline data were collected from July 2014–July 2016. Depressive symptoms were measured with the Geriatric Depression Scale. Cognitive functioning was measured via a 3-4 hour neuropsychological evaluation. Generalized linear regression models examined depressive symptoms as a predictor of decline in global cognition, executive functioning (EF), and memory. ResultsParticipants were grouped according to a median split (GDS <5 versus ≥ 5) due to the bimodal distribution of the data. In unadjusted models, depressive symptoms did not predict change in global cognition (b = −0.002, p = .502) or EF (b = 0.000, p = .931), however individuals with GDS ≥ 5 demonstrated faster memory decline in unadjusted (b = −0.008, p = .039) and adjusted models (b = −0.009, p = .019). ConclusionThe presence of 5 or more depressive symptoms predicted mildly faster memory decline in cognitively normal older adults with ET over 36 months. We discuss potential mechanisms and clinical implications.

Predictors of Decline in Renal Function 5 Years after EVAR.

While there exists copious short-term data regarding renal function following infra-renal endovascular abdominal aortic aneurysm repair (EVAR), long-term analysis is sparse. This is a single institution retrospective review of predictors of renal function decline 5 years after elective EVAR. All EVAR between 2007 and 2015 were queried. Patients in whom renal function was documented 5 years postoperatively were included in analysis. Exclusion criteria were ruptured aneurysm, mortality before 56 months, lack of follow-up, ESRD status, and concomitant renal intervention. The primary outcome investigated was a 20% or greater drop in glomerular filtration rate (GFR) 5 years postoperatively. The following variables at the time of surgery were investigated as potential predictors: age, gender, hypertension, hyperlipidemia, diabetes, CAD or prior MI, COPD, prior stroke, baseline eGFR under 60mL/min/1.73m2, supra-renal fixation, infra-renal fixation, neck diameter, neck length, and number of contrast CT. 354 EVAR were identified of which 143 met inclusion criteria (211 excluded). Univariate analysis revealed female gender (OR 2.7), hypertension (OR 9.4), baseline renal insufficiency (OR 3.8), larger neck diameter, and supra-renal fixation (OR 2.32) all predictive (P < .05) of GFR drop at 5 years. Multivariate binary logistic regression analysis found female gender (multivariate OR 3.9, P = .023) and baseline renal insufficiency (multivariate OR 3.0, P = .029) as significant predictors of greater than 20% GFR drop at 5 years. Only 2 patients of the 143 progressed to dialysis requirement at 5 years. Females and patients with baseline renal insufficiency are more vulnerable to significant decline in renal function 5 years following EVAR. Consistent with analogous literature, supra-renal fixation appears moderately deleterious toward renal function with no clinical significance in those with baseline normal renal function. The potential benefit of avoidance of supra-renal fixation in female patients with baseline renal insufficiency is worth further investigation in a more robust multi-center study.

Progression in Parkinson's Disease: Variation in Motor and Non-motor Symptoms Severity and Predictors of Decline in Cognition, Motor Function, Disability, and Health-Related Quality of Life as Assessed by Two Different Methods.

Parkinson's disease (PD) is multi-symptom disease with variable progression. We performed a longitudinal study to address the evolution of motor symptoms (MS) and non-motor symptoms (NMS), predictors of motor-, cognitive-, disability-, and health-related quality of life (HRQL) status and the relative usefullness of a battery of separate NMS scales (BSS) versus the Non-Motor Symptom Scale (NMSS). Seventy-two patients were assessed at baseline and 4 years later with the NMSS and BSS. We assessed the following outcomes: cognition (Montreal Cognitive Assessment scale [MoCA]), disability (Unified Parkinson's Disease Rating Scale Part II [UPDRS II], Schwab and England [S&E]), motor dysfunction (Unified Parkinson's Disease Rating Scale Part III [UPDRS III], Hoehn and Yahr [HY]), and HRQL (EuroQol [EQ] EQ-vertical visual analogue scale [VAS] and EQ-Index). Statistical analysis included a comparison between scales scores at both time points and multivariate regression analysis to calculate the impact of each baseline symptom in outcomes. NMSS and BSS were introduced in separate models. NMSS Domain 4: perception/hallucinations, Parkinson's Psychosis Questionnaire, Apathy Scale, NMSS Domain 7: urinary, S&E, UPDRS II, HY, and MoCA scores worsened significantly. Dementia increased to a 4-year prevalence of 39.8%. In the multivariate model using BSS, cognitive state variation was significantly predicted by baseline HY, EQ-Index, and S&E. Using the NMSS, MoCA change was significantly associated with NMSS Domain 4: perceptions/hallucination score, cognitive status with UPDRS III score, HRQL with NMSS Domain 4: perception/hallucinations score, and S&E. Our study suggests that NMS progress heterogeneously, BSS approach being more sensitive to change than NMSS. The multivariate analysis has shown that S&E and NMSS Domain 4: perception/hallucinations scores are the stronger predictors of HRQL and cognitive dysfunction variation, favoring NMSS over the BSS approach.

Predicting decreased health-related quality of life (HRQL) in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

10043 Background: This study examines temporal patterns in HRQL among adult survivors of childhood cancer, and socio-demographic, lifestyle and health status predictors of decline in HRQL. Methods: Adult survivors of childhood cancer (4755, 55.2% female, 86.9% non-Hispanic white) completed baseline (T0) and follow-up (T1 in 2003, T2 in 2014) surveys (median[SD] age 32.4[7.5] at T1, time since diagnosis to T1 23.0[4.5], T1-T2 interval 11.7[0.6] years). Socio-demographic (e.g., age, sex, educational attainment, annual family income), lifestyle (physical inactivity, smoking) and health status predictors were collected at T0 and T1. Chronic conditions graded ≥2 by CTCAE defined as presence, and mental and cognitive status with ≥1SD from norms defined as poor. SF-36 Physical and Mental Component Summary (PCS/MCS; mean 50/SD 10) at T1 and T2 classified HRQL as optimal (≥40) or suboptimal ( &lt; 40). Multivariable logistic regression identified risk factors (T0, T1 or status change T0-T1) of decreased HRQL (i.e., optimal to suboptimal) using a backward selection method (p &lt; 0.1), adjusting for sex, race, age at T1 and years between T1-T2. The sample was randomly split into training (80%) and test (20%) datasets to develop and validate prediction models; Area Under the ROC Curve (AUC) evaluated model performance. Results: From T1-T2, 8.1% and 8.3% of survivors reported decreased PCS and MCS. AUCs of training/test models were 0.75/0.74 for decreased PCS and 0.72/0.68 for decreased MCS. Risk factors at T0 or T1 predicting decreased PCS included female sex (OR 1.67, 95%CI 1.25-2.24), younger age (OR 1.04, 95%CI 1.02-1.06), &lt; college/vocational education (OR 1.59, 95%CI 1.02-2.46), family income &lt; $20,000 (OR 2.00, 95%CI 1.21-3.30), obesity (OR 1.97, 95%CI 1.32-2.92), chronic health conditions (neurologic OR 2.47, 95%CI 1.69-3.60; musculoskeletal OR 2.27, 95%CI 1.42-3.64; endocrinological OR 2.25, 95%CI 1.44-3.52; gastrointestinal OR 1.89, 95%CI 1.32-2.69; pulmonary OR 1.66, 95%CI 1.06-2.59; cardiovascular OR 1.53, 95%CI 1.14-2.06) and depression (OR 1.79, 95%CI 1.20-2.67). Risk factors at T0 or T1 predicting decreased MCS included unemployment (OR 1.68, 95%CI 1.19-2.38), smoking (OR 2.03, 95%CI 1.37-3.00), physical inactivity (OR 1.48, 95%CI 1.05-2.09), poor mental health (depression OR 4.29, 95%CI 2.44-7.55; somatization OR 1.63, 95%CI 1.05-2.53) and poor cognitive status (task efficiency OR 1.90, 95%CI 1.34-2.68; organization OR 1.67, 95%CI 1.12-2.48). Conclusions: Nearly 10% of childhood cancer survivors have significant late-onset decline in HRQL. Chronic health conditions predict decreased physical HRQL, whereas smoking, physical inactivity and poor mental health predict decreased mental HRQL. Interventions targeting modifiable lifestyle and health conditions should be considered to prevent decreased HRQL for childhood cancer survivors.

Effectiveness of individually tailored exercise on functional capacity and mobility in nursing home residents

Deterioration of physical and functional capacities is often seen in nursing homes. The present study aimed at assessing the effectiveness of an individually tailored physical exercise intervention on mobility and functional decline in nursing home residents in a 1-year follow-up period. Information on gender, age, education, profession and cognitive status was collected at baseline and at 6 and 12 months of the intervention. The decline in functional capacity and mobility was assessed using the Barthel index. Some 221 participants were included. Results from the multivariate logistic regression showed how residents who never participated in physical activities had a five-fold higher risk of mobility decline compared with residents who did engage for the whole follow-up time. A lower effect was seen in residents who participated for only 6 months. Although dementia appeared to be a significant predictor of decline, a substantial stabilisation in mobility capacity was noted in patients with both mild and severe dementia performing exercise. The findings suggest that preventing or slowing physical decline in nursing home residents is an achievable goal, and even those with a higher degree of cognitive decline may benefit from a tailored physical activity plan.

Hospitalized older adult: predictors of functional decline.

Objective:to identify the predictors of functional decline in hospitalized individuals aged 70 or over, between: baseline and discharge; discharge and follow-up, and baseline and three-month follow-up.Method:a prospective cohort study conducted in internal medicine services. A questionnaire was applied (clinical and demographic variables, and predictors of functional decline) at three moments. The predictors were determined using the binary logistic regression model.Results:the sample included 101 patients, 53.3% female, mean age of 82.47 ± 6.57 years old. The predictors that most contributed to decline in hospitalization were the following: previous hospitalization (OR=1.8), access to social support (OR=4.86), cognitive deficit (OR=6.35), mechanical restraint (OR=7.82), and not having a partner (OR=4.34). Age (OR=1.18) and medical diagnosis (OR=0.10) were the predictors between discharge and follow-up. Being older, delirium during hospitalization (OR=5.92), and presenting risk of functional decline (OR=5.53) were predictors of decline between the baseline and follow-up.Conclusion:the most relevant predictors were age, previous hospitalization, cognitive deficit, restraint, social support, not having a partner, and delirium. Carrying out interventions aimed at minimizing the impact of these predictors can be an important contribution in the prevention of functional decline.