Post-acute sequelae of SARS-CoV-2 infection (Long COVID) in older adults.

Long COVID, also known as PASC (post-acute sequelae of SARS-CoV-2), is a complex infection-associated chronic condition affecting tens of millions of people worldwide. Many aspects of this condition are incompletely understood. Among them is how this condition may manifest itself in older adults and how it might impact the older population. Here, we briefly review the current understanding of PASC in the adult population and examine what is known on its features with aging. Finally, we outline the major gaps and areas for research most germane to older adults.

Longitudinal Assessment of Mobility and Self-care Among Critically Ill Older Adults. An Age-Friendly Health Systems Initiative Quality Improvement Study.

BACKGROUND: Early mobility in the intensive care unit (ICU) is vital to maintaining an older adult patient's performance of activities of daily living, functional mobility, and overall quality of life. Prior studies have shown reduced length of inpatient stay and onset of delirium in patients with early mobilization. Despite these benefits, many ICU patients are often labeled as too sick to participate in therapy and frequently do not receive physical (PT) or occupational therapy (OT) consults until they are considered floor status. This delay in therapy can negatively affect a patient's capacity to participate in his/her self-care, add to the burden on caregivers, and limit disposition options. OBJECTIVES: Our goals were to perform a longitudinal assessment of mobility and self-care among older patients through their medical ICU (MICU) stays and to quantify visits by therapy services to identify areas for improvement in achieving early intervention in this at-risk population. METHOD: This was a retrospective quality improvement analysis of a cohort of admissions to the MICU at a large tertiary academic medical center between November 2018 and May 2019. Admission information, PT and OT consult information, Perme Intensive Care Unit Mobility Score, and Modified Barthel Index scores were entered into a quality improvement registry. Inclusion criteria consisted of age older than 65 years and at least 2 distinct visits by PT and/or OT for evaluation. Patients without consults and patients with weekend-only MICU stays were not assessed. RESULTS: There were 302 MICU patients 65 years or older admitted during the study period. Forty-four percent (132) of these patients received PT/OT consults, and among these, 32% (42) had at least 2 visits to allow comparison of objective scores. Seventy-five percent of patients had improved Perme scores (median, 9.4%; interquartile range, 2.3%-15.6%), and 58% of patients had improved Modified Barthel Index scores (median, 3%; interquartile range, -2% to 13.5%). However, 17% of potential therapy days were missed because of inadequate staffing/time, and 14% were missed because of being sedated or unable to participate. CONCLUSIONS: In our cohort of patients older than 65 years, receipt of therapy in the MICU led to modest improvements in score-assessed mobility and self-care before transfer to floor. Staffing, time constraints, and patient sedation or encephalopathy appeared to interfere most with further potential benefits. In the next phase, we plan to implement strategies to increase PT/OT availability in the MICU and implement a protocol to increase identification and referral of candidates for whom early therapy can prevent loss of mobility and ability to perform self-care.

Brain function complexity during dual-tasking is associated with cognitive impairment and age.

BACKGROUND AND PURPOSE: Early diagnosis of cognitive impairment is important because symptoms can be delayed through therapies. Synaptic disconnections are the key characteristics of dementia, and through nonlinear complexity analysis of brain function, it is possible to identify long-range synaptic disconnections in the brain. METHODS: We investigated the capability of a novel upper-extremity function (UEF) dual-task paradigm in the functional MRI (fMRI) setting, where the participant flexes and extends their arm while counting, to differentiate between cognitively normal (CN) and those with mild cognitive impairment (MCI). We used multiscale entropy (MSE) complexity analysis of the blood oxygen-level dependent time-series across neural networks and brain regions. Outside of the fMRI, we used the UEF dual-task test, while the elbow kinematics were measured using motion sensors, to record the motor function score. RESULTS: Results showed 34% lower MSE values in MCI compared to CN (p<.04 for all regions and networks except cerebellum when counting down by one; effect size = 1.35±0.15) and a negative correlation between MSE values and age (average r2 of 0.30 for counting down by one and 0.36 for counting backward by three). Results also showed an improvement in the logistic regression model sensitivity by 14-24% in predicting the presence of MCI when brain function measure was added to the motor function score (kinematics data). CONCLUSIONS: Current findings suggest that combining measures of neural network and motor function, in addition to neuropsychological testing, may provide an accurate tool for assessing early-stage cognitive impairment and age-related decline in cognition.

Frailty Identification Using Heart Rate Dynamics: A Deep Learning Approach.

Previous research showed that frailty can influence autonomic nervous system and consequently heart rate response to physical activities, which can ultimately influence the homeostatic state among older adults. While most studies have focused on resting state heart rate characteristics or heart rate monitoring without controlling for physical activities, the objective of the current study was to classify pre-frail/frail vs non-frail older adults using heart rate response to physical activity (heart rate dynamics). Eighty-eight older adults (≥65 years) were recruited and stratified into frailty groups based on the five-component Fried frailty phenotype. Groups consisted of 27 non-frail (age = 78.80±7.23) and 61 pre-frail/frail (age = 80.63±8.07) individuals. Participants performed a normal speed walking as the physical task, while heart rate was measured using a wearable electrocardiogram recorder. After creating heart rate time series, a long short-term memory model was used to classify participants into frailty groups. In 5-fold cross validation evaluation, the long short-term memory model could classify the two above-mentioned frailty classes with a sensitivity, specificity, F1-score, and accuracy of 83.0%, 80.0%, 87.0%, and 82.0%, respectively. These findings showed that heart rate dynamics classification using long short-term memory without any feature engineering may provide an accurate and objective marker for frailty screening.

The association between heart rate behavior and gait performance: The moderating effect of frailty.

INTRODUCTION: Research suggests that frailty not only influence individual systems, but also it affects the interconnection between them. However, no study exists to show how the interplay between cardiovascular and motor performance is compromised with frailty. AIM: To investigate the effect of frailty on the association between heart rate (HR) dynamics and gait performance. METHODS: Eighty-five older adults (≥65 years and able to walk 9.14 meters) were recruited (October 2016-March 2018) and categorized into 26 non-frail (age = 78.65±7.46 years) and 59 pre-frail/frail individuals (age = 81.01±8.17) based on the Fried frailty phenotype. Participants performed gait tasks while equipped with a wearable electrocardiogram (ECG) sensor attached to the chest, as well as wearable gyroscopes for gait assessment. HR dynamic parameters were extracted, including time to peak HR and percentage increase in HR in response to walking. Using the gyroscope sensors gait parameters were recorded including stride length, stride velocity, mean swing velocity, and double support. RESULTS: Among the pre-frail/frail group, time to peak HR was significantly correlated with all gait parameters (p<0.0001, r = 0.51-0.59); however, for the non-frail group, none of the correlations between HR dynamics and gait performance parameters were significant (p>0.45, r = 0.03-0.15). The moderation analysis of time to peak HR, demonstrated a significant interaction effect of HR dynamics and frailty status on walking velocity (p<0.01), and the interaction effect was marginally non-significant for other gait parameters (p>0.10). CONCLUSIONS: Current findings, for the first time, suggest that a compromised motor and cardiac autonomic interaction exist among pre-frail/frail older adults; an impaired HR performance (i.e., slower increase of HR in response to stressors) may lead to a slower walking performance. Assessing physical performance and its corresponding HR behavior should be studied as a tool for frailty screening and providing insights about the underlying cardiovascular-related mechanism leading to physical frailty.

Physical and Cognitive Function Assessment to Predict Postoperative Outcomes of Abdominal Surgery.

BACKGROUND: Current evaluation methods to assess physical and cognitive function are limited and often not feasible in emergency settings. The upper-extremity function (UEF) test to assess physical and cognitive performance using wearable sensors. The purpose of this study was to examine the (1) relationship between preoperative UEF scores with in-hospital outcomes; and (2) association between postoperative UEF scores with 30-d adverse outcomes among adults undergoing emergent abdominal surgery. METHODS: We performed an observational, longitudinal study among adults older than 40 y who presented with intra-abdominal symptoms. The UEF tests included a 20-sec rapid repetitive elbow flexion (physical function), and a 60-sec repetitive elbow flexion at a self-selected pace while counting backwards by threes (cognitive function), administered within 24-h of admission and within 24-h prior to discharge. Multiple logistic regression models assessed the association between UEF and outcomes. Each model consisted of the in-hospital or 30-d post-discharge outcome as the dependent variable, preoperative UEF physical and cognitive scores as hypothesis covariates, and age and sex as adjuster covariates. RESULTS: Using UEF physical and cognitive scores to predict in-hospital outcomes, an area under curve (AUC) of 0.76 was achieved, which was 17% more sensitive when compared to age independently. For 30-d outcomes, the AUC increased to 0.89 when UEF physical and cognitive scores were included in the model with age and sex. DISCUSSION: Sensor-based measures of physical and cognitive function enhance outcome prediction providing an objective practicable tool for risk stratification in emergency surgery settings among aging adults presenting with intra-abdominal symptoms.

IL-6 can singlehandedly drive many features of frailty in mice.

Frailty is a geriatric syndrome characterized by age-related declines in function and reserve resulting in increased vulnerability to stressors. The most consistent laboratory finding in frail subjects is elevation of serum IL-6, but it is unclear whether IL-6 is a causal driver of frailty. Here, we characterize a new mouse model of inducible IL-6 expression (IL-6TET-ON/+ mice) following administration of doxycycline (Dox) in food. In this model, IL-6 induction was Dox dose-dependent. The Dox dose that increased IL-6 levels to those observed in frail old mice directly led to an increase in frailty index, decrease in grip strength, and disrupted muscle mitochondrial homeostasis. Littermate mice lacking the knock-in construct failed to exhibit frailty after Dox feeding. Both naturally old mice and young Dox-induced IL-6TET-ON/+ mice exhibited increased IL-6 levels in sera and spleen homogenates but not in other tissues. Moreover, Dox-induced IL-6TET-ON/+ mice exhibited selective elevation in IL-6 but not in other cytokines. Finally, bone marrow chimera and splenectomy experiments demonstrated that non-hematopoietic cells are the key source of IL-6 in our model. We conclude that elevated IL-6 serum levels directly drive age-related frailty, possibly via mitochondrial mechanisms.

An assisted living interprofessional education and practice geriatric screening clinic (IPEP-GSC): a description and evaluation.

As the U.S. population ages and lives longer, we need to assure that future providers are prepared to work in highly functioning interprofessional teams to deliver person-centered care for older adults with complex chronic conditions. Assisted living facilities are ideal venues in which to train interprofessional health sciences students in providing such care. After monthly clinics involving interprofessional students (from the colleges of medicine, nursing, pharmacy, public health, and school of social work) providing team-based care to older adults, students' post-clinic evaluations indicated perceived improvements in knowledge, attitudes, and perceptions about aging and care of older adults. In addition, participating older adults reported improved self-worth and enjoyment. The curriculum, evaluation outcomes, and lessons learned are described to support program replication.

Mechanisms of Racial Disparities in Cognitive Aging: An Examination of Material and Psychosocial Well-Being.

OBJECTIVES: We tested the hypothesis that education's effect on cognitive aging operates in part through measures of material and psychosocial well-being. METHOD: Our sample was of non-Latino black and white participants of the National Social Life Health and Aging Project who had valid cognitive assessments in Waves 2 and 3 (n = 2,951; age range: 48-95). We used structural equation modeling to test for mediation and moderated mediation by income, assets, perceived stress, social status, and allostatic load on the relationships between race, education, and cognition at two time points. RESULTS: Education consistently mediated the race-cognition relationship, explaining about 20% of the relationship between race and cognition in all models. Income and assets were moderated by race; these factors were associated with cognition for whites but not blacks. Social status mediated the association between race and cognition, and social status and perceived stress mediated the education-cognition pathway. Allostatic load was not a mediator of any relationship. DISCUSSION: Education remains the best explanatory factor for cognitive aging disparities, though material well-being and subjective social status help to explain a portion of the racial disparity in cognitive aging.

Psychotropic medication use patterns in home-based primary care: A scoping review.

INTRODUCTION: Up to a third of patients seen by home-based primary care (HBPC) providers suffer from mental health problems. These conditions tend to be underrecognized and undertreated for patients receiving HBPC. The purpose of this scoping review is to evaluate current psychotropic use patterns for patients receiving HBPC services. METHODS: The following databases were searched for articles reporting on studies conducted in HBPC settings that identified patterns of psychotropic medication prescription and use: Ovid/MEDLINE, Cochrane Library, Embase, Scopus, Web of Science, CINAHL, and PsycInfo. Studies that only reported on patients in hospice, rehabilitation, or long-term care facilities were excluded as were drug trials, opinion pieces, case studies, case series, meeting abstracts, and other reviews. RESULTS: Of 4542 articles initially identified, 74 were selected for full text screening. Of these, only 2 met full criteria and were included in the data extraction and analysis. In 1 study, 41.7% patients enrolled were prescribed an antidepressant, 21.5% were prescribed an antipsychotic (12.7% prescribed both), and 5% to 7% of patients were prescribed benzodiazepines/hypnotics. In the other study, 9% of patients were prescribed an antipsychotic, and 7% were prescribed a benzodiazepine. DISCUSSION: There are extremely limited data on psychotropic prescribing patterns in HBPC in published studies. Because a significant number of HBPC patients suffer from mental health conditions in addition to other chronic illnesses, treatment can be complex. More studies are needed on current psychotropic prescribing trends to help determine what type of interventions are needed to promote patient safety in this setting.

Correction to: SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes.

The affiliation of the second author (Kenneth S. Knox) should have been Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA instead of Department of Medicine, University of Arizona-Phoenix, Phoenix, AZ 85004, USA.

SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes.

SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30-50,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.

Frailty Syndrome, Cognition, and Dysphonia in the Elderly.

PURPOSE: The purpose of the current study is to determine the relation of frailty syndrome to acoustic measures of voice quality and voice-related handicap. METHODS: Seventy-three adults (52 community-dwelling participants and 21 assisted living residents) age 60 and older completed frailty screening, acoustic assessment, cognitive screening, and the Voice Handicap Index-10 (VHI-10). Factor analysis was used to consolidate acoustic measures. Statistical analysis included multiple regression, analysis of variance, and Tukey post-hoc tests with alfa of 0.05. RESULTS: Montreal Cognitive Assessment (MoCA) and exhaustion explained 28% of the variance in VHI-10. MoCA and sex explained 27% of the variance in factor 1 (spectral ratio), age and MoCA explained 13% of the variance in factor 2 (cepstral peak prominence for speech), and slowness explained 10% of the variance in factor 3 (cepstral peak prominence for sustained /a/). There were statistically significant differences in two measures across frailty groups: VHI-10 and MoCA. Acoustic factor scores did not differ significantly among frailty groups (P > 0.05). CONCLUSIONS: Voice-related handicap and cognitive status differed among robust and frail older adults, yet vocal function measures did not. The components of frailty most related to VHI-10 were exhaustion and weight loss rather than slowness, weakness, or inactivity. Based on these findings, routine screening of physical frailty and cognition are recommended as part of a complete voice evaluation for older adults.

The role of social and behavioral risk factors in explaining racial disparities in age-related cognitive impairment: a structured narrative review.

Alzheimer's disease (AD) is a growing public health concern with large disparities in incidence and prevalence between African Americans (AAs) and non-Hispanic whites (NHWs). The aim of this review was to examine the evidence of association between six modifiable risk factors (education, smoking, physical inactivity, obesity, social isolation, and psychosocial stress) and Alzheimer's disease risk in AAs and NHWs. We identified 3,437 studies; 45 met inclusion criteria and were included in this review. Of the examined risks, education provided the strongest evidence of association with cognitive outcomes in AAs and NHWs. This factor may operate directly on Alzheimer's disease risk through the neurocognitive benefits of cognitive stimulation or indirectly through social status.

State inequality, socioeconomic position and subjective cognitive decline in the United States.

BACKGROUND: Social gradients in health have been observed for many health conditions and are suggested to operate through the effects of status anxiety. However, the gradient between education and Alzheimer's disease is presumed to operate through cognitive stimulation. We examined the possible role of status anxiety through testing for state-level income inequality and social gradients in markers of socioeconomic position (SEP) for Alzheimer's disease risk. METHODS: Using data from the cross-sectional 2015 and 2016 Behavioral Risk Factor Surveillance System (BRFSS) and the U.S. Census Bureau's American Community Survey, we tested for the association between U.S. state-level income inequality and individual SEP on subjective cognitive decline (SCD) - a marker of dementia risk - using a generalized estimating equation and clustering by state. RESULTS: State income inequality was not significantly associated with SCD in our multivariable model (OR 1.2; 95% CI: 0.9, 1.6; p=0.49). We observed a clear linear relationship between household income and SCD where those with an annual household income of 50k to 75k had 1.4 (95% CI: 1.3, 1.6) times the odds and those with household incomes of less than $10,000 had 4.7 (95% CI: 3.8, 5.7) times the odds of SCD compared to those with household income of more than $75,000. We also found that college graduates (ref.) and those who completed high school (OR: 1.1; 95% CI 1.04, 1.2) fared better than those with some college (OR: 1.3, 95% CI 1.2, 1.4) or less than a high school degree (OR: 1.5; 95% CI: 1.4, 1.7). CONCLUSIONS: Income inequality does not play a dominant role in SCD, though a social gradient in individual income for SCD suggests the relationship may operate in part via status anxiety.

Frailty as a prognostic factor for the critically ill older adult trauma patients.

BACKGROUND: Frailty is highly prevalent in the elderly and confers high risk for adverse outcomes. We aimed to assess the impact of frailty on critically ill older adult trauma patients. METHODS: We analyzed the ACS-TQIP(2010-2014) including all critically-ill trauma patients ≥65y. The modified frailty index (mFI) was calculated. Following stratified into frail and non-frail, propensity score matching was performed. Our primary outcome measure was in-hospital complications. Secondary outcome measures included mortality and discharge disposition. RESULTS: We identified 88,629 patients, of which 34,854 patients (frail: 17,427, non-frail: 17,427) were matched. Overall 14% died. Frail patients had higher rates of complications (34% vs. 18%, p < 0.001), mortality (18.1% vs. 9.7%, p < 0.001), and were more likely to be discharged to rehab/SNF (58.7% vs. 21.2% p < 0.001) compared to non-frail patients. CONCLUSION: critically-ill frail patients are more likely to have higher morbidity and mortality. Frailty can be used as an objective measure to identify high-risk patients.

The acute inflammatory response after trauma is heightened by frailty: A prospective evaluation of inflammatory and endocrine system alterations in frailty.

BACKGROUND: Frailty is a geriatric syndrome characterized by decreased physiological reserves, increased inflammation, and decreased anabolic-endocrine response. The biomarkers associated with frailty are poorly understood in trauma. The aim of this study was to analyze the association between frailty and immune: IL-1ß, IL-6, IL-2Rα, tumor necrosis factor (TNF)-α, and endocrine biomarkers: insulin-like growth factor-1 and growth hormone in trauma patients. METHODS: We conducted a 1-year (2017-2018) prospective analysis of geriatric (≥65 years) trauma patients admitted to our Level I trauma center. Frailty was measured using the trauma-specific frailty index (TSFI) and blood samples were collected within 24 hours of admission. Patients were stratified into two groups: frail (TSFI > 0.25) and nonfrail (TSFI ≤ 0.25). We then measured the levels of immune and endocrine biomarkers by a colorimetric output that was read by a spectrophotometer (Quantikine ELISA). The outcome measures were the levels of the immune and endocrine markers in the two groups. Multivariable linear regression was performed. RESULTS: A total of 100 geriatric trauma patients were consented and enrolled. The mean age was 77.1 ± 9.8 years and 34% were female. Thirty-nine (39%) patients were frail. Frail patients were more likely to present after falls (p = 0.01). There was no difference in age (p = 0.78), sex (p = 0.77), systolic blood pressure (p = 0.16), and heart rate (p = 0.24) between the two groups. Frail patients had higher levels of TNF-α (p = 0.01), IL-1ß (p = 0.01), and IL-6(p = 0.01) but lower levels of growth hormone (p = 0.03) and insulin-like growth factor-1 (p < 0.04) compared with nonfrail patients. There was no difference in the level of IL-2Rα (p = 0.25). On regression analysis, frailty was positively correlated with the levels of proinflammatory biomarkers, that is, TNF- α, IL-1 ß, and IL-6 and negatively correlated with endocrine biomarkers. CONCLUSION: This study supports the association between frailty and immune and endocrine markers. Frailty acts synergistically with trauma in increasing the acute inflammatory response. Moreover, frail patients have lower levels of anabolic hormones. Understanding the inflammatory and endocrine response in frail trauma patients may result in better therapeutic strategies.