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Background: The kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk of Alzheimer’s disease and related dementias (ADRD). Objective: The objective of this study was to determine the associations of plasma KP metabolites (kynurenine [KYN], kynurenic acid [KA], and tryptophan [TRP]) with a panel of plasma ADRD biomarkers (Aβ42/ β40 ratio, pTau-181, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and cognitive performance in a subset of older adults drawn from the Duke Physical Performance Across the LifeSpan (PALS) study. Methods: The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. We used multivariate multiple regression to evaluate associations of the KYN/TRP and KA/KYN ratios with MoCA score and plasma ADRD biomarkers at baseline and over two years (n = 301; Age = 74.8±8.7). Results: Over two years, an increasing KYN/TRP ratio was associated with increasing plasma concentrations of plasma p-Tau181 (β= 6.151; 95% CI [0.29, 12.01]; p = 0.040), GFAP (β= 11.12; 95% CI [1.73, 20.51]; p = 0.020), and NfL (β= 11.13; 95% CI [2.745, 19.52]; p = 0.009), but not MoCA score or the Aβ42/Aβ40 ratio. There were no significant associations of KA/KYN with MoCA score or plasma ADRD biomarkers. Conclusion: Our findings provide evidence that greater concentrations of KP metabolites are associated longitudinally over two years with greater biomarker evidence of neurofibrillary tau pathology (pTau-181), neuroinflammation (GFAP), and neurodegeneration (NfL), suggesting that dysregulated KP metabolism may play a role in ADRD pathogenesis.

This report summarizes the presentations, discussions, and recommendations of the most recent American Geriatrics Society and National Institute on Aging research conference, "Cancer and Cardiovascular Disease," on October 18-19, 2021. The purpose of this virtual meeting was to address the interface between cancer and heart disease, which are the two leading causes of death among older Americans. Age-related physiologic changes are implicated in the pathogenesis of both conditions. Emerging data suggest that cancer-related cardiovascular disease (CVD) involves disrupted cell signaling and cellular senescence. The risk factors for CVD are also risk factors for cancer and an increased likelihood of cancer death, and people who have both cancer and CVD do more poorly than those who have only cancer or only CVD. Issues addressed in this bench-to-bedside conference include mechanisms of cancer and CVD co-development in older adults, cardiotoxic effects of cancer therapy, and management of comorbid cancer and CVD. Presenters discussed approaches to ensure equitable access to clinical trials and health care for diverse populations of adults with CVD and cancer, mechanisms of cancer therapy cardiotoxicity, and management of comorbid CVD and cancer, including the role of patient values and preferences in treatment decisions. Workshop participants identified many research gaps and questions that could lead to an enhanced understanding of comorbid CVD and cancer and to better and more equitable management strategies.

Background Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients. Methods We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery. Results There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml−1 [65] vs 378 pg ml−1 [38], respectively; P=0.001). Controlling for age, APOE4 carriers had significantly greater preoperative functional connectivity than non-carriers between several brain regions implicated in Alzheimer's disease, including between the left posterior cingulate cortex and left angular gyrus (β [95% confidence interval, CI], 0.218 [0.137–0.230]; PFWE=0.016). APOE4 carriers, but not non-carriers, experienced significant connectivity decreases from before to 6 weeks after surgery between several brain regions including between the left posterior cingulate cortex and left angular gyrus (β [95% CI], –0.196 [–0.256 to –0.136]; PFWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aβ levels. Conclusions Postoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.

BACKGROUND Some older adults show exaggerated responses to drugs that act on the brain. The brain's response to anesthetic drugs is often measured clinically by processed electroencephalogram (EEG) indices. Thus, we developed a processed EEG-based measure of the brain's resistance to volatile anesthetics and hypothesized that low scores on it would be associated with postoperative delirium risk. METHODS We defined the Duke Anesthesia Resistance Scale (DARS) as the average bispectral index (BIS) divided by the quantity (2.5 minus the average age-adjusted end-tidal minimum alveolar concentration [aaMAC] inhaled anesthetic fraction). The relationship between DARS and postoperative delirium was analyzed in 139 older surgical patients (age ≥65) from Duke University Medical Center (n = 69) and Mt Sinai Medical Center (n = 70). Delirium was assessed by geriatrician interview at Duke, and by research staff utilizing the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) instrument at Mt Sinai. We examined the relationship between DARS and delirium and used the Youden index to identify an optimal low DARS threshold (for delirium risk), and its associated 95% bootstrap confidence bounds. We used multivariable logistic regression to examine the relationship between low DARS and delirium risk. RESULTS The relationship between DARS and delirium risk was nonlinear, with higher delirium risk at low DARS scores. A DARS threshold of 28.755 maximized the Youden index for the association between low DARS and delirium, with bootstrap 95% confidence bounds of 26.18 and 29.80. A low DARS (

Age-related macular degeneration (AMD) is a prevalent disease impeding vision. More recently, AMD has also been linked to cognitive impairment, such as deficits in language and memory skills. In order to better understand the extent of AMD-related changes in the whole brain structure and connectivity, we have conducted an MRI diffusion acquisition study on 40 participants (20 diagnosed with AMD and 20 controls). These acquisitions were then performed again in a follow up two years later. We developed novel analysis methods for diffusion based tractography and connectomes to better determine which, if any, brain region connections saw the greatest changes between the AMD and the age-matched control groups. Using voxel-based analysis, we identified atrophy in AMD participants in the cuneate gyrus, which has been associated with vision, and the left superior temporal gyrus, which has been associated with language, while later acquisitions compounded this with a deficiency in the bilateral cingulate gyrus, itself linked to higher cognition and memory. These regional atrophy findings support that people with AMD experience widespread neuronal degradation that is not limited to retinal neurons. Regions that saw drastically lowered fractional anisotropy among AMD vs. control included the visual cortex, such as the bilateral occipital lobe and the frontoparietal cortex. Tensor Network Principal Component Analysis (TN-PCA) isolated lingual and temporal connections as important differentiators of AMD connectomes compared to controls, thus supporting our morphometric and texture findings in regions related to vision, but also connectopathies of language and memory brain regions. Bundle based analyses in baseline data revealed that the lingual gyrus had greater spread of tracts overall in the AMD participants, which may be explained by prior reorganization in this area, demonstrating a connection between retinal health and lingual structure. Moreover, we noted group differences in the interhemispheric temporal connections, and lingual cerebellar connections, supporting extensive downstream effects of vision loss. Our bundle-based analyses expand the toolset available for neuroimaging-based phenotyping, and reveal widespread changes in AMD participants beyond brain regions and tractography networks directly involved in vision processing, including those involved in language and memory.

AMD has been linked to memory deficits, with no established neural mechanisms. In order to describe how resting-state, brain network functional connectivity relates to memory and AMD status in older adults without dementia, we collected resting-state brain fMRI and standardized verbal recall tests from 42 older adults with AMD and 41 age-matched controls. We used seed-based whole brain analysis to quantify the strength of functional connectivity between hubs of the default mode network (DMN) and a network of medial temporal regions relevant for memory. Our results indicated neither memory performance nor network connectivity differed by AMD status. However, the AMD participants exhibited stronger relationships than the controls between memory performance and connectivity from the memory network hub (left parahippocampal) to two other regions: the left temporal pole and the right superior/middle frontal gyri. Also, the connectivity between the medial prefrontal cortex and posterior cingulate cortex of DMN correlated more strongly with memory performance in AMD compared to control. We concluded that stronger brain-behavior correlation in AMD may suggest a role for region-specific connectivity in supporting memory in the context of AMD.

Objectives To develop a prognostic model for hospital admissions over a 1-year period among community-dwelling older adults with self-reported hearing and/or vision impairments based on readily obtainable clinical predictors. Design Retrospective cohort study. Setting Medicare Current Beneficiary Survey from 1999 to 2006. Participants Community-dwelling Medicare beneficiaries, aged 65 years and older, with self-reported hearing and/or vision impairment (N = 15,999). Measurements The primary outcome was any hospital admission over a predefined 1-year study period. Candidate predictors included demographic factors, prior healthcare utilization, comorbidities, functional impairment, and patient-level factors. We analyzed the association of all candidate predictors with any hospital admission over the 1-year study period using multivariable logistic regression. The final model was created using a penalized regression method known as the least absolute shrinkage and selection operator. Model performance was assessed by discrimination (concordance statistic (c-statistic)) and calibration (evaluated graphically). Internal validation was performed via bootstrapping, and results were adjusted for overoptimism. Results Of the 15,999 participants, the mean age was 78 years and 55% were female. A total of 2,567 participants (16.0%) had at least one hospital admission in the 1-year study period. The final model included seven variables independently associated with hospitalization: number of inpatient admissions in the previous year, number of emergency department visits in the previous year, activities of daily living difficulty score, poor self-rated health, and self-reported history of myocardial infarction, stroke, and nonskin cancer. The c-statistic of the final model was 0.717. The optimism-corrected c-statistic after bootstrap internal validation was 0.716. A calibration plot suggested that the model tended to overestimate risk among patients at the highest risk for hospitalization. Conclusion This prognostic model can help identify which community-dwelling older adults with sensory impairments are at highest risk for hospitalization and may inform allocation of healthcare resources.

Background Ocular conditions are common following stroke and frequently occur in combination with pre-existing ophthalmologic disease. The Medicare International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding system for identifying vision related health conditions provides a much higher level of detail for coding these complex scenarios than the previous ICD-9 system. While this new coding system has advantages for clinical care and billing, the degree to which providers and researchers are utilizing the expanded code structure is unknown. The purpose of this study was to describe the use of ICD-10 vision codes in a large cohort of stroke survivors. Methods Retrospective cohort design to study national 100% Medicare claims files from 2015 through 2017. Descriptive data analyses were conducted using all available ICD-10 vision codes for beneficiaries who had an acute care stay because of a new stroke. The outcome of interest was ≥1 ICD-10 visual code recorded in the claims chart. Results The cohort (n = 269,314) was mostly female (57.1%) with ischemic stroke (87.8%). Approximately 15% were coded as having one or more ocular condition. Unspecified glaucoma was the most frequently used code among men (2.83%), those over 85+ (4.80%) and black beneficiaries (4.12%). Multiple vision codes were used in few patients (0.6%). Less than 3% of those in the oldest group (85+ years) had two or more vision codes in their claims. Conclusions Ocular comorbidity was present in a portion of this cohort of stroke survivors, however the vision codes used to describe impairments in this population were few and lacked specificity. Future studies should compare ophthalmic examination results with billing codes to characterize the type and frequency of ocular comorbidity. It important to understand how the use of ICD-10 vision codes impacts clinical decision making, recovery, and outcomes.

SIGNIFICANCE Outpatient vision rehabilitation improves function in veterans with vision impairment, but the prevalence of cognitive impairment and the degree to which it may affect rehabilitation outcomes in the Veterans Affairs system are unknown. PURPOSE The purpose of this study was to determine the prevalence of cognitive impairment among veterans receiving outpatient vision rehabilitation in the Veterans Affairs system and compare the benefits of rehabilitation in veterans with and without cognitive impairment. METHODS We conducted cognitive assessments and a nested longitudinal cohort study in veterans with eye disorders at two outpatient rehabilitation sites. Cognition was assessed with the Modified Telephone Interview for Cognitive Status administered in person. Eligible veterans and their companions in the longitudinal study responded to questions about the veteran's function at baseline and 90 days later. Visual function was measured with the 48-item Low Vision Visual Function Questionnaire (LV-VFQ-48) and items from the Activity Inventory. RESULTS Of 291 veterans assessed (mean ± standard deviation age, 78.2 ± 12 years), 136 (46.7%) were cognitively intact (Modified Telephone Interview for Cognitive Status scores, ≥33), whereas 58 (19.9%) had borderline scores of 30 to 32, 82 (28.2%) had scores suggesting mild/moderate cognitive impairment (scores of 20 to 29), and 15 (5.2%) had scores suggesting severe cognitive impairment (score of

Numerous investigators have theorized that postoperative changes in Alzheimer's disease neuropathology may underlie postoperative neurocognitive disorders. Thus, we determined the relationship between postoperative changes in cognition and cerebrospinal (CSF) tau, p-tau-181p, or Aβ levels after non-cardiac, non-neurologic surgery in older adults.Participants underwent cognitive testing before and 6 weeks after surgery, and lumbar punctures before, 24 h after, and 6 weeks after surgery. Cognitive scores were combined via factor analysis into an overall cognitive index. In total, 110 patients returned for 6-week postoperative testing and were included in the analysis.There was no significant change from before to 24 h or 6 weeks following surgery in CSF tau (median [median absolute deviation] change before to 24 h: 0.00 [4.36] pg/mL, p = 0.853; change before to 6 weeks: -1.21 [3.98] pg/mL, p = 0.827). There were also no significant changes in CSF p-tau-181p or Aβ over this period. There was no change in cognitive index (mean [95% CI] 0.040 [-0.018, 0.098], p = 0.175) from before to 6 weeks after surgery, although there were postoperative declines in verbal memory (-0.346 [-0.523, -0.170], p = 0.003) and improvements in executive function (0.394, [0.310, 0.479], p 0.001). There were no significant correlations between preoperative to 6-week postoperative changes in cognition and CSF tau, p-tau-181p, or Aβ42 changes over this interval (p 0.05 for each).Neurocognitive changes after non-cardiac, non-neurologic surgery in the majority of cognitively healthy, community-dwelling older adults are unlikely to be related to postoperative changes in AD neuropathology (as assessed by CSF Aβ, tau or p-tau-181p levels or the p-tau-181p/Aβ or tau/Aβ ratios).clinicaltrials.gov (NCT01993836).

OBJECTIVES: Although emerging evidence suggests that hearing loss is an independent risk factor for falls, it is unclear how hearing loss may impact falls risk in adults with vestibular dysfunction and non-vestibular dizziness. The purpose of this study was to characterize the impact of hearing loss on falls in patients with vestibular dysfunction and non-vestibular dizziness relative to a group of patients without dizziness. In addition, this study aimed to evaluate whether there was an interactive effect between hearing loss and vestibular dysfunction or non-vestibular dizziness on the odds of falling. DESIGN: The authors conducted a retrospective cross-sectional study of 2,750 adult patients with dizziness evaluated at a tertiary care center vestibular clinic between June 1, 2015 and October 7, 2020. Only patients with available self-reported falls status, as extracted from the electronic medical record, were included. Patients were classified into the following diagnostic groups based on rotary chair testing and videonystagmography: Benign Paroxysmal Positional Vertigo (BPPV, n = 255), Unilateral Vestibular Hypofunction (UVH, n = 456), Bilateral Vestibular Hypofunction (BVH, n = 38), Central Dysfunction (n = 208), Multiple Diagnoses (n = 109), and Dizzy, Non-Vestibular (n = 1,389). A control group of patients without dizziness (n = 295) was identified by a random sample of audiology patients. Degree of hearing loss was characterized by the 4-frequency pure-tone average (PTA) (0.5, 1, 2, and 4 kHz) of the better hearing ear. Demographic variables, comorbidities, cognitive impairment status, and falls-associated medications were extracted from the electronic medical record and included as covariates during analysis. Potential associations between PTA and falls status and possible interactions between diagnostic group and PTA were explored using multivariate logistic regression. RESULTS: The BVH and Central Dysfunction groups had the highest rates of self-reported falls at 26.3% and 26.9% respectively. The control group had the lowest rate of self-reported falls at 6.4%. With the exception of the Multiple Diagnoses group, all diagnostic groups had elevated odds of falling compared to the control group, when adjusting for demographics, comorbidities, cognitive impairment status, and falls-associated medications. There was no significant association between degree of hearing loss and falls status (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 0.93, 1.11, p = .713) when adjusting for diagnostic group and all other covariates. Furthermore, there were no significant interactions between diagnostic group and degree of hearing loss on the odds of falling. CONCLUSIONS: These results indicate that hearing loss was not associated with falls in patients with vestibular dysfunction or non-vestibular dizziness, while adjusting for demographics, comorbidities, and falls-associated medications. There was no significant interactive effect observed between hearing loss and vestibular dysfunction or non-vestibular dizziness on the odds of falling. As previously reported, vestibular dysfunction and non-vestibular dizziness were independently associated with falls relative to a group of patients without dizziness. A population-based study utilizing more robust falls data is needed to explore a potential association between hearing loss and falls in those with vestibular dysfunction.

This article summarizes the presentations and discussions from a workshop, "Using Functional Assessment to Define Therapeutic Goals and Treatment," which took place on November 30 to December 1, 2017. This workshop brought together transdisciplinary leaders in the fields of function and disability and clinical investigators engaged in research on geriatric populations to outline opportunities and challenges for incorporating measures of function in clinical research. Topics addressed included reliable and clinically feasible measures of function and key domains of health (eg, musculoskeletal, cognitive, and sensory) that are most strongly associated with patients' perceptions of well-being, independence, and quality of life across a wide array of diseases and interventions. The workshop also focused on the importance of function in medical decision making to inform communications between specialty physicians and patients about prognosis and goals of care. Workshop participants called for more research on the role of function as a predictor of an intervention's effectiveness and an important treatment outcome. Such research would be facilitated by development of a core set of simple, short, functional measures that can be used by all specialties in the clinical setting to allow "big data" analytics and a pragmatic research. J Am Geriatr Soc 67:1782-1790, 2019.

Background Approaches for quantifying physical resilience in older adults have not been described. Methods We apply two conceptual approaches to defining physical resilience to existing longitudinal data sets in which outcomes are measured after an acute physical stressor. A “recovery phenotype” approach uses statistical methods to describe how quickly and completely a patient recovers. Statistical methods using a recovery phenotype approach can consider multiple outcomes simultaneously in a composite score (eg, factor analysis and principal components analysis) or identify groups of patients with similar recovery trajectories across multiple outcomes (eg, latent class profile analysis). An “expected recovery differential” approach quantifies how patients’ actual outcomes are compared to their predicted outcome based on a population-derived model and their individual clinical characteristics at the time of the stressor. Results Application of the approaches identified different participants as being the most or least physically resilient. In the viral respiratory cohort (n = 186) weighted kappa for agreement across resilience quartiles was 0.37 (0.27–0.47). The expected recovery differential approach identified a group with more comorbidities and lower baseline function as highly resilient. In the hip fracture cohort (n = 541), comparison of the expected recovery differentials across 10 outcome measures within individuals provided preliminary support for the hypothesis that there is a latent resilience trait at the whole-person level. Conclusions We posit that recovery phenotypes may be useful in clinical applications such as prediction models because they summarize the observed outcomes across multiple measures. Expected recovery differentials offer insight into mechanisms behind physical resilience not captured by age and other comorbidities.

Topic OCT is a noninvasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral-domain (SD) OCT measurements with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) remains unclear. Hence, we conducted a systematic review and meta-analysis to examine the SD OCT measurements in AD and MCI. Clinical Relevance Current methods of diagnosing early AD are expensive and invasive. Retinal measurements of SD OCT, which are noninvasive, technically simple, and inexpensive, are potential biomarkers of AD. Methods We conducted a literature search in PubMed and Excerpta Medica Database to identify studies published before December 31, 2017, that assessed the associations between AD, MCI, and measurements of SD OCT: ganglion cell–inner plexiform layer (GC-IPL), ganglion cell complex (GCC), macular volume, and choroidal thickness, in addition to retinal nerve fiber layer (RNFL) and macular thickness. We used a random-effects model to examine these relationships. We also conducted meta-regression and assessed heterogeneity, publication bias, and study quality. Results We identified 30 eligible studies, involving 1257 AD patients, 305 MCI patients, and 1460 controls, all of which were cross-sectional studies. In terms of the macular structure, AD patients showed significant differences in GC-IPL thickness (standardized mean difference [SMD], –0.46; 95% confidence interval [CI], –0.80 to –0.11; I2 = 71%), GCC thickness (SMD, –0.84; 95% CI, –1.10 to –0.57; I2 = 0%), macular volume (SMD, –0.58; 95% CI, –1.03 to –0.14; I2 = 80%), and macular thickness of all inner and outer sectors (SMD range, –0.52 to –0.74; all P Conclusions Our results confirmed the associations between retinal measurements of SD OCT and AD, highlighting the potential usefulness of SD OCT measurements as biomarkers of AD.

OBJECTIVES To examine the association between self-reported vision impairment (VI), hearing impairment (HI), and dual-sensory impairment (DSI), stratified by dementia status, on hospital admissions, hospice use, and healthcare costs. DESIGN Retrospective analysis. SETTING Medicare Current Beneficiary Survey from 1999 to 2006. PARTICIPANTS Rotating panel of community-dwelling Medicare beneficiaries, aged 65 years and older (N = 24 009). MEASUREMENTS VI and HI were ascertained by self-report. Dementia status was determined by self-report or diagnosis codes in claims data. Primary outcomes included any inpatient admission over a 2-year period, hospice use over a 2-year period, annual Medicare fee-for-service costs, and total healthcare costs (which included information from Medicare claims data and other self-reported payments). RESULTS Self-reported DSI was present in 30.2% (n = 263/871) of participants with dementia and 17.8% (n = 4112/23 138) of participants without dementia. In multivariable logistic regression models, HI, VI, or DSI was generally associated with increased odds of hospitalization and hospice use regardless of dementia status. In a generalized linear model adjusted for demographics, annual total healthcare costs were greater for those with DSI and dementia compared to those with DSI without dementia ($28 875 vs $3340, respectively). Presence of any sensory impairment was generally associated with higher healthcare costs. In a model adjusted for demographics, Medicaid status, and chronic medical conditions, DSI compared with no sensory impairment was associated with a small, but statistically significant, difference in total healthcare spending in those without dementia ($1151 vs $1056; P

Background While social distancing policies protect older adults with advanced chronic kidney disease (CKD) from exposure to COVID-19, reduced social interaction may also have unintended consequences. Methods To identify subgroups of patients at risk for unintended health consequences of social distancing, we conducted a cross-sectional analysis of data from a national cohort study of older veterans with advanced CKD (n = 223). Characteristics included activities of daily living (ADLs), instrumental ADLs (IADLs), cognition score, depression score, social support, financial stress, symptom burden, and number of chronic conditions. Unintended consequences of social distancing included restricted Life Space mobility, low willingness for video telehealth, reduced in-person contact with caregivers, and food insecurity. We identified subgroups of patients at risk of unintended consequences using model-based recursive partitioning (MoB). Results Participants had a mean age of 77.9 years, 64.6% were white, and 96.9% were male. Overall, 22.4% of participants had restricted Life Space, 33.9% reported low willingness for video telehealth, 19.0% reported reduced caregiver contact, and 3.2% reported food insecurity. For Life Space restriction, 4 subgroups partitioned (ie, split) by IADL difficulty, cognition score, and ADL difficulty were identified. The highest rate of restricted Life Space was 54.7% in the subgroup of participants with >3 IADL difficulties. For low willingness for telehealth and reduced caregiver contact, separate models identified 2 subgroups split by cognition score and depression score, respectively. Conclusions Measures of function, cognition, and depressive symptoms may identify older adults with advanced CKD who are at higher risk for unintended health consequences of social distancing.

Objective Population segmentation has been recognized as a foundational step to help tailor interventions. Prior studies have predominantly identified subgroups based on diagnoses. In this study, we identify clinically coherent subgroups using social determinants of health (SDH) measures collected from Veterans at high risk of hospitalization or death. Study design and setting SDH measures were obtained for 4684 Veterans at high risk of hospitalization through mail survey. Eleven self-report measures known to impact hospitalization and amenable to intervention were chosen a priori by the study team to identify subgroups through latent class analysis. Associations between subgroups and demographic and comorbidity characteristics were calculated through multinomial logistic regression. Odds of 180-day hospitalization were compared across subgroups through logistic regression. Results Five subgroups of high-risk patients emerged-those with: minimal SDH vulnerabilities (8% hospitalized), poor/fair health with few SDH vulnerabilities (12% hospitalized), social isolation (10% hospitalized), multiple SDH vulnerabilities (12% hospitalized), and multiple SDH vulnerabilities without food or medication insecurity (10% hospitalized). In logistic regression, the "multiple SDH vulnerabilities" subgroup had greater odds of 180-day hospitalization than did the "minimal SDH vulnerabilities" reference subgroup (odds ratio: 1.53, 95% confidence interval: 1.09-2.14). Conclusion Self-reported SDH measures can identify meaningful subgroups that may be used to offer tailored interventions to reduce their risk of hospitalization and other adverse events.

BackgroundSome older adults show exaggerated responses to drugs that act on the brain, such as increased delirium risk in response to anticholinergic drugs. The brain’s response to anesthetic drugs is often measured clinically by processed electroencephalogram (EEG) indices. Thus, we developed a processed EEG based-measure of the brain’s neurophysiologic resistance to anesthetic dose-related changes, and hypothesized that it would predict postoperative delirium.MethodsWe defined the Duke Anesthesia Resistance Scale (DARS) as the average BIS index divided by the quantity 2.5 minus the average age-adjusted end-tidal MAC (aaMAC) inhaled anesthetic fraction. The relationship between DARS and postoperative delirium was analyzed in derivation (Duke; N=69), validation (Mt Sinai; N=70), and combined estimation cohorts (N=139) of older surgical patients (age ≥65). In the derivation cohort, we identified a threshold relationship between DARS and for delirium and identified an optimal cut point for prediction.ResultsIn the derivation cohort, the optimal DARS threshold for predicting delirium was 27.0. The delirium rate was 11/49 (22.5%) vs 11/20 (55.0%) and 7/57 (12.3%) vs 6/13 (46.2%) for those with DARS ≥ 27 vs those with DARS < 27 in the derivation and validation cohorts respectively. In the combined estimation cohort, multivariable analysis found a significant association of DARS ConclusionsThese results suggest than an intraoperative processed EEG-based measure of lower brain anesthetic resistance (i.e. DARS

Objective:To determine the relationship between affective measures and cognition before and after non-cardiac surgery in older adults.Methods:Observational prospective cohort study in 103 surgical patients age ≥ 60 years old. All participants underwent cognitive testing, Center for Epidemiologic Studies-Depression, and State Anxiety Inventory screening before and 6 weeks after surgery. Cognitive test scores were combined by factor analysis into 4 cognitive domains, whose mean was defined as the continuous cognitive index (CCI). Postoperative global cognitive change was defined by CCI change from before to after surgery, with negative CCI change indicating worsened postoperative global cognition and vice versa.Results:Lower global cognition before surgery was associated with greater baseline depression severity (Spearman’s r = −0.30, p = 0.002) and baseline anxiety severity (Spearman’s r = −0.25, p = 0.010), and these associations were similar following surgery (r = −0.36, p < 0.001; r = −0.26, p = 0.008, respectively). Neither baseline depression or anxiety severity, nor postoperative changes in depression or anxiety severity, were associated with pre- to postoperative global cognitive change.Conclusions:Greater depression and anxiety severity were each associated with poorer cognitive performance both before and after surgery in older adults. Yet, neither baseline depression or anxiety symptoms, nor postoperative change in these symptoms, were associated with postoperative cognitive change.

Fellows and junior faculty conducting aging research have encountered substantial new challenges during the COVID-19 pandemic. They report that they have been uncertain how and whether to modify existing research studies, have faced difficulties with job searches, and have struggled to balance competing pressures including greater clinical obligations and increased responsibilities at home. Many have also wondered if they should shift gears and make COVID-19 the focus of their research. We asked a group of accomplished scientists and mentors to grapple with these concerns and to share their thoughts with readers of this journal.

Importance Despite recognition of the association between individual social and behavioral determinants of health (SDH) and patient outcomes, little is known regarding the value of SDH in explaining variation in outcomes for high-risk patients. Objective To describe SDH factors among veterans who are at high risk for hospitalization, and to determine whether adding patient-reported SDH measures to electronic health record (EHR) measures improves estimation of 90-day and 180-day all-cause hospital admission. Design, setting, and participants A survey was mailed between April 16 and June 29, 2018, to a nationally representative sample of 10 000 Veterans Affairs (VA) patients whose 1-year risk of hospitalization or death was in the 75th percentile or higher based on a VA EHR-derived risk score. The survey included multiple SDH measures, such as resilience, social support, health literacy, smoking status, transportation barriers, and recent life stressors. Main outcomes and measures The EHR-based characteristics of survey respondents and nonrespondents were compared using standardized differences. Estimation of 90-day and 180-day hospital admission risk was assessed for 3 logistic regression models: (1) a base model of all prespecified EHR-based covariates, (2) a restricted model of EHR-based covariates chosen via forward selection based on minimizing Akaike information criterion (AIC), and (3) a model of EHR- and survey-based covariates chosen via forward selection based on AIC minimization. Results In total, 4685 individuals (response rate 46.9%) responded to the survey. Respondents were comparable to nonrespondents in most characteristics, but survey respondents were older (eg, >80 years old, 881 [18.8%] vs 800 [15.1%]), comprised a higher percentage of men (4391 [93.7%] vs 4794 [90.2%]), and were composed of more White non-Hispanic individuals (3366 [71.8%] vs 3259 [61.3%]). Based on AIC, the regression model with survey-based covariates and EHR-based covariates better estimated hospital admission at 90 days (AIC, 1947.7) and 180 days (AIC, 2951.9) than restricted models with only EHR-based covariates (AIC, 1980.2 at 90 days; AIC, 2981.9 at 180 days). This result was due to inclusion of self-reported measures such as marital or partner status, health-related locus of control, resilience, smoking status, health literacy, and medication insecurity. Conclusions and relevance Augmenting EHR data with patient-reported social information improved estimation of 90-day and 180-day hospitalization risk, highlighting specific SDH factors that might identify individuals who are at high risk for hospitalization.

Highlights • AMD patients show weaker connection in the splenium and left optic radiation. • Verbal fluency scores correlate with connection in the splenium and left IFOF/ILF. • AMD is linked with weaker correlations of cognition and white matter connection., Age-related macular degeneration (AMD) is a common retina disease associated with cognitive impairment in older adults. The mechanism(s) that account for the link between AMD and cognitive decline remain unclear. Here we aim to shed light on this issue by investigating whether relationships between cognition and white matter in the brain differ by AMD status. In a direct group comparison of brain connectometry maps from diffusion weighted images, AMD patients showed significantly weaker quantitative anisotropy (QA) than healthy controls, predominantly in the splenium and left optic radiation. The QA of these tracts, however, did not correlate with the visual acuity measure, indicating that this group effect is not directly driven by visual loss. The AMD and control groups did not differ significantly in cognitive performance. Across all participants, better cognitive performance (e.g. verbal fluency) is associated with stronger connectivity strength in white matter tracts including the splenium and the left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus. However, there were significant interactions between group and cognitive performance (verbal fluency, memory), suggesting that the relation between QA and cognitive performance was weaker in AMD patients than in controls. This may be explained by unmeasured determinants of performance that are more common or impactful in AMD or by a recruitment bias whereby the AMD group had higher cognitive reserve. In general, our findings suggest that neural degeneration in the brain might occur in parallel to AMD in the eyes, although the participants studied here do not (yet) exhibit overt cognitive declines per standard assessments.

Older patients presenting with acute myocardial infarction (AMI) often have comorbidities. Our objective was to examine how outcomes differ by cognitive and vision status in older AMI patients. We use data from a prospective cohort study conducted at 94 hospitals in the United States between January 2013 and October 2016 that enrolled men and women aged ≥75 years with AMI. Cognitive impairment (CI) was defined as telephone interview for cognitive status (TICS) score

Background Previous epidemiologic studies have suggested an association between AMD and AD, and several therapeutic agents are being developed based on this principle. However, prior studies have provided conflicting results due in part to their reliance on clinical diagnoses that are not based on gold-standard histopathology. Objective To use histopathologic standards for diagnosis in order to determine the co-prevalence of AD among patients with and without AMD. Methods This is a cross-sectional study of 157 autopsy ocular specimens from patients with and without AMD that were greater than 75 years of age at death. Sarks staging was used to document the severity of AMD, and Braak and Braak staging was used to assess the severity of AD in corresponding brain specimens. The prevalence of AD within different severities of AMD was determined using univariable and multivariable logistic regression. Results 58% of autopsy eyes had AMD. The prevalence of AD was lower in AMD subjects (63%) compared to non-AMD subjects (73%), even when grouped by severity (all p > 0.15). The likelihood of AD was significantly less in AMD subjects, even after adjusting for age and sex in multivariable analysis (OR 0.47, p = 0.049). Conclusion Histopathologic diagnoses fail to support an increase in prevalence of AD among subjects with AMD, even when disease severity is considered.

BackgroundClinically similar older adults demonstrate variable responses to health stressors, heterogeneity attributable to differences in physical resilience. However, molecular mechanisms underlying physical resilience are unknown. We previously derived a measure of physical resilience after hip fracture—the expected recovery differential (ERD)—that captures the difference between actual recovery and predicted recovery. Starting with biomarkers associated with physical performance, morbidity, mortality, and hip fracture, we evaluated associations with the ERD to identify biomarkers of physical resilience after hip fracture.MethodsIn the Baltimore Hip Studies (N = 304) sera, we quantified biomarkers of inflammation (TNFR-I, TNFR-II, sVCAM-1, and IL-6), metabolic and mitochondrial function (non-esterified fatty acids, lactate, ketones, acylcarnitines, free amino acids, and IGF-1), and epigenetic dysregulation (circulating microRNAs). We used principal component analysis, canonical correlation, and least absolute shrinkage and selection operator regression (LASSO) to identify biomarker associations with better-than-expected recovery (greater ERD) after hip fracture.ResultsParticipants with greater ERD were more likely to be women and less disabled at baseline. The complete biomarker set explained 37% of the variance in ERD (p < .001) by canonical correlation. LASSO regression identified a biomarker subset that accounted for 27% of the total variance in the ERD and included a metabolic factor (aspartate/asparagine, C22, C5:1, lactate, glutamate/mine), TNFR-I, miR-376a-3p, and miR-16-5p.ConclusionsWe identified a set of biomarkers that explained 27% of the variance in ERD—a measure of physical resilience after hip fracture. These ERD-associated biomarkers may be useful in predicting physical resilience in older adults facing hip fracture and other acute health stressors.

Background/Objectives To address the underrepresentation of older adults in clinical research, the National Institutes of Health will require investigators to include individuals across the lifespan. As investigators from other fields endeavor to recruit participants who are more representative of the patient population, geriatricians may have the opportunity to influence a broad range of research studies in older adults. Our aims were to elicit challenges to inclusion of older adults in clinical research and to develop a preliminary framework for communicating these challenges to non–geriatrics‐trained researchers. Design Communication framework development. Setting Academic hospital and Veterans Affairs Medical Center. Participants Nongeriatrician researchers and staff, aging research experts. Measurements Interviews were used to elicit challenges nongeriatrician investigators and research staff experience when conducting research that includes older adults and then solicit experienced aging researchers' responses to these challenges. Results Challenges described by nongeriatrician investigators included lack of knowledge, rigid study structures, and a disease‐focused approach. Responses from our geriatrics experts included communicating practical advice for avoiding common pitfalls. Our resulting framework is the 5Ts: Target Population, Team, Tools, Time, and Tips to Accommodate. This tool complements the 5Ms (Mind, Mobility, Medications, Multicomplexity, and Matters Most to Me) model for geriatric care and emphasizes representation of the Target Population, building research Teams that include aging expertise, incorporating appropriate Tools for function and patient‐reported outcomes, anticipating Time for longer study visits, and accommodating common needs with practical Tips. Limitations include convenience sampling and lack of formal qualitative thematic analysis. Conclusion Communicating with nongeriatrician researchers using the 5Ts may offer a practical approach to avoiding barriers to inclusion of older adults in research and complements an existing framework for communicating the value of geriatric medicine. Next steps in developing the 5Ts will be to include additional stakeholders (eg, national samples of nongeriatrician investigators, older adults and their families) and evaluating the impact of its implementation. J Am Geriatr Soc 67:342–346, 2019.

BACKGROUND Geriatricians are often confronted with unexpected health outcomes in older adults with complex multimorbidity. Aging researchers have recently called for a focus on physical resilience as a new approach to explaining such outcomes. Physical resilience, defined as the ability to resist functional decline or recover health following a stressor, is an emerging construct. METHODS Based on an outline of the state-of-the-art in research on the measurement of physical resilience, this article describes what tests to predict resilience can already be used in clinical practice and which innovations are to be expected soon. RESULTS An older adult's recovery potential is currently predicted by static tests of physiological reserves. Although geriatric medicine typically adopts a multidisciplinary view of the patient and implicitly performs resilience management to a certain extent, clinical management of older adults can benefit from explicitly applying the dynamical concept of resilience. Two crucial leads for advancing our capacity to measure and manage the resilience of individual patients are advocated: first, performing multiple repeated measurements around a stressor can provide insight about the patient's dynamic responses to stressors; and, second, linking psychological and physiological subsystems, as proposed by network studies on resilience, can provide insight into dynamic interactions involved in a resilient response. CONCLUSION A big challenge still lies ahead in translating the dynamical concept of resilience into clinical tools and guidelines. As a first step in bridging this gap, this article outlines what opportunities clinicians and researchers can already exploit to improve prediction, understanding, and management of resilience of older adults. J Am Geriatr Soc 67:2650-2657, 2019.

Objectives Focus on decline in performance of activities of daily living (ADL) has not been matched by studies of recovery of function. Advised by a broad conceptual model of physical resilience, we ascertain characteristics that identify (1) maintenance, (2) decline, and (3) recovery of personal self-maintenance activities over six years in an older, community representative, African American and white sample. Design Longitudinal study, analyses included descriptive statistics and repeated measures proportional hazards. Setting/Participants Community-representative participants of the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE), unimpaired at baseline (n = 3187; 46% white, 54% African American; 64% female, 36% male), followed annually for up to 6 years. Measures Data included information on basic activities of daily living (BADL), demographic characteristics, health status, social services provided and received, household size, neighborhood safety, and survival status. Results Over 6 years, ∼75% remained unimpaired, of whom 30% were unimpaired when they dropped out or died. Of ∼25% who became impaired, just under half recovered. Controlled analyses indicated that those who became impaired were in poorer health, younger, and more likely to be African American. Characteristics of recovery included younger age, not hospitalized in the previous year, and larger household size. Conclusions/Implications Maintenance of health status facilitated continued unimpaired BADL. While decline was associated with poorer health, younger age, and being African American, recovery was also associated with younger age, together with larger household size, and no further deterioration in health as measured here. Maintenance of good health is preferred, but following decline in functioning, increased effort to improve health and avoid further decline, which takes into account not only physical but also personal social conditions, is needed.