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Background: We recently demonstrated that more intensive blood pressure (BP) treatment lowered risk of orthostatic hypotension (OH) measured with a seated-to-standing protocol. However, seated-to-standing OH assessments are less sensitive than supine-to-standing and could miss clinically relevant OH. Objectives: Using data from the Syst-Eur trial (Systolic Hypertension in Europe), we examined the effect of hypertension treatment on incidence of OH based on the difference in BP from 3 body positions. Methods: Syst-Eur was a multi-center, randomized trial that enrolled adults with isolated systolic hypertension to investigate whether active hypertension treatment could reduce cardiovascular events. Participants underwent BP measurement in supine, seated, and standing positions. Using differences in BP between the 3 body positions (seated minus supine, standing minus seated, and standing minus supine), we defined OH as a drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg. We included measurements from baseline and follow-up visits. Results: Among 4695 participants (mean age, 70.2±6.7 years; 66.9% female) with 42 636 BP measurements, OH was present in 4.9% of measures with supine-to-seated, 7.9% with seated-to-standing, and 11.4% with supine-to-standing protocols, respectively. Compared with placebo, BP treatment did not increase OH with any set of maneuvers, OR, 0.79 (95% CI, 0.65–0.95) with seated-to standing, 1.03 (95% CI, 0.86–1.24) with supine-to-seated, and 0.99 (95% CI, 0.86–1.15) with supine-to-standing. Conclusions: Regardless of protocol, active hypertension treatment did not increase the risk of OH, reinforcing evidence that OH should not be viewed as a complication of hypertension treatment. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02088450.

Orthostatic hypotension affects roughly 10% of individuals with hypertension and is associated with several adverse health outcomes, including dementia, cardiovascular disease, stroke, and death. Among adults with hypertension, orthostatic hypotension has also been shown to predict patterns of blood pressure dysregulation that may not be appreciated in the office setting, including nocturnal nondipping. Individuals with uncontrolled hypertension are at particular risk of orthostatic hypotension and may meet diagnostic criteria for the condition with a smaller relative reduction in blood pressure compared with normotensive individuals. Antihypertensive medications are commonly de-prescribed to address orthostatic hypotension; however, this approach may worsen supine or seated hypertension, which may be an important driver of adverse events in this population. There is significant variability between guidelines for the diagnosis of orthostatic hypotension with regards to timing and position of blood pressure measurements. Clinically relevant orthostatic hypotension may be missed when standing measurements are delayed or when taken after a seated rather than supine position. The treatment of orthostatic hypotension in patients with hypertension poses a significant management challenge for clinicians; however, recent evidence suggests that intensive blood pressure control may reduce the risk of orthostatic hypotension. A detailed characterization of blood pressure variability is essential to tailoring a treatment plan and can be accomplished using both in-office and out-of-office monitoring.

Background Slow gait is predictive of functional impairments in older adults, while concomitant slow gait and cognitive complaints are associated with a greater risk for cognitive decline and dementia. However, functional neural correlates for gait speed maintenance are unclear. As the sensorimotor network (SMN) and frontoparietal network (FPN) are integral components of these functions, this study investigated differences in SMN and FPN in older adults with/without gait speed decline over 24 months; and whether these networks were associated with the maintenance of cognitive function. Methods We included 42 community-dwelling older adults aged >70 years from the MOBILIZE Boston Study. Resting-state fMRI was performed at the study baseline. Participant characteristics, gait speed, Mini-Mental State Examination, and Hopkins Verbal Learning Test (HVLT) were assessed at baseline and at 24-month follow-up. Decliners were identified as individuals with >0.05 meters/second decline in gait speed from baseline to 24 months. Of the 26 decliners and 16 maintainers, decliners exhibited a significant decline in delayed-recall performance on the HVLT over 24 months. Results Controlling for baseline age and multiple comparisons, contrary to initial hypothesis, maintainers exhibited lower baseline primary motor and premotor connectivity (p = .01) within the SMN, and greater baseline ventral visual–supramarginal gyrus connectivity within the FPN (p = .02) compared to decliners. Lower primary motor–premotor connectivity was correlated with maintenance of delayed-recall performance on the HVLT (p = .04). Conclusion These findings demonstrated a potential compensatory mechanism involved in the link between the decline in gait speed and episodic memory, whereby baseline connectivity of the SMN and FPN may underlie subsequent maintenance of gait speed and cognitive function in old age.

Background The association between volume and outcomes has led to recommendations that patients undergo surgery at high-volume centers. We aimed to determine if older patients with rectal cancer are undergoing operations at high-volume centers. Methods We identified patients ≥50 years old who underwent rectal cancer resection using the NCDB (2004–2015). Tertiles were used to categorize facility volume and distance traveled. Results Higher facility volume was associated with improved outcomes. Patients >75 years old were less likely than patients 50–59 years old to be treated at high-volume centers. Traveling >16.8 miles was associated with treatment at high-volume facilities, however patients >75 years old were less likely to travel >16.8 miles. Conclusions Higher facility volume is associated with improved outcomes after rectal cancer resection. However, older patients are less likely to be treated at high-volume facilities. Older patients travel shorter distances for care, suggesting that care integration across networks must be optimized.

Orthostatic hypotension (OH) based on a change from seated-to-standing blood pressure (BP) is often used interchangeably with supine-to-standing BP.The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a randomized trial of vitamin D3 supplementation and fall in adults aged ≥70 years at high risk of falls. OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mmHg, measured at pre-randomization, 3-, 12-, and 24-month visits with each of 2 protocols: seated-to-standing and supine-to-standing. Participants were asked about orthostatic symptoms, and falls were ascertained via daily fall calendar, ad hoc reporting, and scheduled interviews.Among 534 participants with 993 paired supine and seated assessments (mean age 76 ± 5 years, 42% women, 18% Black), mean baseline BP was 130 ± 19/68 ± 11 mmHg; 62% had a history of high BP or hypertension. Mean BP increased 3.5 (SE, 0.4)/2.6 (SE, 0.2) mmHg from sitting to standing, but decreased with supine to standing (mean change: -3.7 [SE, 0.5]/-0.8 [SE, 0.3] mmHg; P-value 0.001). OH was detected in 2.1% (SE, 0.5) of seated versus 15.0% (SE, 1.4) of supine assessments (P 0.001). While supine and seated OH were not associated with falls (HR: 1.55 [0.95, 2.52] vs 0.69 [0.30, 1.58]), supine systolic OH was associated with higher fall risk (HR: 1.77 [1.02, 3.05]). Supine OH was associated with self-reported fainting, blacking out, seeing spots and room spinning in the prior month (P-values 0.03), while sitting OH was not associated with any symptoms (P-values ≥ 0.40).Supine OH was more frequent, associated with orthostatic symptoms, and potentially more predictive of falls than seated OH.

Age-associated changes in DNA methylation have been implicated as 1 mechanism to explain the development of frailty; however, previous cross-sectional studies of epigenetic age acceleration (eAA) and frailty have had inconsistent findings. Few longitudinal studies have considered the association of eAA with change in frailty. We sought to determine the association between eAA and change in frailty in the MOBILIZE Boston cohort. Participants were assessed at 2 visits 12–18 months apart. Intrinsic, extrinsic, GrimAge, and PhenoAge eAA were assessed from whole-blood DNA methylation at baseline using the Infinium 450k array. Frailty was assessed by a continuous frailty score based on the frailty phenotype and by frailty index (FI). Analysis was by correlation and linear regression with adjustment for age, sex, smoking status, and body mass index. Three hundred and ninety-five participants with a frailty score and 431 with an FI had epigenetic and follow-up frailty measures. Mean (standard deviation) ages were 77.8 (5.49) and 77.9 (5.47) for the frailty score and the FI cohorts respectively, and 232 (58.7%) and 257 (59.6%) were female. All participants with epigenetic data identified as White. Baseline frailty score was not correlated with intrinsic or extrinsic eAA, but was correlated with PhenoAge and, even after adjustment for covariates, GrimAge. Baseline FI was correlated with extrinsic, GrimAge, and PhenoAge eAA with and without adjustment. No eAA measure was associated with change in frailty, with or without adjustment. Our results suggest that no eAA measure was associated with change in frailty. Further studies should consider longer periods of follow-up and repeated eAA measurement.

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Assessments of postural control provide important insights into health. We created a smartphone App-based assessment of standing posture—completed with the phone placed in the user’s pocket—to enable remote monitoring of the function while minimizing the need for in-person assessment or contact. We tested the reliability of App-derived postural sway metrics, as well as their sensitivity to age and task conditions. Fifteen older and 15 younger adults completed two separate laboratory visits. They followed multimedia instructions provided by the App to complete three 30-s trials of eyes-open (EO), eyes-closed (EC), and dual-task (DT) standing. Sway data were recorded by the App and a force plate. Participants also used the App to complete the assessment in their homes on three separate days. Sway path length and root-mean square were derived from the angular velocity and acceleration acquired from phone’s internal motion sensor, and from the center-of-pressure signal from force plate. App-derived path length and root-mean-square of acceleration and angular velocity across conditions demonstrated moderate-to-excellent test–retest reliability (intraclass correlation coefficients (ICCs) = 0.69 − 0.97) for both younger and older adults. Reliability was comparable to metrics derived from the force plate (ICCs = 0.44 − 0.93). As expected, App-derived sway outcomes exhibited somewhat greater variability when tested across days at home (ICCs = 0.14 − 0.79). All App-derived metrics were sensitive to age ( $F>43.8$ , $p ) and testing condition ( $F>31.8$ , $p ) in both laboratory and home settings, revealing that the smartphone App enabled reliable and sensitive assessment of standing posture in both healthy younger and older adults.

Background In older adults, elevated gait variability when walking has been associated with both cognitive impairment and future falls. This study leveraged 3 existing data sets to determine relationships between gait variability and the strength of functional connectivity within and between large-scale brain networks in healthy older adults, those with mild-to-moderate functional impairment, and those with Parkinson’s disease (PD). Method Gait and resting-state functional magnetic resonance imaging data were extracted from existing data sets on: (i) 12 older adults without overt disease yet with slow gait and mild executive dysfunction; (ii) 12 older adults with intact cognitive-motor function and age- and sex-matched to the first cohort; and (iii) 15 individuals with PD. Gait variability (%, coefficient of variation of stride time) during preferred walking speed was measured and correlated with the degree of functional connectivity within and between 7 established large-scale functional brain networks. Results Regression models adjusted for age and sex revealed that in each cohort, those with less gait variability exhibited greater negative correlation between fluctuations in resting-state brain activity between the default network and the dorsal attention network (functionally limited older: β = 4.38, p = .027; healthy older: β = 1.66, p = .032; PD: β = 1.65, p = .005). No other within- or between-network connectivity outcomes were consistently related to gait variability across all 3 cohorts. Conclusion These results provide strong evidence that gait variability is uniquely related to functional connectivity between the default network and the dorsal attention network, and that this relationship may be independent of both functional status and underlying brain disease.

Background Treatments of freezing of gait (FOG) in Parkinson's disease are suboptimal. Objective The aim of this study was to evaluate the effects of multiple sessions of transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex and primary motor cortex (M1) on FOG. Methods Seventy-seven individuals with Parkinson's disease and FOG were enrolled in a double-blinded randomized trial. tDCS and sham interventions comprised 10 sessions over 2 weeks followed by five once-weekly sessions. FOG-provoking test performance (primary outcome), functional outcomes, and self-reported FOG severity were assessed. Results Primary analyses demonstrated no advantage for tDCS in the FOG-provoking test. In secondary analyses, tDCS, compared with sham, decreased self-reported FOG severity and increased daily living step counts. Among individuals with mild-to-moderate FOG severity, tDCS improved FOG-provoking test time and self-report of FOG. Conclusions Multisession tDCS targeting the left dorsolateral prefrontal cortex and M1 did not improve laboratory-based FOG-provoking test performance. Improvements observed in participants with mild-to-moderate FOG severity warrant further investigation. © 2021 International Parkinson and Movement Disorder Society.

Background: In a recent individual level meta-analysis, intensive versus standard blood pressure (BP) treatment reduced participants’ risk of orthostatic hypotension (OH). Whether OH modified the relationship between intensive treatment and risk of cardiovascular disease (CVD) or death is unknown. Methods: We performed an individual participant data meta-analysis, updating a previous systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022, which included randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) on CVD or death. CVD events were adjudicated and included coronary heart disease, stroke, and congestive heart failure. OH was defined as a drop in SBP ≥20 mmHg and/or DBP ≥10 mmHg after changing positions from sitting to standing. Ultimately, 8 trials were identified with OH and outcomes data. Effects were examined overall and by trial type (BP goal or active agent), using Cox proportional hazard models adjusted for age and sex. Results: There were 27,974 participants followed for median of 4 years (mean age 69.5±10.7 years; 48.5% female; 8.6% with OH). Baseline OH was associated with a higher risk of CVD or death (HR 1.24; 95% CI: 1.10, 1.39). More intensive BP treatment or active therapy lowered risk of CVD or death among those without OH at baseline (HR 0.82; 95% CI: 0.76, 0.88) and with OH at baseline (HR 0.79; 95% CI: 0.63, 0.98). Effects did not differ by baseline OH ( P -interaction 0.78) ( Table ). Conclusion: While baseline OH was associated with CVD or death, it did not increase the risk of CVD or death from intensive treatment. OH prior to the initiation of intensive therapy should not be viewed as a reason to avoid BP treatment.

Introduction: We hypothesized that subclinical disruption in blood pressure (BP) dynamics, captured by lower complexity and higher variability, may contribute to dementia risk, above and beyond BP levels. Methods: This prospective cohort study followed 1835 older adults from 1997 to 2016, with BP complexity quantified by sample entropy and BP variability quantified by coefficient of variation using beat-to-beat BP measured at baseline. Results: Three hundred thirty-four participants developed dementia over 20 years. Reduced systolic BP (SBP) complexity was associated with a higher risk of dementia (hazard ratio [HR] comparing extreme quintiles: 1.55; 95% confidence interval [CI]: 1.09-2.20). Higher SBP variability was also associated with a higher risk of dementia (HR comparing extreme quintiles: 1.57; 95% CI: 1.11-2.22. These findings were observed after adjusting for age, sex, apolipoprotein E (APOE) genotype, mean SBP, and other confounding factors. Discussions: Our findings suggest that lower complexity and higher variability of beat-to-beat SBP are potential novel risk factors or biomarkers for dementia.

BACKGROUND: Discharge from the hospital to a post–acute care setting can be complex and potentially dangerous, with opportunities for errors and lapses in communication between providers. Data collected through the Extension for Community Health Outcomes–Care Transitions (ECHO-CT) model were used to identify and classify transition-of-care events (TCEs). METHODS: The ECHO-CT model employs multidisciplinary videoconferences between a hospital-based team and providers in post–acute care settings; during these conferences, concerns regarding the patient’s care transition were identified and recorded. The videoconferences took place from January 2016 to October 2018 and included patients discharged from inpatient medical and surgical services to a total of eight participating post–acute care facilities (skilled nursing facilities or long-term acute care hospitals). RESULTS: During the interdisciplinary videoconferences in this period, 675 patients were discussed. A total of 139 TCEs were identified; 58 (41.7%) involved discharge communication or coordination errors and 52 (37.4%) were classified as medication issues. CONCLUSION: The TCEs identified in this study highlight areas in which providers can work to reduce issues arising during the course of discharge to post–acute care facilities. Standardized processes to identify, record, and report TCEs are necessary to provide high-quality, safe care for patients as they move across care settings.

BackgroundWe recently reported that individuals with impaired plantar sensation and high fall risk due to sensory peripheral neuropathy (PN) improved gait and balance function following 10 weeks of use of Walkasins®, a wearable lower limb sensory prosthesis that provides directional tactile stimuli related to plantar pressure measurements during standing and walking (RxFunction Inc., MN, USA). Here, we report 26-week outcomes and compare pre- and in-study fall rates. We expected improvements in outcomes and reduced fall rates reported after 10 weeks of use to be sustained.MethodsParticipants had clinically diagnosed PN with impaired plantar sensation, high fall risk (Functional Gait Assessment, FGA score ResultsWe assessed falls and self-reported outcomes from 44 individuals after 26 weeks of device use; 30 of them conducted in-person testing of clinical outcomes. Overall, improvements in clinical outcomes seen at 10 weeks of use remained sustained at 26 weeks with statistically significant increases compared to baseline seen in FGA scores (from 15.0 to 19.2), self-selected gait speed (from 0.89 m/s to 0.97 m/s), and 4-Stage Balance Test (from 25.6s to 28.4s), indicating a decrease in fall risk. Non-significant improvements were observed in TUG and fast gait speed. Overall, 39 falls were reported; 31 of them did not require medical treatment and four caused severe injury. Participants who reported falls over 6 months prior to the study had a 43% decrease in fall rate during the study as compared to self-report 6-month pre-study (11.8 vs. 6.7 falls/1000 patient days, respectively, pConclusionA wearable sensory prosthesis can improve outcomes of gait and balance function and substantially decreases incidence of falls during long-term use. The sustained long-term benefits in clinical outcomes reported here lessen the likelihood that improvements are placebo effects.Trial registrationClinicalTrials.gov (#NCT03538756)

Background/objectives In April 2020, Massachusetts nursing homes (NHs) became a hotspot for COVID-19 infections and associated deaths. In response, Governor Charles Baker allocated $130 million in additional funding for 2 months contingent on compliance with a new set of care criteria including mandatory testing of all residents and staff, and a 28-point infection control checklist. We aimed to describe the Massachusetts effort and associated outcomes. Design Longitudinal cohort study. Setting A total of 360 Massachusetts NHs. Participants The Massachusetts Senior Care Association and Hebrew SeniorLife rapidly organized a Central Command team, targeted 123 "special focus" facilities with infection control deficiencies for on-site and virtual consultations, and offered all 360 facilities weekly webinars and answers to questions regarding infection control procedures. The facilities were also informed of resources for the acquisition of personal protective equipment (PPE), backup staff, and SARS-CoV-2 testing. Measurements We used two data sources: (1) four state audits of all NHs, and (2) weekly NH reports to the Massachusetts Center for Health Information and Analysis. Primary independent process measures were the checklist scores and adherence to each of its six core competencies. Primary outcomes were the average weekly rates of new infections, hospitalizations, and deaths in residents and staff. We used a hurdle mixed effects model adjusted for county COVID-19 prevalence to estimate relationships between infection control process measures and rates of new infections or deaths. Results Both resident and staff infection rates started higher in special focus facilities, then rapidly declined to the same low level in both groups. Adherence to infection control processes, especially proper wearing of PPE and cohorting, was significantly associated with declines in weekly infection and mortality rates. Conclusion This statewide effort could serve as a national model for other states to prevent the devastating effects of pandemics such as COVID-19 in frail NH residents.

ObjectiveTo test the hypothesis that orthostatic hypotension (OH) might cause cerebral hypoperfusion and injury, we examined the longitudinal relationship between OH or orthostatic symptoms and incident neurologic outcomes in a community population of older adults.MethodsCardiovascular Health Study participants (≥65 years) without dementia or stroke had blood pressure (BP) measured after lying down for 20 minutes and after standing 3 for minutes. Participants reported dizziness immediately upon standing and any dizziness in the past 2 weeks. OH was defined as a drop in standing systolic/diastolic BP ≥20/≥10 mm Hg. We determined the association between OH or dizziness with (1) MRI brain findings (ventricular size, white matter hyperintensities, brain infarcts) using linear or logistic regression, (2) cognitive function (baseline and over time) using generalized estimating equations, and (3) prospective adjudicated events (dementia, stroke, death) using Cox models. Models were adjusted for demographic characteristics and OH risk factors. We used multiple imputation to account for missing OH or dizziness (n = 534).ResultsPrior to imputation, there were 5,007 participants (mean age 72.7 ± 5.5 years, 57.6% women, 10.9% Black, 16% with OH). OH was modestly associated with death (hazard ratio [HR] 1.11; 95% confidence interval 1.02–1.20), but not MRI findings, cognition, dementia, or stroke. In contrast, dizziness upon standing was associated with lower baseline cognition (β = −1.20; −1.94 to −0.47), incident dementia (HR 1.32; 1.04–1.62), incident stroke (HR 1.22; 1.06–1.41), and death (HR 1.13; 1.06–1.21). Similarly, dizziness over the past 2 weeks was associated with higher white matter grade (β = 0.16; 0.03–0.30), brain infarcts (OR 1.31; 1.06–1.63), lower baseline cognition (β = −1.18; −2.01 to −0.34), and death (HR 1.13; 1.04–1.22).ConclusionsDizziness was more consistently associated with neurologic outcomes than OH 3 minutes after standing. Delayed OH assessments may miss pathologic information related to cerebral injury.

Balance impairment and falls are among the most prevalent and morbid conditions affecting older adults. A critical contributor to balance and gait function is the vestibular system; however, there remain substantial knowledge gaps regarding age-related vestibular loss and its contribution to balance impairment and falls in older adults. Given these knowledge gaps, the National Institute on Aging and the National Institute on Deafness and Other Communication Disorders convened a multidisciplinary workshop in April 2019 that brought together experts from a wide array of disciplines, such as vestibular physiology, neuroscience, movement science, rehabilitation, and geriatrics. The goal of the workshop was to identify key knowledge gaps on vestibular function and balance control in older adults and develop a research agenda to make substantial advancements in the field. This article provides a report of the proceedings of this workshop. Three key questions emerged from the workshop, specifically: (i) How does aging impact vestibular function?; (ii) How do we know what is the contribution of age-related vestibular impairment to an older adult’s balance problem?; and more broadly, (iii) Can we develop a nosology of balance impairments in older adults that can guide clinical practice? For each of these key questions, the current knowledge is reviewed, and the critical knowledge gaps and research strategies to address them are discussed. This document outlines an ambitious 5- to 10-year research agenda for increasing knowledge related to vestibular impairment and balance control in older adults, with the ultimate goal of linking this knowledge to more effective treatment.

Objective Symptomatic head trauma associated with American-style football (ASF) has been linked to brain pathology, along with physical and mental distress in later life. However, the longer-term effects of such trauma on objective metrics of cognitive-motor function remain poorly understood. We hypothesized that ASF-related symptomatic head trauma would predict worse gait performance, particularly during dual task conditions (ie, walking while performing an additional cognitive task), in later life. Methods Sixty-six retired professional ASF players aged 29 to 75 years completed a health and wellness questionnaire. They also completed a validated smartphone-based assessment in their own homes, during which gait was monitored while they walked normally and while they performed a verbalized serial-subtraction cognitive task. Results Participants who reported more symptomatic head trauma, defined as the total number of impacts to the head or neck followed by concussion-related symptoms, exhibited greater dual task cost (ie, percentage increase) to stride time variability (ie, the coefficient of variation of mean stride time). Those who reported ≥1 hit followed by loss of consciousness, compared to those who did not, also exhibited greater dual task costs to this metric. Relationships between reported trauma and dual task costs were independent of age, body mass index, National Football League career duration, and history of musculoskeletal surgery. Symptomatic head trauma was not correlated with average stride times in either walking condition. Interpretation Remote, smartphone-based assessments of dual task walking may be utilized to capture meaningful data sensitive to the long-term impact of symptomatic head trauma in former professional ASF players and other contact sport athletes. ANN NEUROL 2020;87:75-83.