The Physiologic Complexity of Prefrontal Oxygenation Dynamics Is Associated With Age and Executive Function: An Exploratory Study.

BACKGROUND: The hemodynamics of prefrontal cortex (PFC) oxygenation are regulated by numerous processes operating over multiple temporal scales, producing complex patterns in its output fluctuations. Age may alter this multiscale regulation of PFC oxygenation, leading to diminished physiologic complexity of this important regulatory process. We aimed to characterize the effects of age on such complexity and its relationship to performance of an executive n-back task. METHODS: Twenty-four younger (aged 28 ±â€…3 years) and 27 older (aged 78 ±â€…6 years) adults completed this study. Continuous oxygenation (HbO2) and deoxygenation (HHb) signals of PFC were recorded using functional near-infrared spectroscopy (fNIRS) while participants stood and watched a blank screen (blank), clicked a mouse when an X appeared (IdX), or when a letter was repeated from "2-back" in a sequence shown on a screen (2-back). We used multiscale entropy to quantify the HbO2 and HHb complexity of fNIRS signals. RESULTS: Older adults exhibited lower HbO2 and HHb complexity compared to younger adults, regardless of task (p = .0005-.002). Both groups exhibited greater complexity during the IdX and 2-back than blank task (p = .02-.04). Across all participants, those with greater HbO2 and/or HHb complexity during the blank task exhibited faster IdX and 2-back reaction time (ß = -0.56 to -0.6, p = .009-.02). Those demonstrating greater increase in HbO2 and/or HHb complexity from IdX to 2-back task had lower percent increase in reaction time from IdX to 2-back task (ß = -0.41 to -0.37, p = .005-.01). CONCLUSIONS: The complexity of fNIRS-measured PFC oxygenation fluctuations may capture the influence of aging on the regulation of prefrontal hemodynamics involved in executive-function-based task performance.

Exercise to Mitigate Cerebrovascular Aging: A Geroscience Perspective.

Aging is characterized by a progressive loss of cellular functions that increase the risk of developing chronic diseases, vascular dysfunction, and neurodegenerative conditions. The field of geroscience has identified cellular and molecular hallmarks of aging that may serve as targets for future interventions to reduce the risk of age-related disease and disability. These hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Several studies show that exercise may favorably affect these processes and thereby have antiaging properties. The primary mechanisms through which exercise confers protective benefits in the brain are still incompletely understood. To better understand these effects and leverage them to help promote brain health, we present current findings supporting the notion that adaptive responses to exercise play a pivotal role in mitigating the hallmarks of aging and their effects on the aging cerebrovasculature, and ultimately contribute to the maintenance of brain function across the healthspan.

The physiologic complexity of beat-to-beat blood pressure is associated with age-related alterations in blood pressure regulation.

The fluctuations in resting-state beat-to-beat blood pressure (BP) are physiologically complex, and the degree of such BP complexity is believed to reflect the multiscale regulation of this critical physiologic process. Hypertension (HTN), one common age-related condition, is associated with altered BP regulation and diminished system responsiveness to perturbations such as orthostatic change. We thus aimed to characterize the impact of HTN on resting-state BP complexity, as well as the relationship between BP complexity and both adaptive capacity and underlying vascular characteristics. We recruited 392 participants (age: 60-91 years), including 144 that were normotensive and 248 with HTN (140 controlled- and 108 uncontrolled-HTN). Participants completed a 10-min continuous finger BP recording during supine rest, then underwent measures of lying-to-standing BP change, arterial stiffness (i.e., brachial-ankle pulse wave velocity), and endothelial function (i.e., flow-mediated vasodilation). The complexity of supine beat-to-beat systolic (SBP) and diastolic (DBP) BP was quantified using multiscale entropy. Thirty participants with HTN (16 controlled-HTN and 14 uncontrolled-HTN) exhibited orthostatic hypotension. SBP and DBP complexity was greatest in normotensive participants, lower in those with controlled-HTN, and lowest in those in uncontrolled-HTN (p < 0.0005). Lower SBP and DBP complexity correlated with greater lying-to-standing decrease in SBP and DBP level (ß = -0.33 to -0.19, p < 0.01), greater arterial stiffness (ß = -0.35 to -0.18, p < 0.01), and worse endothelial function (ß = 0.17-0.22, p < 0.01), both across all participants and within the control- and uncontrolled-HTN groups. These results suggest that in older adults, BP complexity may capture the integrity of multiple interacting physiologic mechanisms that regulate BP and are important to cardiovascular health.

Cardiovascular Disorders and Falls Among Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Falls are a common cause of injury, hospitalization, functional decline, and residential care admission among older adults. Cardiovascular disorders are recognized risk factors for falls. This systematic review assesses the association between cardiovascular disorders and falls in older adults. METHODS: Systematic searches were conducted on MEDLINE and Embase, encompassing all literature published prior to December 31, 2022. Included studies addressed persons aged 50 years and older, and assessed the association between cardiovascular disorders and falls or the efficacy of cardiovascular-based interventions to reduce falls. Two reviewers independently extracted data and assessed study quality utilizing a modified Newcastle-Ottawa scale for observational studies, and the Cochrane Risk of Bias 2 tool for interventional studies. A systematic narrative analysis of all cardiovascular outcomes, and meta-analyses of unadjusted odds ratios (ORs) were performed. RESULTS: One hundred and eighty-four studies were included: 181 observational and 3 interventional. Several cardiovascular disorders, including stroke, coronary artery disease, valvular heart disease, arterial stiffness, arrhythmia, orthostatic hypotension, and carotid sinus hypersensitivity, were consistently associated with falls. In meta-analysis of unadjusted ORs, the largest positive pooled associations with falls during a 12-month reporting interval were for stroke (OR: 1.90, 95% confidence interval [CI]: 1.70-2.11), peripheral arterial disease (OR: 1.82, 95% CI: 1.12-2.95), atrial fibrillation (OR: 1.52, 95% CI: 1.27-1.82), and orthostatic hypotension (OR: 1.39, 95% CI: 1.18-1.64). CONCLUSIONS: Several cardiovascular disorders are associated with falls. These results suggest the need to incorporate cardiovascular assessments for patients with falls. This review informed the cardiovascular recommendations in the new World Guidelines for falls in older adults.Clinical Trials Registration Number: CRD42021272245.

Orthostatic Blood Pressure Change, Dizziness, and Risk of Dementia in the ARIC Study.

BACKGROUND: Abnormal orthostatic blood pressure (BP) regulation may result in cerebral hypoperfusion and brain ischemia and contribute to dementia. It may also manifest as early symptoms of the neurodegenerative process associated with dementia. The relationship between the magnitude and timing of orthostatic BP responses and dementia risk is not fully understood. METHODS: We conducted a prospective cohort analysis of the associations of orthostatic BP changes and self-reported orthostatic dizziness with the risk of dementia in the Atherosclerosis Risk in Communities study (ARIC). We calculated changes in BP from the supine to the standing position at 5 measurements taken within 2 minutes after standing during the baseline visit (1987-1989). The primary outcome was adjudicated dementia ascertained through 2019. RESULTS: Among 11 644 participants (mean [SD] age, 54.5 [5.7] years; 54.1% women; 25.9% Black), 2303 dementia cases were identified during a median follow-up of 25.9 years. Large decreases in systolic BP from the supine to standing position measured at the first 2 measurements ≈30 and 50 seconds after standing, but not afterward, were associated with orthostatic dizziness and a higher risk of dementia. Comparing a decrease in systolic BP of ≤-20 or >-20 to -10 mm Hg to stable systolic BP (>-10 to 10 mm Hg) at the first measurement, the adjusted hazard ratios were 1.22 (95% CI, 1.01-1.47) and 1.10 (95% CI, 0.97-1.25), respectively. CONCLUSIONS: Abnormal orthostatic BP regulation, especially abrupt drops in BP within the first minute, might be early risk markers for the development of dementia. Transient early orthostatic hypotension warrants more attention in clinical settings.

Long-term Tai Chi practice in older adults is associated with "younger" functional abilities.

Age-related alterations in physiology lead to declines in physical function that are associated with numerous adverse outcomes among older adults. Utilizing a hybrid design, we aimed to understand whether both long-term and short-term Tai Chi (TC) training are associated with age-related decline in physical function in healthy older adults. We first conducted cross-sectional comparisons among TC-naïve older adults (n = 60, 64.2 ± 7.7 years), TC-expert older adults (n = 27, 62.8 ± 7.6 years, 24.5 ± 12 years experience), and TC-naïve younger adults (n = 15, 28.7 ± 3.2 years) to inform long-term effects of TC training on physical function, including single leg stance time with eyes closed, grip strength, Timed Up and Go, maximum walking speed, functional reach, and vertical jump for lower-extremity power. There were significant differences among the three groups on all the six tests. For most functional tests, TC-experts performed better than age-matched TC-naïve controls and were statistically indistinguishable from young healthy adult controls. Long-term TC training was associated with higher levels of physical function in older adults, suggesting a potential preventative healthy aging effect. In the randomized longitudinal trial, TC-naïve subjects were randomized (n = 31 to Tai Chi group, n = 29 to usual care control group) to evaluate the short-term effects of TC over 6 months on all outcomes. TC's short-term impacts on physical function were small and not statistically significant. The impact of short-term training in healthy adults is less clear. Both potential longer-term preventive effects and shorter-term restorative effects warrant further research with rigorous, adequately powered controlled clinical trials.

Preoperative electroencephalographic alpha-power changes with eyes opening are associated with postoperative attention impairment and inattention-related delirium severity.

BACKGROUND: In the eyes-closed, awake condition, EEG oscillatory power in the alpha band (7-13 Hz) dominates human spectral activity. With eyes open, however, EEG alpha power substantially decreases. Less alpha attenuation with eyes opening has been associated with inattention; thus, we analysed whether reduced preoperative alpha attenuation with eyes opening is associated with postoperative inattention, a delirium-defining feature. METHODS: Preoperative awake 32-channel EEG was recorded with eyes open and eyes closed in 71 non-neurological, noncardiac surgery patients aged ≥ 60 years. Inattention and other delirium features were assessed before surgery and twice daily after surgery until discharge. Eyes-opening EEG alpha-attenuation magnitude was analysed for associations with postoperative inattention, primarily, and with delirium severity, secondarily, using multivariate age- and Mini-Mental Status Examination (MMSE)-adjusted logistic and proportional-odds regression analyses. RESULTS: Preoperative alpha attenuation with eyes opening was inversely associated with postoperative inattention (odds ratio [OR] 0.73, 95% confidence interval [CI]: 0.57, 0.94; P=0.038). Sensitivity analyses showed an inverse relationship between alpha-attenuation magnitude and inattention chronicity, defined as 'never', 'newly', or 'chronically' inattentive (OR 0.76, 95% CI: 0.62, 0.93; P=0.019). In addition, preoperative alpha-attenuation magnitude was inversely associated with postoperative delirium severity (OR 0.79, 95% CI: 0.65, 0.95; P=0.040), predominantly as a result of the inattention feature. CONCLUSIONS: Preoperative awake, resting, EEG alpha attenuation with eyes opening might represent a neural biomarker for risk of postoperative attentional impairment. Further, eyes-opening alpha attenuation could provide insight into the neural mechanisms underlying postoperative inattention risk.

Orthostatic Hypotension, Hypertension Treatment, and Cardiovascular Disease: An Individual Participant Meta-Analysis.

Importance: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension. Objective: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension. Data Sources: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022. Study Selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with orthostatic hypotension assessments. Data Extraction and Synthesis: Individual participant data meta-analysis extracted following PRISMA guidelines. Effects were determined using Cox proportional hazard models using a single-stage approach. Main Outcomes and Measures: Main outcomes were CVD or all-cause mortality. Orthostatic hypotension was defined as a decrease in systolic BP of at least 20 mm Hg and/or diastolic BP of at least 10 mm Hg after changing position from sitting to standing. Standing hypotension was defined as a standing systolic BP of 110 mm Hg or less or standing diastolic BP of 60 mm Hg or less. Results: The 9 trials included 29 235 participants followed up for a median of 4 years (mean age, 69.0 [SD, 10.9] years; 48% women). There were 9% with orthostatic hypotension and 5% with standing hypotension at baseline. More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline orthostatic hypotension (hazard ratio [HR], 0.81; 95% CI, 0.76-0.86) similarly to those with baseline orthostatic hypotension (HR, 0.83; 95% CI, 0.70-1.00; P = .68 for interaction of treatment with baseline orthostatic hypotension). More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85), and nonsignificantly among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18). Effects did not differ by baseline standing hypotension (P = .16 for interaction of treatment with baseline standing hypotension). Conclusions and Relevance: In this population of hypertension trial participants, intensive therapy reduced risk of CVD or all-cause mortality regardless of orthostatic hypotension without evidence for different effects among those with standing hypotension.

Timing of orthostatic hypotension and its relationship with falls in older adults.

BACKGROUND: There is inconsistent evidence on the optimal time after standing to assess for orthostatic hypotension. We determined the prevalence of orthostatic hypotension at different time points after standing in a population of older adults, as well as fall risk and symptoms associated with orthostatic hypotension. METHODS: We performed a secondary analysis of the Study to Understand Fall Reduction and Vitamin D in You (STURDY), a randomized clinical trial funded by the National Institute on Aging, testing the effect of differing vitamin D3 doses on fall risk in older adults. STURDY occurred between July 2015 and May 2019. Secondary analysis occurred in 2022. Participants were community-dwelling adults, 70 years or older. In the orthostatic hypotension assessment, participants stood upright from supine position and underwent six standing blood pressure measurements (M1-M6) in two clusters of three measurements (immediately and 3 min after standing). Cox proportional hazard models were used to examine the relationship between orthostatic hypotension at each measurement and subsequent falls. Participants were followed until the earlier of their 24-month visit or study completion. RESULTS: Orthostatic hypotension occurred in 32% of assessments at M1, and only 16% at M5 and M6. Orthostatic hypotension from average immediate (M1-3) and average delayed (M4-6) measurements, respectively, predicted higher fall risk (M1-3 = 1.65 [1.08, 2.52]; M4-6 = 1.73 [1.03, 2.91]) (hazard ratio [95% confidence interval]). However, among individual measurements, only orthostatic hypotension at M5 (1.84 [1.16, 2.93]) and M6 (1.85 [1.17, 2.91]) predicted higher fall risk. Participants with orthostatic hypotension at M1 (3.07 [1.48, 6.38]) and M2 (3.72 [1.72, 8.03]) were more likely to have reported orthostatic symptoms. CONCLUSIONS: Orthostatic hypotension was most prevalent and symptomatic immediately within 1-2 min after standing, but more informative for fall risk after 4.5 min. Clinicians may consider both intervals when assessing for orthostatic hypotension.

Standing Blood Pressure and Risk of Falls, Syncope, Coronary Heart Disease, and Mortality.

BACKGROUND: ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of low standing systolic BP (SBP) < 110 mm Hg due to unclear benefits. METHODS: The Atherosclerosis Risk in Communities (ARIC) Study measured supine and standing SBP in adults aged 45-64 years between 1987 and 1989. We used Cox regression to evaluate the associations of low standing SBP (<110 mm Hg) with risk of falls, syncope, coronary heart disease (CHD), and mortality through December 31, 2019. Falls and syncope were ascertained by hospitalization and outpatient claims; CHD events were adjudicated. Associations were examined overall and in strata of hypertension stage, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and sex. RESULTS: Among 12,467 adults followed a median of 24 years (mean age at enrollment 54.1 ±â€…5.8 years, 55% women, 26% Black adults), 3,000 (24%) had a standing SBP < 110 mm Hg. A standing SBP < 110 mm Hg compared to standing SBP ≥ 110 mm Hg was not significantly associated with falls or syncope, and was associated with a lower risk of CHD events and mortality with HRs of 1.02 (95% CI 0.94, 1.11), 1.02 (0.93, 1.11), 0.88 (0.80, 0.97), and 0.91 (0.86, 0.97), respectively. There were no clinically meaningful differences when stratified by hypertension stage, 10-year ASCVD risk, age, and sex. CONCLUSIONS: In this community-based population, low standing SBP was common and not significantly associated with falls or syncope, but was associated with a lower risk of CHD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events.

Higher intake of dietary flavonols, specifically dietary quercetin, is associated with lower odds of frailty onset over 12 years of follow-up among adults in the Framingham Heart Study.

BACKGROUND: Polyphenolic antioxidants derived from plant foods may reduce oxidative stress and frailty, but the effect of the polyphenol subclass of dietary flavonoids and their subclasses on frailty is uncertain. OBJECTIVES: To determine the association between dietary flavonoids, their subclasses, quercetin (a specific flavonol), and frailty onset in adults. METHODS: This prospective cohort study included individuals from the Framingham Heart Study with no frailty at baseline. Intake of total flavonoids, subclasses of flavonoids (flavonols, flavan-3-ols, flavonones, flavones, anthocyanins, and polymeric flavonoids), and quercetin were estimated via semi-quantitative FFQ along with frailty (Fried phenotype), and covariates at baseline (1998-2001). Frailty was re-evaluated in 2011-2014. Logistic regression estimated OR and 95% CIs for each flavonoid variable and frailty onset. RESULTS: Mean age was 58.4 y (SD ± 8.3, n = 1701; 55.5% women). The mean total flavonoid intake was 309 mg/d (SD ± 266). After 12.4 (SD ± 0.8) y, 224 (13.2%) individuals developed frailty. Although total flavonoid intake was not statistically associated with frailty onset (adjusted OR: 1.00; 95% CI: 0.99-1.01), each 10 mg/d of higher flavonol intake was linked with 20% lower odds of frailty onset (OR: 0.80; 95% CI: 0.67-0.96). Other subclasses showed no association (P values range: 0.12-0.99), but every 10 mg/d of higher quercetin intake was associated with 35% lower odds of frailty onset (OR: 0.65; 95% CI: 0.48-0.88). CONCLUSIONS: Although no association was observed between total flavonoid intake and frailty onset in adults, a higher intake of flavonols was associated with lower odds of frailty onset, with a particularly strong association for quercetin. This hypothesis-generating study highlights the importance of assessing specific subclasses of flavonoids and the potential of dietary flavonols and quercetin as a strategy to prevent the development of frailty.

The age-related contribution of cognitive function to dual-task gait in middle-aged adults in Spain: observations from a population-based study.

BACKGROUND: Poor dual-task gait performance is associated with a risk of falls and cognitive decline in adults aged 65 years or older. When and why dual-task gait performance begins to deteriorate is unknown. This study aimed to characterise the relationships between age, dual-task gait, and cognitive function in middle age (ie, aged 40-64 years). METHODS: We conducted a secondary analysis of data from community-dwelling adults aged 40-64 years that took part in the Barcelona Brain Health Initiative (BBHI) study, an ongoing longitudinal cohort study in Barcelona, Spain. Participants were eligible for inclusion if they were able to walk independently without assistance and had completed assessments of both gait and cognition at the time of analysis and ineligble if they could not understand the study protocol, had any clinically diagnosed neurological or psychiatric diseases, were cognitively impaired, or had lower-extremity pain, osteoarthritis, or rheumatoid arthritis that could cause abnormal gait. Stride time and stride time variability were measured under single-task (ie, walking only) and dual-task (ie, walking while performing serial subtractions) conditions. Dual-task cost (DTC; the percentage increase in the gait outcomes from single-task to dual-task conditions) to each gait outcome was calculated and used as the primary measure in analyses. Global cognitive function and composite scores of five cognitive domains were derived from neuropsychological testing. We used locally estimated scatterplot smoothing to characterise the relationship between age and dual-task gait, and structural equation modelling to establish whether cognitive function mediated the association between observed biological age and dual tasks. FINDINGS: 996 people were recruited to the BBHI study between May 5, 2018, and July 7, 2020, of which 640 participants completed gait and cognitive assessments during this time (mean 24 days [SD 34] between first and second visit) and were included in our analysis (342 men and 298 women). Non-linear associations were observed between age and dual-task performance. Starting at 54 years, the DTC to stride time (ß=0·27 [95% CI 0·11 to 0·36]; p<0·0001) and stride time variability (0·24 [0·08 to 0·32]; p=0·0006) increased with advancing age. In individuals aged 54 years or older, decreased global cognitive function correlated with increased DTC to stride time (ß=-0·27 [-0·38 to -0·11]; p=0·0006) and increased DTC to stride time variability (ß=-0·19 [-0·28 to -0·08]; p=0·0002). INTERPRETATION: Dual-task gait performance begins to deteriorate in the sixth decade of life and, after this point, interindividual variance in cognition explains a substantial portion of dual-task performance. FUNDING: La Caixa Foundation, Institut Guttmann, and Fundació Abertis.

Body Position and Orthostatic Hypotension in Hypertensive Adults: Results from the Syst-Eur Trial.

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.

Sensorimotor and Frontoparietal Network Connectivity Are Associated With Subsequent Maintenance of Gait Speed and Episodic Memory in Older Adults.

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.

Brain activity during dual-task standing in older adults.

BACKGROUND: In older adults, the extent to which performing a cognitive task when standing diminishes postural control is predictive of future falls and cognitive decline. The neurophysiology of such "dual-tasking" and its effect on postural control (i.e., dual-task cost) in older adults are poorly understood. The purpose of this study was to use electroencephalography (EEG) to examine the effects of dual-tasking when standing on brain activity in older adults. We hypothesized that compared to single-task "quiet" standing, dual-task standing would decrease alpha power, which has been linked to decreased motor inhibition, as well as increase the ratio of theta to beta power, which has been linked to increased attentional control. METHODS: Thirty older adults without overt disease completed four separate visits. Postural sway together with EEG (32-channels) were recorded during trials of standing with and without a concurrent verbalized serial subtraction dual-task. Postural control was measured by average sway area, velocity, and path length. EEG metrics included absolute alpha-, theta-, and beta-band powers as well as theta/beta power ratio, within six demarcated regions-of-interest: the left and right anterior, central, and posterior regions of the brain. RESULTS: Most EEG metrics demonstrated moderate-to-high between-day test-retest reliability (intra-class correlation coefficients > 0.70). Compared with quiet standing, dual-tasking decreased alpha-band power particularly in the central regions bilaterally (p = 0.002) and increased theta/beta power ratio in the anterior regions bilaterally (p < 0.001). A greater increase in theta/beta ratio from quiet standing to dual-tasking in numerous demarcated brain regions correlated with greater dual-task cost (i.e., absolute increase, indicative of worse performance) to postural sway metrics (r = 0.45-0.56, p < 0.01). Lastly, participants who exhibited greater alpha power during dual-tasking in the anterior-right (r = 0.52, p < 0.01) and central-right (r = 0.48, p < 0.01) regions had greater postural sway velocity during dual-tasking. CONCLUSION: In healthy older adults, alpha power and theta/beta power ratio change with dual-task standing. The change in theta/beta power ratio in particular may be related to the ability to regulate standing postural control when simultaneously performing unrelated, attention-demanding cognitive tasks. Modulation of brain oscillatory activity might therefore be a novel target to minimize dual-task cost in older adults.

Extended effects of a wearable sensory prosthesis on gait, balance function and falls after 26 weeks of use in persons with peripheral neuropathy and high fall risk-The walk2Wellness trial.

Background: We 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 specific mechanical tactile stimuli related to plantar pressure measurements during standing and walking (RxFunction Inc., Eden Prairie, MN, United States). 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. Materials and methods: Participants had clinically diagnosed PN with impaired plantar sensation, high fall risk (Functional Gait Assessment, FGA score < 23) and ability to sense tactile stimuli above the ankle at the location of the device. Additional outcomes included 10 m Gait Speed, Timed Up and Go (TUG), Four-Stage Balance Test, and self-reported outcomes, including Activities-Specific Balance Confidence scale and Vestibular Disorders Activities of Daily Living Scale. Participants tracked falls using a calendar. Results: We 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 to 0.97 m/s), and 4-Stage Balance Test (from 25.6 to 28.4 s), 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, p < 0.004), similar to the 46% decrease reported after 10 weeks of use. Conclusion: A 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. Clinical trial registration: ClinicalTrials.gov, identifier #NCT03538756.