Olfactory Dysfunction Predicts 5-Year Mortality in Older Adults

Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57–85 were studied in 2005–6 (Wave 1) and their mortality determined in 2010–11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p<0.001), a “dose-dependent” effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process.     

Estimating Energy Expenditure from Heart Rate in Older Adults: A Case for Calibration

Background

Accurate measurement of free-living energy expenditure is vital to understanding changes in energy metabolism with aging. The efficacy of heart rate as a surrogate for energy expenditure is rooted in the assumption of a linear function between heart rate and energy expenditure, but its validity and reliability in older adults remains unclear.

Objective

To assess the validity and reliability of the linear function between heart rate and energy expenditure in older adults using different levels of calibration.

Design

Heart rate and energy expenditure were assessed across five levels of exertion in 290 adults participating in the Baltimore Longitudinal Study of Aging. Correlation and random effects regression analyses assessed the linearity of the relationship between heart rate and energy expenditure and cross-validation models assessed predictive performance.

Results

Heart rate and energy expenditure were highly correlated (r = 0.98) and linear regardless of age or sex. Intra-person variability was low but inter-person variability was high, with substantial heterogeneity of the random intercept (s.d. = 0.372) despite similar slopes. Cross-validation models indicated individual calibration data substantially improves accuracy predictions of energy expenditure from heart rate, reducing the potential for considerable measurement bias. Although using five calibration measures provided the greatest reduction in the standard deviation of prediction errors (1.08 kcals/min), substantial improvement was also noted with two (0.75 kcals/min).

Conclusion

These findings indicate standard regression equations may be used to make population-level inferences when estimating energy expenditure from heart rate in older adults but caution should be exercised when making inferences at the individual level without proper calibration.     

Longitudinal Neurostimulation in Older Adults Improves Working Memory

An increasing concern affecting a growing aging population is working memory (WM) decline. Consequently, there is great interest in improving or stabilizing WM, which drives expanded use of brain training exercises. Such regimens generally result in temporary WM benefits to the trained tasks but minimal transfer of benefit to untrained tasks. Pairing training with neurostimulation may stabilize or improve WM performance by enhancing plasticity and strengthening WM-related cortical networks. We tested this possibility in healthy older adults. Participants received 10 sessions of sham (control) or active (anodal, 1.5 mA) tDCS to the right prefrontal, parietal, or prefrontal/parietal (alternating) cortices. After ten minutes of sham or active tDCS, participants performed verbal and visual WM training tasks. On the first, tenth, and follow-up sessions, participants performed transfer WM tasks including the spatial 2-back, Stroop, and digit span tasks. The results demonstrated that all groups benefited from WM training, as expected. However, at follow-up 1-month after training ended, only the participants in the active tDCS groups maintained significant improvement. Importantly, this pattern was observed for both trained and transfer tasks. These results demonstrate that tDCS-linked WM training can provide long-term benefits in maintaining cognitive training benefits and extending them to untrained tasks.     

The Influence of Perceptual Training on Working Memory in Older Adults

Normal aging is associated with a degradation of perceptual abilities and a decline in higher-level cognitive functions, notably working memory. To remediate age-related deficits, cognitive training programs are increasingly being developed. However, it is not yet definitively established if, and by what mechanisms, training ameliorates effects of cognitive aging. Furthermore, a major factor impeding the success of training programs is a frequent failure of training to transfer benefits to untrained abilities. Here, we offer the first evidence of direct transfer-of-benefits from perceptual discrimination training to working memory performance in older adults. Moreover, using electroencephalography to evaluate participants before and after training, we reveal neural evidence of functional plasticity in older adult brains, such that training-induced modifications in early visual processing during stimulus encoding predict working memory accuracy improvements. These findings demonstrate the strength of the perceptual discrimination training approach by offering clear psychophysical evidence of transfer-of-benefit and a neural mechanism underlying cognitive improvement.     

Impaired Heart Rate Recovery in Patients with Endemic Fluorosis

The objective of the present study was to determine the heart rate recovery index (HRRI), a marker of autonomic nervous system function in patients with endemic fluorosis. Forty patients with endemic fluorosis (16 men/24 women) and 40 age-, sex-, and body mass index-matched healthy controls (16 men/24 women) with normal fluoride intake were enrolled in this study. HRRI was calculated by subtracting the heart rate values at the first, second, and third minutes of the recovery phase from the peak heart rate (HRRI 1, HRRI 2, HRRI 3). Urine fluoride levels of fluorosis patients were significantly (P?<?0.001) higher than control subjects as expected. HRRI 2 was significantly lower in fluorosis patients than in the controls. The incidence of abnormal HRRI 1 was significantly higher in fluorosis patients than in the controls (P?<?0.05). We observed that HRRI, a marker of autonomic nervous system function, is impaired in patients with chronic fluorosis.     

Gender Differences in Anthropometric Predictors of Physical Performance in Older Adults

BackgroundBoth high body fat and low muscle mass have been associated with physical disability in older adults. However, men and women differ markedly in body composition; men generally have more absolute and relative lean muscle mass and less fat mass than women. It is not known how these anthropometric differences differentially affect physical ability in men and women.ObjectivesThis study examines differences in anthropometric predictors of physical performance in older women and men.MethodsParticipants were 470 older women and men 72.9 (7.9) years of age. Body composition was measured using dual-energy x-ray absorptiometry. Maximum leg strength and power were measured using a leg press. Muscle quality (MQ) was calculated as relative strength (leg press strength per kilogram of leg muscle mass). Gait speed and chair rise were used to assess mobility performance and functional strength.ResultsBody mass index (BMI), age, and MQ emerged as predictors (P < 0.05) of functional strength and mobility in men and women somewhat differently. After accounting for age and sample, leg MQ was related to chair rise time and gait speed in men but not women. BMI was related to gait speed in both men and women, but BMI was related to chair rise time only in women.ConclusionResults implicate the prioritized importance of healthy weight and muscle maintenance in older women and men for maintained physical functioning with aging.     

Gender-Specific Differences in the Relationship between Autobiographical Memory and Intertemporal Choice in Older Adults

As the population of older adults grows, their economic choices will have increasing impact on society. Research on the effects of aging on intertemporal decisions shows inconsistent, often opposing results, indicating that yet unexplored factors might play an essential role in guiding one''s choices. Recent studies suggest that episodic future thinking, which is based on the same neural network involved in episodic memory functions, leads to reductions in discounting of future rewards. As episodic memory functioning declines with normal aging, but to greatly variable degrees, individual differences in delay discounting might be due to individual differences in the vitality of this memory system in older adults. We investigated this hypothesis, using a sample of healthy older adults who completed an intertemporal choice task as well as two episodic memory tasks. We found no clear evidence for a relationship between episodic memory performance and delay discounting in older adults. However, when additionally considering gender differences, we found an interaction effect of gender and autobiographical memory on delay discounting: while men with higher memory scores showed less delay discounting, women with higher memory scores tended to discount the future more. We speculate that this gender effect might stem from the gender-specific use of different modal representation formats (i.e. temporal or visual) during assessment of intertemporal choice options.     

Continuous Multi-Parameter Heart Rate Variability Analysis Heralds Onset of Sepsis in Adults

Background

Early diagnosis of sepsis enables timely resuscitation and antibiotics and prevents subsequent morbidity and mortality. Clinical approaches relying on point-in-time analysis of vital signs or lab values are often insensitive, non-specific and late diagnostic markers of sepsis. Exploring otherwise hidden information within intervals-in-time, heart rate variability (HRV) has been documented to be both altered in the presence of sepsis, and correlated with its severity. We hypothesized that by continuously tracking individual patient HRV over time in patients as they develop sepsis, we would demonstrate reduced HRV in association with the onset of sepsis.

Methodology/Principal Findings

We monitored heart rate continuously in adult bone marrow transplant (BMT) patients (n = 21) beginning a day before their BMT and continuing until recovery or withdrawal (12±4 days). We characterized HRV continuously over time with a panel of time, frequency, complexity, and scale-invariant domain techniques. We defined baseline HRV as mean variability for the first 24 h of monitoring and studied individual and population average percentage change (from baseline) over time in diverse HRV metrics, in comparison with the time of clinical diagnosis and treatment of sepsis (defined as systemic inflammatory response syndrome along with clinically suspected infection requiring treatment). Of the 21 patients enrolled, 4 patients withdrew, leaving 17 patients who completed the study. Fourteen patients developed sepsis requiring antibiotic therapy, whereas 3 did not. On average, for 12 out of 14 infected patients, a significant (25%) reduction prior to the clinical diagnosis and treatment of sepsis was observed in standard deviation, root mean square successive difference, sample and multiscale entropy, fast Fourier transform, detrended fluctuation analysis, and wavelet variability metrics. For infected patients (n = 14), wavelet HRV demonstrated a 25% drop from baseline 35 h prior to sepsis on average. For 3 out of 3 non-infected patients, all measures, except root mean square successive difference and entropy, showed no significant reduction. Significant correlation was present amongst these HRV metrics for the entire population.

Conclusions/Significance

Continuous HRV monitoring is feasible in ambulatory patients, demonstrates significant HRV alteration in individual patients in association with, and prior to clinical diagnosis and treatment of sepsis, and merits further investigation as a means of providing early warning of sepsis.     

Longitudinal Associations between Physical and Cognitive Performance among Community-Dwelling Older Adults

To assess the directionality of the association between physical and cognitive decline in later life, we compared patterns of decline in performance across groups defined by baseline presence of cognitive and/or physical impairment [none (n = 217); physical only (n = 169); cognitive only (n = 158), or both (n = 220)] in a large sample of participants in a cognitive aging study at the Knight Alzheimer’s Disease Research Center at Washington University in St. Louis who were followed for up to 8 years (3,079 observations). Rates of decline reached 20% for physical performance and varied across cognitive tests (global, memory, speed, executive function, and visuospatial skills). We found that physical decline was better predicted by baseline cognitive impairment (slope = -1.22, p<0.001), with baseline physical impairment not contributing to further decline in physical performance (slope = -0.25, p = 0.294). In turn, baseline physical impairment was only marginally associated with rate of cognitive decline across various cognitive domains. The cognitive-functional association is likely to operate in the direction of cognitive impairment to physical decline although physical impairment may also play a role in cognitive decline/dementia. Interventions to prevent further functional decline and development of disability and complete dependence may benefit if targeted to individuals with cognitive impairment who are at increased risk.     

Physical Predictors of Cognitive Performance in Healthy Older Adults: A Cross-Sectional Analysis

There is ample evidence that physical and cognitive performance are related, but the results of studies investigating this relationship show great variability. Both physical performance and cognitive performance are constructs consisting of several subdomains, but it is presently unknown if the relationship between physical and cognitive performance depends on subdomain of either construct and whether gender and age moderate this relationship. The aim of this study is to identify the strongest physical predictors of cognitive performance, to determine the specificity of these predictors for various cognitive subdomains, and to examine gender and age as potential moderators of the relationship between physical and cognitive performance in a sample of community-dwelling older adults. In total, 98 men and 122 women (average age 74.0±5.6 years) were subjected to a series of performance-based physical fitness and neuropsychological tests. Muscle strength, balance, functional reach, and walking ability (combined score of walking speed and endurance) were considered to predict cognitive performance across several domains (i.e. memory, verbal attention, visual attention, set-shifting, visuo-motor attention, inhibition and intelligence). Results showed that muscle strength was a significant predictor of cognitive performance for men and women. Walking ability and balance were significant predictors of cognitive performance for men, whereas only walking ability was significant for women. We did not find a moderating effect of age, nor did we find support for a differential effect of the physical predictors across different cognitive subdomains. In summary, our results showed a significant relationship between cognitive and physical performance, with a moderating effect of gender.     

运动后心力及心率同时遥测的心力恢复趋势与心率恢复趋势的对比研究

为了更加全面地研究和评估心肌的变时性和变力性,研制了能够在运动场地同时采集心力和心率的心音信号遥测系统。采集了50名体育系学生和30名其他系学生在完成规定运动量的登梯运动后,5min内连续变化的心音信号。对采集的数据经过3次样条插值、均匀采样和小波变换滤波后,得到了平滑的心力恢复趋势曲线和心率恢复趋势曲线。统计分析表明,大负荷运动量下的心脏储备主要来自于心力储备而不是心率储备(P<0.001),和其他系学生相比,体育系学生具有的高水平心功能不仅在于具有更大的心力储备指数(P<0.001),而且还在于具有更快的心力恢复速度(P<0.001)。同时检测心力恢复趋势与心率恢复趋势会有益于全面评估心脏功能。     

Drawing to Remember: External Support of Older Adults’ Eyewitness Performance

Although healthy aging is accompanied by a general decline in memory functioning, environmental support at retrieval can improve older adults’ (+65 years) episodic remembering. Despite those over the age of 65years representing a growing proportion of the population, few environmental retrieval support methods have been empirically evaluated for use with older witnesses and victims of crime. Here, the efficacy of a novel retrieval technique, the Sketch Mental Reinstatement of Context, is compared with a standard Mental Reinstatement of Context and a no support control (Control). Fifty-one participants witnessed an unexpected live event, and 48 hours later were interviewed using one of three aforementioned techniques. In line with predictions emanating from cognitive theories of aging and the environmental support hypothesis, participants in the Sketch Mental Reinstatement of Context condition recalled significantly more correct information and fewer inaccurate items. The Sketch Mental Reinstatement of Context technique appears to scaffold memory retrieval in an age-appropriate manner during a post-event interview, possibly by encouraging more effortful retrieval and reducing dual-task load. As such, this procedure offers an effective alternative to current approaches, adding to the toolbox of techniques available to forensic and other interviewers.     

Up-Training Loading Responses in Older Adults

This randomized, experimental-control group, multiple-observation study examined the ability of older adults to use center of pressure feedback to up-train the vertical loading response (LR) and the impact that such training had on changes in clinical tests of balance. Eleven community ambulators, aged at least 65 years, with no recent history of falls were recruited by convenience sampling. Each group received 6 baseline sessions and 6 control/training sessions, followed by 1 posttest session. All sessions included visual cueing about stance equilibrium followed by 30 randomly timed dynamic, toes-up perturbations (8 degrees, 66 degrees per second). Training consisted of verbal instructions with visual and auditory feedback of a 225 msec response window to shape an increase in total LR following perturbations. Subjects in the experimental group demonstrated a tendency to decrease vertical loading relative to baseline regardless of visual and verbal feedback encouraging strategies to increase it. Specifically, the T3 or 150–225 msec component of the response window showed a decline from session 7 to session 12. Up-training, however, appears to cause a faster rate of rise to the maintenance window, but this event probably occurs too late to correct for a loss of balance. No correlation was found between change in load values and change in performance on clinical balance tests.     

Resting Heart Rate Variability Predicts Safety Learning and Fear Extinction in an Interoceptive Fear Conditioning Paradigm

This study aimed to investigate whether interindividual differences in autonomic inhibitory control predict safety learning and fear extinction in an interoceptive fear conditioning paradigm. Data from a previously reported study (N = 40) were extended (N = 17) and re-analyzed to test whether healthy participants'' resting heart rate variability (HRV) - a proxy of cardiac vagal tone - predicts learning performance. The conditioned stimulus (CS) was a slight sensation of breathlessness induced by a flow resistor, the unconditioned stimulus (US) was an aversive short-lasting suffocation experience induced by a complete occlusion of the breathing circuitry. During acquisition, the paired group received 6 paired CS-US presentations; the control group received 6 explicitly unpaired CS-US presentations. In the extinction phase, both groups were exposed to 6 CS-only presentations. Measures included startle blink EMG, skin conductance responses (SCR) and US-expectancy ratings. Resting HRV significantly predicted the startle blink EMG learning curves both during acquisition and extinction. In the unpaired group, higher levels of HRV at rest predicted safety learning to the CS during acquisition. In the paired group, higher levels of HRV were associated with better extinction. Our findings suggest that the strength or integrity of prefrontal inhibitory mechanisms involved in safety- and extinction learning can be indexed by HRV at rest.     

Cross-Sectional and Longitudinal Associations of Different Sedentary Behaviors with Cognitive Performance in Older Adults

Background

The deleterious health effects of sedentary behaviors, independent of physical activity, are increasingly being recognized. However, associations with cognitive performance are not known.

Purpose

To estimate the associations between different sedentary behaviors and cognitive performance in healthy older adults.

Methods

Computer use, time spent watching television (TV), time spent reading and habitual physical activity levels were self-reported twice (in 2001 and 2007) by participants in the SUpplémentation en Vitamines et MinérauX (SU.VI.MAX and SU.VI.MAX2) study. Cognitive performance was assessed at follow-up (in 2007–2009) via a battery of 6 neuropsychological tests used to derive verbal memory and executive functioning scores. Analyses (ANCOVA) were performed among 1425 men and 1154 women aged 65.6±4.5 at the time of the neuropsychological evaluation. We estimated mean differences with 95% confidence intervals (95%CI) in cognitive performance across categories of each type of sedentary behavior.

Results

In multivariable cross-sectional models, compared to non-users, participants using the computer for >1 h/day displayed better verbal memory (mean difference = 1.86; 95%CI: 0.95, 2.77) and executive functioning (mean difference = 2.15; 95%CI: 1.22, 3.08). A negative association was also observed between TV viewing and executive functioning. Additionally, participants who increased their computer use by more than 30 min between 2001 and 2007 showed better performance on both verbal memory (mean difference = 1.41; 95%CI: 0.55, 2.27) and executive functioning (mean difference = 1.41; 95%CI: 0.53, 2.28) compared to those who decreased their computer use during that period.

Conclusion

Specific sedentary behaviors are differentially associated with cognitive performance. In contrast to TV viewing, regular computer use may help maintain cognitive function during the aging process.

Clinical Trial Registration

clinicaltrial.gov (number {"type":"clinical-trial","attrs":{"text":"NCT00272428","term_id":"NCT00272428"}}NCT00272428).     

Evaluation of an Exercise Field Test Using Heart Rate Monitors to Assess Cardiorespiratory Fitness and Heart Rate Recovery in an Asymptomatic Population

Purpose

Measures of cardiorespiratory fitness (CRF) and heart rate recovery (HRR) can improve risk stratification for cardiovascular disease, but these measurements are rarely made in asymptomatic individuals due to cost. An exercise field test (EFT) to assess CRF and HRR would be an inexpensive method for cardiovascular disease risk assessment in large populations. This study assessed 1) the predictive accuracy of a 12-minute run/walk EFT for estimating CRF () and 2) the accuracy of HRR measured after an EFT using a heart rate monitor (HRM) in an asymptomatic population.

Methods

Fifty subjects (48% women) ages 18–45 years completed a symptom-limited exercise tolerance test (ETT) (Bruce protocol) and an EFT on separate days. During the ETT, was measured by a metabolic cart, and heart rate was measured continuously by a HRM and a metabolic cart.

Results

EFT distance and sex independently predicted. The average absolute difference between observed and predicted was 0.26±3.27 ml·kg⁻¹·min⁻¹ for our model compared to 7.55±3.64 ml·kg⁻¹·min⁻¹ for the Cooper model. HRM HRR data were equivalent to respective metabolic cart values during the ETT. HRR at 1 minute post-exercise during ETT compared to the EFT had a moderate correlation (r = 0.75, p<0.001).

Conclusion

A more accurate model to estimate CRF from a 12-minute run/walk EFT was developed, and HRR can be measured using a HRM in an asymptomatic population outside of clinical settings.     

Heart Rate Variability during Performance of Various Resultive Tasks

Heart rate variability was studied in 30 subjects before and after the assembling of a single-type color mosaic. The heart rate analysis was performed by evaluating its statistical structure (variation curves, scatter plots, and standard deviation). The wave structure of a series of cardiointervals was assessed by calculating and plotting the autocorrelation function. Certain heart rate parameters in different subjects reflected to various extents their success in achieving the useful end result of the visuomotor design task.     

The Ethics of Deprescribing in Older Adults

Deprescribing is the term used to describe the process of withdrawal of an inappropriate medication supervised by a clinician. This article presents a discussion of how the Four Principles of biomedical ethics (beneficence, non-maleficence, autonomy, and justice) that may guide medical practitioners’ prescribing practices apply to deprescribing medications in older adults. The view of deprescribing as an act creates stronger moral duties than if viewed as an omission. This may explain the fear of negative outcomes which has been reported by prescribers as a barrier to deprescribing. Respecting the autonomy of older adults is complex as they may not wish to be active in the decision-making process; they may also have reduced cognitive function and family members may therefore have to step in as surrogate decision-makers. Informed consent is intended as a process of information giving and reflection, where consent can be withdrawn at any time. However, people are rarely updated on the altered risks and benefits of their long-term medications as they age. Cessation of inappropriate medication use has a large financial benefit to the individual and the community. However, the principle of justice also dictates equal rights to treatment regardless of age.